SFL Policy Insights & Newsletters

After two years of interruption due to the pandemic, SFL welcomed its team, clients and partners in Basel for its traditional Spring Apéro.

On 4 May 2022, SFL organized its Spring Apéro in Basel, Switzerland. More than 130 clients, partners and team members attended the event.

Shayesteh Fürst-Ladani, Senior Vice President at SFL and Head of the SFL Group, welcomed the participants. She highlighted key milestones of SFL’s history and that the acquisition by Veristat will further broaden SFL’s service portfolio across the entire lifecycle of drugs, devices, combined products and diagnostics. She thanked SFL clients and partners for their continued trust and affirmed that SFL deeply values the longstanding relationships and is committed to continue supporting them.

Montserrat Barceló Rieria, Vice President Europe at Veristat, welcomed SFL in the Veristat family. She underlined that SFL and Veristat share common values, including a commitment to scientific excellence, a key requisite for a success. She highlighted how complementary the service areas and geographical scopes of SFL and Veristat are and expressed her confidence that SFL, as a Veristat company, will be in a position to continue providing high quality support for its clients and partners and further extend its service offering.

Christof Klöpper, CEO of Basel Area, recalled that Basel is an international hub for life sciences, comparable to Boston, where Veristat is headquartered. Over the years, a vibrant ecosystem has flourished in Basel, composed of leading pharmaceutical, medtech and biotech companies, a rich network of innovative SMEs such as SFL and excellent academic and research institutions.

After the opening speeches, discussions, laughter, fine food, live music and dance punctuated the evening.

As of 26 May 2022, new rules will apply to IVDs in the EU (IVDR) and in Switzerland (Ordinances on IVDs and clinical trials with medical devices).

The In Vitro Diagnostics Regulation (Regulation 2017/746, IVDR), that enters into application on 26 May 2022, brings significant changes to the regulation of IVDs in the EU. Among other, it introduces a risk-based classification, a notified body (NB) conformity assessment for most IVDs, enhanced requirements for performance studies and increased post-market obligations and transparency. Certificates for IVDs issued by a NB under the IVD Directive remain valid until 26 May 2025. Transition periods from 2025 to 2027 apply for IVDs for which the IVDR introduces a conformity assessment involving an NB.

In Switzerland, on 4 May 2022, the Federal Council adopted the new framework for in vitro diagnostics (IVDs), which aims to align the Swiss legislation with the EU IVDR. The texts – new Ordinance on IVDs and the revised Ordinance on clinical trials with medical devices – will enter into application in Switzerland on 26 May 2022, parallel to the IVDR in the EU. Like the IVDR, the Ordinance on IVDs sets transition periods for IVDs with a certificate granted under the previous framework and IVDs for which the text introduces a conformity assessment requirement.

Due to the absent update of the Mutual Recognition Agreement with the EU, the mutual recognition of conformity assessments for IVDs is no longer guaranteed. As for medical devices, manufacturers based in the EU/EEA or which have appointed an authorized representative based in the EU/EEA, will need to appoint a Swiss authorized representative to place IVDs on the Swiss market after 26 May 2022. The Ordinance on IVDs foresees the following transition periods to appoint a representative: 31 December 2022 for class D IVDs, 31 March 2023 for Class B and C IVDs and 31 July 2023 for Class A IVDs.

The Commission aims to strengthen and harmonize the framework for intellectual property and to ensure access to critical goods during crises.

The European Commission is currently reviewing the EU intellectual property (IP) framework. Its goal is to harmonize and enhance the protection of intellectual property rights in the EU, as foreseen in the Intellectual Property Action Plan. Since its adoption in November 2020, there have been several key initiatives focusing on:

• Supplementary protection certificates (SPC): An evaluation report published in 2020 concluded that the SPC system, which extends patent protection for specific medicinal products, remains relevant but suffers from fragmented implementation. This leads to inefficiencies and a lack of transparency and predictability, which hinders innovators and generic producers and impedes access to treatment. The Commission is preparing a proposal that aims to increase legal certainty, provide a unitary protection and improve transparency. Policy options include a unitary SPC and/or a single unified procedure for granting national SPCs. The Commission held a call for evidence in March-April 2022. The adoption of the proposal is planned for Q4 2022.

• Compulsory licensing: In the EU, compulsory licensing of patents is currently regulated at the national level, which creates uncertainties for holders and user of IP rights and, from the authorities’ perspective, difficulties to tackle EU-wide crises such as the COVID-19 pandemic. The Commission is preparing a revision of the framework with a view to enhance compulsory licensing efficiency, reduce fragmentation and ensure an effective procedure for exports. Options under consideration include an EU-level compulsory license. A call for evidence was held in April 2022. A public consultation is planned later in 2022. The adoption of the proposal is planned for Q1 2023.

• Standard-essential patents (SEPs): A number of SEP users find that the current system for licensing SEPs is not sufficiently transparent, predictable or efficient. The Commission is working on a proposition that aims to create a fair and balanced licensing framework for patents protecting technology essential to standards. Following a call for evidence in February-May 2022, a proposal is planned to be adopted in Q4 2022.

The Commission recently detailed planned actions to implement the HTA Regulation. The EMA and the EUnetHTA also published a joint plan.

On 10 March 2022, the European Commission published a rolling plan for the implementation of the Regulation 2021/2282 on health technology assessment (HTA), which will enter into application on 12 January 2025 (Article 7(2) introduces different transition periods for joint clinical assessments of certain products). The rolling plan gives an overview of the planned activities to prepare for the entry into application:

• Setup of the Coordination Group, in charge of overseeing the work of the different subgroups (Q2 2022),
• Setup of the subgroups which will carry out the joint activities foreseen in the Regulation (development of guidance, clinical assessments, scientific consultations, identification of emerging health technologies) (Q4 2022-Q1 2024),
• Setup of the Stakeholder Network, which will provide input on HTA activities (Q1 2023),
• Preparation and adoption of implementing acts (Q4 2024-Q4 2026).

On 22 June 2022, the Commission will present the HTA Regulation during a dedicated one-day conference. The European Network for HTA (EUnetHTA) will organize the second open calls for joint scientific consultations from 6 June to 31 August 2022. The consultations are expected to start in November 2022.

On 12 April 2022, the European Medicines Agency (EMA) published a joint work plan with the European HTA bodies. Areas for collaboration include joint scientific consultations, exchange on information on assessments, generation of data, horizon scanning activities and development of study methods and guidelines on real world evidence.

The Head of SFL Group of Companies presented insights on digital health and clinical trials. SFL will host a webinar on the European health policy & regulatory agenda.

Shayesteh Fürst-Ladani, Senior Vice President at SFL and Head of the SFL Group, presented at ‘Scale-Up to Switzerland’ organized by the Ontario Bioscience Innovation Organization (OBIO) on 5 April 2022. She provided an overview of the framework for clinical trials for medicinal products and medical devices in the European Union and Switzerland and shared her insights on submitting applications for clinical trials in Europe.

On 28 April 2022, Shayesteh moderated the webinar on ‘Early lessons on the developing regulatory framework for digital health and outlook on AI policy’ hosted by the Medtech & Pharma Platform Association (MPP). She presented the EU framework for products combining medicinal products, medical devices and digital health (e.g. apps, software) components (so-called ‘combined products’) and proposals on digital health and artificial intelligence currently under discussion within the Parliament and the Council. She underlined the regulatory challenges linked to the absence of unified framework for combined products.

On 21 June 2022, 4-5 pm CEST SFL will organize a webinar on ‘Policy & regulatory intelligence in the health sector in Europe: Latest developments and outlook for innovative product development’. The webinar, presented by SFL’s Public Affairs team, will give an overview of recent developments policy and regulatory for innovative products in the EU, the United Kingdom and Switzerland, with a focus on clinical trials and advanced therapies. It will provide relevant insights and illustrate how public affairs can support organizations active in the healthcare sector. Registration for the webinar is open.

Veristat conducted a webinar hosted by TOPRA on “Expediting Access to Novel/Medicinal Products in the US and EU” with a focus on when and how to apply expedited pathways.

In April, Veristat conducted a webinar hosted by TOPRA on “Expediting Access to Novel/Medicinal Products in the US and EU” with a focus on when and how to apply expedited regulatory pathways. Our regulatory experts Mara Holinger, Xavier Luria and Kevin Hennegan shared their experiences on how developers of novel drug therapies can utilize some or multiple programs/pathways to accelerate approval in the US and Europe.

Bringing novel medicinal products to market is a long, complex, and expensive process which requires drug developers to balance the need for rigorous testing with the goal of getting medicines to patients quickly. As such, US and EU regulators have made accommodations for clinical trials involving indications challenged by small patient populations and other data-constraining hurdles. Expedited pathways are intended to accelerate the approval process for therapies that treat serious conditions and unmet medical needs.

The webinar highlighted the requirements, benefits, and procedures for following US pathways: Accelerated Approval, Breakthrough Therapy Designation, Fast Track, and Priority Review Designation. Veristat experts also reviewed the similarities and differences to the EU pathways: Accelerated Assessment, Conditional Marketing Application (CMA), and Priority Medicines Scheme (PRIME). The presentation concluded with real-world examples and success stories offered by our experts.

Watch the webinar on-demand here.

On 3 May 2022, the European Commission adopted the legislative proposal for the creation of a European Health Data Space (EHDS). The EHDS will build on the horizontal framework for data and provide specific rules for the health sector. The Commission opened a public consultation on the proposal, which will run until 29 June 2022. Received feedback will be fed into the legislative debate.

The proposal covers the use of health data for healthcare delivery (primary purpose) and for research, innovation and policymaking (secondary purpose). It grants citizens the rights to access, share and modify their health data and introduces a mandatory self-certification of health electronic records (EHR). National bodies will grant permits to use health data for secondary purpose; the data will be anonymized and limited to what is relevant for the proposed use. The proposal seeks to ensure that no additional layer will be added for medical devices and artificial intelligence high-risk systems.

On 13 May 2022, the European Commission published an evaluation report on Directive 2011/24/EU on patients’ rights in cross-border healthcare, accompanied by a study to support its evaluation and data on patient mobility under the Directive. The evaluation concludes that the Directive has brought legal clarity regarding patients’ rights in cross-border healthcare and remains relevant to ensure the free movement of healthcare services. Among the benefits from the Directive identified in the evaluation are reinforced patients’ rights, a more consistent approach to reimbursement of cross-border healthcare and increased transparency on prices.

The evaluation report nonetheless points out several obstacles to the implementation of the Directive. They include a low level of awareness about patients’ rights, inadequate patient information, administrative burden and uncertainty regarding healthcare costs abroad and reimbursement.

The report sets out a series of follow-up actions spanning until 2026 to improve the implementation of the Directive, such as the use of digital tools, the extension of the voluntary prior notification system regarding the level of reimbursement, actions to improve information and a better integration of European Reference Networks into national healthcare systems.

On 16 February 2022, the European Parliament adopted the report prepared by its Special Committee on Beating Cancer (BECA). The report stresses the burden of cancer for individuals and healthcare systems and underlines remaining inequalities in access to screening and treatment across Europe. It calls for a comprehensive, multi-disciplinary and coordinated approach to cancer prevention, diagnosis and treatment and outlines a series of recommendations. They include launching an EU-supported cancer screening scheme, developing common screening protocols, supporting the implementation of the Directive on cross-border healthcare, encouraging generic and biosimilar medicines, supporting production capacity for medicines and enabling cost-free access to treatments for patients.

As foreseen under Europe’s Beating Cancer Plan, the European Commission will propose a revision of the Council Recommendation on cancer screening in Q3 2022. The Commission held a public consultation on the initiative in January-February 2022. In support of the revision, on 2 March 2022, the European Commission’s Group of Chief Scientific Advisors published a scientific opinion on cancer screening. They provide recommendations to improve existing screening programs and advocate extending them to lung and prostate cancer.

On 15 May 2022, the Swiss citizens adopted the revision of the Transplantation Act. The revision was presented by the Federal Council as a counterproposal to the popular initiative ‘Encourage organ donation – save lives’. The current framework is based on the principle of explicit consent. The revision seeks to a introduce a principle of presumed consent for organ donation. Relatives would continue to be consulted when no clear consent was expressed.

From August to September 2021, the UK Medicines and Health products Regulatory Agency (MHRA) held a public consultation on the Early Access to Medicines Scheme (EAMS). Created in 2014, the EAMS aims to enable access to medicines not yet approved by the MHRA for patients with a life-threatening or serious debilitating condition. Since its establishment, the scheme granted 100 medicines a Promising Innovative Medicine status.

Following the public consultation, the MHRA informed that it prepared a proposal to amend the Human Medicines Regulations 2012 to introduce specific EAMS provisions and will develop guidance on the scheme. The proposal will among other include provisions to simplify the supply of EAMS medicines, facilitate real-world data evidence collection, clarify the liability for prescribers and patients and enhance pharmacovigilance requirements.

European Union

• Revision of the blood, tissues and cells legislation (proposal expected in Q2 2022)
• Revision of the Council Recommendation on cancer screening (proposal expected in Q3 2022)
• Initiative on antimicrobial resistance (proposal expected in Q4 2022)
• Revision of the general pharmaceutical legislation (proposal expected in Q4 2022)
• Revision of the orphan and pediatric legislation (proposals expected in Q4 2022)
• Revision of the SPC system (proposal expected in Q4 2022)
• Revision of the framework for SEPs (proposal expected in Q4 2022)

Switzerland

• Consultation on the revision of the Swiss Ordinances on Health Insurance and Health Benefits (expected in May-September 2022)

The acquisition by Veristat enables SFL to extend its support to clients with Veristat’s longstanding experience in clinical trial planning and execution.

SFL is very pleased to announce the acquisition by the science-driven, Boston-based clinical research organization (CRO) Veristat, combining the strengths of two organizations with a shared commitment to quality and scientific integrity.

SFL’s founder and CEO, Shayesteh Fürst-Ladani, will continue her role as Head of the SFL Group and play a leadership role within Veristat. Also the SFL team will carry forward client’s projects without interruption.

SFL chose to join Veristat to foster the common abilities to solve complex drug and medical product challenges with scientific-minded thinking and supporting our clients’ ongoing and future needs.

The combination of our teams further supports our ability to positively influence the scientific progress, regulatory assessment and launch success of treatments for patients with difficult-to-treat diseases and conditions. Veristat brings more than 27 years’ experience in clinical trial planning and execution, with deep expertise in novel therapeutics. They offer bold thinking and a comprehensive range of services to solve the unique and complex challenges associated with accelerating therapies through clinical development to regulatory approval and commercialization.

Overall, the SFL team’s longstanding experience in providing strategic advice and operational support for all stages of product development, with in-house expertise for a broad range of product types including small molecules, biologics, drug-device combination products, medical devices, in vitro diagnostics (IVDs) and advanced therapy medicinal products (ATMPs) is amended by a substantial range of clinical development services such as global clinical operations, biostatistics and programming.

Please learn more about the combination of SFL and Veristat by reading the press release here.

SFL hosted a free webinar providing an overview of the framework for orphan drugs in the EU, the UK and Switzerland, and insights into the revision of the EU legislation.

On 24 February 2022, SFL organized a free webinar on ‘Regulatory considerations for orphan medicinal products’, attended by more than 170 participants. SFL’s regulatory affairs experts presented the incentives for the development of orphan medicinal products, the requirements for orphan drug designation (ODD), and the marketing authorization application pathways in the EU, the UK, and Switzerland. They provided an overview of international collaborations such as Project Orbis. Comparing the different procedures and requirements, the speakers shared their insights into the regulatory strategies for companies seeking for an ODD or to market an orphan medicinal product in Europe.

The webinar also took stock of the state of play of the discussions regarding the revision of the orphan drug legislation in the EU, with the adoption of a legislative proposal expected in Q4 2022. The revision aims to foster the development and accelerate the access to therapies in areas of high unmet needs and will review the current incentives system.

Enhanced role for the EMA during health crises for the definition and monitoring of critical products, and the coordination of the EU’s response.

The Regulation revising the mandate of the European Medicines Agency (EMA) (2022/123) entered into application on 1 March 2022, except for the provisions on monitoring and mitigating shortages of critical medical devices (articles 21-29), set to enter into application on 2 February 2023.

The Regulation extends the mandate of the EMA for monitoring, prevention, and reporting on shortages of medicinal products and medical devices as well as coordinating actions during public health emergencies. The EMA will also provide support for the expert panels for certain high-risk medical devices and in vitro diagnostics (IVDs) under the Medical Devices and In Vitro Diagnostics Regulations (2017/745, MDR; 2017/746, IVDR). The Agency will among other provide administrative and technical support, ensure their work is carried out independently, publish their opinions, views and advice as well as report on their work.

Monitoring of events

The EMA will continuously monitor any events likely to lead to the following situations:

• A public health emergency, defined as a situation of public health emergency recognized by the Commission in accordance with article 12(1) of Decision 1082/2013/EU,
• A major event, which is defined as an event “likely to pose a serious risk to public health in relation to medicinal products in more than one Member State”.

The EMA will cooperate with the Member States and the European Centre for Disease Prevention and Control (ECDC). EU national competent authorities (NCAs) for medicinal products will report any such events to the EMA.

Response to public health emergencies and major events

The Regulation foresees the creation of several bodies within the EMA to be activated during public health emergencies or major events.

When it comes to medicinal products that have the potential to address a public health emergency, the Emergency Task Force (ETF) will provide scientific advice on the development of treatments and vaccines, review relevant available data, provide free of charge advice on clinical trial protocols, support clinical trials and provide scientific recommendations for relevant products.

The Medicine Shortages Steering Group (MSSG) and the Medical Device Shortages Steering Group (MDSSG), comprised of representatives from the EMA, the European Commission, and EU Member States, will establish and update lists of critical medicinal products and medical devices, monitor their supply and demand, and report on the monitoring to the Commission and NCAs. The EMA will publish information on actual shortages of the products on the lists. The MSSG and MDSSG may provide advice and recommendations to the European Commission, Member States, manufacturers, notified bodies or other stakeholders to prevent or mitigate shortages. The information on shortages, demand and supply of medicinal products will be centralized in a European shortages monitoring platform (ESMP), to be set up and monitored by the EMA.

Cooperation between the stakeholders

The Agency is tasked to ensure cooperation between the MSSG and MDSSG, as well as the ETF and the expert panels. The MSSG and MSSSG may be tasked by the European Commission to coordinate the measures taken by the different actors to prevent or mitigate shortages.

The Regulation sets requirements for the different actors including marketing authorization holders and medical device manufacturers. If a public health emergency or major event is declared, the EMA will establish lists of single points of contact for marketing authorization holders whose medicinal products are on the MSSG list and medical device manufacturers, their importers and notified bodies for the devices on the MDSSG list. Concerned marketing authorization holders and manufacturers, their representatives, importers, distributors, and notified bodies shall provide the information requested by the EMA. Marketing authorization holders and medical device manufacturers shall take into account the recommendations form the MSSG or the MDSSG and report on the measures taken. Notified bodies can be made to prioritize the conformity assessments of products on the MDSSG list.

Member States shall provide the information requested by the EMA on medicinal products and medical devices on the MSSG and MDSSG lists, respectively. They shall also take into account the recommendations and guidelines from the European Commission and inform the MSSG and MDSSG of the measures taken.

The European Commission is tasked to draft guidelines and recommendations for the different actors when appropriate, facilitate coordination in the EU and internationally. The Commission will inform the MSSG and MDSSG of the actions taken and may request them to provide recommendations or coordinate measures. Furthermore, it will evaluate the Regulation by the end of 2026 and will assess in particular the implementation of the obligations to provide information to the EMA as well as the opportunity to extend the remit of the ESMP.

The entry into application of the CTR marks an important step for the harmonization and acceleration of clinical trials in the EU.

Entry into application of the CTR

The Clinical Trials Regulation (Regulation 536/2014, CTR), adopted in 2014, entered into application on 31 January 2022. On the same day, the Clinical Trials Information System (CTIS), which supports its implementation, went live. The entry into application of the CTR will contribute to harmonize the process for the submission, assessment, and supervision of clinical trials in the EU. The CTR will enable sponsors to submit one application for trials in several European countries via the CTIS and national regulators to collaboratively process applications.

The following transition periods apply:

• Until 30 January 2023, sponsors may choose to run a new trial under the CTR or the Clinical Trials Directive (2001/20),
• By 31 January 2025, the CTR will apply to all ongoing trials in the EU approved under the Clinical Trials Directive.

The European institutions are taking steps to support the implementation of the CTR. The European Medicines Agency (EMA) launched a public website on clinical trials, published training materials and is organizing trainings to help stakeholders get acquainted with the CTIS. The European Commission updated several guidance documents:

• Questions and Answers about the CTR,
• Guidance on the management of clinical trials during the COVID-19 pandemic,
• Guideline on the requirements for quality documentation concerning biological investigational medicinal products (IMP) in clinical trials,
• Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning IMP in clinical trials.

ACT EU initiative

On 13 January 2022, the European Commission, the EMA and the Heads of Medicines Agencies (HMA) launched an initiative aiming to improve clinical trials initiation, design and conduct in the EU, called “Accelerating Clinical Trials in the EU” (ACT EU). The initiative aims to optimize the environment for clinical research in the EU, promote the development of high quality, safe, and effective medicines, especially in area of unmet medical needs, rare diseases, as well as for public health crises and pandemics, and better integrate clinical research in the health system. The ACT EU will be co-led by the Commission, the EMA and the HMA.

A related strategy paper identifies several priority actions for the period 2022-2023, including the timely implementation of the CTR, the establishment of a multi-stakeholder platform, the adaptation of Good Clinical Practices to international developments, reinforcing the coordination between the scientific advice on clinical trial approval and design, and publishing guidance on various aspects such as decentralized trials or the interface between the CTR and the In Vitro Diagnostics Regulation (2017/746, IVDR).

Commission defines rules for coordinated safety assessment and updates guidance

On 7 January 2022, the European Commission adopted an Implementing Regulation laying down the rules for the application of the CTR regarding the cooperation of EU Member States in safety assessment of  annual safety reports on active substances used in IMP and information submitted as suspected unexpected serious adverse reactions. It covers aspects such as the selection of safety assessing Member States, the development of recommendations, the assessment of substantial modifications to the reference safety information, and the coordination regarding the implementation of corrective measures and risk mitigation actions. It applies to all active substances used in IMP for clinical trials authorized in at least two EU Member States. The document became applicable on 31 January 2022.

In December 2021, the Council of the EU and the European Parliament adopted the Regulation on health technology assessment (2021/2282, HTA Regulation), proposed by the European Commission in January 2018. The text entered into force in January 2022. The Regulation will apply as of 12 January 2025. Article 7(2) of the Regulation introduces different transition periods for joint clinical assessments.

The HTA Regulation provides a permanent framework for cooperation between HTA authorities for medicines and high-risk medical devices for joint clinical assessments, scientific consultations, and the identification of emerging health technologies. The Regulation also lays out provisions for voluntary cooperation in other areas such as economic aspects of health technologies. Subgroups composed of national experts will carry out the work in different areas, under the supervision of a Coordination Group composed of representatives from national HTA bodies. The text adopted by the Council and the European Parliament is significantly less ambitious than the original proposal on several aspects. For instance, Member States are only required to give consideration to joint assessment reports and may decide to complement them, whereas the original proposal required them to apply the reports and not to carry out additional assessments.

From December 2021 to February 2022, the European Medicines Agency (EMA) carried out a survey to define the priorities for the future QIG. The QIG, which will be composed of experts from different EMA working groups and potentially other network or academic experts, will be a platform for discussion with developers and academia. The objective of the initiative is to facilitate the uptake of and remove technical and regulatory barriers to innovation in chemistry, manufacture and controls (CMC). The consultation aimed to gain a comprehensive overview of recent developments regarding analytical, manufacturing and control technologies, materials, manufacturing facility designs, and combinations of medicinal products with medical devices and digital solutions.

As of 1 January 2022, applications for clinical trials in the UK must be submitted via the combined review. The process, developed by the UK Health Research Authority (HRA) and Medicines and Health products Regulatory Agency (MHRA), enables a single application and a coordinated review process for trial authorization by the MHRA and the opinion from the Research Ethics Committee. Clinical trials sponsors will receive a single UK decision for a trial. The combined review is also applicable to combined trials of a medicinal product and a medical device. The HRA published guidance on the process and technical submission guidelines.

On 17 January 2022, the MHRA opened a public consultation to revise the UK framework for clinical trials. The initiative follows several objectives: streamlining clinical trial approvals, fostering innovation, enhancing transparency, enabling high risk proportionality, and promoting patients’ and public involvement. Selected measures proposed in the consultation include the involvement of patients and healthcare professionals in the design, management, and conduct of trials, the introduction of a validity period for the clinical trial approval and a risk-based approach to trial approval and conduct. The consultation is open until 14 March 2022.

In December 2021 and early 2022, the European Commission published several documents to support the implementation of the Medical Devices Regulation (2017/745, MDR) and In Vitro Diagnostics Regulation (2017/746, IVDR):

• Implementing Decision 2022/6 adds 9 standards to the list of harmonized standards in support of the MDR and Implementing Decision 2022/15 adds 5 standards in support of the IVDR,
• Implementing Regulation 2021/2226 sets out the conditions under which the instructions for use may be provided in an electronic form under the MDR,
• Notice to third countries manufacturers of SARS-CoV-2 in vitro diagnostics (IVDs) (Medical Device Coordination Group MDCG 2022-1) highlights issues that EU national competent authorities have identified in the course of their market surveillance activities,
• MDCG guidance on clinical evidence for IVDs (MDCG 2022-2) describes the approach by which collection, generation, and documentation of supporting data for an IVD may be conducted prior to the placing on the market and addresses principles related to post-market surveillance,
• MDCG guidance on the verification of class D IVDs by notified bodies (MDCG 2022-3),
• MDCG guidance on appropriate surveillance regarding the transitional provisions under article 120 MDR (MDCG 2022-4),
• Updated IVDR implementation plan,
• Updated timeline for EUDAMED: the European database on medical devices (EUDAMED) is expected to be fully functional by Q2 2023 and to go live in Q4 2023. Its use would only become mandatory in Q2 2025 for the obligations and requirements related to the UDI/Devices and NB & Certificates modules.

The European Medicines Agency (EMA) published for feedback draft guidance on the consultation by a notified body on companion diagnostics, which covers procedural aspects to facilitate the consultation procedure under IVDR article 48(3), (4), (7) and (8). The consultation on the draft closed on 20 February 2022.

The creation of the EHDS aims to promote exchange of and access to health data for primary and secondary uses as well as to reinforce health data protection. The EHDS will be based on three pillars: data governance and rules for exchange, data quality and strong infrastructure and interoperability. Preparatory work for the EHDS was carried out in 2020. A public consultation on the roadmap was held from December to February 2021 and a consultation on the initiative from May to July 2021. Respondents underlined that the EHDS should support research, promote citizens’ control over their personal health data, and facilitate cross-border access to healthcare. They expressed support for options such as the mandatory appointment of a national body to grant access to health data by third parties and additional rules to access health data for secondary purpose. The adoption of the legislative proposal by the European Commission is planned in Q1 2022.

The revision of the BTC legislation aims to update the legislation and address shortcomings identified in an evaluation by the European Commission in 2019. A public consultation on the roadmap was held from November to December 2020 and a public consultation on the revision from January to April 2021. Respondents confirmed the conclusions of the evaluation report. They expressed support for the definition of technical rules by technical bodies for the collection and management of BTC and donor and offspring protection. Most respondents also agreed with the need for enhanced oversight and the creation of an EU body to harmonize the decision on substance classification. The adoption of the legislative proposal(s) by the European Commission is scheduled in Q1 2022.

The Swiss Federal Council plans to open a public consultation on a new Ordinance on devitalized human tissues in April 2022. Until now, these products were treated as medical devices in Switzerland. Due to the adaptation of the framework for medical devices to the European framework, they need to be regulated separately.

The proposal for a Council Regulation on medical countermeasures, adopted by the European Commission in September 2021, aims to set up a framework of measures which could be activated in case of a public health emergency. The proposal’s objective is to complement the Union Health Emergency preparedness and Response Authority (HERA) in the area of crisis response. The Council of the EU reached a political agreement on the text on 20 December 2021. The formal adoption by the Council of the EU is pending.

The proposal for a Regulation on the mandate of the European Centre for Disease prevention and Control (ECDC), adopted by the European Commission in November 2020 as part of the European Health Union package, aims to extend the mandate of the ECDC in the areas of surveillance, early warning, preparedness and response to fight infectious diseases. The European Parliament and the Council of the EU reached a political agreement in December 2021, which was adopted by the Parliament’s Committee on Environment, Public Health and Food Safety on 13 January 2022. The formal adoption of the agreement by both institutions is expected in Q1 2022.

The Swiss Federal Council plans to open a public consultation on a revision of the Health Insurance Ordinance (Verordnung über die Krankenversicherung, KVV / Ordonnance sur l’assurance-maladie, OAMal) and Health Benefits Ordinance (Krankenpflege-Leistungsverordnung, KLV / Ordonnance sur les prestations de l’assurance-maladie, OPAS). The consultation, initially planned from February to May 2022, aims to implement measures for cost containment, streamline processes, enhance transparency and amend the regime for the reimbursement of medicines in individual cases under Article 71a-d KVV/OAMal.

SFL continued to provide high quality support and shape the discussions on regulatory frameworks.

SFL’s CEO, Shayesteh Fürst-Ladani, as well as the whole SFL team, would like to thank you for this year’s collaboration on very interesting projects to accelerate the development of, and improve patients’ access to, innovative and safe diagnostics, medicines, and medical devices.

SFL’s team spirit and work climate again received an external recognition this year. For the second time, SFL was awarded a Best Place to Work award by the independent global organization Great Place To Work. SFL was ranked third best employer in the small companies category with 93% of SFL’s employees considering SFL a great place to work and 100% emphasizing the camaraderie at work. SFL intends to continue its efforts in maintaining its friendly and adaptative work environment.

In August, SFL published an article providing a comprehensive overview of the marketing authorization application procedures and strategic considerations to ensure timely market access in Switzerland in the journal of Regulatory Affairs Professional Society (RAPS).

SFL held training courses during which experts from SFL shared their insights on the regulatory, quality, devices, combination products, advanced therapy medicinal products (ATMP) and reimbursement requirements. Offering webinars as well as customized trainings will continue in 2022. SFL team members also helped shaping the current debates on medicinal products and medical devices in different international fora.

SFL is pleased to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages. SOS Children’s Villages supports children in 560 villages on 3 continents. For more information visit their website here.

SFL offers strategic and operational support covering the whole lifecycle of medicinal products, including biologics products and ATMP, medical devices, combination products and in vitro diagnostics.

The new format for interactions with medicines manufacturers replaces meetings with written responses as of 1 January 2022.

On 22 November 2021, the European Medicines Agency (EMA) introduced a new format for pre-submission meetings on marketing authorization application (MAA) via the centralized procedure:

• Applicants will be asked to send in their questions using a new pre-submission interactions request form along with the necessary background documents,
• The consolidated responses prepared by the EMA product team will be circulated to the applicant in writing within 3 weeks,
• The applicant may also request a virtual meeting with the EMA, in case further clarifications are needed on the responses received,
• For identified complex applications (product/regulatory and/or drug development etc.) or if clarifications cannot be provided in writing, the EMA will suggest organizing a virtual meeting with the applicant.

The EMA updated its pre-authorization procedural guidance accordingly. There will be transition period until 31 December 2021, during which MAA applicants can choose between the previous and new interaction models. As of 1 January 2022, only the new interaction format will apply.

SFL can support your organization in all your interactions with the EMA and can act as an MAA applicant and marketing authorization holder in the EU.

The EU and US regulators seek to foster alignment for global product development.

On 15 September 2021, the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA) announced the launch of a pilot program for joint scientific advice for hybrid/complex generic products and published general principles. The aim of the pilot is to provide parallel scientific advice for the development of products that fall under the EU’s definition of a hybrid application (Article 10(3) of Directive 2001/83/EC) and are defined as a complex generic product by the FDA. Both agencies see the pilot as a way to foster harmonization and convergence as well as to provide applicants with a clearer understanding of the regulatory requirements and scientific recommendations for both agencies.

The process will consist of 3 phases:

• Phase 1: Applicants request a meeting with the EMA and the FDA. The agencies assess the request and make a decision within 14 days,
• Phase 2: If the EMA and the FDA both grant the request, the following steps ensue:
• Applicants submit a draft meeting package to the EMA via the IRIS portal. Once the package has been validated by the EMA, the final version is sent to the EMA and the FDA, which both start the procedure. The process is expected to take around 1 month,
• The EMA and the FDA review the meeting package within 120 days. A bilateral meeting between the EMA and the FDA is organized during this period,
• Trilateral meeting with the applicant,
• Phase 3: The EMA and the FDA communicate written responses to the applicant within a month.

SFL’s regulatory affairs team provides strategic regulatory advice for global drug development and can act as marketing authorization application applicant and holder in the EU and conduct submissions in the US.

Validity of GMP/GDP certificates extended till end 2022 and use of IRIS platform for inspections.

On 30 September 2021, the European Commission, the European Medicines Agency (EMA), and the Heads of Medicines Agencies (HMA) published an updated notice to stakeholders on the regulatory expectations for medicinal products for human use during the pandemic. In order to avoid disruptions in the supply of medicines, the document informs that the validity of the following documents is extended automatically until the end of 2022:

• Good Manufacturing Practices (GMP) certificates for manufacturing/importing sites of active substances and/or finished products in the EEA and time-limited authorizations/registrations to manufacture/import. This also applies to sites located outside the EEA, provided the issuing/supervising authority does not take any action that affects the certificate validity,
• Good Distribution Practices (GDP) certificates and time-limited wholesale authorizations.

The validity of these documents is extended without any need for further action by the document holder. The extension does not apply when restrictions in the validity period are stated in the GMP/GDP certificate and does not cover changes in the scope of the documents. The EMA reminds that GMP/GDP requirements continue to apply.

In September, the EMA announced the addition of the EMA coordinated GMP inspections features to the IRIS platform. This function will also be extended to GCP inspections. The EMA held a training on the new IRIS function on 10 November 2021, the recording of which was made available, and updated its user guide for IRIS. Marketing authorization applicants and holders will now communicate with the EMA on GMP inspections requested by the agency’s scientific committees through the platform.

SFL’s quality assurance team provides strategic and hands-on operational quality assurance support, establishes quality management systems, prepares establishment license applications, and provides full inspection readiness services.

The CTR will come into application soon and Swissmedic took position on decentralized settings for clinical trials.

The Commission and the EMA lay the ground for adoption of the CTR

On 7 October 2021, the European Medicines Agency (EMA) published a roll-out plan for the Clinical Trial Information System (CTIS) under Regulation 536/2014 on clinical trials on medicinal products for human use (CTR). The document provides an overview of the remaining activities for the go-live of the CTIS, scheduled for 31 January 2022.

The EMA also made available principles for sponsor organization modelling for the CTIS. The document outlines key considerations for sponsors to organize their access to the CTIS, the responsibilities and user roles and presents several organization models. Sponsors need to consider which organizations and individuals should have access to the CTIS as well as the extent of the data that will be viewable by CTIS users. On 29 November 2021, the EMA hosted a webinar to present the new processes under the CTR and the CTIS functionalities to small- and medium-sized companies (SMEs) and academia. The EMA made available an updated version of its sponsors handbook on 2 December 2021.

On 4 October 2021, the Commission published a guidance on the preparation and the dissemination of summaries of clinical trials results in lay language. Such summaries are a requirement for sponsors introduced in the CTR. This guidance document aims to support sponsors in preparing, writing, translating, and disseminating these summaries. The Commission also made available an updated version of the Questions & Answers document on the CTR on 14 October 2021.

Swissmedic and swissethics take position on DCTs

On 1 November 2021, Swissmedic and swissethics published a joint position paper on Decentralized Clinical Trials (DCTs). DCTs aim to reduce the obstacles to trial participation by partly transferring participants’ visits from trial sites to their homes. This impacts different aspects of trials such as digital recording and/or transmitting for trial-related intervention data (e.g. recruitment), delivery of the investigational medicinal product (IMP) to the participants’ homes and trial-related interventions performed in the participants’ homes by trial nurses.

Whereas DCTs fall within the existing framework for clinical trials, the paper calls on sponsors to liaise with Swissmedic and the Ethics Committees to clarify specific questions related to the conduct of DCTs. The document states that the current experience is not sufficient to assess whether additional legislation is needed for DCTs. It outlines key considerations on several aspects, including participants’ recruitment, interventions outside the trial site, IMP dispensing, data capture and remote data verification.

SFL’s regulatory affairs experts can help support you for the preparation of clinical trials related documents in the EU and in Switzerland.

Ongoing legislative revisions aim to enhance transplant safety as well as to improve patients’ access to innovative therapies.

From 12 May to 2 September 2021, the Federal Council held a public consultation on a partial revision of the Federal Act on the Transplantation of Organs, Tissues and Cells (Transplantation Act). The revision aims to:

• Increase data protection: The requirements for databases for patient health data, which are currently laid out in ordinances, would be enshrined in the law,
• Regulate cross-transplants: The revision sets out requirements for a program on organ transplant,
• Strengthen vigilance: The revision introduces a reporting obligation for serious adverse events and reactions regarding organs, tissues, and cell transplants,
• Adapt the current framework: The revision proposes a series of measures to address identified shortcomings in the existing legislation, e.g.
  • Legal classification of novel cell therapies as transplant products,
  • Potential special authorization for transplant products manufactured and used on individual patients in hospital setting,
  • Enhanced requirements to store, import and export organs, tissues, and cells, and
  • Swissmedic extended competence to authorize clinical trials in the field of transplantation medicine and adapted requirements for stem cells.

The development of advanced therapies benefits from convergence of legislative and regulatory frameworks for these innovative products across different regions worldwide. In this context, SFL’s CEO, Shayesteh Fürst-Ladani, took part in the Swiss-Korean Life Science Symposium on ‘Envisioning the post-pandemic era’ hosted by the Swiss-Korean Life Science Initiative on 3 November 2021. She presented the regulatory framework for advanced therapies in Switzerland and the European Union and shared her insights on the challenges and opportunities for the development and marketing of cell and gene therapies in Europe.

SFL’s multi-disciplinary team is well versed in the framework for advanced therapy medicinal products (ATMP) and can provide strategic advice as well as operational support covering the whole ATMP lifecycle.

The UK to set up a new framework for medical devices fostering innovation whilst maintaining international convergence.

From 16 September to 25 November 2021, the MHRA held a public consultation on the future framework for medical devices and in vitro diagnostics (IVDs) in the UK. The initiative aims to achieve and reconcile the following goals: 1) improved safety, 2) greater transparency of regulatory decision and medical device information, 3) alignment with international best practice, 4) flexibility and proportionality. The new framework will:

• Create new pathways for medical devices,
• Set up a framework for software and artificial intelligence (AI) as medical devices,
• Reform the IVD regulation to update the classification and include an extended patient risk review,
• Define measures to foster the re-use and re-manufacture of medical devices.

Changes under consideration include the review of the device classification system and the scope of general medical devices, the introduction of a unique device identifier requirement, the expansion of the information manufacturers are required to submit to register a device, strengthening of the device assessment process, increased monitoring and scrutiny of devices, and enabling the approval process to consider international quality management system accreditation programs or creating a pathway for innovative devices. The new legislation is expected to enter into force on 1 July 2023, to align with the end of the transition period for CE-marked medical devices in Great Britain.

In addition, the MHRA published a work program outlining upcoming changes on the framework for software and AI as a medical device. The program entails several work packages, targeting reforms across the medical device software lifecycle, with 3 key objectives: 1) ensuring the devices are safe and function as intended, 2) having clear requirements, 3) avoiding duplication and divergence by fostering collaboration with key stakeholders. The agency announced it would bring forward key initiatives for each work package until summer 2023.

SFL can support EU-based companies in adapting to changes in the regulatory framework for devices in the UK and submitting applications to the MHRA to register their medical devices or IVDs.

The EU Commission proposed a progressive roll-out of the IVDR and published new guidance documents on the MDR.

The Commission proposes new transition periods to address the lack of IVDR preparedness

On 14 October 2021, the European Commission published a legislative proposal to amend the transitional periods foreseen in the IVDR. The initiative aims to avoid disruption in the supply of in vitro diagnostics (IVDs) in the EU. This follows calls from industry and patient organizations, the European Parliament, as well as the Council of the EU warning about the low level of IVDR preparedness and the limited number of Notified Bodies (NB) designated under the IVDR – only 6 so far, whereas the IVDR significantly increases the number of IVDs which will be subjected to a NB assessment (around 78% of all IVDs expected to enter the market).

The proposal, which has yet to be approved by the Council of the EU and the European Parliament, modifies the current transition periods and introduces new ones:

• The transition period for IVDs with a certificate issued by a NB under the IVD Directive, initially set until 26 May 2024, would be extended until 26 May 2025,
• The proposal would create transition periods for those IVDs for which the IVDR introduces a conformity assessment involving an NB:
• 26 May 2025 for Class D IVDs,
• 26 May 2026 for Class C IVDs,
• 26 May 2027 for Class B and Class A sterile IVDs.

The proposal sets out the conditions required to benefit from these transition periods. The general application date of the IVDR remains 26 May 2022. In particular, it will apply in full as of this date to CE-marked IVDs that do not require the involvement of an NB (i.e. class A non-sterile devices) and to ‘new’ IVDs (i.e. those not covered by a certificate or a manufacturer’s declaration of conformity issued prior to 26 May 2022). The Commission also proposes a deferred application of the requirement for devices manufactured and used within the same health institution (so-called ‘in-house devices’). To ensure a timely adoption, the Council of the EU decided not to amend the proposal and to directly approve the European Parliament’s first reading position if it does not change the Commission’s proposal.

On 29 October 2021, the Commission published a joint implementation and preparedness plan which outlines priority actions for the Commission and Member States to prepare for the IVDR:

• Contingency planning and monitoring: Priority actions include discussion within the Medical Device Coordination Group (MDCG) on potential risks of shortages and measures taken to ensure the availability of IVDs and a monitoring exercise to assess the level of preparedness and identify barriers which could lead to shortages,
• Availability of NBs: Measures include considering how NBs can perform assessments during the pandemic and stepping up discussions on pathways to increase NB capacity,
• EU reference laboratories: The document outlines several actions, including a discussion between the Commission and Member States on practical aspects, carrying out a survey to assess the required capacity and issuing a call for application.

The document also identifies actions which are deemed beneficial for the implementation of the IVDR, such as the adoption of common specifications, guidance for NBs on designation codes, batch testing and significant changes as well as additional guidance on performance evaluation. Beyond 26 May 2022, further guidance is also envisaged in areas such as performance studies, companion diagnostics and qualification of devices used in clinical trials of medicinal products.

EU authorities continue to accompany the implementation of the MDR

The Commission made available a series of documents to support the MDR implementation, including the following:

• MDCG guidance on medical device classification (MDCG 2021-24): The document explains how to carry out medical device classification and provides details on individual rules,
• Revised Questions & Answers on requirements relating to NBs (MDCG 2019-6): The update concerns question I.6 on the possibility for NBs to provide pre-certification services. The document reminds that NBs are not allowed to provide consultancy services, i.e. services which could fall under the definition of conformity assessment activities performed outside of an application,
• MDCG guidance on ‘legacy devices’ (MDCG 2021-25): The document determines the applicability of MDR requirements to ‘legacy devices’ and ‘old’ devices (cf definition p.5),
• Standard on the requirements for regulatory purposes of quality management systems for medical devices (ISO 13485:2016/A11:2021) adopted by the European Committee for Standardization (CEN). The standard is applicable as of 31 March 2022.

The Commission also continues to set up the bodies and tools foreseen in the MDR. Since the beginning of October, NBs and Certificates and Unique Device Identifier (UDI) / Devices registration modules (modules 2 and 3) of the European database on medical devices (EUDAMED) are available. Economic operators and NBs can start entering data on a voluntary basis. The remaining modules will be released once EUDAMED is fully functional.

In October, the Commission also published guidance on the exchange of information between medical device competent authorities on borderline and classification cases. The document presents an updated version of the system agreed at the Medical Device Competent Authorities meeting in Helsinki in 2002 to allow consultations on borderline and classification issues for medical devices, to take into account the entry into application of the MDR and the upcoming application of the IVDR.

SFL’s medical devices team can support your company with all aspects of MDR and IVDR implementation for medical devices, combination products and in vitro diagnostics.

Revision of the framework for pharmaceutical products, pediatric and orphan medicines as well as cross-border healthcare and creation of HERA.

As foreseen under the EU Pharmaceutical Strategy, the European Commission is holding a public consultation on the revision of the EU general pharmaceutical legislation until 21 December 2021. The consultation focuses on areas such as the performance of the current legislation, unmet medical needs, incentives for innovation, antimicrobial resistance and repurposing of medicines. The adoption of the new legislation is scheduled for Q4 2022.

The revision of the orphan and pediatric legislation is also ongoing. The report published by the Commission on the public consultations, which lasted from 7 May to 30 July 2021, highlights shortcomings in the current legislation related to insufficient development in areas of unmet medical needs, unequal access to treatment, limited adaptation to scientific and technological developments as well as barriers to research and development. Respondents expressed a preference for additional incentives and rewards for orphan medicines and provided feedback on the criteria to assess orphan drugs as well as on the definition of unmet therapeutic needs. Suggested measures to foster the development of orphan and pediatric drugs include funding for research and development, adaptation of the authorization procedures and additional support from the European Medicines Agency (EMA). The adoption of the legislative proposal is scheduled for Q1 2022.

The launch of the European Health Emergency Preparedness and Response Authority (HERA) in September is another building block towards the creation of a European Health Union to reinforce the EU preparedness and response to health crises. As a provisional agreement has been found in trilogue between the Council of the EU and the European Parliament on the legislative proposals for the extension of the mandates of the EMA and the European Centre for Disease Prevention and Control, their adoption of the proposals is expected in early 2022. The Council of the EU and the European Parliament are still in talks to reach an agreement on the proposal on serious cross-border threats to health.

SFL’s public affairs team can provide customized regulatory intelligence and impact analysis to help you stay on top and prepare for legislative and policy developments impacting your company’s portfolio.

SFL organized and moderated the discussions on combined products at the Medtech & Pharma Platform Association 2021 Annual Conference.

The Medtech & Pharma Platform Association (MPP) 2021 Annual Conference (MPP2021) took place in a virtual setting on 21 October 2021. More than 460 professionals from the pharma, medtech and ICT industries, patient organizations, academia, regulatory and notified bodies registered to attend the conference and to take advantage of the networking opportunities offered by the virtual conference platform. The Program Committee chaired by Dorit Prüfer (Roche) and comprising senior experts including SFL’s Head of Quality Assurance Beatrice Oberle-Rolle set a precedence for a high-level program.

After the opening by SFL’s CEO Shayesteh Fürst-Ladani, in her function as MPP President, and Kaspar Sutter (Canton of Basel-Stadt), Jacqueline Huh (Stop TB Partnership) drew lessons from her experience in the fight against tuberculosis for global health and healthcare during her keynote address. She advocated for a multi-disease approach to health and to the access and delivery of healthcare services.

Salvatore Scalzo (European Commission), Khair ElZarrad (US Food & Drug Administration), Anthony Humphreys (European Medicines Agency), Birka Lehmann (University of Bonn), Jonathan Sutch (Team-NB) and Jack Turner (UK Medicines and Health Products Regulatory Agency) shared global perspectives on the future framework for combined products during a panel discussion moderated by Shayesteh Fürst-Ladani. They agreed on the necessity to achieve a certain degree of convergence. The panelists evoked different pathways to ensure that the framework is fit for new technologies, such as the creation of regulatory sandboxes and new ways to engage with stakeholders. The audience was given the opportunity to ask question and take part in the discussions via several polls. The panel discussion was covered in the latest edition of MedNous (paywall).

In the afternoon, attendees took part in four sessions during which experts presented their experience and shared their views on different topics relevant for combined products. Attendees had the opportunity to interact with the experts during Q&A sessions.

The MPP 9^th Annual Conference “How combined products address health challenges” will take place in Basel, Switzerland, on 8 September 2022. More information will be made available in due time on the MPP website.

SFL’s cross-functional team has long standing experience providing strategic advice and hands-on support for the development of medicinal products, medical devices, combination products and in vitro diagnostics globally.

The article provides a comprehensive overview of the MAA procedures and strategic considerations to ensure timely market access in Switzerland.

The article co-authored by SFL’s Head Global Regulatory Affairs and Deputy CEO Anja Bührer, Senior Regulatory Affairs Manager David Berner and CEO Shayesteh Fürst-Ladani, was published in the Regulatory Affairs Professionals Society (RAPS) on 31 August 2021.

Entitled ‘Regulatory pathways for innovative medicinal products for Switzerland’, the article provides a comprehensive overview of Swiss marketing authorization pathways for medicinal products with a new active substance.

The article presents the Swiss regulatory framework and outlines key characteristics and eligibility criteria for different procedures available for products with a new active substance:

• Standard marketing authorization procedure: this is the regulatory pathway generally accessible for products with a new active substance, with a review timeline from Swissmedic of 330 days,
• Fast track procedure: this pathway is reserved for medicinal products with expected high therapeutic benefit addressing unmet medical needs. If Swissmedic agrees that the eligibility criteria are fulfilled, the fast track route allows for an accelerated assessment with reduced Swissmedic review timeline of 140 instead of 330 days,
• Temporary authorization: this type of authorization can be granted for medicinal products for the treatment of life-threatening diseases based on an incomplete set of clinical data. The review timeline is also reduced to 140 days and the authorization is valid for two years. To be eligible for the procedure, medicinal products must fulfill a series of strict conditions,
• Prior notification procedure: the Swissmedic review timeline can be reduced to 264 days if the company informs about the intended filling well in advance and if Swissmedic agrees to this procedure,
• Authorization via Article 13 of the Therapeutic Products Act (TPA): certain medicinal products (e.g. FDA/EMA-approved Orphan Drugs, products for transmissible infectious diseases) already authorized in recognized countries can be authorized by a facilitated procedure considering the results of the assessment of the reference authority.

The article also explores the possibilities for simultaneous submission and review of marketing authorization applications (MAAs) on the basis of collaboration between Swissmedic and other regulatory health authorities (Access Consortium, Project Orbis).

The article furthermore outlines strategic considerations to be taken into account when choosing a marketing authorization procedure to ensure an efficient and timely market access.

SFL’s regulatory affairs experts can provide strategic and operational support to define the most suitable marketing authorization pathway for your medicinal product laying the ground for a successful and timely market access.

SFL organizes and will moderate the discussions at the virtual Medtech & Pharma Platform Annual Conference (MPP2021), which will gather stakeholders from the medtech, pharma and digital sectors to foster cross-sectoral exchange.

As the organizer of the MPP2021, SFL is proud to announce that this year’s MPP Annual Conference will take place virtually and free of charge to allow for a broad participation from an international audience.

The MPP Annual Conference is dedicated to products and solutions combining medicinal product, medical device, and digital components (hereafter referred to as combined products). The conference gathers stakeholders from industry, patient organizations, academia, medicines agencies and public health authorities to exchange knowledge, collaborate in technology and regulatory areas, as well as to promote product development and innovation.

This year’s conference will focus on ‘Achieving agility to foster innovation and bring value to patients’. The MPP2021 will open on a keynote address which will be delivered by Jacqueline Huh, Head of External Affairs & Strategic Initiative at the Stop TB Partnership. Ms. Huh will discuss current challenges for global health and the benefits of digitalization in the healthcare sector.

SFL’s CEO Shayesteh Fürst-Ladani will moderate a high-level panel on the framework for combined products. The panel will feature speakers from the European Commission, the European Medicines Agency (EMA), the US Food & Drug Administration (FDA), the UK Medicines and Health products Regulatory Agency (MHRA), BSI/Team-NB and the University of Bonn. They will share complementary and forward-looking perspectives on the framework for the development and authorization of combined products.

The afternoon will be punctuated by expert sessions focusing on topics of interest for combined products. SFL’s Head of Quality Assurance, Pharmacovigilance & Supply Chain Beatrice Oberle-Rolle will chair a session dedicated to the framework for combined products. She will engage in discussions with speakers from Medicines For Europe, the notified body TÜV SÜD, and the Austrian national competent authority. The three other sessions will address digitalization in healthcare, patient engagement, and innovative approaches for combined products.

The virtual setting of the conference will increase the networking opportunities for all stakeholders. The conference virtual platform will display speakers, participants and sponsor profiles. A dedicated tool will also enable participants to set up video meetings throughout the day.

More information about the conference and how to register is available on the MPP website.

SFL’s cross-functional team has long standing experience providing strategic advice and hands-on support for the development of medical devices, combination products and in vitro diagnostics in Switzerland and in the EU.

The International Coalition of Medicines Regulatory Authorities (ICMRA) report sets out recommendations to address the regulatory challenges posed by the use of artificial intelligence (AI) throughout medicines’ lifecycle.

The ICMRA published a report entitled ‘Horizon scanning assessment report – artificial intelligence’ on 16 August 2021. The report details the result of the horizon scanning exercise on AI for medicine development performed by the ICMRA Informal Network on Innovation.

The report outlines the different applications of AI in medicines development, from target profile identification to post-marketing requirements, and reviews ongoing initiatives by the regulatory authorities from ICMRA members.

On the basis of two hypothetical case studies aimed to test the current regulatory framework, the report identifies regulatory challenges and outlines recommendations in the following areas:

• International collaboration: the report proposes the creation of a permanent ICMRA working group, enhanced collaboration between ethic committees’ network and AI expert groups as well as with other regulators, industries or government agencies with experience in AI,
• Approach: the report recommends the development of a risk-based approach to assessing and regulating AI, with a sufficient level of understandability and accessibility to the algorithms and datasets. The report also mentions that limits to validation and predictability might be considered for AI systems which evolve autonomously, which would be considered as high-risk AI uses,
• Governance: the report
• Recommends for sponsors, developers, and pharmaceutical companies to strengthen their governance to oversee AI uses linked to the benefit/risk of a medicinal product (e.g. trial automation), for instance through a multi-disciplinary committee and the early involvement of health professionals,
• Evokes the possibility to create a Qualified Person responsible for AI and algorithm oversight compliance,
• Guidance: the report underlines the necessity for regulators to develop appropriate guidelines including:
• AI-specific guidance by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH),
• Regulatory guidelines for AI development and Apps, with a focus on topics such as data provenance and standardization, external validation, processes for ensuring reliability, monitoring of real-world performance and pharmacovigilance. The report also mentions the need to update existing guidelines on software as a medical device.

The report also provides specific recommendations for the EU:

• Develop a clear definition and risk categorization of AI use in medicines and ensure that the use of AI determines the risk classification for medical devices,
• Develop cooperation between medicine and medical device competent authorities and notified bodies to facilitate the AI oversight, especially when the software is marketed separately but could affect the medicinal product,
• Draft legislation for AI which impacts a medicinal products’ use and benefit/risk. The report cites the enhanced requirements for in vitro diagnostics used in combination with medicinal products under the In Vitro Diagnostics Regulation (IVDR, 2017/746) as a possible approach,
• Ensure adequate AI expertise and training within inspection bodies,
• Adapt the requirements on post-authorization management of medicines e.g. risk-based approach to updates.

SFL’s experienced team can support you throughout the medicines’ lifecycle.

Pharmaceutical companies need to prepare for the CTR requirements and the CTIS before 31 January 2022.

On 31 July 2021, the European Commission decision on the EU Clinical Trials Information System (CTIS) defined under art. 80 of the Clinical Trials Regulation (CTR, 536/2014) was published. The decision confirms the CTIS’ full functionality and compliance with the specifications drawn by the European Medicines Agency (EMA). The publication of the decision triggers a six-month period for the entry into application of the CTR and the go-live of the CTIS, both scheduled on 31 January 2022.

Once it enters into application, the CTR will have a significant impact on the authorization, management and supervision of clinical trials conducted in the EU, with the CTIS as the single entry point for clinical trials information. To help trial sponsors prepare for the CTR and familiarize themselves with the CTIS, EMA organized several webinars and recently published a handbook on the CTIS.

SFL’s regulatory affairs and medical affairs team can provide regulatory advice and hands-on support for clinical trial applications and support you to ensure your company’s full readiness for the CTR and its CTIS.

Although the documents provide additional clarifications, requirements for combined products which do not form a single integral combination remain unclear.

Reflecting the trend towards the increasing diversity and complexity of products combining medicinal products and medical devices (hereafter referred to as combined products), the Medical Devices Regulation (MDR, 2017/745) introduces requirements with some uncertainties regarding the device components. The long-awaited guidelines aiming at clarifying these uncertainties have been published by the European Medicines Agency (EMA).

On 29 June 2021, EMA published a revised version of its Questions & Answers document for the implementation of the MDR and In Vitro Diagnostics Regulation (IVDR, 2017/746). In addition to the revision of all sections, the updated document confirms the possibility to use valid certificates obtained under Medical Devices Directive (MDD, 93/42/EEC) in support of a marketing authorization application (MAA) for combined products and clarifies the labelling requirements for co-packaged combined products.

On 23 July 2021, EMA published a guideline on quality documentation for medicinal products when used with a medical device. The guideline, which outlines the information to be included in product information and the quality section of marketing authorization dossiers for combined products, will come into effect on 1 January 2022.

Although these documents provide much needed guidance, they create uncertainties e.g. by inconsistently using the term “drug-device combinations” and introducing new concepts such as “administration device” which have no legal basis in the MDR. The documents are also characterized by a lack of clarity on the risk classification of certain products (such as pre-filled syringes without a staked needle) and the regulatory requirements for integral non-CE-marked Class I medical devices. Moreover, the responsibilities of the marketing authorization holders in the context of the distribution of co-packaged combined products have not been clearly defined, leaving the door open to interpretation and legal uncertainty.

The enhanced requirements and remaining issues for combined products highlight the necessity to collaborate and seek expert advice for the development, marketing, and surveillance of combined products.

SFL is a founding member of the only industry association focusing on combined products, the Medtech & Pharma Platform (MPP), which provides a unique cross-sectoral forum for exchange and collaboration in development and regulatory areas pertinent to combined products. SFL’s multidisciplinary team can support with all aspects of MDR implementation for combined products.

A recent report shows that SMEs make an increased used of the support offered by the EMA

On 28 June 2021, the European Medicines Agency (EMA) published a report on the support offered to micro, small and medium-sized enterprises (SMEs)  by its SME office during the period 2016-2020.

The report takes stock of the experience with the SME Regulation, adopted in 2005 to promote the development of medicines by SMEs through administrative and financial support.

The report notes a steady increase in the number of SMEs registered with EMA, to reach 1’900 in 2020 (with 40% of them being micro-enterprises, with less than 10 employees) It notes the continued interest for the development tools offered by EMA such as the scientific advice and protocol assistance. It also underlines the increased use of the PRIME scheme by SMEs, which supports the development of medicines targeting unmet medical needs. SMEs received 43% of the granted PRIME designations over the period.

The success rate for marketing authorization applications from SMEs substantially increased from 40% to 89% between 2016 and 2020. Sixteen positive opinions were granted to SMEs in 2020, including 8 for orphan medicines. The report stresses the key role played by SMEs in pharmaceutical innovation. SMEs indeed account for 11% of the positive opinions for new medicines and 22% of the development of new medicines.

SFL’s cross-functional team can support your company for the preparation of the marketing authorization application as well as for all post-authorization activities. SFL has longstanding experience in working with SMEs in the pharmaceutical sector and can act as marketing authorization applicant and holder in the EU and Switzerland.

The guidance published by the Commission brings clarification but the level of IVDR preparedness is deemed problematic.

Guidance for economic operators and competent authorities under the MDR/IVDR

The Commission recently published guidance aimed at bringing clarification on the implementation of the Medical Devices Regulation (MDR, 2017/745) and In Vitro Diagnostics Regulation (IVDR, 2017/746):

• Revised version of Medical Device Coordination Group (MDCG) Questions and Answers (Q&A) on registration in the European database on medical devices (EUDAMED) of actors other than manufacturers, authorized representatives and importers subject to the obligations of Article 31 of the MDR and article 28 of the IVDR (MDCG-13 rev.1): The revision clarifies that importers assuming the manufacturers’ obligations according to Article 16(1) of the MDR/IVDR have to register as manufacturers in EUDAMED,
• Exploratory note (MDCG 2021-14) on IVDR codes, which are used to define the notified body (NB) scope of designation and describe the qualification of staff members and the required qualification for a device. The document aims to ensure the harmonized use of those codes, in particular for the allocation of resources for the device conformity assessment,
• First harmonized standards under the MDR (Implementing Decision 2021/1182) and the IVDR (Implementing decision 2021/1195),
• Guidance (MDCG 2021-20) for competent authorities regarding the generation of a Union-wide unique single identification number (CIV-ID) for clinical investigations.

While the Commission drives the entry into application of the IVDR, the level of preparedness is problematic

The entry into application of the IVDR continues to be a source of concern. Following the call from European industry and patient organizations to delay its entry into application, the Council of the EU expressed concerns about the level of preparedness to the IVDR as well the capacity of IVDR- designated NBs in its conclusions from 16 June 2021. In the document, the Council calls on the Commission to take legislative action to tackle the challenge.

The new EU and Swiss frameworks require device manufacturers to adapt their QMS

Device manufacturers need to ensure that their Quality Management System (QMS) efficiently facilitates compliance with the MDR/IVDR and the Swiss regulatory framework for medical devices.

The MDR/IVDR require manufacturers to keep their QMS updated and to continuously improve it to ensure compliance with these Regulations. The maintenance of the QMS under the MDR/IVDR is not a one-off undertaking. A continuous effort is needed to ensure that new guidance is swiftly translated into the QMS procedures. The Medical Device Coordination Group (MDCG) guidance on integrating the Unique Device Identification (UDI) into a QMS (MDCG 2021-19) illustrates that a good understanding of the regulator’s intention and the company’s cross-functional process landscape are required to ensure that the QMS reflects all ramifications of what may appear to be a simple technicality (here: a product identifier) at the outset.

The absence of update of the Mutual Recognition Agreement (MRA) between Switzerland and the EU poses additional challenges for medical device manufacturers intending to market their products in Switzerland. These are partly due to Switzerland no longer having access to EUDAMED. To ensure a reasonable level of market surveillance, Swissmedic put in place an alternative system for the registration of economic operators and devices as well as for the communication and document exchange between stakeholders. Its implications will have to be carefully assessed and reflected in the manufacturer’s QMS, but also in the procedures of importers, Swiss authorized representatives and distributors.

SFL’s team provides support with all aspects of MDR/IVDR implementation for medical devices (including software), combination products and IVDs, including companion diagnostics, genetic tests, and near-patient testing device and can support manufacturers in adapting their QMS to be compliant with the EU and Swiss regulatory framework.

SFL will host a training on global regulatory considerations for medicines development.

SFL will host a virtual training course on “Regulatory considerations for global drug development” on 3 November 2021, 3.00-6.00 pm CET. This training will address the global drug development process, with a specific focus on Europe and the US. SFL experts will share their insights on the role of regulatory affairs and opportunities and challenges for the development of medicines and pathways for marketing approval. A follow-up training course will take place early 2022. More information will be made available in due time.

SFL also provides customized training, tailored to your organization’s needs, on topics related to medicinal products and medical devices.

This award is a testimony of SFL’s approach to management and endeavor to foster employees’ development.

SFL is proud to announce that is has been named a best place to work in Switzerland by the independent global organization Great Place to Work for the second time. On the basis of an anonymously completed survey by SFL employees earlier this year, SFL was ranked third best employer in the small companies category (20-49 employees) with 93% of SFL’s employees considering SFL a great place to work and 100% emphasizing the camaraderie at work at SFL.

Shayesteh Fürst-Ladani, CEO of SFL said “I am deeply honoured to receive this award and team excellent rating, it confirms our continuous commitment to creating a friendly and adaptive work environment and to supporting our employees’ professional and personal development”.

Visit SFL’s website to find out about current job openings and how to join our team.

Revised/new ordinances on devices and IVDs to adapt Switzerland’s legislation to the EU MDR/IVDR and to accommodate its new ‘third country’ status.

New framework for medical devices

On 26 May 2021, the Swiss Federal Council announced its decision to end the negotiations with the EU on the institutional framework agreement between the EU and Switzerland. As a consequence, the CH-EU mutual recognition agreement (MRA) could not be updated for medical devices before the entry into application of the EU Regulation 2017/745 on medical devices (MDR) on the same date. Moreover, no agreement was found on the Commission proposal (brought forward on 31 March 2021) for a limited amendment of the MRA to introduce a transitional validity for certificates for existing devices until May 2025, due to disagreements on market surveillance stipulations.

As a result, since 26 May 2021, Switzerland has a ‘third country’ status to the EU, with no access to EUDAMED and the European cooperation regarding market surveillance. This situation has wide-ranging consequences for economic operators, including:

• Swiss manufacturers will be treated as third country manufacturers,
• Swiss manufacturers have to ensure that their medical devices are certified by conformity assessment bodies established in the EU before being placed on the EU market, if such a certification is required under the applicable regulations,
• Existing certificates issued under the MRA by conformity assessment bodies established in Switzerland are no longer considered as valid in the EU,
• Swiss manufacturers must appoint an authorized representative in the EU.

In order to mitigate the consequences of the absence of an update of the MRA, on 19 May 2021 the Federal Council approved an amendment of the Ordinance on medical devices (MedDO) of 1 July 2020 with the aim of reducing the risk of supply disruptions on the Swiss market. The amendment entered into application on 26 May 2021 together with the revised MedDO of 1 July 2020. It includes provisions to:

• Unilaterally recognize conformity assessment certificates issued by conformity assessment bodies located in the EU/EEA and designed under the MDR and the EU Regulation 2017/746 on in vitro diagnostics (IVDR), provided the EU/EEA assessment procedures and qualification of the conformity assessment bodies are equivalent to the Swiss standards,
• Define transition periods for the designation of a Swiss authorized representative, required for devices under MDR as well as under the MDD placed on the Swiss market after 26 May 2021:
• For class III devices, class IIb implantable devices and active implantable devices – until 31 December 2021,
• For class IIb non implantable devices and class IIa devices – 31 March 2022,
• For class I devices – 31 July 2022.
• Compensate for the exclusion from the information exchange via EUDAMED:
• Reporting and information about non-conforming devices or devices presenting a serious risk to public health noticed in Switzerland have to be made to Swissmedic, irrespective whether the manufacturer is located in Switzerland,
• Manufacturers, Swiss authorized representatives and importers, as well as Unique Device Identifiers (UDI) and related data have to be registered with Swissmedic,
• A summary of Safety and Clinical Performance has to be made available by the manufacturers, e.g. on their homepage.

The revised/amended MedDO shall be valid until an agreement with the EU has been achieved or a Swiss legislation independent of the EU legislation has been put in place.

New framework for in vitro diagnostics (IVDs)

For IVDs, according to the amendments approved on 19 May 2021, the stipulations contained in the ordinance of 17 October 2001 on medical devices continue to be applicable until a new dedicated ordinance for IVDs is adopted. This includes continued benefits as granted by the MRA:

• the actor placing an IVD on the Swiss market does not have to be identified on the label if the EU/EEA company which first placed the IVD on the market is identified on the label,
• a separate registration of the IVD in Switzerland is not needed.

On 14 April 2021, the Federal Council opened a public consultation on a new Ordinance on IVDs (IvDO) and the revision of the Ordinance on clinical trials with medical devices (ClinO-MD). The aim of the revision is to integrate the provisions of the IVDR into Swiss law. Both texts are currently expected to enter into application on the same day as the IVDR, on 26 May 2022. However, this might change if the Federal Council decided that legislative approaches should be pursued similar to the one currently taken, or considered (legislation independent of the EU), for medical devices.

Outlook for Swiss-EU relations

The future of Swiss-EU relations and its implications on the medtech sector are characterized by great uncertainty. The Swiss Federal Council declared that it intends to pursue the existing model of bilateral relations with sector specific agreements. However, this strategy might prove difficult given the long-standing position of the European Commission that, without an institutional framework agreement, “the modernization of [the Swiss-EU] relationship will not be possible and [the] bilateral agreements will inevitably age”.

SFL’s experienced multidisciplinary team provides strategic advice and hands-on support to ensure compliance with the applicable legislation reaching and keeping your products on the market.

The EU Pharmaceutical Strategy, adopted in November 2020, foresees the revision of the pharmaceutical, pediatric and orphan drug legislation.

Revision of the EU general pharmaceutical legislation

On 30 March 2021, the Commission opened a public consultation on a combined evaluation roadmap / inception impact assessment for the revision of the EU general pharmaceutical legislation, namely Directive 2001/83/EC and Regulation (EC) 726/2004. The evaluation will focus on the legislation’s effectiveness, coherence and complementarity with other pieces of legislation (e.g. the medical devices, the pediatric and orphan drug legislation), responsiveness to scientific and technological developments and the administrative burden attached to its implementation.

The revision aims to address identified shortcomings and issues such as unmet medical needs not covered by the pediatric and orphan drug legislation (e.g. antimicrobial resistance), unequal access to medicines, adaptation to innovation (e.g. combination products), vulnerabilities in the medicines supply and sustainability. The revision will be driven by the objectives of the Pharmaceutical Strategy, i.e. to ensure access to affordable medicines, enable innovation, enhance the security of supply and reduce the regulatory burden. Whereas the policy options remain yet to be determined, the Commission announced that the revision could include a common notion of unmet medical needs, provisions for the simplification and futureproofing of the legislation, revised provisions on competition as well as enhanced requirements for medicines supply.

The revision might also entail a review of the provisions for medicines containing or consisting of genetically modified organisms (GMOs). On 29 April 2021, the Commission published a study on new genomic techniques (NGTs), which takes stock of the current development of NGTs in the EU and outlines the challenges posed to the current legislative framework. Concerning medicinal products, the study underlines stakeholders’ concerns about the application of the GMO legislation to medicines, including the duplication of assessment under the GMO and pharmaceutical frameworks and the lack of expertise on gene therapies of GMO authorities.

The preliminary consultation closed on 27 April 2021. A public consultation on the proposal(s) will take place in Q4 2021. The Commission intends to adopt (a) legislative proposal(s) in Q4 2022.

Revision of the pediatric and orphan drug legislation

In parallel, the Commission is also carrying out the revision of Regulation (EC) 1901/2006 on medicinal products for pediatric use and EU Regulation (EC) 141/2000 on orphan medicinal products. The revision aims to tackle the shortcomings identified by the joint evaluation of the Regulations, published in August 2020, namely:

• Insufficient development in areas of unmet medical needs,
• Divergences in availability and accessibility of treatments,
• Limited responsiveness to scientific progress,
• Administrative burden.

Policy options under consideration include actions to better identify unmet medical needs, such as the definition of criteria, revision of the requirements regarding clinical studies for pediatric medicines and the revision of the incentives system.

A public consultation on the revision was opened on 7 May 2021, in order to gather stakeholders’ input on the main obstacles regarding treatments for rare diseases and children and potential ways to overcome those. Feedback can be submitted until 30 July 2021. The adoption of legislative proposal(s) by the Commission is planned in Q1 2022.

Pilot project on launching strategies for orphan and cancer drugs

In addition to the abovementioned policy initiatives, the Commission and EMA launched a pilot project ‘Market launch of centrally authorized medicinal products’ (CAPs) on 25 March 2021. Focusing on orphan medicines and medicines to treat cancer, the pilot’s objective is to reach a better understanding of the planned marketing of CAPs as well as the reasons behind delayed market launch. Marketing authorization applicants are invited to make declarations of their market launch intentions. The pilot will last until August 2022.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, and can provide customized intelligence reports, stakeholder mappings, impact assessments and outreach advice.

The recently published document brings clarifications on the preparation and application for global pediatric oncology developments in the EU and the US.

It covers considerations related to key issues, including:

• Overall development of the medicinal product: the document underlines the necessity for medicines developers to focus on the product’s overall uniqueness, mechanism of action and its therapeutic positioning,
• Waivers: the default position of EMA is that no age specific waiver is needed, unless there is sufficient justification for one of the three waiver reasons for a lower age threshold. The guidance outlines the criteria for the consideration of waivers by the FDA based on prevalence or excessed toxicity,
• Non-clinical studies: the document emphasizes considerations to be taken into account when assessing a need of juvenile toxicity and pharmacology studies for PIPs. The guidance underlines that juvenile toxicity studies are generally not needed for iPSPs, while rationales for additional pharmacology studies are to be provided,
• Quality development: the document provides quality development considerations particularly related to risk-based approach on the choice of excipients, with aligned view for EMA and the FDA,
• Timelines for deferrals.

Manufacturers who properly address the common issues prior to the cluster calls would benefit from focused discussions on the global pediatric oncology developments plans with the regulators.

SFL’s leading regulatory experts provide strategic regulatory advice and hands-on operational support for drugs, biologics and advanced therapy medicinal products (ATMPs) including gene therapy products. Our experience covers all life cycle stages, including pre-market authorization application activities, such as PIPs.

The Commission recently published several guidance documents to accompany the entry into application of the MDR and the future entry into application of IVDR.

On 26 May 2021, the EU Regulation (EU) 2017/745 on medical devices (MDR) entered into application. The date of application of Regulation (EU) 2017/746 on IVDs (IVDR) is scheduled on 22 May 2022. Devices with valid certificates under the Directive 93/42/CEE on medical devices (MDD) or Directive 98/79/EC on IVDs (IVDD) can continue to be placed on the market until May 2025. The Commission has recently published documents and made announcements related to the entry into application of the MDR and IVDR.

Expert panels

On 1 April 2021, the Commission announced that the medical device expert panels, set up in January 2021 under the MDR and the IVDR, are open for submissions from Notified Bodies (NB) for the clinical evaluation consultation procedure. There are 11 panels based around medical disciplines (e.g. neurology, orthopedics) and a screening panel which determines whether there is a need for a scientific opinion. The Commission published rules of procedures for the panels in February 2021.

Harmonized standards for medical devices and IVDs

On 15 May 2020, the Commission adopted an implementing decision requesting the European Committee for Standardization (CEN) and the European Committee for Electrotechnical Standardization (Cenelec) to revise existing harmonized standards and adopt new ones to support the implementation of the MDR and the IVDR. The request includes standards related to the design and manufacture of devices, risk management and the obligations of economic operators and sponsors. On 12 May 2021, CEN and Cenelec announced that they accepted the standardization request.

In parallel, the Commission published on 16 April 2021 the Medical Devices Coordination Group (MDCG) document MDCG 2021-5 on standardization for medical devices. The document provides information on the general framework for harmonized European standards, harmonized European standards in support of the EU legislation on medical devices, and the governance structure for standards in the medical devices sector.

Preparation for the roll-out of EUDAMED

On 4 May 2021, the Commission released the first version of the European Medical Device Nomenclature (EMDN). Following a public consultation, the second version of EMDN will be released in Q3 2021. In addition, new terms and descriptions for medical device software (under Categories J, W and Z) will be rolled-out in the second release. As defined in art. 26 of the MDR and art. 23 of the IVDR, the EMDN aims at supporting the functioning of the European database on medical devices (EUDAMED). Among its various uses, it will be utilized by manufacturers for the registration of medical devices in EUDAMED, where it will be associated to each Unique Device Identifier – Device Identifier (UDI-DI). The Commission published a FAQ on the EMDN on 4 June 2021.

On 26 May 2021, the Commission announced that the Unique Device Identification and Device Registration and Notified Bodies and Certificates modules of EUDAMED are scheduled to be released in the second half of 2021, whereas the Commission is currently evaluating the possibility of a gradual release of the remaining modules.

Clinical investigation under the MDR

On 23 April 2021, the Commission published a MDCG 2021-6 Q&A document on clinical investigation under the MDR. The document addresses:

• General questions e.g. the main changes under the MDR, the regulatory pathways and safety reporting requirements,
• Modifications to clinical investigations,
• Timeline considerations for clinical investigations,
• Clinical investigation reports,
• Arrangements for the transitional period,
• The annexes outline the regulatory pathway for clinical investigation under the MDR and provide a non-exhaustive list of modifications which may be interpreted as substantial.

Preparation for the IVDR

On 7 June 2021, the Commission published a joint implementation and preparedness plan for the IVDR, with the aim of identifying priority actions for the Commission and Member States and monitor their implementation. The document defines 3 areas where actions are deemed essential:

• Contingency planning and monitoring: e.g. market monitoring to assess the level of preparedness of different stakeholders,
• Availability of NB,
• EU reference laboratories, including the adoption of implementing acts on their tasks and the designation of the laboratories.

The document also sets out high priority actions in areas such as common specifications, guidance for NB and standards.

Some stakeholders are asking for the postponement of the entry into application of the IVDR, pointing to the limited number of NB and delays in the certification process which hinder the timely implementation of the Regulation.

SFL’s team provides support with all aspects of MDR/IVDR implementation for medical devices (including software), combination products and IVDs, including companion diagnostics, genetic tests, and near-patient testing devices.

The Commission published a legislative proposal to regulate the use of AI technologies and a roadmap for the creation of the European Health Data Space (EHDS).

Proposal for rules on artificial intelligence

Following the adoption of the white paper on AI in February 2020, the Commission published a proposal for a Regulation laying down harmonized rules on AI (AI Act) on 21 April 2021, with the objectives of promoting the development of AI whilst addressing the risks linked to its use.

The AI Act introduces a risk-based approach to AI technologies, differentiating between:

• Unacceptable risk: AI systems which pose a clear threat to the safety, livelihoods and rights of people (e.g. social scoring by government) will be banned in the EU,
• High risk: the AI systems identified as high-risk include
• AI systems used in sectors defined in Annex III of the Regulation, such as safety components of products (e.g. AI application in robot-assisted surgery), essential private and public services or critical infrastructures,
• Any AI system (1) intended to be used as a safety component of a product or itself a product covered by the EU harmonization legislation (Annex II) and (2) if the product – or the AI system itself as a product – requires a third-party conformity assessment before being placed on the market or put into service. The list of legislation in Annex II includes Regulation 745/2017 on medical devices (MDR) and Regulation 746/2017 on in vitro diagnostics (IVDR). AI systems will be subject to the same ex-ante and ex-post compliance and enforcement mechanisms of the products of which they are a component.
• Limited risk: the proposal sets transparency obligations for those AI systems,
• Minimal risk: the Commission proposes to allow the free use of AI systems which pose a minimal risk (e.g. spam filter).

The proposal sets out requirements for AI systems identified as high-risk, including:

• Conformity assessment before putting the system on the market or in case of substantial changes,
• Establishment of a risk management system,
• Use of high-quality datasets,
• Establishment of documents to ensure traceability,
• Clear and adequate information to the user,
• Appropriate human oversight.

Member States’ competent authorities will supervise the application of those provisions. A European Artificial Intelligence Board will be created to facilitate the harmonized implementation of the Regulation.

The Commission intends to bring forward a proposal for EU rules on liability for new technologies including AI in Q4 2021/Q1 2022. The AI Act could enter into application in the second half of 2024, with the possibility for a transitional period starting in the second half of 2022.

Towards the creation of a European Data Space, including a Health Data Space

The creation of a European Data Space is one of the priorities of the current Commission. On 3 June 2021, following the opening of a public consultation on the roadmap on 28 May 2021, the Commission opened a public consultation on a proposal for a regulation on data (Data Act), which will include the review of Directive 96/9/EC on the legal protection of databases.

This legislative initiative aims to create a fair data economy by ensuring access to and use of data for legitimate purposes, including in business-to-business and business-to-government situations. This Act will be an important component of the planned EU data spaces. The Data Act follows up on and complements the Data Governance regulation proposed by the Commission in November 2020, the first deliverable under the European strategy for data.

The consultation will focus on topics such as business-to-government data sharing for the public interest, B2B data sharing, tools for data sharing and intellectual property rights. Feedback can be submitted until 3 September 2021. The adoption of the proposal is planned in Q4 2021.

The Commission is also working towards the creation of a European Data Space in the health sector, with the aim to foster exchange and access to different types of health data for primary use (to support healthcare delivery) and secondary use (research and policy making) as well as to ensure citizen’s control over their personal data.

On 3 May 2021, a public consultation was opened on a proposal for the creation of the EHDS. The consultation aims to gather feedback on several points, including the following:

• Impact of the cross-border healthcare Directive on data sharing,
• Objectives of a European framework on the access and exchange of personal health data,
• Necessary requirements to ensure an easy, lawful and trusted exchange of health data across borders (rights regarding personal health data, modes of access to health data, etc),
• Governance for the development and implementation of harmonized standards,
• Incentives to foster primary and secondary use of health data,
• Expected cost of the policy options.

Feedback can be submitted until 26 July 2021. The adoption of a legislative proposal by the Commission is scheduled in Q4 2021.

SFL’s Public Affairs & Regulatory Intelligence Team can help you navigate the policy and legislative developments in the EU and in Switzerland as well as to identify key stakeholders, the impact of specific initiatives and to prepare your outreach activities.

The recently held consultation paves the way for greater capacity in crisis preparedness and response

From 31 March to 12 May 2021, the European Commission organized a public consultation on a proposal for a Regulation on the Health Emergency Preparedness and Response Authority (HERA). The HERA is a component of the European Health Union, announced by the Commission in November 2020, along with three other legislative proposals, currently under discussion within the Council of the EU and the European Parliament, concerning the revision of EMA and the European Centre for Disease Prevention and Control (ECDC) mandate and enhanced coordination for cross-border health threats.

The overall objective of the initiative is to transform the ad hoc solutions adopted during the pandemic into a permanent preparedness and response mechanism at the EU level. The creation of the HERA is meant to address the following issues:

• Fragmentation of public and private efforts for preparedness and crisis management in the EU,
• Shortcomings in threat and risk assessment, monitoring and intervention instruments,
• Market and supply chain vulnerabilities,
• Limited scale of countermeasures.

The adoption of the proposal by the Commission is scheduled in Q3 2021.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, and can provide customized intelligence reports, stakeholder mappings, impact assessments and outreach advice.

SFL’s webinars and training courses provide expert insight into the most recent developments in the fields of pharma, medical devices and combination/combined products

On 11 May 2021, SFL hosted a webinar with Swiss Medtech on ‘Combined products in EU and CH: Regulatory framework, challenges & opportunities’. SFL’s CEO Shayesteh Fürst-Ladani and experts in the field of pharma and medical devices from Swiss Medtech and Novartis presented the EU and Swiss regulatory frameworks for products combining a medicinal product and medical device components.

The SFL training series continued during the second quarter, with a training on an ‘Introduction to the Swiss regulatory & reimbursement pathways for medicines’ on 9 June 2021. SFL regulatory affairs and market access experts presented the Swiss regulatory framework and the main challenges for companies wanting to market their medicinal products in Switzerland.

SFL’s quality assurance experts took part in a joint webinar with Basel Area on 29 June 2021. They provided an overview of the requirements to obtain a Swiss establishment license with Swissmedic.

Upcoming training courses and events will be announced on SFL’s website in due time.

SFL’s in-house team of experts provides customized trainings, tailored to your company’s needs.

The certification reflects SFL’s approach to management and commitment to employee development

SFL is proud to have been certified as a Great Place to Work® by the independent global organization Great Place to Work for the second time. In an anonymously completed survey completed by SFL employees earlier this year, SFL achieved more than 90% approval ratings for overall satisfaction and trust. Both of these scores exceeded the average achieved by the “best” Swiss companies in the small companies category (20-49 employees, 2018-2020).

The excellent ratings and certification are a great honor and confirm SFL’s continuous commitment to creating a friendly and adaptive work environment and to supporting our employees’ professional and personal development.

Can bilateral agreements of the EU and Switzerland with the UK mitigate the loss of single market efficiency?

New frameworks for the relationship with the UK

Now that the Brexit transition period has ended, Switzerland and the EU’s relations with the UK are governed by new trade agreements, both covering medicinal products and medical devices:

• The EU-UK trade and cooperation agreement (TCA) has applied provisionally since 1 January 2021,
• The CH-UK trade agreement entered into force on 1 January 2021. The content of the trade agreement is modelled on pre-existing bilateral agreements between Switzerland and the EU.

Differences and similarities between the agreements

Under both agreements, there will be no tariffs or quotas on the trade of medicinal products between the UK and the EU/Switzerland where products meet the relevant rules of preferential origin[1]. However, the proof of claimed preferential origin will require customs procedures. The TCA facilitates free transfer through the parties’ territories whereas the CH-UK trade agreement requests the direct transfer of preferential origin goods between Switzerland and the UK. Since preferential origin rules differ between both agreements and are of a strictly bilateral nature, the opportunities of suppliers of goods to UK benefitting from preferential customs tariffs are limited; this may impact pre-existing value-added chains.

Annex TBT-2 of the TCA guarantees the mutual recognition of GMP inspections as well as the acceptance of official GMP documents (with an option to reject them in certain circumstances). The UK and the EU remain free to conduct their own GMP inspections (with a notification requirement if they inspect facilities deemed compliant by the other party).

The TCA does not foresee the recognition of batch certification and official batch release. The UK unilaterally recognizes batch testing conducted in the EEA at least until 1 January 2023. The UK’s acceptance of batch testing done in EEA countries will be reviewed before 31 December 2022. A two-year notice period will be given in the case of changes.

Exceptions to the new requirements for imports of drugs from Great Britain (GB) into some EU countries are provided. A Commission notice indeed provides regulatory flexibilities until 31 December 2021, under which the competent authorities of Malta, Cyprus, Ireland, and the UK with regards to Northern Ireland may authorize import from GB of:

• medicinal products by wholesalers who are not in possession of a manufacturing authorization required by EU law,
• investigational medicinal products by sponsors who are not in possession of a manufacturing authorization required by EU law,
• medicinal products for which batch testing is carried out in GB,
• medicinal products bearing non-decommissioned unique identifier

The CH-UK trade agreement sets out provisions for the mutual recognition of GMP inspection and batch certification. The agreement defines specific procedures for information exchange between the parties and for the filing of inspection outcome reports and authorizations.

GB regulatory regime for medicinal products

All existing EU Marketing Authorizations (MAs) for centrally approved products (CAPs) have been automatically converted into UK MAs effective in GB and issued with a UK MA number on 1 January 2021. MA holders (MAHs) are required to submit an initiation electronic Common Technical Document (eCTD) sequence within a year of this date. For grandfathered CAP MAs with a non-UK MAH, there is a requirement to establish a MAH in the UK by 1 January 2023.

The UK MA for medicinal products (for which the assessment has still been ongoing in the EU on 1 January 2021) can be obtained through an in-flight assessment conducted in parallel with the EU assessment, or on the basis of a position opinion from the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) (cf the UK Medicines and Healthcare products Regulatory Agency (MHRA) guidance). For new Marketing Authorization Applications (MAAs), companies must use one of the procedures described in a specific MHRA guidance.

In the future, a new regulatory regime for medicines may be adopted in the UK. The Medicines and Medical Devices Bill currently under discussion in the British Parliament creates delegated power allowing to amend the UK regulatory framework for medicines and medical devices.

Specific regime for Northern Ireland (NI)

Medicines can be supplied from the GB market to NI without requiring additional regulatory importation controls (i.e. manufacture and import authorization, batch testing and qualified person certification done in NI or an EEA state) until 31 December 2021. The procedures are detailed in the dedicated MHRA guidance.

SFL’s offices in Switzerland, the EU and the UK support companies to accommodate the limitations under the new trade frameworks and establish their presence and products in Switzerland, the EU and GB in compliance with respective regulations.

[1] Art. GOODS.5 and GOODS.6 of the EU-UK TCA prohibit tariffs on goods originating from the UK or the EU when destined for domestic consumption. Art. 3 of the EU-CH free trade agreement, incorporated in the CH-UK new trade agreement (under art. 1), prohibits tariffs on industrial goods.

Bilateral agreements between the EU and Switzerland and the UK only partially cover medical devices and IVDs.

Under the EU-UK trade and cooperation agreement and the CH-UK trade agreement, medical devices are exempted from tariffs and quotas provided the rules of preferential origin are met. This implies the need for customs procedures (see article above).

However, neither of the agreements grant the mutual recognition from which medical devices benefited whilst the UK was member of the EU. Since Great Britain is no longer goverened by the shared laws and regulations of the EU single market, mutual recognition of conformity assessments is no longer possible in the relation to the EU; nor are medical devices covered in the mutual recognition agreement (MRA) between Switzerland and the UK which has been in place since 1 January 2021.

To facilitate a viable transition for medical devices, Directives No. 90/385/EEC, No. 93/42/EEC and No. 98/79/EC will remain applicable in the UK for the time being. Furthermore, the UK will not fully transpose the EU Medical Devices Regulation (MDR) and In Vitro Diagnostic Medical Devices Regulation (IVDR) and may instead adopt new legislations on medical devices and IVDs once the Medicines and Medical Devices Bill is adopted.

Swiss and EU manufacturers must appoint a UK authorized representative and register their devices with the UK Medicines and Healthcare products Regulatory Agency (MHRA) in order to be able to place medical devices on the market in Great Britain. Staggered registration deadlines apply depending on the risk class of the medical devices. Specific procedures apply for Northern Ireland (NI) which remains factually in the EU single market according to the NI-protocol of the withdrawal agreement. Manufacturers must also comply with requirements described in the MHRA guidance. You can find more on this in the previous edition of our newsletter.

Vice versa, UK manufacturers must appoint a Swiss authorized representative to be able to place their devices on the market in Switzerland. EU manufacturers will also have to comply with this requirement if the EU-CH MRA is not updated by 26 May 2021.

UK manufacturers need to appoint an authorized representative based in the EU or in NI to be able to place medical devices on the EU market. The assessment conducted by the UK Approved Bodies (replacing the UK Notified Bodies [NB]) and the UK conformity assessment mark (UKCA) are not recognized in the EU. Products carrying both the CE and UKCA marks can be placed on the EU market. Specific requirements apply for the marking of medical devices to be placed on the market in NI.

SFL provides support for all regulatory and quality needs to ensure compliance of your products under the new regulations and agreements in EU, Switzerland and the UK.

The go-live of the CTIS, planned for January 2022, will trigger the application of the EU Clinical Trials Regulation

Adopted in 2014, the Clinical Trials Regulation No. 536/2014 (CTR) aims to harmonize the processes for the assessment and supervision of clinical trials as well as to increase their transparency in the EU. It will replace the current Clinical Trials Directive No. 2001/20/EC.

The Clinical Trials Information System (CTIS) is the centralized EU portal and database for clinical trials foreseen by the Regulation. All submissions related to clinical trials in the EU will be performed through the CTIS. While National Authorities will remain competent for the authorization and oversight of clinical trials, the European Medicines Agency (EMA) will oversee the management of the CTIS and the publication of the relevant data.

The application of the CTR has been postponed several times due to delays in the rolling out of the CTIS. According to the latest information communicated by EMA, the CTIS is scheduled to go live on 31 January 2022 and the CTR could enter into application in January 2022.

The application of the CTR is pending the confirmation of the full functionality of the CTIS by an independent auditor. A transition period of three years is expected for ongoing trials as well as clinical trial applications submitted within a year after the entry into application of the CTR, provided that sponsors submit their application under the regime of the Clinical Trials Directive.

In order to prepare for the go-live of the CTIS, EMA organized trainings for Member States and for clinical trials sponsors. The training sessions for sponsors took place on 22 February and 4 March 2021, attended by the SFL team. Experts from EMA provided participants with an overview of the functioning of the CTIS and gave insight into the functioning of the CTIS.

SFL’s leading regulatory experts provide strategic regulatory advice and hands-on operational support for drugs, biologics, ATMPs, devices and combined products. Our Regulatory Affairs team is well attuned to the CTR and its CTIS and can support you with strategic and operational advice to ensure your company’s full readiness.

Following its contribution to Project Orbis in 2020, Swissmedic has joined the project on a permanent basis

On 17 February 2021, Swissmedic (the Swiss Agency for Therapeutic Products) announced that it will participate in Project Orbis on a permanent basis from 1 March 2021.

Project Orbis is a program coordinated by the US Food and Drug Administration (FDA) that aims to accelerate the approval process for new cancer treatments worldwide. It provides a framework for the parallel submission and review of medicinal products in the field of oncology. Launched in 2019, it is composed of several regulatory authorities including Health Canada and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Swissmedic already participated in the project on an ad hoc basis in 2020 and approved a targeted oncology drug. SFL supported the approval of this very innovative oncology product, acting as applicant of the marketing authorization application as well as marketing authorization holder (MAH) ad-interim.

Swissmedic published guidance that details the marketing authorization process for oncology medicinal products within Project Orbis.

SFL can act as MAA applicant and MAH in Switzerland, EU and the UK as well as support you with submissions to the FDA, Health Canada and other regulatory authorities.

The Commission appointed the experts who will provide advice on medical devices and IVDs under the MDR and IVDR

In January 2021, the European Commission published the list of experts appointed to the 12 expert panels established under the Medical Devices Regulation (No. 2017/745, MDR) and In Vitro Diagnostic Regulation (No. 2017/746, IVDR). The panels, focusing on areas covering high-risk medical devices and IVDs, will provide advice on the safety and performance of devices to the Commission and its Medical Devices Coordination Group (MDCG), as well as to Member States, Notified Bodies (NBs) and manufacturers. Manufacturers may consult with the relevant panel regarding their clinical evaluation and clinical investigation strategy, while NBs must consult the panels regarding clinical evaluations and performance evaluations of certain high-risk medical devices and IVDs.

SFL’s team provides support with all aspects of MDR/IVDR implementation for medical devices (including software), combination products and IVDs, including companion diagnostics, genetic tests, and near-patient testing devices.

The Commission plans to adopt a legislative proposal in Q4 of 2021, adapting the BTC legislation to the latest scientific developments

On 21 January 2021, the European Commission opened a public consultation on proposed policy options to the revision of the EU blood, tissues and cells legislation (BTC legislation); the BTC legislation consists of Directive No. 2002/98/EC on safety and quality of human blood and blood components and Directive No. 2004/23/EC on safety and quality of human tissues and cells. The policy options range from strengthened quality and safety requirements defined by blood and tissue establishments to common binding detailed safety and quality requirements defined in the BTC legislation. The introduction of measures for enhanced oversight will also be assessed. The consultation is open until 15 April 2021.

The objectives of the revision are to:

• Ensure safety and quality for patients, donors and children born with the help of medically assisted reproduction treatments,
• Optimize the access to BTC therapies and avoid shortages,
• Ensure that the regulatory framework facilitates the development of innovative therapies.

The Commission intends to put forward a legislative proposal in Q4 of 2021 to address the shortcomings identified in the evaluation of the BTC legislation. The COVID-19 pandemic shed additional light on the risks of supply interruptions, the deficiencies of the current requirements for donor protection and the need to adapt the legislation to innovation.

Published in October 2019, the evaluation report highlights that the legislation has contributed to an increase in safety and quality of blood, tissues and cells in the EU by establishing common minimum requirements and oversight processes. The report also highlighted shortcomings in the implementation of the BTC legislation in several areas including safety and quality requirements, oversight, protections of donors and recipients, rules applicable to donations and the security of supply of BTCs.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, and can provide customized intelligence reports, stakeholder mappings, impact assessments and outreach advice.

The opening of the public consultation on the roadmap marked the start of the evaluation process of the Directive

On 15 January 2021, the Commission launched a public consultation on the Roadmap on the evaluation of patients’ rights in cross-border healthcare, the first step in the evaluation and fitness check of the Directive (No. 2011/24/EU). The public consultation on the evaluation is scheduled for Q2 of 2021.

The Directive aims to ease access to safe and high-quality cross-border healthcare in the EU as well as foster cooperation on healthcare between Member States. It grants patients the right to seek planned healthcare in another EU country and to claim reimbursement from their national health system or health insurance provider. The Directive covers healthcare costs as well as the prescription and delivery of medication and medical devices.

Ten years after the adoption of the Directive, and in light of the reinforced need for cross-border cooperation during the COVID-19 pandemic, the evaluation aims to take stock of its implementation. The objective is to evaluate its relevance, the efficiency of the system and to identify potential administrative burdens and obstacles to access to healthcare and reimbursement thereof.

The evaluation will focus on the following aspects:

• Responsibilities of the Member States where the treatment is performed and where the patient is insured,
• Information provided to patients by the National Contact Points,
• Administrative procedures,
• Recognition of prescriptions issued in other Member States,
• Mutual assistance and cooperation in border regions,
• Development of the European Reference Networks for rare and low prevalence complex diseases and cooperation in the field of rare diseases.

Although the Directive triggered EU cooperation in promoting European e-health initiatives that foster health technology assessments (HTA) within the EU, the European Commission is evaluating respective provisions separately as part of the planned European Health Data Space and the proposal for an HTA Regulation.

The evaluation process will last until mid-2022.

SFL’s Public Affairs and Regulatory Intelligence team continuously monitors policy and regulatory developments and can provide customized intelligence reports, impact assessments, stakeholder mappings and outreach advice. SFL’s Market Access team provides strategic advice on national early access programs, writes HTA/reimbursement dossiers for submission to national HTA bodies and prepares documentation for liaison with private healthcare insurances.

The Swiss FOPH published an evaluation report taking stock of the implementation of art. 71a-d OAMal and outlining options for improvement

On 12 December 2020, the Swiss Federal Office of Public Health (FOPH, Bundesamt für Gesundheit) published an evaluation report on articles 71a-d of the Swiss Ordinance on compulsory health care (OAMal, Verordnung über die Krankenversicherung), which allows the reimbursement of medicines outside of the Specialties List (SL) under certain conditions.

The evaluation report focused on the implementation status of art. 71a-d OAMal, the appropriateness and efficacy of respective measures, and the identification of potential optimization areas. All consulted stakeholders highlighted that art. 71a-d OAMal is effective in enabling patients to access medicines that are not included in the SL (or not for the desired indication).

However, the report highlighted a significant increase in the number of cost reimbursement applications in recent years (44% increase to 38,000 between 2017 and 2019). This increase suggests that the system no longer corresponds to the originally conceived exemption under art. 71a-d OAMal.

The report also brings to light several issues for the implementation of art. 71a-d OAMal:

• Insurers play a central role in the reimbursement in individual cases. Patient organizations criticized a lack of transparency in the context of negative decisions,
• It is associated with a high administrative burden,
• Approval rates differ strongly depending on the insurer (from 46% to 95%). This difference is partly caused by variations in the benefit assessment, although insurers use the same assessment tool (OLUtool).

To remedy these issues, the report recommends revising the legislative framework, setting up an online platform for the applications, increasing transparency in the context of negative decisions and an expert committee to review complex cases.

In its position on the evaluation report, the FOPH outlined the following areas of action:

• Increase the efficiency of the system: creation of a unique digital platform for service providers, insurers, and pharmaceutical companies, as well as to decrease administrative burden,
• Harmonize the benefit assessment process: specifications for a uniform use of the OLUtool and a clear definition of the concept of “great benefit”,
• Foster a clear framework for economic efficiency and cost containment: possibility to reimburse less expensive therapies off-label in individual cases,
• Remove unintended incentives: price reduction after a certain period of time in order to incentivize companies to apply for authorization under the SL list,
• Increase assessment transparency: creation of a registry and publication of the assessments discussed between the FOPH and the insurers.

Earlier this year, the Federal Council adopted a report on rare diseases that takes stock, among other aspects, of the result of the evaluation. In this area, the report highlights that the increase of the extent of reimbursement in individual cases is a result of different aspects, such as longer timelines between authorization and reimbursement of new medicinal products, more complex assessments for new therapies, as well as high price expectations of the pharmaceutical industry.

The FOPH is currently in the process of establishing measures and developing proposals with revised ordinance provisions, together with the support of a dedicated stakeholders working group.

SFL’s Public Affairs team has extensive experience in monitoring policy and regulatory developments and can provide impact analyses of Swiss healthcare legislation for clients. SFL’s Market Access team provides strategic advice on national early access programs, writes HTA/reimbursement dossiers for submission to national HTA bodies and prepares documentation for liaison with private healthcare insurances.

SFL offers expert trainings for medicinal products and medical devices throughout 2021

The SFL expert training series provides an overview on topics relevant to the pharma and/or medtech industries for developing and marketing products in the EU and/or Switzerland. Led by highly-experienced members of the SFL cross-functional team, including Regulatory Affairs, Quality Assurance, Medical Affairs, Medical Devices, Combination Products & IVDs, Market Access and Supply Chain, they will provide practical tips for success.

This year’s first virtual training took place on 11 February 2021 and provided an introduction to the Good Distribution Practices (GDP) required to acquire and maintain a Swiss establishment license. The speakers presented the Swiss regulatory framework for the establishment license, the responsibilities and requirements of the Swiss Responsible Person (RP) and the European Commission guidelines on GDP. They shared insights on the creation of a Quality Management System and preparation for an inspection.

SFL team members continue to attend and actively participate in major events in the fields of pharma and medtech and engage in in-depth discussions with various stakeholders.

Shayesteh Fürst-Ladani, SFL’s CEO, represented the Medtech & Pharma Platform (MPP) at the DIA Euromeeting Diamond Session on 19 March 2021, where she advocated for knowledge exchange, enhanced dialogue on connected combined products and increased oversight on the safety and efficacy of individually marketed combined products.

The dates of the next trainings as well as events where SFL team will speak are posted regularly on SFL website.

SFL’s in-house team of experts provides customized trainings, tailored to your company’s needs.

SFL’s CEO Shayesteh Fürst Ladani extends her thanks and holiday greetings to all clients, partners, and friends for their support over this challenging year.

Dear clients, partners, friends

As the turn of the year approaches, we would like to thank all our partners and clients for your ongoing trust in our services and support.

This newsletter highlights some key developments and their impacts on the pharma and medtech landscape, including the new EU Pharmaceutical Strategy, MHRA requirements for drugs and devices in 2021, the revision to the Swiss patent system, and updates on the ongoing implementation of both the Medical Devices Regulation (MDR) and the In Vitro Medical Devices Regulation (IVDR).

We are also pleased to be able to share some exciting news on some of SFL recent activities, including the successful approval of Obiltoxaximab SFL for which SFL Pharmaceuticals Deutschland acts as Marketing Authorization Holder, the ongoing SFL expert training series, and the recent journal publication by the SFL team on Scientific Advice procedures in the EU.

We look forward to continuing to support our valued clients with our cross-functional team in providing the most comprehensive and tailored solutions to achieve your goals in 2021.

We wish you a relaxing holiday season, with every success in the new year

Shayesteh Fürst-Ladani, CEO and the SFL Team

The 5-year strategy specifies objectives to support innovative and affordable medicines, and develop a crisis-resilient EU pharmaceutical system.

On 25 November 2020, the European Commission issued a Communication detailing the new EU Pharma Strategy “Pharmaceuticals – safe and affordable medicines”. The strategy aims to ensure Europe’s supply of safe and affordable medicines to meet patients’ needs and support European pharmaceutical innovation, including through futureproofing the regulatory framework, supporting practical application of technology, addressing market gaps, such as antimicrobials, and market failures, including lessons learned from COVID-19. Its objectives are structured around four areas: access, affordability, digitalization, and innovation, as well as ensuring the EU’s independence and competitiveness. Among other proposals, the strategy suggests the deployment of the following initiatives:

• Revision of various aspects falling under the pharma legislation including anti-microbial resistance (AMR), market competition, incentives and obligations including the supplementary protection certificates (SPC) system, incentives for innovative products, and the security of supply and issues of shortages (target dates: 2022)
• Revision of the legislation on medicines for children and rare diseases to address unmet needs (target date: 2022)
• Develop cooperation in a group of competent authorities, based on mutual learning and best‑practice exchange on pricing, payment, and procurement policies (target date: 2021-2024)

In November, the Commission also published a set of proposals to creating a European Health Union with a view to strengthen the EU’s health security framework, and to reinforce the crisis preparedness and response role of key European agencies. One of these agencies is the European Medicines Agency (EMA), whose mandate could be extended to cover shortages of drugs and medical devices, coordinate clinical trials and host expert panels under the Medical Devices Regulation (MDR) and the In vitro Diagnostics Regulation (IVDR) on a permanent basis, among other things.

A key focus of EU leaders for future innovation in Europe, including for pharma and medical devices, is Artificial Intelligence (AI). The Commission published multiple AI-related documents in Q1 and Q3 (see SFL’s March and September newsletters) and the European Parliament adopted Resolutions on the regulation of AI in the European Union on 20 October 2020. These proposals notably outline a “framework of ethical aspects of AI, robotics and related technologies” and a civil liability framework for high-risk AI. These Resolutions are not binding legislation, but recommendations aimed at facilitating the EU to become a global leader in the development of AI. Using its “own-initiative procedure”, the European Parliament can request the European Commission to put forward a legislative proposal. The Commission proposal on AI is expected in early 2021.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, and can provide customized intelligence reports and impact assessments to inform clients on how to best respond to new regulatory changes affecting their products.

SFL Pharmaceuticals Deutschland acts as the Marketing Authorization Holder in the EU.

On 18 November 2020, the European Commission granted Marketing Authorization for Obiltoxaximab SFL. The approval comes after the Committee for Medicinal Products for Human Use (CHMP) had recommended on 17 September 2020 the granting of Marketing Authorization under exceptional circumstances for the orphan medicinal product Obiltoxaximab SFL.

SFL Pharmaceuticals Deutschland GmbH acts as Marketing Authorization Holder (MAH) in EU on behalf of Elusys Therapeutics Inc, the originator of the product.

Obiltoxaximab SFL (obiltoxaximab) is indicated in all age groups:

• In combination with appropriate antibacterial drugs for treatment of inhalational anthrax due to Bacillus anthracis.
• For post-exposure prophylaxis of inhalational anthrax when alternative therapies are not appropriate or are not available.

“Obtaining EU marketing authorization is an important milestone to enable making Obiltoxaximab SFL available for treatment of inhalation anthrax. This was possible due to excellent cooperation between Elusys and SFL teams” said Shayesteh Fürst-Ladani CEO of SFL group of companies.

Patient-specific preparations are now considered non-standardized medicinal products.

The revision of the Swiss Therapeutic Products Act (TPA) addressed the growing trend towards the development of new therapeutic approaches using patients’ own bodies substances. Under the previous version of the TPA, these preparations were classified as medicinal products, and subject to authorization as a medicinal product in accordance with Art. 9, para. 1 of the Therapeutic Products Act (TPA, SR812.21) unless they fell under the exemption ruling on formula-based clinical trial preparations and non-standardized medicinal products, as stated in Art. 9 para. 2 TPA.

Swissmedic has now announced that certain patient-specific preparations can be classified as non-standardized medicinal products according to Art. 9 para. 2 let. e of the revised TPA and are exempt from authorization as a medicinal product. The new classification provides various options for patient-specific preparations and replaces an earlier interpretation and classification of certain autologous serum preparations (see Guidance document).

The exemption will not apply to non-standardized medicinal products whose safety or efficacy profile is inadequately known or which bear a risk to patients due to composition, dosage, or application; mandatory authorization will continue to apply to these products.

Manufacturers of non-standardized medicinal products will still require an establishment license issued by Swissmedic and must also comply with GMP requirements according to the Medicinal Products Licensing Ordinance (MPLO).

Swissmedic also announced that it will provide, as of 1 December 2020, scientific and pre-submission advice on essential human medicines free of charge in order to facilitate the authorization for those products and to avoid shortages.

Essential human medicines are defined in Art. 1 of the Swiss Ordinance on the Essential Human Medicine Reporting Office as therapeutical products authorized by Swissmedic that are not or only scarcely substitutable and whose prolonged shortage would have serious health consequences.

Under the new regime, companies can request free of charge clarifications on scientific or regulatory issues pertaining to authorization of human medicines containing active substances listed in Annex 1 of the ordinance.

SFL’s Regulatory experts provide strategic advice and support with scientific advice and MAA submissions accelerating the approval and access of medicinal products to the Swiss market.

Guidance includes new assessment procedures for medicinal products and the UKNI requirements for medical devices.

The MHRA medicinal product licensing guidance was updated with information on changes to Marketing Authorization (MA) applications, effective from end of the transition period (1 January 2021).

• For EU Centrally Authorized Products (CAPs) utilizing the EU Community MA procedure, Great Britain (GB) will adopt decisions taken by the EU Commission on the approval of these products for two years. The assessment routes for CAPs will include ‘In-flight assessment’ in parallel with the EU assessment or the ‘Reliance Route’ based on the EU decision.
• An accelerated procedure will be introduced providing an opinion within 150 days. Eligible MA applications include for orphan drug approval in GB, conditional and full MAs, as well as submissions for approval under exceptional circumstances
• A rolling review route can be requested for new active substances, including biological products, if a ‘full dossier’ is submitted to MHRA when applying for a GB MA
• The Decentralized Procedure and the Mutual Recognition Procedure (including repeat-use) will no longer apply in the UK
• Applications must be submitted via the MHRA portal and the MAH will need to be established in the UK.

Similarly, the latest MHRA medical device guidance updates clarifies the grace period for registration of medical devices for the UK, including the Northern Ireland (NI) market, applicable from 1 January 2021.

Class I devices, custom-made devices and general IVDs that are currently required to register their devices with the MHRA. Manufacturers must continue registering these devices, and previously unregistered devices, including those for the NI market, from 1 January 2021

Grace periods for registration with MHRA are as follows:

• Class IIIs and Class IIb implantables, all active implantable medical devices and IVD List A products must be registered from 1 May 2021
• Other Class IIb, all Class IIa devices and IVD List B products and Self-Test IVDs must be registered from 1 September 2021

All registrations to access the UK market by non-UK-based manufacturers will require a UK Responsible Person and registered place of business. Devices placed on the NI market by UK-based manufacturers will need an EU- or NI-based Authorized Representative.

For conformity and device labelling, an EU CE-mark will continue to be recognized in Great Britain (UK excluding NI) until 30 June 2023, after which time a UKCA mark will be required. For NI, if a UK-based Notified Body is used for conformity assessment a UKNI-mark will be required in addition to the CE‑mark. Goods bearing the CE and UKNI markings granted after assessment by a UK-based Notified Body will not be accepted on the EU market. Further UKNI information is available here.

All devices placed on the NI market will need to meet requirements of the EU medical device and in vitro diagnostics regulations (MDR & IVDR) after their respective dates of application. Post-market surveillance and vigilance for the UK, including NI, will need to be reported to MHRA.

SFL can provide support for all regulatory and quality needs to ensure compliance of your products under the new proposed UK and NI regulations, including choosing the optimal submission pathway and acting as UK MAH for your medicinal product, and designating a UK Responsible Person and UKCA marking of your medical devices.

Modernizing the Swiss Patent Act aims to make Switzerland more attractive for SMEs and individual inventors.

A partial revision of the Swiss Patents Act was proposed by the Federal Council on 14 October 2020. Currently, the Swiss Federal Institute of Intellectual Property (IPI) examines patent applications for only a few legal requirements, such as whether the invention is contrary to public policy or morality, but does not examine whether an invention is innovative. The proposed revision seeks to increase legal certainty for patent owners and third parties, as well as to strengthen enforceability.

A core recommendation of the revision is that the IPI does its own full examination based on international standards. This is expected to reduce the complexity and costs for patenting by small and medium-sized enterprises (SMEs), and individual investors, by circumventing their need to employ the European Patent Office to perform a full examination.

The partial revision also introduces a quicker and cheaper form of protection for technical inventions for innovators than a patent, modelled after the so-called “petty patent” in place in other countries. This new form of protection would be granted without a substantive examination of the invention.

This “utility model” protection would be similar to a patent; qualifying for the ‘patent box’ and associated tax relief, but offering only ten years protection i.e., half of the maximum lifespan of a patent.

Consultation is currently open on the partial revision until 1 February 2021, and further information can be found here.

SFL’s multi-disciplinary teams has extensive experience in impact analysis of Swiss healthcare legislation for clients.

Actor registration information on EUDAMED and Commission standardization request for the MDR and IVDR.

The European Commission published a new EUDAMED Actor’s registration module webpage on 20 October 2020. The Actor registration module, making up the first of six EUDAMED modules, was made available to Member States and economic operators, along with access to the EUDAMED database and webpage on 1 December 2020. However, economic operators from the UK, Switzerland and Turkey will only be able to submit actor registration requests in EUDAMED at a later stage. The new website provides information on the single registration number (SRN), actor registration, registered users, a user guide for Economic Operators and technical documentation.

The SRN section provides information of specific actor roles, templates for documents to be submitted with requests; including declaration on information security responsibilities and the Mandate Summary document (for non-EU manufacturers), with guidances also available for download (see article on MDCG provides overview of guidances under development in this newsletter).

The European Commission has also taken action on harmonization of standards for EU Medical Devices and In Vitro Diagnostics Medical Devices Regulations (MDR & IVDR). It released a draft standardization request for submission to the European Committee for Standardization (CEN) and the European Committee for Electrotechnical Standardization (Cenelec) on 29 October 2020.

The draft request has two annexes listing standards to be revised or newly drafted for the MDR and IVDR, respectively. A third annex outlines general requirements for the listed standards. For the MDR, 151 standards are identified for revision and 13 are to be newly drafted. For the IVDR, 45 standards are identified for revision and 3 are to be newly drafted. Standards for revision or drafting include for implants, sterilization (including with ethylene oxide), processing, measurement, biocompatibility, electrical equipment, device connectivity and security, and clinical safety and performance. The indicated deadline for adoption of all indicated standards is 27 May 2024. Submissions providing feedback on this initiative were taken until 13 November 2020.

SFL provides full support for compliance of medical devices and IVDs under the MDR and IVDR by cross-functional Medical Devices, Regulatory Affairs, Supply Chain, Quality Assurance, Vigilance and Medical Affairs teams.

The MDCG releases new IVDR guidance and overview of guidances under development.

The European Commission issued “Guidance on Classification Rules for in vitro Diagnostic Medical Devices under Regulation (EU) 2017/746” (MDCG 2020-16) on 13 November 2020. The much-anticipated document provides guidance to manufacturers, notified bodies and health institutions on how to classify an in vitro diagnostic medical device (IVD) prior to placing it on the market, making it available on the market or putting into service in the EU. For each of the seven classification rules described in Annex VIII of the in vitro Diagnostics Medical Devices Regulations (IVDR), the guidance provides a rationale explaining the rule and its application, notes providing clarity on specific device types and several examples of devices that the rule applies to. Examples for classifying IVDs intended to be used together are also provided in the document Annex. The guidance in the document also encompasses diagnostic or information society services performed on EU patients or devices put into service through distance sales.

The European Commission published the October 2020 update of “Ongoing guidance development within MDCG Subgroups” document, indicating 46 documents currently under development across thirteen Medical Device Coordination Group (MDCG) subgroups. Twenty documents are planned for release before the end of 2020, including the recently released IVD Classification Rules guidance, with a further 15 expected to be released in 2021 including four in Q1.

Aligning with the recent announcements on the EUDAMED actors database and draft standardization proposal (see article on medical device updates on EUDAMED and standards harmonization in this newsletter), seven related guidances are all expected by the end of the year:

• Standardization in the medical devices field (newly added since last update)
• Harmonization of EUDAMED administrative practices and alternative technical solutions
• The first release of the European Medical Device Nomenclature (EMDN)
• Rules and processes for the EMDN
• Integration of Unique Device Identifiers (UDI) in manufacturers’ Quality Management Systems
• Adaptation of Annexes to IMDRF N48 ‘UDI System Application Guide’
• Guidelines on specific product types (contact lenses)

Guidances added since the last update that are expected in 2020, include important documents to support current manufacturing activities, including a Q&A on clinical investigation, a guidance on state of the art for COVID-19 antibody tests, and a Q&A on in vitro diagnostic medical devices (IVDs) in the context of COVID-19.

Crucial MDR & IVDR guidances indicated for release by the end of 2020 and in 2021, including:

• Classification of IVDs (2020 – released 13 November)
• Classification of borderline medical devices (2020)
• Legal status of app providers under the MDR and IVDR (2020)
• Taking into account MDSAP for Notified Bodies (2020)
• Borderline with medicinal products (including general guidance, definitions of pharmacological, immunological, and metabolic means of action and diagnosis) (2021)
• Guidance on clinical evaluation consultation procedure (2021)
• Performance evaluation under the IVDR (2021)

SFL’s Medical Device team can support you to prepare MDR and IVDR documentation in alignment with applicable standards and guidances for your products conformity assessment and ongoing marketing.

Medical device manufacturers shall not underestimate the importance of the chemical characterization of their products.

Every medical device that comes into contact with the patient’s body is expected to undergo a biological evaluation to ensure it does not induce any acute or chronic adverse effects. Biological evaluation of medical devices is a risk management process usually conducted within the frameworks of the ISO 10993 standard series. The standards’ most recent revisions emphasize the role of the chemical characterization within the biological evaluation process and underscore that it shall precede any biological testing. Thereby, the results of chemical characterization combined with appropriate toxicological assessment can support medical device manufacturers in determining whether biological tests are at all required. Manufacturers seeking certification of their product under the EU Medical Device Regulations (MDR) can use the chemical characterization process to address the Regulation’s requirements regarding the use of carcinogenic, mutagenic, and reprotoxic chemicals (CMRs), phthalates, and nanomaterials.

The scope of the chemical characterization should reflect the nature and duration of the clinical exposure to a device. It shall start with the determination of the product’s materials of constructions, followed by, as appropriate, their compositional evaluation or determination of the extractables and leachables profiles. Analytical testing is not always required. Chemical characterization takes into account both raw materials and residues associated with manufacturing or device processing. The chemical characterization process is outlined in the ISO 10993-18 standard, whose revised version was published earlier this year.

The main changes compared to the previous version include greater harmonization with other ISO 10993 modules, expansion of the chemical characterization flowchart, clarification of testing approached, more stringent requirements for analytical method qualification, and inclusion of additional informative annexes. As a result, the chemical characterization process has become more stringent and complex. Legacy device manufacturers who evaluated their products in line with the previous ISO 10993-18 version are encouraged to re-assess their biological evaluations and plan additional tests and analyses to bridge the identified gaps.

SFL Medical Device team offers guidance regarding the biological evaluation of medical devices within the framework of ISO 10993, including device classification, gap analyses, providing strategic advice on testing, and collating the biological evaluation report.

The successful training on EU Regulatory Affairs for Medicinal Products is available on-demand.

The latest accredited SFL training took place on 10 November 2020, providing attendees with a thorough “Introduction to EU Regulatory Affairs for Medicinal Products”. The training included overview of the European legislative framework and key details on the pre-submission activities offered by the European Medicines Agency, as well as guiding participants through clinical trial applications, marketing authorization procedures, and lifecycle management activities. The training is now available as an on-demand training, alongside SFL customized training offerings.

The SFL online expert training series will continue in 2021, providing an overview on topics relevant to the pharma and/or medtech industries for developing and marketing products in the EU and/or Switzerland. Future training topics in the series will include; Good Distribution Practice and Good Manufacturing Practice in the EU, the Swiss Establishment License, Swiss Market Access and Supply Chain, Orphan Drug Designation in the EU and Switzerland, Regulatory Affairs in Switzerland, the EU Medical Device Regulation (MDR), the European Regulatory Framework for Combination Products, Medical Device Software (MDSW) and Clinical Evaluation Reports under the EU MDR. For more information, please visit SFL’s trainings webpage.

All SFL trainings are led by highly-experienced members of the SFL cross-functional team, including Regulatory Affairs, Quality Assurance, Medical Affairs, Medical Devices, Reimbursement and Supply Chain, and provide practical tips for success.

SFL accredited training series addresses key aspects in the life-cycle of medicinal products and medical devices. SFL also offers customized trainings, at your company’s site or online, and tailored to your products and strategic objectives. Contact us to find out more.

Regulatory transformation and the release of a position paper were highlights of the MPP 2020 Annual Conference.

The virtual 7th Medtech & Pharma Platform (MPP) Annual Conference (MPP2020) on “Achieving patient-centricity under the new MDR – balancing stakeholder interests” (22‑23 October), addressed challenges for manufacturers in complying and regulators in applying regulations effectively and consistently to harness the benefits of innovative Combined Products.

The keynote address by Zaïde Frias, Head of the EMA’s Digital Business Transformation Task Force, explored digital transformation of regulatory pathways to improve assessment and advice on combined products, including a concept of a future integrated pathway where products combining drug, device, diagnostic, or digital components are submitted to a central EU portal, from which advice, evaluation and surveillance is coordinated.  This was also discussed in a panel moderated by SFL CEO and MPP President Shayesteh Fürst-Ladani, with representatives from the European Commission, the Austrian competent authority (AGES), a Notified Body (TÜV SÜD) and EU associations representing Pharma (EFPIA), Medtech (Medtech Europe) and Combined Products (MPP). The panelists discussed key Combined Products topics: clinical studies, single integral drug-device combinations, co-packaged and cross-labelled products assessment, and manufacturing using of platform approaches.

Sessions with excellent expert presentations and panel discussions addressed new technologies, innovative product development, advances in manufacturing processes, incorporating patient needs in development, and patient engagement with future healthcare.

A report on the MPP2020 Annual Conference was published in Mednous.

The Conference coincided with the release of the new MPP Position Paper on the legislative framework for Connected Combined Products (CCPs) – products defined as, “connecting the use of a medicinal product with two or more of the following: a (delivery) device, in vitro diagnostic (IVD), standalone software, mobile platform, and/or a cloud application, with the aim to deliver a medicinal product to patients and/or to monitor certain data and parameters”. It provides examples of CCPs and identifies current regulatory gaps and challenges, such as data protocols, validation of components, the lifecycle of software parts, clinical data, and user research. A need for ensuring cybersecurity and safe interoperability of “connected” elements of CCPs through appropriate regulation is highlighted as crucial for promoting innovation and maximizing patient safety in future healthcare. It also foreshadows the release of an MPP White Paper addressing these aspects in more detail as a basis for future dialogue with regulators to address these “connected” challenges.

Contact the MPP Association to find out how your company can become a member and get involved in the association activities, including MPP’s advocacy actions and next year’s MPP Annual Conference.

The EMWA article highlights SFL expert knowledge on EU scientific advice procedures.

SFL’s Head of Regulatory Affairs Anja Bührer, Director of Medical Affairs Daniela Kenzelmann Broz, and Medical Affairs Manager Gabriele Galliverti have published the article “Scientific advice procedures in the EU – an overview of the regulatory background“ in Medical Writing, the journal of the European Medical Writers Association (EMWA). The article provides an overview of scientific advice procedures offered by the EMA and National Competent Authorities of EU Member States. scientific advice aims to provide guidance on the generation of appropriate evidence and accelerate patient access to novel treatments.

Scientific advice procedures provide companies with guidance from a panel of experts on quality, nonclinical, clinical, or other aspects of their development strategy. This ensures that Marketing Authorization Applications (MAAs) have an appropriate and robust data package that demonstrates a medicinal product’s quality, and its efficacy and safety in the proposed indication. Utilization of Scientific Advice procedures is of particular benefit in the case of novel treatment modalities, new substances, or rare indications.

SFL’s has extensive experience in supporting manufacturers to utilize Scientific Advice procedures in preparing high-quality MAA submissions, and thereby accelerate the approval of pharmaceutical products and their access to EU and Global markets.

SFL continues its long-standing support of the charity SOS Children’s Villages to improve the lives of children worldwide.

SFL is pleased to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages. SOS Children’s Villages supports children in almost 550 villages worldwide in 136 countries and on 5 continents. For more information visit their website here.

The SFL Regulatory Affairs & Scientific Communication team prepared the MAA submitted by SFL Pharmaceuticals Deutschland GmbH, which will act as the future MAH.

On 17 September 2020, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the orphan medicinal product Obiltoxaximab SFL. The European Commission final decision (marketing authorization) is expected in November 2020.

SFL Pharmaceuticals Deutschland GmbH filed the marketing authorization application (MAA) and will act as future marketing authorization holder (MAH) in the EU on behalf of Elusys Therapeutics Inc, the originator of the product.

Obiltoxaximab SFL (obiltoxaximab) is indicated in all age groups:

• In combination with appropriate antibacterial drugs for treatment of inhalational anthrax due to Bacillus anthracis.
• For post-exposure prophylaxis of inhalational anthrax when alternative therapies are not appropriate or are not available.

Shayesteh Fürst-Ladani, CEO of SFL group of companies acknowledged in her comments the strong partnership between the companies as the key to this success; “I would like to thank our partner Elusys Therapeutics Inc. for the trust to manage the entire MAA filing on their behalf. I would like to thank SFL multi-disciplinary team for their excellent support to achieve this important milestone”.

Elizabeth Posillico, President and CEO of Elusys highlighted the work of SFL’s multi-disciplinary teams in ensuring this successful outcome; “I would like to thank the SFL team for providing comprehensive support for all steps of the EU filing and approval process from orphan drug designation (ODD), through to MAA filing and review, as well as acting as future MAH on behalf of Elusys in the EU. The cooperation between the Elusys and SFL team has been excellent and we are pleased to have achieved this important milestone.”

SFL’s multi-disciplinary teams provide successful support across the entire product life cycle, including preparation and filing of marketing authorization applications (MAA) and acting as marketing authorization holder (MAH) in Switzerland and the EU.

The evaluation of the EU’s orphan drug and pediatric medicine legislations highlights areas of success, but also indicates a need for improvement via regulatory updates.

The European Commission published its joint evaluation on the EU Orphan Regulation (141/2000) and Pediatric Regulation (1901/2006). The analysis is the first comprehensive evaluation since the adoption of the legislation for orphan and pediatric medicinal products. Both have been evaluated together due to the overlap between rare diseases and diseases affecting children.

Among the positive outcomes, the evaluation concludes that the Regulations have fostered the development and availability of medicines for patients with rare diseases and for children, by redirecting investment toward previously neglected areas through incentives, obligations and rewards. Conversely, it also highlights that both Regulations have not adequately managed to support development in areas where the need for medicines is greatest. In this context, the Commission points out that the Pediatric Regulation, for example, does not address the need for treatments of children’s cancers and newborns.

While the evaluation shows that incentives remain relevant to encourage the development of medicines for rare diseases, it questions the merits of the 10-year market exclusivity for such products. It also addresses the definition of rare disease, questioning whether the current prevalence criterion is still an appropriate definition. With respect to costs, the evaluation confirms that both Regulations have increased costs for healthcare systems, but also emphasizes that many patients with rare diseases have benefited from an improvement in their quality of life and that “benefits the legislation brought for children appear to outweigh the costs imposed on both industry and society”.

Based on the outcome of the evaluation, the Commission reported that it will examine the impacts of possible future policy options to update the legal framework on pediatric and orphan pharmaceutical incentives. A preliminary impact assessment is expected to be published for public feedback this Autumn. The review of the Regulations, which will have to go through the full legislative process, will be conducted in parallel to the development of the EU Pharmaceutical Strategy that aims to create a future-proof regulatory framework for pharmaceuticals in Europe.

SFL’s multi-disciplinary teams provide strategic public affairs and regulatory support, with extensive experience in impact analysis of EU healthcare legislation and preparation of ODD and PIP documentation.

The recent EU Resolution and policy documents foreshadow action to prevent supply chain disruptions and futureproof supply of medicinal products in the EU.

The European Parliament adopted its Resolution on medicines shortages on 17 September 2020. The drafting of the Resolution was amended during preparation to incorporate learnings from the impacts of the COVID-19 pandemic.

Key areas of the Resolution are:

• Creation of a European contingency reserve of medicines of strategic importance, acting as “an emergency European pharmacy” to minimize shortages; all member states should have equal access through a new mechanism of just distribution.
• Prioritization of domestic production of essential and strategic medicines
• Restoration of the manufacturing capabilities of Europe’s critical health infrastructure by:
  (1) screening and assessing impacts of direct foreign investment in drug manufacturing
  (2) introduction of financial incentives for companies to produce active pharmaceutical ingredients and medicines in Europe
• A call for a directive on minimum standards for quality healthcare systems in member states

The Resolution recognizes that a dependence on non-EU countries has undermined the ability of the EU to effectively respond to the COVID-19 pandemic. The Resolution outlines steps towards future harmonization of legislation and co-operation between member states, as well as relocation of pharmaceutical manufacturing to Europe. This is likely to influence the Commission in development of the Pharmaceutical strategy for Europe, which has as its first objective to “make sure that patients across Europe have new medicines and therapies in their countries quickly and under all circumstances and that there are fewer shortages of medicines.”

The Resolution also aligns with aspects of the EU’s 2020 Strategic Foresight Report (10 September 2020) and the draft European medicines agencies network strategy to 2025 that identify healthcare supply chains as a vulnerability and a need to secure the supply of pharmaceuticals towards a more resilient Europe. The draft strategy is also considering new supply chain requirements for medicinal product Marketing Authorization Applications (MAAs) that should improve EU resilience against future supply chain disruptions and shortages of medicinal products. These changes would require MAA applicants to provide a risk assessment of the supply chain from the API to the finished product, including risk mitigation measures to strengthen supply chain resilience, and a conclusion about the sourcing of API and starting materials in various regions of the world.

SFL’s Supply Chain, Regulatory Affairs, and Quality Assurance teams work closely to support clients in setting up and maintaining international supply chains, and with our Public Affairs and Regulatory Intelligence team can provide strategic and operational support on the impacts of changing legislation, such as the proposed new MAA supply chain requirements.

Stakeholder feedback highlights an interest in strengthening innovation and uptake of AI, while identifying shortcomings of current legislation.

The European Commission published a summary report on the public consultation on White Paper on Artificial Intelligence (AI) initiated earlier this year.

Key findings of the report, include the following aspects:

• Strengthening research and innovation communities: development of public-private partnerships (PPPs) for industrial research was considered very important by a majority of respondents.
• Supporting the uptake of AI by SMEs: the role of Digital Innovation Hubs (DIHs) to support knowledge transfer is mostly considered very important.
• New legislation required: Most respondents were concerned about the possibility of AI breaching fundamental rights or leading to discriminatory outcomes and found the introduction of a new regulatory framework on AI, or modification of existing legislation, necessary.
• High-risk applications: Opinions were divided on whether new compulsory requirements should be limited to high-risk applications, interestingly respondents from industry and business were more likely to agree with limiting new compulsory requirements to high-risk applications with a percentage of 54.6%.
• Safety and liability: In regards to safety and liability implications of AI, two-third of respondents supported a revision of the existing EU Product Liability Directive to cover particular risks linked to certain AI applications, while a minority suggested that national liability rules should also be adapted for all AI applications. In addition, a majority of respondents also prioritized cyber and personal security risks among the particular AI related risks to be covered by legislation. Moreover, many participants supported that the safety legislative framework should consider a risk assessment procedure for products subject to important changes during their lifetime.

This public consultation is part of a broader stakeholder consultation process that will contribute to the preparation of various regulatory options. Next, the European Commission will use these consultation results to prepare an in-depth analysis and a detailed impact assessment to be used as a basis for a regulatory proposal.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, providing customized intelligence reports and impact assessments.

FDA guidance on multiple function products and EU moves forward with cybersecurity considerations and MDR/IVDR implementation.

To address some challenges faced by the manufacturers of new technologies, the US FDA published guidance outlining its policy and regulatory approach for products with multiple functions where only some are subject to FDA regulatory oversight as medical devices.

The concept of multiple function products was introduced in the context of software by the 21^st Century Cure Act, which also granted FDA the authority to assess the impact of the software non‑device function on the safety and effectiveness of the software device function. The current guidance applies to all multiple function device products and clarifies when and how FDA intends to assess the impact of “other functions” on the safety and effectiveness of a device function subject to FDA review. The term “other functions”, in addition to non-device functions, comprises device functions exempt from pre-market review and those for which FDA does not intend to enforce compliance with applicable regulatory controls. Multiple function device manufacturers should assess impact of this guidance on their product development and risk management processes.

The European Commission’s Medical Device Coordination Group (MDCG) published a position paper confirming that Eudamed actor registration module will be deployed on 1 December 2020. The actor registration module will allow for the creation of a unique single registration number (SRN) with collating and processing information necessary to identify manufacturers, EU authorized representatives and importers of medical devices. As such, the actor module constitutes a prerequisite for the use of other database modules. MDCG strongly encourages the use of the registration module by all relevant actors and discusses the strategy for avoiding double registration requirements for actors.

The economic operations in Switzerland will be able to register in Eudamed’s actor module only when a valid Mutual Recognition Agreement (MRA) between the EU and Switzerland is achieved and the revised Swiss medical devices legislation enters into force (see article on CH – Switzerland adapts its medical device legislation in line with EU developments).

Europe is moving forward with the implementation of the new Medical Devices Regulation (MDR). As per 29 September 2020, seventeen notified bodies (NBs) have been designated against the MDR with seven more in line-up. These numbers seem to secure the capacity of NBs for MDR certification. However, the situation for the In Vitro Diagnostic Medical Devices Regulation (IVDR) certifications is less optimistic. As per 29 September 2020, only four NBs hold IVDR designation one of which located in the UK will soon be no longer able to certify EU IVDs due to Brexit. Even though at least four more organizations are awaiting IVDR designations, this is unlikely to be sufficient to processing all IVDR submissions before the deadline imposed by the IVDR date of application i.e. 26 May 2022.

As part of its continuing efforts to address challenges linked to the digital transformation, the Commission published a report on the European perspective on cybersecurity. In addition to evaluating the growth of cybersecurity over the last 40 years and identifying the areas for improvement, the report discusses cybersecurity challenges for connected medical devices.

SFL Medical Device and Quality teams provide regulatory and quality assurance support to ensure compliance of your medical devices, including software, with the applicable regulatory requirements.

Switzerland continues the harmonization of the Swiss medical devices legislation to minimize disruption with the EU MDR and IVDR.

The harmonization of the Swiss with the EU medical devices legislation is a basis for the mutual recognition of the conformity assessment (MRA) and is fundamental for the participation of Switzerland in a single European market for medical devices.

The Swiss Federal Council approved the updated MedDO and a new Ordinance on Clinical Trials for Medical Devices (ClinO-MD) to transpose the MDR requirements related to clinical trials and other relevant aspects into the Swiss legislation. Both ordinances will enter into force on 26 May 2021, i.e., the MDR application date. In order to prevent medical device shortages as seen during the COVID-19 outbreak, the Council adopted a MedDO amendment on 1 August 2020 allowing for the placing on the market and putting into service of medical devices even if they have not undergone a conformity assessment procedure. This derogation, concerns products used for the treatment of life-threatening conditions or the impairment of body function in situations where no CE-marked equivalent device exists and the patient has agreed to the potential risks.

Harmonization of the Swiss legislation with the IVDR is planned to start with consultations in summer 2021.

SFL’s multi-disciplinary teams closely follow the developments regarding the MRA and Swiss medical devices legislation and provide full support to respond to regulatory changes, as well as to maintain device compliance and supply under the MDR and IVDR.

The guidance introduces new registration obligations and registration route to obtain a ‘UK CE‑mark’ (UKCA) for devices.

The MHRA published a guidance document on the regulation of medical devices and in vitro diagnostics (IVDs) on 1 September 2020, to take effect after the Brexit transition period which ends on 31 December 2020. The Medical Device and In Vitro Diagnostics Regulations (MDR and IVDR) are not EU laws that will automatically be retained by the EU Withdrawal Agreement Act and will therefore not automatically apply in the UK.

Of note, the guidance introduces the following proposals for the regulation of medical devices and IVDs:

• Recognition of CE mark in the UK: certificates issued by European Economic Area (EEA)‑based Notified Bodies will continue to be recognized and the CE mark used until 30 June 2023.
• Introduction of a new route: On 1 January 2021, a new UK Conformity Assessed (UKCA) mark will be introduced and be available to manufacturers of medical devices and IVDs; only UK approved Notified Bodies will be able to conduct conformity assessment. This new mark will not be recognized in the EU, EEA or Northern Ireland markets. From 1 July 2023, the UKCA mark will be compulsory to put products on the Great Britain market.

In addition, all medical devices, IVDs and custom-made medical devices will need to be registered with the MHRA as of 1 January 2021. The MHRA will only register devices where the manufacturer has a registered place of business in the UK. Consequently, a manufacturer based outside the UK will need to designate a UK Responsible Person that has a registered place of business in the UK in order to register its product. The guideline mentions that a grace period will be implemented for the registration of products and designation of UK Responsible Persons based on the following timelines:

• 4 months (until 30 April 2021) for Class III medical devices, Class IIb implantable and all active implantable medical devices, and IVD List A
• 8 months (until 31 August 2021) for other Class IIb, all Class IIa medical devices, IVD List B and self-test IVDs
• 12 months (until 31 December 2021) for Class I devices and general IVDs; this grace period will not apply to manufacturers of Class I devices and general IVDs that are currently required to register with the MHRA.

Special requirements applicable to Northern Ireland are also included in the guidance.

The proposals outlined in this guidance notice will take effect through legislative changes that will be introduced later in 2020. They are still therefore subject to parliamentary approval.

Overall, the new rules detailed in this guidance are likely to create a hurdle for manufacturers to place their products onto the UK market and incur additional costs, especially as of 30 June 2023 when the UK conformity assessment will become compulsory. This will impact on manufacturers considering whether and when to enter the UK market.

SFL’s Device team can provide support for all regulatory and quality needs to ensure compliance of your products under the proposed UK regulations, including on the designation of a UK Responsible Person and registration of your product under the UKCA mark. SFL can also support in the preparation of your personnel by providing customized trainings.

SFL announces a virtual training series by its in-house experts for medicinal products and medical devices.

The SFL online expert training series will provide an overview on topics relevant to the pharma and/or medtech industries for developing and marketing products in the EU and/or Switzerland. Led by highly-experienced members of the SFL cross-functional team, including Regulatory Affairs, Quality Assurance, Medical AffairsMedical Devices, Reimbursement and Supply Chain, they will provide practical tips for success.

The first virtual training will take place on 10 November 2020 (2-5 pm CET; registration) and provide an introduction to EU Regulatory Affairs for medicinal products. The trainers will present the European legislative framework, provide details on the pre-submission activities offered by the European Medicines Agency, and guide participants through clinical trial application dossiers, marketing authorization procedures, and lifecycle management activities.

Dates of future virtual training courses will be published on the SFL website. Topics that will be covered in the training series include; Good Distribution Practice and Good Manufacturing Practice in the EU, the Swiss Establishment License, Swiss Market Access and Supply Chain, Orphan Drug Designation in the EU and Switzerland, Regulatory Affairs in Switzerland, the EU Medical Device Regulation (MDR), the European Regulatory Framework for Combination Products, Medical Device Software (MDSW) and Clinical Evaluation Reports under the EU Medical Device Regulation.

SFL and its highly-experienced, cross-functional team offer accredited training courses, across key aspects in the life-cycle of medicinal products and medical devices. SFL also offers customized trainings, at your company’s site or online, and tailored to your products and strategic objectives. Contact us to find out more.

SFL’s CEO will moderate a panel discussion, while SFL Heads of Medical Devices and of Supply Chain will chair and present at the upcoming MPP Annual Conference on 22-23 October.

This year’s 2020 Digital MPP Annual Conference (MPP2020) is on “Achieving patient-centricity under the new MDR – balancing stakeholder interests” (22‑23 October, 2020). A high-quality program will focus on topics across all aspects of medical devices and combined products life cycle, headlined by the Keynote presentation from Zaïde Frias, Head of the Digital Business Transformation Task Force at the European Medicines Agency (EMA). A high-level panel moderated by SFL’s CEO and the President of the MPP, Shayesteh Fürst-Ladani, will include Erik Hannson (Deputy Head of Medical Devices at the European Commission), Ilona Reischl (AGES-MEA), Serge Mathonet (EFPIA & Sanofi), Julia Frese (TÜV SÜD), Merlin Reitschel (Medtech Europe), as well as MPP members Stephan Affolter (Ypsomed) and Mike Wallenstein (Novartis). SFL’s Head of Medical Devices Karin Schulze, will chair the session “From ideation to innovative products”, while SFL’s Head of Supply Chain Barbara Polek, will present on “Promoting patient safety through new supply chain controls under the Medical Device Regulation and the Falsified Medicines Directive.” Additional session presentations from leading organizations will discuss new and emerging technologies, ideation, innovation, development, patient needs, patient engagement and value-based healthcare. Visit the speaker webpage for details on all the Annual Conference speakers, or to register online and take advantage of a reduced price for the virtual conference.

A joint MPP and Swiss Medtech lunch webinar will be held on “Opportunities and challenges to shape the regulatory environment for combined products” (14 October 2020, 12 pm CEST; Registration). It will host experts from the MPP member companies discussing this complex area, the impacts of the new MDR legislation on combined products, and how future legislative changes could affect the continued development of and access to these innovative products.

An accredited online training providing an “Overview of Medical Devices Regulation and Impacts on Combination Products” also took place on 29 September 2020. Details of trainings can be found on the MPP training webpage.

Contact the MPP Association to find out how your company can become a member and get involved in the Association activities. To stay up-to-date with all the latest news, events and trainings, follow the MPP LinkedIn or Twitter accounts.

With Vifor Pharma, Biogen, Retina Suisse, the Swiss Hemophilia Society and Prof. Dr. Pascal Escher joining as members, the RDAF develops and reinforces its collaborative, multi-stakeholder approach.

The Rare Disease Action Forum (RDAF) welcomes five new members, expanding the Associations’ diverse stakeholder membership base. The new members; Vifor Pharma, Biogen, Retina Suisse, the Swiss Hemophilia Society, and Prof. Dr. Pascal Escher, an expert in ophthalmogenetics, bring extensive expertise in areas of pharma, biotech, and patient health and care for rare diseases. The new members add to the existing collaborative stakeholder base comprising industry, patient organizations, healthcare professionals, and research organizations, to further reinforce the unique multi-stakeholder approach for future RDAF activities.

SFL’s CEO Shayesteh Fürst-Ladani is the President of the RDAF, and SFL public affairs team manages the secretariat of the RDAF.

If you are active in the field of rare diseases and would like to engage with other stakeholders to drive improvements for patients with rare diseases, contact the RDAF Association about member benefits (see also our new brochure, and access the latest RDAF news and activities on LinkedIn and Twitter.

SFL’s regulatory team supports approval of the first product by Swissmedic under the project Orbis initiative. Swissmedic’s cooperation with other regulatory authorities is further highlighted by the first MAGHP procedure approval.

Swissmedic approved the first products under two new regulatory initiatives; the US FDA’s project Orbis initiative and Swissmedic’s Marketing Authorization for Global Health Products (MAGHP) procedure, both of which harness greater cooperation between National Regulatory Authorities (NRAs) to accelerate access to important medicines.

Project Orbis is the US FDA Oncology Center of Excellence’s initiative for concurrent submission and review of oncology drug applications. Through collaboration and exchange of information between the US FDA and participating international regulatory agencies, including Australia’s TGA, Health Canada, EMA, Japan’s PMDA and Switzerland’s Swissmedic. The initiative aims to accelerate patient access to innovative oncology treatments.

On 7 May 2020, Swissmedic approved a targeted (anti-HER2) oncology drug developed by a US headquartered cancer-focused biotechnology company; the first product approved by Swissmedic under the initiative and the first approval of this innovative breast cancer drug outside of the US. SFL’s regulatory team supported with the preparation of the Marketing Authorization Application (MAA) dossier and submitted to Swissmedic, utilizing the novel project Orbis procedure. Swissmedic combined phase I-II reviews, issued rolling questions to the applicant and had extensive interactions with the other involved health authorities to make a short process deadline of 123 days in total possible. Swissmedic approved the product four months after SFL’s MAA submission and less than one month after FDA approval in the US, with a comparable review period. This outcome highlights the benefits of this new regulatory process to facilitate rapid access to innovative new cancer drugs for Swiss patients.

On 13 May 2020, Swissmedic also announced the first authorization of a medicinal product via the MAGHP procedure, involving participation of the NRAs of Uganda, Kenya, Tanzania, South Sudan, Nigeria, Democratic Republic of Congo and Ethiopia. Eligible products are medicinal products with a new or known active substance, and medicinal products with a known active substance for a new indication intended as a health intervention or therapeutic product in low- and middle-income countries. The product approved by Swissmedic was an injectable solution for the prevention of uterine hemorrhage due to postpartum uterine atony. After submission, the review process follows the same review timeline as products submitted for a MAA in Switzerland and includes a 30-day validation, followed by an evaluation process that involves two steps of 120- and 90-days, prior to a preliminary decision. The MAGHP procedure aims to accelerate approval of essential medicines and build the capacity of collaborating NRAs by making the Swissmedic authorization procedure and the scientific advice procedure accessible to NRAs in low- and middle-income countries, as well as to the World Health Organization (WHO). The procedure builds on the existing procedure for Marketing Authorization for Medicinal Products not intended for the Swiss Market (export registration).

Contact the SFL Regulatory Team and explore how SFL can serve you across the entire product life cycle and/or act as marketing authorization applicant and MAH in Switzerland and the EU, and conduct submissions to FDA, PMDA, Health Canada and other authorities.

Regulatory action to support both Pharma and Medical Device development and their supply in response to challenges from the COVID-19 pandemic, demonstrates regulatory flexibility and a capacity to enhance existing processes.

The European Medicines Agency (EMA) has responded to a need for medicines and vaccines to treat and prevent COVID-19, by implementing initiatives for acceleration of development support and evaluation procedures of these products, under the oversight of a new COVID-19 EMA pandemic Task Force (COVID-ETF). The initiatives include expedited processes for scientific advice, agreement of a Pediatric Investigation Plan (PIP) and compliance checks, and the use of rolling reviews. Expedited procedures will be available for regular and accelerated marketing authorization applications for COVID-19 intended products, or for indication extensions to support repurposing of approved products. The use of the priority medicines scheme (PRIME) has also been encouraged. The EMA will also support availability of certain unauthorized medicinal products by providing recommendations on compassionate use programs for the prevention and treatment of COVID-19. These initiatives also consider guidance on clinical trials during the pandemic published by the EMA and national regulators of Member States.

The European Commission has prioritized actions to support development and use of medical devices in the COVID-19 context and postponed the Date of Application of the Medical Devices Regulation 2017/745 (MDR) to 26 May 2021. This shall prevent shortages of vitally important medical devices within the Union. A Q&A document and a communication were published in May, providing guidance on relevant newly revised harmonized standards, derogations under article 59(3) of the MDR, procedural requirements of EU-wide derogation and the adoption process by implementing acts. Guidelines on COVID-19 testing methodologies and performance for developers were also published in April. These documents discuss COVID-19 RT-PCR tests, antigen and antibody tests, along with validation of their performance, and proposes performance criteria and assessment approaches. A US FDA guidance addressing similar aspects was published in May.

Actions to ensure the supply of COVID-19 medicines and medical devices have been implemented involving cooperation within the EU and neighboring countries, such as Switzerland. This includes joint procurement by the European countries, a common EU stockpile reserve (RescEU) of medical equipment such as ventilators, personal protective equipment, reusable masks, vaccines, therapeutics and laboratory supplies, the EU COVID-19 Clearing House to match supply with demand, and streamlined cross-border transport. In April, the European Commission released a communication on guidelines on the optimal and rational supply of medicines and the Swiss Federal Council approved an amendment (Annex 3) on export of certain medical products and protective equipment for the Ordinance on Measures to Combat the Coronavirus (COVID-19) issued in March and which addresses the provision of essential medicinal products and medical goods.

COVID-19 responses to support development, evaluation and adequate supply of medicines and medical devices have demonstrated positive aspects with implications for their adoption to strengthen the pre-COVID-19 frameworks in these areas. In particular, actions to safeguard supply could be beneficial, if applied in future to a broader subset of products for which shortages in the EU and/or Switzerland occurred prior to COVID‑19. This is expected to be considered in the EU Pharmaceutical Strategy, which will address lessons learned from the COVID-19 pandemic around preparedness and supply chains. The consultation on the roadmap for this strategy is open until 7 July 2020. The US FDA’s Commissioner has also signaled a similar intent to maintain some COVID-19 changes in regulatory processes related to clinical trials, telemedicine and laboratory-developed tests, in a recent video briefing.

SFL’s Regulatory, Medical Devices and Supply Chain teams can support clients developing new COVID‑19 therapies on a strategic and operational level. Contact them to find out how they can support in activities including identification of new opportunities, rapid regulatory approval, actions to ensure supply and providing regulatory intelligence to stay up-to-date with new and proposed requirements and policies.

Recently released MDCG documents include important updates on legacy products and their certification under the MDR, with a focus on clinical evaluation and supporting clinical data quality.

Following the transitional provision for class I devices and guidance on significant changes (reported in the last SFL newsletter), and the postponement of the MDR to 26 May 2021, the MDCG has released a number of guidance documents to facilitate activities toward conformity of new and legacy products under the MDR, with topics including, revised guidance on article 54(2)b interpretation for legacy products, guidance on clinical evidence under the MDR for legacy products, and the use of equivalence in clinical evaluation on products being certified under the MDR.

In April 2020, a revision was published for the MDCG 2019-3 guidance on interpretation of devices under article 54(2)b that are exempt from the involvement of expert panels in pre-market clinical evaluation consultation. The document introduces procedural guidance on documents for lodgment of an application for conformity assessment of legacy products by a Notified Body (NB). However, the important interpretation that article 54(b) refers to devices marketed under the Directives (legacy products) and the “modifications” of these legacy products “needed in order to comply with the new legal requirements introduced by the MDR” remains unchanged. The revision highlights that the application for MDR conformity assessment of a legacy device must clearly state that it is for the same intended purpose and provide a description of modifications introduced to comply with the MDR, as well as the last issued certificate and history. The technical document assessment by the NB will focus on verifying that modifications do not adversely affect the benefit-risk and their impacts on compliance with the general safety and performance requirements (GSPRs).

A guide for manufacturers and NBs on providing sufficient clinical evidence to demonstrate legacy products’ conformity with relevant GSPRs under article 61 of the MDR was published by the MDCG (MDCG 2020-6) in April 2020. For the first MDR conformity assessment of a legacy device, pre-market and post-market clinical data generated for the purpose of MDD/AIMDD can be taken into account. The guide specifically addresses the requirement for a clinical investigation (article 61(4)) for Class III and implantable devices, and clarifies that exemptions can be granted for legacy products; marketed (article 61(6)) or with equivalence to previously marketed devices (article 61(5)), provided sufficient quality and quantity of clinical data exists (article 61(6a)). Non-clinical data for Class III and implantable devices cannot be used to support conformity with GSPRs. Specific aspects of clinical evaluation for legacy devices are detailed, which includes the clinical evaluation plan, available clinical data, pre-market and post-market data sources, clinical data appraisal, generation of new clinical data and clinical data appraisal. Appendices on relevant MEDDEV 2.7/1 rev.4 sections, clinical evaluation plans, and the hierarchy of evidence of clinical evaluation for confirmation of conformity with GSPRs for legacy devices, are also supplied.

In April 2020, the MDCG also published a guidance on equivalence in clinical evaluations; outlining how to use clinical data related to an equivalent device in the clinical evaluation required for a device under MDR conformity assessment. Demonstration of equivalence according to MDR requirements is already integrated in MEDDEV 2.7/1 rev. 4 and the new guidance does not introduce new requirements, but does clearly compare the relevant aspects from both the MDR and MEDDEV 2.7/1 rev. 4 documents on technical, biological and clinical characteristics of the two devices. An Annex also provides an example of an equivalence table that addresses important parameters to consider in demonstrating equivalence on technical, biological and clinical characteristics.

SFL’s Device Team can provide support for all regulatory and quality needs to ensure compliance of your products under the MDR and according to MDCG requirements, including clinical evaluation of novel and legacy devices, as well as implementation and updating of QMS. SFL can also support in the preparation of your personnel by providing customized trainings.

Consultation aims to close gaps in Swiss legislation on human medical and non-medical genetic tests related to access, development and supply of such tests in Switzerland.

A consultation was opened on two ordinances related to the revised Federal Act on the Genetic Testing of Human Beings (GUMG) on 19 May 2020. The consultation comes in response to changes in this area, including “Direct-to-Consumer Genetic Tests” (DTC-GT) and access to medical and non-medical genetic tests via the internet. It aims to identify and close gaps in this legislation due to these changes and clarifies aspects including genetic tests supplied from foreign companies and tests in areas not currently regulated by the existing GUMG. Specifically, it relates to the revision of the Ordinance on Human Genetic Analysis (Verordnung über genetische Untersuchungen beim Menschen; GUMV) and the Ordinance on the Establishment of DNA Profiles in Civil and Administrative Matters (Verordnung über die Erstellung von DNA-Profilen im Zivil- und Verwaltungsbereich; VDZV).

The revised GUMV details, in particular, the following changes:

• Health professionals other than physicians may be allowed to order certain genetic tests
• Obligatory accreditation is required for all genetic laboratories in the medical field
• The scope of the GUMG is extended to genetic testing other than for medical purposes
• It specifies guidelines regarding the protection of samples and genetic data

The entry into force of the law and the ordinances is scheduled for 2021. The consultation is open until 9 October 2020.

SFL provides tailored strategic public affairs support for clients with extensive experience in providing impact analysis of Swiss healthcare legislation.

RDAF’s latest multi-stakeholder workshop focused on the importance of registries for rare diseases in Switzerland.

On 8 April 2020, the Rare Disease Action Forum (RDAF) Association held a multi-stakeholder workshop on “registries for rare diseases in Switzerland” with expert presentations from patients, physicians and industry representatives, who shared their experiences with establishing, maintaining and developing patient registries. The presentations were followed by discussions on this topic, which highlighted that while registries are highly beneficial for improving care of patients with rare diseases, they require constant development and face challenges in sustainable financing and personal resources, as well as balancing data access rights and protections. To maximize benefits of registries, further engagement and cooperation to address harmonization, multi-sponsoring and national/international networking is required.

If you are active in the field of rare disease and would like to engage with other stakeholders to drive positive change for patients with rare diseases, contact the RDAF Association, or see our new brochure to learn more about member benefits.

The MPP Association launches a new Connected Combined Products Working Group, and the advanced program for the MPP Digital 2020 Annual Conference is released.

The Medtech & Pharma Platform (MPP) General Assembly agreed on the formation of a new MPP Working Group on “Connected Combined Products”. It recognizes the increasing importance of complex connected combined products to deliver precision treatments that can greatly enhance the quality of life for patients. This Working Group utilizes the MPP’s recently expanded members representing IT‑engineering companies working on digital health solutions and CRO’s, in addition to the existing medtech and pharma membership base. Among other aspects, the Working Group will define regulatory gaps and innovations to be addressed to enhance the safety and performance of these devices in development and use. The new Working Group will operate alongside the existing “Combined Products Working Group”.

In response to COVID-19 restrictions and uncertainty that has disrupted interactions within and between the Pharma and Medtech communities, and their business operations, MPP has adapted to host the MPP2020 Annual Conference as a live digital conference. Hosting the Annual Conference on a virtual platform provides planning security for all involved parties and offers exciting opportunities to increase accessibility to members of the MPP community independent of their location.

The MPP Digital 2020 Annual Conference on “Achieving patient-centricity under the new MDR – balancing stakeholder interests” will take place from 22-23 October 2020. It will include a keynote presentation, a special high impact stakeholder panel discussion on the implementation of the Medical Devices Regulation (MDR) and Combined Products, and expert presentations. Six sessions will address topics on new technologies, ideation to innovative products, the MDR and Combined Products, innovation for successful development, patient/user needs, and value-based healthcare, patient access and engagement. The conference will be hosted on a browser and mobile phone-supported virtual conference platform, that brings enhanced opportunities for partnering and engagement with sponsors, exhibitors and attendees through live streaming, interactive tools and direct 1-1 video conferencing for participants. The virtual conference platform will be active one month prior to the event and on-demand videos of presentations will be available after the presentations.

Contact the MPP Association to find out how your company can become a member and get involved in the Association activities. All the latest news and registration information for the MPP Digital 2020 Annual Conference can be found on the MPP website.

Simplified assessment procedure, Article 13, expanded to include human medicinal products for prevention of serious communicable diseases.

On 15 January 2020, Swissmedic announced a broadening of the criteria for the application of the simplified assessment procedure, Article 13 of the Swiss Therapeutic Products Act (TPA), to include human medicinal products with new active substances (NAS) indicated for the prevention of a communicable disease, e.g. vaccines. These changes aim to provide patients with earlier access to eligible innovative products and improve public health protection by prevention of primary infection.

Under Article 13 TPA, Swissmedic will review the efficacy, safety and quality of the medicinal product using a reference authority’s assessment report and determine whether the outcome of the foreign authority’s assessment can be adopted for Swissmedic’s authorization decision.

SFL provides tailored regulatory strategy assessments and supports the preparation of MAA filings, with extensive experience in Article 13 procedures in Switzerland.

The EMA’s re-organized structure now includes an integrated Human Medicines Division and four new taskforces to drive transformational change in priority areas.

On 2 March 2020, EMA implemented an internal re-organization of its structure to support continued efficiency and high-quality output for public and animal health following its relocation to Amsterdam. A new Human Medicines Division led by Alexis Nolte that integrates all operations in the area of human medicines. The Veterinary Medicines Division remains unchanged under Ivo Claassen.

Four mission-critical task forces have been established to support the human and veterinary medicines:

• The Digital Business Transformationtask force (Zaide Frias) to oversee strategy, structure and operations of the EMA and its interactions with external stakeholders in adapting to legislative initiatives, digital technologies and global trends.
• The Data Analytics and Methodstask force (Peter Arlett) to ensure capability and capacity to deliver robust evidence for benefit-risk decision-making, with a focus on expert scientific advice, marketing authorization assessments, expert methods advice and data analysis.
• The Regulatory Science and Innovationtask force (Anthony Humphreys) to ‘future-proof’ the EMA by translating key scientific and technological trends into the EMA’s regulatory science strategy, planning and governance, with a focus on engagement of drug developers, small and medium-sized enterprises (SMEs) and academia.
• The Clinical Studies and Manufacturingtask force (Fergus Sweeney) to facilitate clinical studies and manufacturing strategy at the EU and global level.

Other changes include Enrica Alteri’s appointment to Adviser on Human Medicines and Spiros Vamvakas’ appointment to Scientific Adviser on Human Medicines.

SFL Public Affairs and Regulatory Policy team provides regulatory and policy intelligence to keep up-to-date with changes affecting regulatory strategies for healthcare products of pharma and device companies.

Simultaneous National Scientific Advice pilot program aims to provide enhanced and earlier support to develop innovative drugs in EU.

On 22 January 2020, the EMA published a guidance on a pilot program for Simultaneous National Scientific Advice (SNSA) from national competent authorities (NCAs) in the EU to enhance development of innovative medicines. Benefits over existing sequential advice approaches include assisting applicants in earlier identification of regulatory gaps and obtaining alignment or clarification from NCAs on specific critical issues before an application.

In the process, two NCAs can provide national scientific and/or regulatory advice in a single step, ensuring applicants have an earlier opportunity to discuss, clarify and align their approaches to critical regulatory requirements. Furthermore, academic institutions and SMEs developing new medicines shall benefit from tailored guidance addressing their sector-specific challenges.

The approach is expected to support applicants to address critical issues, enhance transitional research processes and complement subsequent EMA Scientific Advice requests.

SFL has extensive experience in supporting clients for Scientific Advice and Pre-submission meetings in the EU.

The Swiss Parliament advises medical device manufacturers to be prepared for a delay in the EU-Switzerland MRA until after MDR implementation in May 2020.

The impending MDR deadline has highlighted the ongoing revision of the mutual recognition agreement (MRA) between Switzerland and the EU that includes medical devices. If this is not agreed before the MDR deadline (currently 26 May 2020), the free access of medical devices between the two Markets as it is practiced so far is likely to be impacted.

On 11 March 2020, the status of the EU-Switzerland MRA and its possible impact on the Medical Device industry after the MDR implementation deadline was addressed by the Federal Council, in a detailed response to the interpellation “Wie weiter mit den Medizinalprodukten?. Federal Councilor Parmelin also released a statement on this topic. Key aspects of the Federal Council’s position are:

• The current provisions on medical devices under the EU Medical Device Directive 93/42 must remain applicable after 26 May 2020 even without an update of the MRA (this position is in contrast to the current position of the European Commission).
• Conditions for market access if the MRA is not updated are being discussed in talks between Switzerland and the EU, with a delay in the updated agreement likely as the EU requires progress on the Framework Agreement before the MRA can be agreed.
• A transitional provision on the fulfilment of the third country requirements violates EU law and is therefore unlikely, as emphasized by Federal Councilor Parmelin.
• Targeted measures to ensure supply and product safety in the event that the MRA is not updated are currently being drawn up.
• The Federal Council assumes that the EU will ultimately support maintaining at least the status quo under the current regulations, so to prevent disruption of medical device supply from Switzerland to the large number of patients in the EU area.

Until details on the measures currently being negotiated by the EU and Switzerland, manufacturers should continue to prepare for impacts that a “no deal” scenario may have, including CE certificates issued by a Swiss NB being no longer valid in the EU and vice versa, and the need for modified product labelling. Furthermore, all manufacturers domiciled in Switzerland will need to have an Authorized Representative in one of the EU Member States.

The SFL Public Affairs and Regulatory Policy team closely follows developments with the EU‑Switzerland MRA and with SFL’s multi-disciplinary service areas can provide full support to respond to regulatory changes and maintain device compliance and supply under the MDR/IVDR, including for third country import/export (e.g., EU-UK or CH-EU).

Ten priority recommendations of the joint EMA and HMA Phase II report include data quality and security, a new EU healthcare platform, big-data driven regulation, and a stakeholder implementation forum.

On 15 January 2020, the joint Big Data Task Force (BDTF) of EMA and the Heads of Medicines Agencies (HMA) published the Phase II report entitled “Evolving Data-Driven Regulation”. The report proposes ten priority recommendations that include; establishing frameworks to ensure data quality and security, strengthening the capacity of the EU workforce and institutions to use and analyze big data, increasing international collaboration and initiatives, as well as creating appropriate expert groups, committee and data platforms to facilitate these goals.

The most ambitious goal is the establishment of an EU platform to access and analyze healthcare data, including real-world data, from across the European Union (Data Analysis and Real World Interrogation Network, or DARWIN). This platform would create a European network of databases of verified quality and content with the highest levels of data security. It would be used to inform regulatory decision-making with robust evidence from healthcare practice.

The report also addresses bioinformatics, algorithms, machine learning and AI to analyze big data to reveal patterns, trends, and associations in the accumulating datasets. Applied to data generated through the lifecycle of medicinal products, including development, clinical testing and post-market use, it has the ability to provide insights to assess the benefit-risk of medicines and inform decision-making.

Harnessing big data in development and assessment of innovative medicines, diagnostic applications and medical devices could deliver life-saving treatments to patients more quickly, and optimize the safety, performance and use of medicines and devices on the market. Furthermore, big data should improve regulatory decision-making by providing complementary evidence to established sources like randomized clinical trials. To realize the potential of big data and its integration into regulatory processes, the report proposes the formation of an EU Big Data ‘stakeholder implementation forum’ to facilitate dialogue between regulators and various stakeholders.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, providing customized intelligence reports and impact assessments.

Innovative and orphan medicines account for up to half of successful approvals in 2019, as applicants make use of approval pathways supporting innovative medicine development.

In the EU, the EMA reported that 80% (66) of MAAs submitted were approved. Of those approved, 45% (30) contained a new active substance (NAS) and 11% (7) were for an orphan indication. Hematology / hemostaseology drugs comprised almost 25% (16) of all approvals and 20% (7) of NAS drug approvals. The approval pathways to support development of innovative drugs and patient access, such as PRIME, accelerated assessment, approval under exceptional circumstances and conditional marketing authorizations, were used in 23% (15) of approved submissions.

In the US, CDER approved 48 drugs with new molecular entities (NMEs). Of those approved, 44% (21) were for orphan diseases. Therapeutic areas with the most NME approvals were neurological and psychiatric disorders accounting for 17% (8), and infectious diseases with 10% (5). Expedited development and review pathways, like fast-track and breakthrough designated drugs or priority review and accelerated approval pathways, were used in 60% (29) of the NME approvals. In addition, CBER approved 21 BLAs.

SFL has extensive experience in supporting clients with regulatory strategy, ODD and MAA/NDA/BLA for innovative and orphan medicinal products.

European Commission’s data strategy and White Paper on AI, identify key areas for new legislation and invite stakeholder input to support digital transformation across the EU.

On 19 February 2020, the European Commission (EC) launched its “Shaping Europe’s Digital Future” initiative to support digital transformation in the EU, publishing a European strategy for data communication and a White Paper on Artificial Intelligence. Both documents have implications for future healthcare in the EU and are open for comment until 19 May 2020. A legislative framework for data governance (Q4 2020) and a possible Data Act (2021) are in development.

The European strategy for data communications recognizes data as important for healthier lives and better healthcare, providing personalized medicine for patients based on data-enabled decisions by doctors. It identifies improved data sharing of sensitive health data for research as important to realizing the potential of the data economy, but that this is challenged by the importance of preserving the individuals’ rights to personal data.

To address data sharing, the strategy proposes the establishment of a Common European health data space to be used to support advances and inform decisions that improve the accessibility, effectiveness and sustainability of the healthcare systems. The space will enable cross-border exchange, the re-use of health data critical for innovation in the healthcare and facilitate electronic health records in accordance with GDPR law on processing of personal data.

The EC White Paper highlights AI as one of the most important applications of the data economy, creating value from ever-increasing data sources. Benefits from AI for citizens, businesses and the public interest, including its use in healthcare, will be dependent upon policy that fosters an “ecosystem of excellence” coupled with a regulatory framework creating an “ecosystem of trust”.

Legislative changes for AI should adopt a risk-based approach dependent on the sector and manner of use. The report identifies risks and situations with the use of AI that are potentially subject to legislative changes. These include changes to support the enforcement of AI breaches of rights, liability of economic operators, and to ensure safety of services based on AI technology or products with integrated AI software. However, it is noted that any legislative changes should consider existing horizontal or sectoral legislation (e.g., medical devices), not be prescriptive or add significant burden for SMEs.

SFL’s Public Affairs and Regulatory Policy team continuously monitors policy and regulatory developments, providing customized intelligence reports and impact assessments.

The release of new risk management, cybersecurity and clinical evaluation guidelines addresses outstanding uncertainties for medical devices and software in the MDR & IVDR.

In December 2019, the update to the standard on “application of risk management to medical devices” (ISO 14971:2019) and the EU Medical Device Coordination Group’s (MDCG) guidance on cybersecurity for medical devices were published. The increased guidance in preparation for conformity assessment shall provide considerable benefit to medical devices, in vitro Diagnostics (IVDs) and Medical Device Software (MDSW) defined under the Medical Device Regulations (MDR) and in vitro Device Regulation (IVDR).

The new guidelines are particularly relevant and timely for IVDs where the proportion of products requiring a Notified Body assessment is expected to increase from 15% to 85% under the IVDR. The new IVDR emphasizes life-cycle management and continuous evaluation of the product, including new risk‑based classification, new general safety and performance requirements (GSPRs) and routes to conformity assessment. Manufacturers will need to demonstrate device compliance to new clinical and performance evidence, quality management systems (QMS), post-market surveillance (PMS), vigilance, traceability and risk management system requirements, that includes meeting the new ISO 14971:2019 standard and MDCG cybersecurity guidelines.

The ISO 14971:2019 standard places more importance on collection of post-market information and the risk-benefit analysis. Proactive collection and evaluation of data and the source from the post-production phase is now mandatory and risks resulting from inadequate data and system security have to be considered. This aligns with MDR/IVDR requirements, facilitated by new definitions of “benefit”, “state of the art”, and “reasonably foreseeable misuse”. It has also been recognized by the US FDA as a consensus standard.

Recognition of the increasing reliance of IVDs and medical devices on software, is addressed in two new MDCG guidance documents on cybersecurity (MDCG2019-16; Jan 2020) and clinical evaluation (MDCG2020-1; Mar 2020) guidance and follows the release of the MDCG Guidance on Qualification and Classification of Software in the MDR and IVDR published in October 2019, providing direction for satisfying the MDR/IVDR requirement that products are developed to the state of the art, including for “information security” and “protection against unauthorized access”. Details include principles for secure design and manufacture, successful post-market cybersecurity surveillance and technical documentation, for IVDs and MDSW. The guidance on clinical evaluation details requirements to provide sufficient clinical evidence to demonstrate conformity with GSPRs under the normal conditions of the device’s intended use. Among other aspects, a benefit-risk analysis based on the assessment of clinical data for the MDSW related to clinical association/scientific validity, technical performance/analytical performance and clinical performance is needed, aligning with recommendations by the International Medical Device Regulators Forum (IMDRF) on software as a medical device (SaMDs), which is also discussed in the recent SFL publication on SaMDs and mHealth.

SFL Medical Device experts can perform gap assessments for compliance of your device documentation with the IVDR and IVDR preparedness checks of your processes, covering for GSPR conformity, technical documentation, QMS, risk management and cybersecurity, as well as support in updates of these aspects, QMS establishment and maintenance, IVD performance evaluation and PMS support.

The European Commission announces new MDR designated Notified Bodies and changes to the implementation of the MDR/IVDR, including a grace period and related guidance for class I devices that will be in higher risk classes under the MDR.

The impending deadline for MDR implementation (currently 26 May 2020) has resulted in numerous announcements to facilitate manufacturers in ensuring conformity and continued supply of devices. In December 2019, the European Parliament agreed to extend recognition of Medical Device Directive (MDD) class I devices that have a valid declaration of conformity at 26 May 2020, for up to a further four years till 26 May 2024. This provides a grace period for otherwise up-classified devices like software, reprocessable and substance-based devices, and applies only to the device while it is not subject to any significant change, as outlined in the Medical Device Coordination Group (MDCG) guidance document published on 16 March 2020. The document provides six flowcharts to support manufacturers in determining if a change to the intended purpose, design performance, software, material or sterilization is considered “significant”. In cases where a manufacturer considers a change to be “non-significant”, they must be able to justify their decision.

The number of designations for Notified Bodies (NBs) and conformity assessment have increased to 12 designations under MDR and 3 designations under IVDR in NANDO (as of 23 March 2020). Notified Body certification of high risk devices will require assessment by expert panels, with the call for experts for both the MDR and IVDR recently closed. For products listed in Annex XVI of the MDR, the call for observers for this subgroup of the MDCG closed on 6 March 2020.

In January 2020, the European Commission issued documents on principles of the classification and Application of the European Medical Device Nomenclature (EMDN), to be used by manufacturers in preparation for registering their medical devices in the EUDAMED database, which is now due on 26 May 2022.

SFL multi-disciplinary services provide full support for device compliance with MDR/IVDR, from gap analysis and remediation support, classification and nomenclature, UDI implementation and traceability management, as well as third country import/export (e.g., EU-UK or CH-EU).

Regulators are seeking to incorporate real-world data as evidence to support pre-and post‑marketing regulatory assessment, highlighting the importance of effective collection and communication of real-world evidence.

The joint Big Data Task Force (BDTF) of the EMA and the HMA priority recommendation to establish the Data Analysis and Real World Interrogation Network (DARWIN) platform (see article: “EU – Recommendations on the use of big data in the regulatory process”) highlights the importance of real-world evidence (RWE) to future regulatory assessments. DARWIN will provide a practical framework to support use of RWE in the EU, with a primary focus to gather real-world data (RWD) across multiple sources and generate RWE to support EU regulatory decision making. It also identifies a path forward that could also be considered by the US FDA, which currently uses RWD and RWE in monitoring post-market safety and adverse events, and published a draft guidance last year on the potential for its expanded use in drugs and biologics assessments.

RWE is clinical evidence generated from RWD; data relating to patient health status and/or the delivery of health care that are routinely collected from a variety of sources. A goal of RWE is to provide complementary evidence to randomized clinical trials (RCTs) or when RCTs are not ethical or feasible. RWE studies can provide important complimentary data to RCTs for complex diseases and/or where patient populations are small and/or heterogenous, where RCT data may underrepresent true end users or be confounded either by the controlled nature of monitoring, overly complex study designs and unexpected events like patient drop-out.

Generation of RWE requires thorough consideration of the design and goals of RWE studies. RWE study designs include observational, prospective or retrospective, and are associated with unique challenges from selection of patient populations and collection of appropriate data, to elimination of confounders, bias and complex data analysis.

RWE can provide valuable support to both efficacy or safety data of medical product assessments, in pre‑approval, indication extension, conditional approval, post-authorization safety, pharmacovigilance and health technology assessment. To benefit from RWE, effective communication of complex RWE according to relevant guidelines is needed, which can establish trust and generate clinical evidence that informs regulatory decisions and accelerates patient access.

SFL Medical Affairs experts, working closely with Regulatory Affairs and Reimbursement teams, can effectively assess and communicate the performance and safety benefits of RWE studies using your medical products.

Dear clients, partners, friends

As the turn of the year approaches, we would like to thank all our partners and clients for your ongoing trust in our services and support.

This newsletter highlights some key developments including the EMA Regulatory Science Strategy 2025 stakeholder meeting, the revision to the Swiss Therapeutic Products Act (TPA) and the ongoing implementation of both the Medical Devices Regulation (MDR) and the In Vitro Medical Devices Regulation (IVDR) that will impact the pharma and medtech landscape, and regulations as of 2020.

We look forward to continuing to support our valued clients with our cross-functional team in providing the most comprehensive and tailored solutions to achieve your goals in 2020.

We wish you a relaxing holiday season, with every success in the new year

Shayesteh Fürst-Ladani, CEO and the SFL Team

EMA Executive Director Guido Rasi stressed the importance of building adaptive regulatory systems that foster innovation in the EU during a stakeholder meeting that took place on 18-19 November 2019. He pointed out that “innovation matters only when patients have access”. Based on received stakeholder input the following five core topics were identified and discussed among others:

1. Fostering innovation in clinical trials

General support for a new strategic initiative or multi- stakeholder, neutral platform was expressed to enable new approaches to clinical trials and to position the EU as a preferred location for innovative clinical research.

2. Promoting use of high-quality real-world data (RWD) in decision making

A “RWD learning initiative” was proposed where regulatory systems would learn from submissions including big data throughout the product lifecycle.

3. Reinforcing patient relevance in evidence generation

The need for an overall framework and more guidance on Patient Reported Outcome versus Patient Relevant Outcome was identified.

4. Contributing to HTA’s preparedness and downstream decision making for innovative medicines

The exchange of information and expertise between regulators, HTA bodies and payers need to be facilitated and aligned.

5. Supporting developments in precision medicine, biomarkers and ‘omics

Greater use of the EMA qualification procedure by accelerating the procedure and making it more flexible is encouraged.

Publication of the final strategy paper is expected for October 2020.

SFL’s Public Affairs & Regulatory Policy team closely follows policy developments. Please contact us for any questions on impacts of new policies on your business.

A free SFL webinar on 28 November 2019 presented key changes of the revised Swiss Therapeutic Products Act (TPA) and their implications for industry stakeholders. One important change is the scope of the Article 13 procedures, which now include biosimilars and products for oncology indications. Other changes include new simplified authorization procedures for products with well-established use and changed conditions under which Swissmedic may temporarily authorize the use of a medicinal product. The revisions also changed requirements for pediatric investigation plans impacting on orphan drugs and data protection and introduced the SwissPAR concept.

SFL has longstanding experience in supporting clients to successfully submit applications for market authorizations in Switzerland.

Implementation of the European regulations for both MDR and IVDR requires increased Notified Body (NB) involvement, leading to concerns on the progress of NB designation, expertise and capacity. As of 10 November 2019, only seven NBs were designated against the MDR and two against the IVDR. Furthermore, a delay in implementation of the Eudamed to 2022 was communicated in November.

The Article 117 of the MDR affects both the medical device sector and pharmaceutical companies that market medicinal products with integral medical devices. Required is a NB opinion on the conformity to relevant General Safety and Performance Requirements (GSPRs), although NBs have not made known the technical documentation requirements.

EMA guidelines on expectations for the quality modules are published. The “Medical Device Coordination Group” (MDCG) published a guidance on classification of software as a medical device.

SFL’s experienced cross-functional team can support your MDR implementation project by performing MDR gap analyses, proposing effective strategies to achieve MDR compliance and providing hands-on support with all aspects of MDR implementation.

The highly reputed Swiss pharmaceutical market provides fast market access via a structured, well timed and less complex pricing and reimbursement process compared to many other countries. A reimbursement application may be submitted already during the marketing authorization application process, after the preliminary decision by Swissmedic. This supports full product launch shortly after the marketing authorization has been granted. SFL has a track record of timely product entries in the positive list of reimbursed products.

Prerequisite for marketing products in Switzerland is to have a Swiss legal entity, a Swissmedic establishment license (EL) and a local supply infrastructure for import and distribution in Switzerland.

SFL has been helping many clients to get their EL, which includes the set-up of an auditable quality management system (QMS). This needs the integration of local Swiss requirements into an existing company-wide QMS without compromising harmonized procedures. SFL is proud that all inspections of SFL supported Swiss QMS have been passed very successfully.

The 6^th Medtech & Pharma Platform (MPP) annual conference co-organized by SFL was the largest and most successful to date, with almost 300 delegates attending from the pharma, medtech and software industries and associated stakeholders, including regulators and associations. The event was opened by State Councilor Christoph Brutschin, Head of the Department of Economics, Social and Environmental Affairs of the Canton Basel-City and Shayesteh Fürst- Ladani, President of the MPP and CEO of SFL.

The conference explored the theme of “Pharma and medtech innovation in times of societal, technological and regulatory shifts”.

At the latest MPP training on the MDR and combination products on 27 November, SFL’s Karin Schulze and Theresa Jeary, as well as Stephan Affolter from Ypsomed, presented new regulatory requirements including Rule 21 and integral and co-packaged drug- device combinations. The next MPP expert training will be in Q1 2020.

During 2019, SFL cross-functional teams further expanded their presence to operate in Switzerland, the US, Germany, the Netherlands, Austria, Belgium, Spain and the UK. Globally, the SFL team and its over 200 local partners provide extensive support to clients in more than 50 countries.

SFL is happy to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages.

On 30 January 2020, the SFL Medical Affairs and Regulatory Affairs teams will provide the next free expert webinar, this time focusing on “Orphan drug designation application in the EU.

SFL’s Market Access and Supply Chain experts to present free webinar on Swiss-specific requirements for access to medicinal products in Switzerland.

Switzerland is an attractive pharmaceutical market based on the foundations of an efficient and high‑quality healthcare system. However, as Switzerland is not part of the European Union (EU) and the EU’s single market, specific Swiss requirements must be satisfied before market authorization is granted. Accordingly, SFL Market Access and Supply Chain experts; Barbara Polek Head of Supply Chain, Daniel Dröschel Senior Manager Market Access and Health Economics and Outcomes Research and Anna Ulbricht Senior Medical Affairs Manager, are presenting a free webinar (2 October, 4-5pm CET) addressing these requirements and opportunities for manufacturers.

The webinar will present how access to the Swiss market from a reimbursement and supply chain perspective is different/similar to the markets in EU member states. Specific topics include discussion of requirements needed to commercially supply products to patients in Switzerland, including the establishment of local supply infrastructure for import and distribution, what is required for reimbursement by the Swiss compulsory health insurance, with an overview of the process and timelines, and how products can qualify for pre-launch access to the Swiss market.

Register now to take advantage of the expert insights provided by the SFL team on this important topic and take the first steps to placing your product on the Swiss market.

SFL provides strategic and operational support for regulatory, quality as well as commercial projects, including pre- and post-launch activities, analysis of markets and healthcare professional (HCP) target groups and the establishment or maintenance of supply chains.

With Edwards Lifesciences, Philips Innovation Services and LabCorp/Covance joining, MPP continues to foster cross-sectoral representation.

The Medtech & Pharma Platform (MPP) has been continuously strengthening its cross-sectoral membership since it started its association activities in 2018. The MPP recently welcomed Edwards Lifesciences, Philips Innovation Services and LabCorp-Covance as members, expanding its representation to include IT-engineering companies working on digital health solutions and CRO’s in addition to the existing medtech and pharma membership base.

MPP’s cross-sectoral membership makes it uniquely equipped among European industry associations to reflect the increasing complex and multifaceted nature of modern devices and combined products. By harnessing the expertise of its members from diverse sectors, the MPP is able to provide holistic perspectives on policy solutions to support the development of complex combined products at the intersection of pharmaceuticals, medical devices and digital healthcare applications.

Accordingly, the MPP’s working group submitted comments to the EMA public consultation ‘Guideline on the quality requirements for drug-device combinations’ (August 2019) and comments to the consultation of the Swiss Federal Office of Public Health on the draft ordinance of medical devices (September 2019).

The 6th annual conference MPP2019 on “pharma and medtech innovation in times of societal, technological and regulatory shifts” will take place on the 24-25 October, 2019 in Basel. Keynote presentations will be on Developing Digital Healthcare Solutions from Dr Hans Hofstraat, Vice President of Philips Research, and Dr Sam Shah, NHS England Director for Digital Development, on Digital Health and the interplay between software and medicine. SFL’s Karin Schulze will be chair of the session “Are new regulations going to slow down innovation?” that includes talks from the Notified Body TÜV SÜD and Swissmedic. SFL’s Theresa Jeary will give a presentation on “Regulatory and data protection considerations using software as medical device (SaMD) in drug development.” Overall, a total of 25 presentations from leading organizations will discuss new technology, regulations, innovative ecosystems, precision medicines, development, software and digital health over six sessions.

The MPP2019 Exhibition will host Pharma and Medtech companies. The recent activation of the 1‑1 partnering tool has seen participants arranging 1-1 appointments to meet and discuss future collaboration in the partnering sessions over the two days. You can reserve your exhibition booth or become a sponsor by contacting office@medtech-pharma.com and secure a place at the Networking Gala Dinner on 24 October.

A MPP partner event with Bosch on connected devices will also take place on 23 October 2019 in Basel. The event will welcome invited guests to discuss the opportunities for enhancing the integration of connected device in tomorrow’s healthcare.

Contact the MPP Association for your company to become a member or register for MPP2019 and join internationally active and local industry leaders in shaping innovative health solutions for the future.

Stella Kyriakides designated as Commissioner-candidate to oversee governance related to pharmaceuticals and medical devices

On 10 September 2019, the names of the nominated Commissioner-candidates and their mission statements were officially released.

Stella Kyriakides (The European People’s Party EPP), from Cyprus, is proposed as the candidate to head the Commission’s Directorate-General (DG) for Health and Food Safety (DG SANTE). Ms. Kyriakides, who is a medical psychologist by training, has almost three decades experience in healthcare with the Cyprus Ministry of Health. At the national level, she has been a member of Cyprus’ Parliament since 2006, and at European level has been the President of EUROPA DONNA – the European Breast Cancer Coalition between 2004 and 2006.

Sylvie Goulard, from France, is designated as Commissioner-candidate for DG Internal Market, Industry, Entrepreneurship and SMEs (DG GROW) and a new defense and space department. Her experience is based in foreign policy and defense and she has spent seven years as a member of the European Parliament as a member of the Alliance of Liberals and Democrats for Europe (ALDE).

These two nominations accompany an announcement of the Commission’s plan to implement changes in the distribution of portfolios, which will lead to a greater concentration of health responsibilities under one DG. Under the new Commission, the medical device portfolio will be transferred from DG GROW to DG SANTE. This portfolio includes the critical topic of the implementation of the Medical Devices and In Vitro Diagnostics Regulations (MDR & IVDR). Another intended change is the reshaping of the roles of Vice-Presidents, who coordinate the European Commission efforts in areas where multiple Commissioners are involved. The health portfolio will fall under the new title responsibility of “protecting the European way of life”. The title of this responsibility may change based on some controversial discussion.

The Commissioner-candidates were designated by the Commission’s President-elect Ursula von der Leyen and the Council of the European Union in early September. The European Parliament plays a key role in the process leading to the confirmation of the new Commission. Commissioner-candidates will be questioned by the relevant parliamentary Committees in three-hour hearings, which will take place on 1 and 2 October for Ms. Kyriakides and Ms. Goulard, respectively. These hearings are expected to be taken very seriously, as the parliament has already declined two (as of 30 September) nominated candidates in other areas before any hearing.

The Parliament’s plenary will vote on the whole Commission on 23 October. If accepted, the new Commission will take office on 1 November 2019.

Understanding of the EU institutions, processes and politics will be crucial to understand developments and identify how they impact your organization’s activities. SFL’s experienced Public Affairs team can support you to navigate the increasingly turbulent political environment and ultimately to ensure your voice is heard by policy makers.

Continued challenges with MDR raise concerns about Notified Body capacity and devices shortages in the EU

The new Regulation (EU) 2017/745 on medical devices (MDR) impacts several stakeholders like the Notified Bodies (NB) the Competent Authorities and the manufacturers. The question is now how ready are these stakeholders to meet MDR Requirements?

As of 30th September, only 5 NB’s (TÜV SÜD (DE), TÜV Rheinland (DE), BSI (UK), DEKRA (DE) and IMQ (ITA)) have been designated under MDR, covering different scopes. This small number, compared to around 60 under the outgoing MDD, indicates an acute shortage of NB’s on the market, especially for medical devices where the involvement of a NB is a new requirement under the Regulation (devices that are now classified under the new risk class Ir, re-processable surgical instruments). The transition period ends on the 26 May 2020 and these devices need to undergo conformity assessment against MDR requirements by the end of the transition period to be allowed to be placed on the Market.

Consistent with a shortage of designed NB under MDR, the European Commission is considering an amendment to the MDR deadline date for the new class Ir devices by initiating a “Corrigendum procedure” for the MDR. The proposed amendment would delay the implementation of the new MDR conformity assessment requirements for class Ir devices and consequently extend the transition period beyond the current 26 May 2020 deadline. The aim would be to ensure patient safety by allowing a focus on certification of high-risk devices and prevent an undersupply of class Ir medical devices.

Additionally, the EC acknowledged in a factsheet referring to the increased number of devices requiring NB oversight under the new MDR/IVDR, that there may be some shortages of available devices. Due to the lack of NB capacity manufacturers may not have device conformity approved before the implementation of the MDR. This has even led to calls from the US urging a delay in the implementation of the MDR/IVDR for three 3 years.

Beside the shortage of NB’s, the manufacturers also have to work on the implementation of the new MDR within their own companies. The manufacturers will need to define a strategy to remediate gaps in their clinical data or processes for collecting data, to fulfil the new regulatory expectations for such data.

Switzerland is in the process of adopting the MDR into Swiss law. This requires a number of steps to be finalized, including the adjustment of the existing mutual recognition agreement between Switzerland and the EU in this area. SFL recently took part in Swissmedic Roundtable meeting designed to engage with different stakeholders in Switzerland in recognition of the potential impacts that will be associated with the implementation of MDR on the medical device industry.

SFL offers expert advice on medical devices to support timely compliance with the new MDR. SFL’s Medical Device and Combination Products teams are led by two former heads of NBs.

Regulatory alignment and interdependence between the EU and the US to increase efficiency and support pharma development

In August 2019, the European Medicine Agency (EMA) reported the outcome of an analysis of marketing authorization application (MAA) decisions in the EU and US, which has been published in Clinical Pharmacology & Therapeutics. The comparison showed a >90% alignment on 107 new medicine applications with a regulatory outcome at both agencies in the period 2014-2016. Reasons for the 10% of diverging decisions were mostly disagreements with efficacy conclusions and differences in clinical data submitted by the applicants. As an example, EMA often reviewed MAAs, including additional or more mature clinical trial data than FDA, resulting in a higher probability of granting standard approval and approving a broader indication, or the use of a medicine as a first-line therapy.

Over the last years, EMA and FDA established close collaborations to align medicine development and regulation by building joint working groups and information-sharing forums. Another aspect of cooperation between the EU and the US is the now fully implemented Mutual Recognition Agreement (MRA) for inspections of medicine manufacturers. Under the MRA, EU and US regulators will now rely on each other’s inspections of manufacturing sites for human medicines. Similarly, Qualified Persons in EU pharmaceutical companies receive a batch testing waiver for human medicines covered by the MRA. This is granted once they have verified that the quality controls have been carried out in the US for products manufactured in and imported from the US. Hence, as a result of the MRA, both agencies will avoid duplicative work and will be able to free up resources to inspect facilities in other countries.

The close cooperation and interdependence between EMA and FDA, especially in aspects of regulatory alignment, supports both agencies in achieving a common goal of maximizing patient access to safe, effective and high-quality medicines. Hence, in light of the high concordance between the EU and US in global harmonization, it is of the utmost importance that companies pursue a global regulatory strategy to develop their medicine in all countries involved.

SFL’s Regulatory Affairs team is experienced in European, Swiss and Global regulatory affairs with a record of successful submissions in different territories and can provide you with services from advice on regulatory strategies in the development of healthcare products to hands-on operational support during product registration and post-marketing activities.

EMA/payer community and FDA stakeholders report on early drug access, unmet medical need and how to optimize medicine development

The European Medicine Agency (EMA) and the US Food and Drug Administration (FDA) organized a stakeholder workshop with 56 regulators from the EU national competent authorities, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) and 64 industry representatives focusing on the support for medicine developers in generating quality data packages for early access approaches. In the EU, the Agency offers early and proactive support in the development of medicines for unmet medical need and provides accelerated timelines for the assessment of such applications through PRIME (PRIority MEdicines, see previous news). Similarly, the US FDA established a Breakthrough Therapy designation program, which expedites the assessment process of drugs intended to treat serious conditions and enables the review of preliminary clinical evidence. Notwithstanding, the underlying challenges in the development of promising medicines for early access are often the timely completion of quality and manufacturing data ensuring that patient safety, efficacy and product quality are not compromised. Focussing on these challenges, the scope of the workshop was to discuss scientific elements, i.e. priorities for biologicals, chemicals and Advanced Therapy Medicinal Products (ATMP), and existing, regulatory tools and procedures. As next steps, the stakeholders proposed to enable the provision of data during post-authorization procedures, provide specific quality development plans and strengthen the inspector-assessor interaction during the development phase. Additionally, a “Toolbox-guidance” for medicinal products addressing unmet medical need, will be developed, hence facilitating the generation of robust quality packages for marketing authorization application review.

Concurrently, EMA met with the Payer Community on 18 June to explore synergies and fosters mutual understanding and cooperation to help improve timely and affordable access of patients to new medicines (meeting minutes available here). Sharing the goal of providing efficacious and safe medicines to patients, the stakeholders recognized that it is of interest to use technical collaborations, including sharing data and analysis of real-world data in patient registries, for post-licensing evidence generation and decision making.

The potential of a common registry for regulators, applicants and payers applies in particular to orphan medicinal products. Furthermore, the participants discussed aspects of unmet medical need and potential delays in the access to medicines. A multiple-criteria decision analysis model has been proposed in order to prioritize activities and to define and weigh criteria related to medicines for unmet medical need. With defined action points and a follow-up meeting in 2020, EMA and the payer community commit to secure sustainable access to medicines.

The SFL team is presenting a webinar about market access and supply chain in Switzerland, as well as similarities / differences to the markets in European Union member states.

Find out what are the upcoming events where you can meet with members of the SFL team to discuss your projects and how SFL can support your products.

The SFL team is regularly invited to speak and contribute to industry-leading regulatory and policy events to actively shape and keep at the forefront of the latest developments, and provide our clients with the highest quality services.

Take the opportunity to meet and speak with the SFL team at these upcoming events. Please contact us prior to the event to arrange a meeting.

SFL expands its internal expertise with the formation of a dedicated Combination Products group.

The new Combination Products group led by Theresa Jeary compliments the highly successful Medical Devices group led by Karin Schulze since 2018. Theresa, like Karin, is a former head of a Notified Body (NB) making SFL the only consultancy with two former NB heads.

Theresa is an expert in combination products with over 10 years NB experience in the conformity assessment process, as well as experience in the development of Class III medical devices utilizing animal tissue and containing an ancillary medicinal substance. She is a frequent presenter and trainer on the topic of combination products and the impacts of the new Medical Devices and In vitro Diagnostics Regulations (MDR/IVDR). Furthermore, she has broad experience in companion diagnostics (CDx).

With Theresa joining the team, SFL can further increase its activities in supporting client readiness for the impending implementation of the new MDR and IVDR that will become applicable in May 2020 and May 2022, respectively. The increased requirements of the new Regulations are high for all stakeholders, and all economic operators need to work actively on plans to comply with the new Regulations.

Theresa and Karin provided training at an SFL webinar on 27 June 2019 about the “MDR update and the impact of Article 117 on combination products”. If you missed these, please sign up to our mailing list and be informed of the next training to be performed by our medical devices experts.

Major impacts include the clinical evaluation and clinical evidence expectations, implementing new requirements into quality management systems, additional reporting needs such as PSURs, UDIs and SRNs, increased technical documentation requirements and provision of evidence of new requests described in the General Safety and Performance Requirements, classification changes and new classification rules.

Both new Regulations, which aim to catalyse the integration of science and technology in the development of therapeutics, will introduce new roles and responsibilities for EMA and national competent authorities. EMA will have a role in the review of CDx and can be consulted for complex products that are considered borderline between medicinal products and other regulatory frameworks (see the article entitled “EMA 2018 annual report” for more details on this topic).

SFL’s Medical Devices and Combination Products groups can advise you on what steps you should take to ensure all your products are compliant with the new MDR and IVDR. You can also contact us for an in‑house training specifically tailored to your company’s products and needs.

EMA 2018 annual report highlights EMA’s role in combination products and borderline products assessments.

EMA emphasizes in their 2018 annual report that they aim to continue their support of the European Commission and Member States in the implementation of the new Medical Devices Regulation (MDR), and to catalyze the integration of science and technology in medicine development. EMA is involved in the assessment of combination products where the ancillary substance is derived from human blood or human plasma. EMA continues to provide a mandatory scientific opinion to Notified Bodies (NBs) in the assessment of medical devices with ancillary human blood derivatives and a NB must seek a scientific opinion from either EMA or a national competent authority in the case of a medical device with ancillary medicinal substance or for medical devices that are absorbed by the human body to achieve their intended device (Rule 21). The MDR foresees that the European Commission may consult EMAs scientific committees on borderline products with medicines.

In early June, EMA released a draft guideline on the quality requirements for drug-device combination products in the context of regulatory submissions, i.e. marketing authorization applications and subsequently during the product lifecycle.

The increased requirements of the various new regulations impose a high responsibility and burden to all stakeholders, and all economic operators should be actively working on plans to meet the new regulations. To bolster the support offered to our clients, SFL has fostered its expertise and capacity, and increased the team with a new Lead on Combination Products (see the article entitled “Medical Devices and Combination Products: SFL is strengthening the team” for more details).

The new MDR Rule 21 indicates an increased involvement of the EMA’s scientific committees in combination and borderline product assessments. Contact SFL’s dedicated Combination Products group to find out the steps you should take to ensure your products comply with the new MDR and IVDR.

SFL publication assesses the impact of different Brexit scenarios in the context of data exchanges in clinical trials.

SFL’s Associate Legal Counsel and Data Protection Officer Lorelei Garagancea, together with Chief Scientific Officer Walter Fürst, have published the article “Legal impact assessment of Brexit: Clinical Trials data exchange and Data Protection” in the European Pharmaceutical Law Review. The article discusses how different Brexit scenarios and, in particular, the subsequent regulatory divergence from ongoing EU policies, could impact on clinical data exchange and data protection.

The aim of this article is to provide a twofold overview of i) the consequences of a no-deal scenario between UK and EU; and ii) several mitigation measures addressing business risks entailed by the current uncertainties and by the future grey period between the withdrawal date and the application of newly agreed terms between the EU and UK. Such mitigation measures are necessary irrespective of the outcome of Brexit: from hard to soft Brexit or even Brexit in Name Only (‘BINO’), for either an immediate or an open-end transition.

From a data protection perspective, once the UK becomes a third country, the GDPR rules concerning data transfers may apply. Even if the GDPR is already implemented in UK law, this does not streamline the data transfers between the two jurisdictions per se. Please refer to the Comparative Table of Means to Transfer Data between EU and Third Countries (Report, p. 7) for a comprehensive comparative outlook at the applicability of these new rules.

Apart from the implications on data transfer across a potential UK-EU border, Brexit (if it ever takes place) will further complicate already challenging processes related to: marketing authorizations, orphan drug designations, supply chains and batch releases, SME status and other regulatory measures (see Comparative Table of Suggested Mitigation Measures for Several Brexit Scenarios, Report, p. 3).

SFL’s legal and data protection team can support your business to be prepared for any Brexit scenario.

SFL’s integrated commercial solutions offer support to SMEs and facilitate Swiss access to orphan drugs.

Many orphan drugs are developed, and increasingly marketed, by Small and Medium Size Enterprises (SME). When entering the European market, both regulatory as well as commercial planning need to consider that Switzerland is not part of the European Union (EU) and its single market where good can be moved freely across all member states. Accordingly, not only separate regulatory approval and processes, but also a separate supply chain and commercial set-up, need to be considered to benefit from the potential of the highly reputed market in Switzerland. A prerequisite for a Marketing Authorization Application (MAA) in Switzerland includes an incorporated company that has an Establishment License granted by Swissmedic after inspection of the company’s Quality Management System (QMS). This is different to the European Union where any incorporated company without an Establishment License can apply for a MAA.

SFL has a full QMS and Swissmedic Establishment License since 2011 and undergoes regular inspection. In order to reduce the time to market significantly and facilitate regulatory submissions, SFL can submit MAAs on behalf of the Client. Furthermore, SFL offers support for different business models. SFL can act as the Marketing Authorization Holder (MAH) in Switzerland, running the Swiss regulatory and commercial activities (including supply chain, pre- and post-launch activities and MSL support) if a Client does not want to set-up their own affiliate right after approval or only at a later time. Alternatively, SFL can support its Clients in setting up their own affiliate and QMS to obtain a Swissmedic Establishment License in parallel to the ongoing MAA review from Swissmedic.

Also the operative management of such a Swiss affiliate can be supported on a mandate base by SFL’s integrated Regulatory Affairs and Commercial teams. SFL’s comprehensive integrated service offering allows tailored support addressing Clients’ needs to cope with their market access challenges. This may also include SFL staff acting as Responsible Person or as the Pharmacovigilance Responsible Person on behalf of the Client, thus filling these mandatory roles, especially during an initial stage when the Client’s company is not yet fully staffed. There will certainly be a tailored cost-effective solution to any Client challenge, facilitating patients in Switzerland who are affected by a rare disease to get access to an adequate treatment.

SFL’s Commercial team can provide tailored strategies for your orphan drug to access the Swiss Market.

Value-based pricing is increasing interest in drug pricing agreements with implications on development and commercial strategies.

Value-Based Pricing (VBP) has become a key strategy for many healthcare systems in shaping their financing capability, given the increasing number of personalized, progression preventive and highly relieving, if not in some cases curative therapies, that are currently entering the market. Fundamentally designed to incorporate outcomes into pricing, the approach is gaining popularity despite challenges to find a consensus on outcome criteria that define whether a drug works and how the concept can be effectively structured and implemented.

VBP or outcomes-based contracts are a type of ‘pay for performance’, seeking to reimburse only for the value gained by cure, prevention of progression, achieved improvement of patient condition or prevention of other interventions. This is in stark contrast to conventional volume-based reimbursement. Therefore, VBP for potential curative treatments needs to reflect the amount of lifetime health gains (e.g. QALY, DALY, Years of Healthy Life (YHL/HLY), Health-Adjusted Life Expectancy (HALE), Healthy-Year Equivalents (HYE), etc.) and cost offsets vs. long-term healthcare costs for chronic therapies that only manage disease symptoms. VBP-strategies that may be important for potential cures, but which are not part of standard health economic, pricing and reimbursement models, also require inclusion of additional elements of value (e.g. values associated with a particular indication, combination of therapies, product-to-patient strategies [patient support programs]). Other approaches such as limitations to subpopulations with the highest potential for treatment success may still allow justification of a high price, as the overall budget impact for the payor is lower and facilitates affordability within the available budget. However, VBP also needs to reflect substantial uncertainty regarding clinical effectiveness and safety in real world settings compared to the strictly defined and controlled setting of clinical trials.

Examples from different jurisdictions show the increasing utilization of VBP. Almost every US state and territory is implementing value-based care models and payment reform to improve quality of care and distribute high costs for individual treatments over longer periods of time costs. The Louisiana Department of Health is officially seeking to implement a novel subscription-based, or “Netflix” purchasing model for hepatitis C drugs. The model offers a guaranteed price for unfettered access to treatments for responding patients and could be linked to values e.g. in terms of achieving cure or sufficient number of prescriptions. In the UK, VBP is frequently applied within patient access schemes, while in Germany and Switzerland single payors try to reach individual VBP agreements for selected products (e.g. Kymriah® [tisagenlecleucel]) or propose alternative approaches, such as dynamic evidence price models.

SFL’s experienced Market Access experts and integrated Commercial team can analyze your products and determine the strategic advantage of Value-Based Pricing for you.

MPP provides expert training on MDR and SaMDs and assembles distinguished speakers for the annual MPP 2019 conference.

The MPP training course on 17 June 2019 provided a comprehensive overview on the regulatory system and requirements for medical devices in Europe under the Medical Devices Regulation (MDR) presented by Karin Schulze, Head Medical Devices at SFL. A special focus of the training was on the MDR Rule 11 on Software as Medical Device (SaMD), provided by recognized experts in the field from MPP member Novartis.

The training provided perspectives on questions such as classification of software according to the MDR, definition of medical purpose, labelling Apps, software as an accessory and liability issues with regard to software under the MDR. Case studies and practical examples complemented the training.

To be a part of the next expert trainings look at the MPP trainings page on the new MPP website or sign up to the MPP newsletter.

The 6^th MPP2019 annual conference is coming soon (24-25 October, 2019 in Basel) and the advanced program is now available. MPP2019 will explore “pharma and medtech innovation in times of societal, technological and regulatory shifts”.

Keynote presentations will be held at the beginning of each day. Dr. Hans Hofstraat, Vice President of Philips Research will speak on Digital Healthcare Solutions and Dr. Sam Shah, Director for Digital Development at NHS England, will discuss how a user-centric approach is facilitating the implementation of digital health in the NHS .

In addition, 23 presentations covering six sessions on new technology, effects of new regulations on innovation, innovative ecosystems, precision medicines, development strategies and SAMDs and digital health will be given by speakers from organizations including Swissmedic, Microsoft, IBM, Novartis, Roche, GSK, Zühlke, Ypsomed, TÜV SÜD, Dassault, Ernst & Young and SFL.

An exhibition featuring leading companies in the Pharma and Medtech industries and 1-on-1 partnering sessions to support participants in developing future collaborations will take place over both days. Reserve your exhibition booth here. Furthermore, a Networking Gala Dinner on the first day will allow you to network with colleagues and develop new partnerships in a relaxed environment.

Register now or become a sponsor by contacting office@medtech-pharma.com and join around 300 international and local industry leaders in shaping innovative health solutions for the future.

Get involved with the MPP to be at the forefront of the latest Medical and Combination Device developments.

The new Regulation on supplementary protection certificates (SPC) for medicinal products introduces important changes to the intellectual property (IP) landscape in Europe. The legislation is now ready for formal approval by the Council of the European Union and the EU Parliament.

The current legal framework

While a patent lasts 20 years, current SPCs offer an additional protection of up to 5 years (although in most cases less than this), in order to offset some of the costs incurred by the complex development process and regulatory requirements for new medicines. During these 5 additional years, the drug is also fully protected and can only be manufactured or distributed by the company who owns the patent.

The proposed Regulation

The new SPC legislation introduces a manufacturing waiver, which will allow companies to produce, in two possible scenarios, a generic or a biosimilar version of a drug that is still under a valid SPC:

• to create a stock ahead of the expiry of an ongoing SPC, in order to accelerate the entry onto the market of a biosimilar or a generic, upon expiry of the SPC for a medicinal product (“EU Day-one entry”); or
• to already export the drug to a non-EU market where protection has expired or never existed – during a valid EU SPC protection.

Proponents of the introduction of the waiver argue that generic and biosimilar companies are currently disadvantaged compared to their competitors in non-EU markets, because the latter are not prohibited to manufacture, while EU companies have neither the right to produce nor export a drug under an SPC. The SPC Regulation is meant to correct this situation.

The potential implications

The new SPC legislation was initiated with the declared aim of improving access to medicines through biosimilars and generics and enhance EU export sales. However, many stakeholders point out that introduction of the waiver may weaken the IP rights framework in the EU, disincentivizing vital investments that allow for the development of innovative products. This, in turn, may negatively affect patient access to novel life-saving treatments.

From a pragmatic perspective, originator companies may want to closely monitor their IP portfolios, i.e. look for IP infringements, in particular in the EU Member States, where a notification to the IP authority has been made by a competitor in order to announce it is using the SPC manufacturing exemption. The new SPC Regulation introduces an obligation to notify as an anti-diversion measure from the purpose of the SPC manufacturing exemption.

Activities that may fall under the SPC manufacturing exemption are: “the possession, supply, offering to supply, import, using or synthesis of an active ingredient for the purpose of making a medicinal product containing that product, or temporary storage of the product or advertising for the exclusive purpose of export to third country destinations”, as well as related acts undertaken by a company in a contractual relationship with the company benefiting from the SPC manufacturing waiver. Other activities may constitute an infringement of the IP rights of the originator.

Also, export products must be especially labelled with a logo showing the product is exclusively intended for export to third countries. Otherwise, the exported product would not benefit from the SPC manufacturing exemption and may thus face an injunction (here, a prohibition to export) from the manufacturer of the originator product.

SFL is closely monitoring the legislative process of the SPC proposal and advises clients on this health policy dossier.

Falsified medicines impose a growing and worldwide threat to public health. Notably, these products reach patients not only through illegal means but also via legal supply chains. The EU “Falsified Medicines” Directive 2011/62 defines a set of measures to prevent intrusion of falsified medicines into the legal supply chains.

The new safety features in the EU

One of these measures, the requirement for verification of the authenticity of individual packs, has become effective as of 9 February 2019. It involves the application of a unique identifier and an anti-tampering device (both referred to as “safety features”) to most prescription and some over-the-counter medicines. These safety features allow end-to-end verification by all parties involved during the packs’ journey along the supply chain. An elaborate integrated system of central and national data repositories provides the backbone of the verification processes.

According to the European Medicines Verification Organisation (EMVO), not all Marketing Authorisation Holders operating in the EU have onboarded to the verification system by the 9 February 2019 deadline. In order to prevent patients from not being able to get their medication after the deadline, article 48 of the Delegated Regulation 2016/161 foresees a safety net by allowing use of product batches released before the deadline and not yet bearing the safety features until their expiry date. However, such latecomers will have to ensure furture stock fully complies with safety features, by the time the current stocks of product not bearing the safety features are depleted.

In Switzerland

Increased drug safety and the combat against falsified medicines have been strengthened by entry into force of the revised Ordinance on Licensing in the Medicinal Products Sector (Arzneimittel-Bewilligungsverordnung, AMBV) and the right to execute the EU-guideline “Falsified Medicines Directive” in 2019. Compared to the EU, compliance with the Falsified Medicines Directive is currently voluntary and not mandatory in Switzerland.

SFL provides advice and operational support on product labelling, onboarding to the repositories system and tailoring of operating procedures according to the Falsified Medicines Directive requirements.

In February 2018, the FDA issued a final rule on acceptance of data from clinical investigations of medical devices. The FDA updated the requirements and the criteria for acceptance of data from clinical investigations conducted within the United States (US) as well as outside the United States (OUS). FDA requires that data from clinical investigations conducted OUS that began on or after 21 February 2019, originate from investigations conducted in accordance with good clinical practice (GCP).

The final rule is intended to help ensure the quality and integrity of clinical data and the protection of human subjects.

The requirements

The final rule applies to all clinical investigations that support an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a request for De Novo classification, a premarket approval (PMA) application, a humanitarian device exemption (HDE) application, or a product development protocol (PDP) application.

The FDA guidance “FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions” provides further clarification and recommendations regarding these requirements.

Investigations conducted within the US:

• A statement that the investigation was conducted in compliance with applicable requirements in the Protection of Human Subjects regulations in 21 CFR part 50, the Institutional Review Boards regulations in 21 CFR part 56, and the Investigational Device Exemptions regulations in 21 CFR part 812; or
• A statement describing the reasons for noncompliance (if applicable).

Investigations conducted OUS:

The provisions under 21 CFR 812.28 apply. Specifically, the following must be included for each OUS clinical investigation:

• A statement that each investigation was conducted in accordance with GCP as described in 21 CFR 812.28(a)(1);
• Supporting information specified under 21 CFR 812.28(b), as specified in 21 CFR 812.28(a)(2), or a cross-reference to another section of the application or submission where the information is located.

If the OUS clinical investigation did not conform to GCP, then the IDE or device marketing application or submission must include one of the following:

• A waiver request in accordance with 21 CFR 812.28(c); or
• A statement describing the reasons for noncompliance (if applicable).

How to request a waiver for OUS investigations

For OUS investigations or multi-site investigations, sponsors or applicants may ask the FDA to waive any applicable requirements under 21 CFR 812.28.

SFL’s Regulatory Affairs Department provides assistance in compliance with clinical investigations worldwide.

Big data generated through wearable devices, electronic health records, social media, clinical trials or spontaneous adverse reaction reports will be increasingly used by regulators to assess the benefit-risk of medicines across their entire lifecycle. The HMA-EMA Joint Big Data task force, composed of experienced medicines regulators from 14 national competent authorities and the EMA, was established with the aim to acquire a deeper understanding of the big data landscape and develop sufficient expertise to guide, interpret and critically assess big data from a regulatory perspective.

Big data definition and core recommendations

The summary report by the task force primarily defined the meaning of “big data” as ‘extremely large datasets which may be complex, multi-dimensional, unstructured and heterogeneous, which are accumulating rapidly and which may be analyzed computationally to reveal patterns, trends, and associations’.

The task force was split into seven sub-groups, each focusing on recommendations for different categories of datasets: clinical trials and imaging, observational (or “real world”) data, spontaneous adverse drug reports, social media and mobile health, genomics, bioanalytical ‘-omics’ (with a focus on proteomics), as well as a cross-cutting data processing and analytics group. Core recommendations, which span multiple sub-groups were detailed, starting with the importance of data standardization in order to improve data quality across multiple data sources and progressing to efficient data sharing and integration. Furthermore, new analytical approaches for modelling of big data sets for regulatory purposes were endorsed, along with development of regulatory guidance on acceptability of evidence derived from big data sources. Prominence was given to implementation of new regulations for devices and in vitro diagnostics that are based on and generate big data, in order to monitor their safe and effective use. The need for increasing the skills and knowledge of regulators, along with proactive external communication and engagement with stakeholders within the big data landscape, were highlighted.

Areas of impact

Strong support was given to development and establishment of regulatory science in the fields of bioinformatics, data science and personalized medicine, as areas where big data would have the greatest potential impact. The need to increase the capacity to analyze and integrate “real world” evidence into decision making across the product life cycle was reiterated.

EMA welcomes comments on the core recommendations in the summary report until 15 April 2019, particularly on prioritization of future actions.

SFL’s Regulatory and Legal Affairs departments can support you with processing big data in compliance with the EU regulatory framework.

Germany closer to new legislative requirements for orphan drugs to treat rare diseases

Recently, the German parliament passed a bill on the “Law for more safety in the supply of medicines (GSAV)”. According to the Verband forschender Arzneimittelhersteller (VFA), this legislative attempt by German’s Health Minister Jens Spahn raises two threats for orphan drugs (ODs) in Germany:

• The special position of ODs in the Pharmaceuticals Market Reorganisation Act (AMNOG: Arzneimittelmarkt-Neuordnungsgesetz) procedure, will be confined by inclusion of hospital turnover in overall turnover limit
• Increased authority for the Federal Joint Committee to impose data collection requirements and price reductions if registry data does not support added value

In the current situation, patient numbers and annual therapy costs are assessed, with ODs with an annual turnover less than 50 million entitled to receive OD-specific incentives. However, if this annual turnover limit is exceeded, the Federal Joint Committee conducts a completely new in-depth methodical evaluation to assess the additional benefit of the OD.

As these ODs are almost exclusively used in hospitals, the draft bill’s proposal to include sales outside the statutory health insurance physicians care (i.e. hospital sales), comprises a significant change to the calculation of annual turnover, potentially leading more ODs to be subject to extensive additional benefit procedures and loss of the OD-incentives, and discouraging new OD development.

With regard to data collection (registries), criticism among different health systems stakeholders has been voiced that the requirements for these registries and the data collection is intended to be defined on a national, instead of on a European or global level. This reflects the draft bill’s proposal to introduce compulsory registries and impose deductions on the reimbursed price if the Federal Joint Committee does not see any quantifiable additional benefit on the basis of collected data from registries. Considering the low patient numbers and individual heterogeneity in rare diseases, quantifiable and statistically meaningful outcomes to clearly demonstrate additional benefit of orphan drugs may be difficult to identify in small-sized national registries, with identification of additional benefits more likely to be seen by supporting and promoting recruitment into global registries.

Revision of Switzerland’s Therapeutic Products Act enters into force

In Switzerland, modifications following the Ordinary Revision of the TPA (Stage 2) and its right of enforcement entered into force on 1 January 2019. The main goals of the modifications are facilitation of market access, improvement of drug safety and increased transparency (see SFL Newsletter from October 2018 for more details)

New and simpler access opportunities have been created for certain medicinal product categories and are particularly relevant for healthcare companies whose medicinal products have been approved in an EU or EFTA country, as well as for medicinal products with traditional uses and those used in complementary medicine. The new law also introduced the incentive of 15-year data exclusivity for ODs.

Market supervision has been tightened and modernized through changes such as application of Good Vigilance Practice, a broader scope and more detailed definition of reporting obligations.

Furthermore, Swissmedic has increased the scope of information published about the medicinal products submitted and their authorization holders- particularly, publication of SwissPARs – assessment reports for human medicinal products with new active ingredients on which the authorization decisions are based.

SFL can support you in adapting to the changes introduced by the German GSAV and the Swiss revision of the TPA, and will keep you informed about the first experiences with the new legislations.

The Swiss list of aids and appliances (MiGeL), regulating the reimbursement of medical devices that patients receive according to a doctor’s prescription, has not been subject to a full systematic review since its entry into force in 1996. However, minor focused reviews have led to the implementation of beneficial changes in the past, including a linear 10% reduction of the maximum reimbursement amounts (HVB) in 2006 and in 2011, a further significant price cut among the three product groups with the highest sales and the entire removal of some product types from the MiGel. Since 2015, the Swiss Federal Office of Public Health (FOPH) has been gradually reviewing the entire MiGeL list, and the revision will be completed this year.

Targets of the revision

The main targets of this recent, systematic MiGeL revision are:

• Adaptation to medical-technical and price developments (a stepwise approach in working groups per positions/product groups for structure and price)
• Implementation of periodic review of effectiveness, appropriateness and economic efficiency (WZW) in accordance with Article 32 paragraph 2 KVG
• Improvement of the applicability of MiGeL (uniqueness, verifiability by insurers).

As a result of these measurements and legislative changes, the number, quantity and type of products reimbursed will be recorded, compared to the current databases and statistics which only record total costs. From 2020 onwards, the MiGeL list will be constantly evaluated, and part of the work on cost monitoring (periodic reviews) and the corresponding reports will be published periodically. Further, invoice control by insurers will be strengthened as part of the cost containment program, and periodic review of the maximum remuneration amounts (HVB) will be carried based on international price comparison. The goal is to guarantee economic efficiency and prevent abuses.

These and further methods and procedural steps for reviewing the effectiveness, appropriateness and economic efficiency (WZW) of medical devices have been developed, and detailed information will be published on the FOPH website during this year.

SFL provides market access and reimbursement support to facilitate successful market entry of medical devices and pharmaceuticals in Switzerland. 

The Medtech & Pharma Platform (MPP) continues its mission to facilitate medtech and pharma collaboration

2019 started off as a busy year for the MPP industry association. With an increased membership and an expanded board of directors, the MPP has intensified its activities and engagement with European institutions. This includes the MPP taking the lead in developing a reflection paper on co-packaged Drug Device Combination products (DDC) in a joint initiative with EFPIA. The paper will help to seek clarification for regulatory gaps arising from the implementation of the Medical Devices Regulation (MDR).

The association’s increasing visibility is also reflected in an article in the latest European Biotechnology Magazine entitled ‘A grey zone in regulation’. It describes the increasing importance of combination products and features an interview with the MPP’s president, Shayesteh Fürst-Ladani.

Further, the MPP association is continuing its commitment to knowledge exchange with the organization of recent training courses on regulatory topics related to medical devices. They provide a comprehensive overview of the changes in the MDR compared to the current Directive, coupled with one of two key sub-topics the MPP has identified in focused workshops. The first workshop was dedicated to clinical evaluation under MDR/ MEDDEV 2.7/1 rev.4, and took place with the training on the 28 March 2019. The second focus workshop will be dedicated to the classification of Software as Medical Device (SaMD) under the MDR, and will take place with the next training on the 17 June 2019. Registration and details for this second training and workshop are now available.

The MPP’s flagship annual event will take place on 24 and 25 October 2019 in Basel under this year’s motto “Pharma and Medtech innovation in times of societal, technological and regulatory shifts”. The Call for Abstracts is open till end of March. For submissions, please use this form.

For more information on the association’s membership and policy work, please contact association@medtech-pharma.com. For any queries related to the MPP annual event or training courses, please get in touch with office@medtech-pharma.com.

The Rare Disease Action Forum (RDAF) and the Swiss Rare Disease Day

The RDAF recently held an internal workshop on the topic of article 71 KVV (Swiss Health Insurance Ordinance) and the corresponding value assessment of orphan drugs. The workshop took place on the 26 March 2019, with guest speakers including experts from health insurers, medical examiners, patient organizations, healthcare professionals and industry.

The internal workshop followed on from the RDAF launch in February of its member working group on ‘Patient access and value assessment for orphan drugs.’ The goal of the working group is to raise awareness of considerations specific to rare diseases that should be included in assessing the value of orphan drugs.

The RDAF also attended the ‘Swiss Rare Disease Day’ event that was organized by ProRaris on 2 March 2019 in Basel. Designed for patients with rare diseases, speakers included Thomas Christen from the Federal Office of Public Health and Dr. Lukas Engelberger, Basel-City State Councillor. The global “Rare Disease Day” aims to raise awareness among the general public and decision-makers about rare diseases. The campaign started in 2008 as a European event and has progressively become a world phenomenon, with hundreds of events organized around the official day of February 28.

If you are interested in becoming a member of the RDAF, please contact the secretariat run by SFL at info@rda-forum.org.

On 26 February 2019, SFL celebrated its first ten years as a business with over 200 guests including clients, partners, colleagues, friends, and representatives from government and business associations. For this special occasion, SFL hosted a dinner with live music and a tombola with prizes. The celebrations were opened by the welcome speeches from Shayesteh Fürst-Ladani – CEO of SFL, Councilor Christoph Brutschin – Head of the Department of Economics, Social Services and Environmental Affairs of the Canton Basel-City, and Mr. Felix Werner – Member of the Executive Committee and Head Labor Market & SMEs at the Basel-City Trade Association (Gewerbeverband Basel-Stadt).

The celebrations were a tribute to all those that contributed to SFL over the last ten years, supporting SFL’s commitment to excellence for its clients and providing the foundation for SFL to develop from a single person, to a team of 35 international professionals covering the areas of Regulatory Affairs, Medical Affairs, Public Affairs, Quality Assurance, Clinical Safety & Pharmacovigilance, Legal & Compliance, Reimbursement, Supply Chain, Commercial Operations and Professional Training.

With its unique service offer throughout the entire product lifecycle, SFL has become a one-stop solution to address and satisfy clients’ needs. While it continues to be headquartered in Basel, it has now expanded with offices in Lausanne, Barcelona, Brussels, London, Lörrach and Vienna, further enhancing its services to clients around the world and providing access to EMA, Swissmedic and FDA.

SFL’s goal is to build upon its excellent team, enhance its offering and become a key reference point in the life sciences landscape. “As we reflect on the remarkable achievements of these first 10 years”, commented SFL’s CEO, “I would like to thank everyone who has been part of this exciting journey, and I look forward to the next decade, being confident in our ability to succeed”.

Pictures of the 10^th anniversary celebrations can be found here.

The European Commission is currently reviewing the intellectual property (IP) incentives for the pharmaceutical industry in relation to their impact on accessibility, availability and affordability of medicines. The evaluation focuses on the legislative framework for orphan and pediatric drugs. Parts of this evaluation are a consultation of invited stakeholders including pharmaceutical companies (launched in September 2018) and a public consultation aiming at citizens and healthcare professionals (opened in October 2018). The Commission expects the evaluation to be completed in the 3rd quarter of 2019 and published in the form of a Commission Staff Working Document.

Depending on the evaluation findings, the European Commission is expected to propose potential remedies as of 2020. This may include proposed changes to the current IP incentives which would affect the backbone of the pharmaceutical industry.

Two recent rulings of the European Court of Justice (ECJ) have shed light on topics relevant for the life sciences industry.

In the “Boston Scientific” case (preliminary ruling), the ECJ assessed that a supplementary protection certificate (SPC) cannot cover a drug-device combination product which is CE-marked as a medical device under the current EU Medical Devices Directive. The reason behind this decision is that a medicinal substance only as part of a medical device is not considered to be authorized under Directive 2001/83 on medicinal products. Without being independently authorized as a medicinal product, a substance does not fall under the scope of the SPC Regulation.

In “Novartis Farma SpA v Agenzia Italiana del Farmaco (AIFA) and Others”, the ECJ concluded that national health authorities who reimburse medicines for their off-label use on economic grounds are not in breach of EU law. Upon decision by the ECJ, AIFA’s reimbursement of the cancer drug Avastin for its off-label use in ophthalmology remains the responsibility of the EU Member States, as it is a matter of the national healthcare system.

Since its foundation in 2009, SFL’s headquarters in Basel have been constantly growing. In line with this growth, SFL will relocate to a new office in February 2019, conveniently located next to the Basel central railway station.

SFL is also going to partner with the Biopôle in Lausanne and a newly founded entity to facilitate the interaction with the highly innovative and diverse life sciences and medtech companies based in the Lemanic region.

The Medtech & Pharma Platform (MPP) association celebrated this year the 5^th anniversary of its annual event with its most successful edition. With many international attendees, the MPP established itself as a ‘go-to’ event for medtech and pharma professionals.

2018 has been an exciting year for the MPP industry association with many important achievements, including an increased membership base (MSD, Novartis, Sanofi, SFL, Swiss Medtech, Ypsomed), an extended board of directors and the establishment of a working group. The MPP association’s activities included advocacy work for combined products at the EU level, collaboration with relevant European industry associations with common regulatory interests, and engagement with European institutions.

Patient registries are frequently used as a source of data for post-authorization monitoring of medicinal products and reimbursement decisions. EMA’s Cross Committee Task Force on Registries has recently published a discussion paper intended to facilitate use of patient registries to support regulatory decision-making.

Emphasis was placed on the selection of patient populations, recording of important events, core data elements, quality management, safety analysis, governance and common terminologies. Comments and suggestions are sought from all interested parties, with the document to be finalized in Q4 2019.

The Rare Disease Action Forum (RDAF) had a successful year in 2018. More than ten new members from the industry, patient organizations and physicians joined the forum, reinforcing its collaborative, multistakeholder approach to contribute towards improving the situation of patients with rare diseases in Switzerland.

In addition, the RDAF organized two multistakeholder events. The latest, which took place on 31 October 2018, was an international event focusing on value assessment of orphan drugs in Switzerland and the EU. International speakers from patient organizations, regulatory authorities and the industry presented and discussed perspectives from the EU, Switzerland, Austria, Germany and France on the topic.

This year, SFL continued its commitment to knowledge sharing by presenting in international conferences on regulatory developments affecting medical devices, orphan drugs and advanced therapies. In addition, SFL’s CEO contributed to a book on FDA regulated products with a chapter on the regulatory framework for drug-device products in the EU and the US.

Further, the SFL team gave a free webinar on reimbursement of medicines and medical devices in Germany and Switzerland, and organized several trainings on the Medical Devices Regulation (MDR).

SFL is happy to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages.

The MPP training on “Overview of the Medical Devices Regulation and Impact on Industry” will take place in Basel on 18 March 2019.

As the new year approaches, we reflect on SFL’s activities in supporting its clients and partners, whilst highlighting key developments that will continue to shape the life sciences industry in 2019. Among other topics, we explore the EU IP incentives review, the latest rulings by the European Court of Justice, and EMA’s discussion paper on the use of patient registries for regulatory purposes.

We wish you a relaxing and enjoyable holiday season, with every success in the new year.

EU Portal and Database

Previously delayed to the second half of 2019, the entry into application of the CTR may now suffer further delays to 2020. The EMA Management Board announced in March and confirmed in June 2018 that the auditable version of the EU portal and database, whose readiness is required for the entry into application of the legislation, will be available in early 2019. Based upon a smooth audit and implementation of subsequent recommendations, the entry into application of the new system can be projected for the first half of 2020. However, the EMA Management Board remains cautious on this topic and has communicated that the official timelines would only be updated after the audit is completed.

Another complicating factor affecting the systems implementation is the EMA’s relocation from London to Amsterdam. The agency devised a continuity plan, which defines the CTR and its IT infrastructure as priority. In June 2018, whilst the EMA Management Board reported that it does not expect the relocation to have a major impact on the implementation timeline, it is nevertheless monitoring possible consequences of the move, such as the greater than expected loss of staff, which could put a strain on the implementation of the CTR.

Implementation documents

The European Commission released a draft Q&A document that addresses a broad range of topics relevant to the CTR. The document is still being discussed by relevant EU expert groups.

Implementation in the UK – Deal or no-deal on a transition period

Negotiations between the UK and the EU are ongoing about a potential deal on a Brexit transition period that would run from 30 March 2019 to 31 December 2020. The implementation of the CTR in the UK depends, to a great extent, on the outcome of these negotiations.

In the scenario of an agreed deal, the CTR would be implemented into UK law through the EU withdrawal bill (or ‘Brexit bill’). The consequences of a no-deal scenario are described in one of the 53 technical notices released by the UK government in view of preparing for such a scenario. The notice, amongst other aspects, reports that the CTR would not be incorporated into national law as it will not have been implemented before 29 March 2019 and consequently, clinical trials within the UK will be managed nationally.

In its non-binding technical notes, the UK government also reassured stakeholders that it intends to remain aligned with the CTR regardless of the negotiations’ outcome on the transition deal. Separately, the NHS Health Research Authority (HRA) reported that a pilot project initiated with the MHRA to improve the management of clinical trials in the UK.

It should be noted, that irrespective of a “deal” or a “no-deal scenario”, whether the UK can use the CTR’s EU portal and database, as well as participate in the single assessment model depends on the outcome of additional agreements between the EU and the UK.

Implementation in the UK – The future relationship with the EU

Looking forward, the future agreement between Brussels and London will be decisive for the future of clinical trials in the UK. In an update published on 6 August 2018, the MHRA highlighted that this agreement will be instrumental in determining whether the UK can use the EU portal and database, and participate in the single assessment model.

The European Council has made clear in its “guidelines on the framework for the future EU-UK relationship” that the future relationship cannot offer the same benefits as EU membership and that the UK as a third country cannot be involved in the decision-making of EU agencies.

SFL can help you stay on top of Brexit developments and ensure a smooth transition for your company’s products and ongoing clinical trials.

The Swiss Therapeutic Products Act (HMG) has undergone its second ordinary revision, which was approved by the Swiss parliament in March 2016. Subsequently, the ordinances associated with the HMG have been revised accordingly (HMV IV). The revised HMG and most of the associated ordinances are expected to come into force on 1 January 2019. This revision aims to facilitate market access, improve drug safety and increase transparency. Pharmaceutical companies will need to proactively act upon these changes, to avoid any negative impact on their businesses.

Key areas affected by the revision

Regulatory changes:

• Marketing authorizations: conditional marketing authorizations, simplified authorizations (well-established use), regulatory data protection
• Variations: harmonization of classification with EU scheme
• Orphan drug provisions
• Pediatrics: pediatric investigation plan (PIP) and incentives
• Product information: black triangle, full declaration, Italian information for healthcare professionals, publication of product information
• Transparency: public assessment reports (SwissPAR), publication of milestones such as MAA submission and decisions
• Antibiotics monitoring

Reimbursement and marketing-related changes:

• Sales categories and self-medication
• Integrity: clarifications regarding pecuniary benefits
• QMS and pharmacovigilance-related changes: Pharmacovigilance: Pharmacovigilance plan, GVP, reporting duties
• AMBV revision: establishment licenses, GMP certificates and RP requirements

Administrative changes:

• New forms and templates
• Fees

Publication of new Swissmedic guidelines and Swissmedic information days

The updated guidelines and forms were published by Swissmedic on 30 September 2018. Consequently, Swissmedic has organized two information events, taking place on 25 October 2018 and 9 November 2018. The updated eCTD specification for module 1 will be published on 1 November 2018.

SFL is closely monitoring the revision and provides comprehensive support to comply with the changing legal framework.

Recent scientific and technological developments have increased our understanding of how inter-individual differences in DNA sequences, or genetic variants, are linked to drug response. This progress has enabled a transition from population-based prescribing, with a “one-size-fits-all” approach, to more individually tailored treatments. Consequently, genomic data have become important in the evaluation of efficacy and safety of medicinal products for regulatory approval.

Content of the EMA guideline

The new EMA guideline on good pharmacogenomic practice describes the requirements related to the choice of appropriate genomic methodologies during the development and the life-cycle of a drug. Identification of genomic variability has focused mainly on variations in genes encoding drug-metabolizing enzymes, drug transporters and drug targets. The guidance underlines the importance of the design of sample acquisition and handling procedures to guarantee sample adequacy and quality.

Furthermore, the requirement to investigate the impact of genomic variation on drug response in clinical studies as well as the consideration of inter-ethnic differences in the distribution of genetic variants in such studies is emphasized. It is essential that the product information is continuously updated with pharmacogenomic data gathered through the life cycle of the product. Development of pharmacogenetic tests (companion diagnostics) as a result of accumulated genetic information is anticipated to enable cost-effective treatment and add value to the process of drug development.

SFL can assist you with impact analysis of the relevant guidelines for the use of genomic biomarkers in drug development.

Advanced Therapy Medicinal Products (ATMPs) are complex and innovative products that may pose specific challenges to the design and conduct of clinical trials. Manufacturing constraints, short shelf-life, mode of application, long-term effects of the product as well as preclinical data generation may require adaptation to specific characteristics of ATMPs.

Focus areas of the guidelines and consultation period

To tackle these issues, a targeted stakeholder consultation on the draft Guidelines on Good Clinical Practice (GCP) for ATMPs is currently open until 31 October. The final Guidelines will be a document that focuses on ATMP specificities only and applies in addition to GCP Guidelines of the International Council for Harmonization (ICH).

In particular, the Guidelines focus on the clinical trial design, content of the protocol and investigator’s brochure, quality of the investigational ATMPs, protection of clinical trial subjects, safety reporting and long-term follow-up. The comments received during the consultation period will be considered by the European Commission in the finalization of the Guidelines.

SFL’s experienced team can assist you with impact assessments complying with the requirements specific to ATMPs.

On 24 September 2018, the Medical Device Coordination Group (MDGC) under the lead of the European Commission DG GROW held its second meeting, this time also hosting several key stakeholders. On behalf of the ‘Medtech & Pharma Platform’ (MPP) association, Shayesteh Fürst-Ladani, President of MPP, participated in the meeting, together with the other relevant European industry associations.

The meeting agenda included an update on the status of MDR/IVDR implementation and related main topics such as the notified body designation process, Joint Research Centers, Eudamed and the implementation of the Unique Device Identification (UDI).

Delegation of European industry associations presented their perspective and concerns

The joint delegation of European industry associations, including MPP, was invited to present their perspective in particular regarding Article 117 of MDR, which was communicated as a joint industry letter of 26 July to the European Commission DG GROW/DG SANTE. MPP was cosignatory to this joint industry letter.

MDCG working groups – Call to stakeholders will be launched soon

Following the Transparency obligations of the European Commission, the MDCG will soon publish a call to stakeholders for expressions of interest to participate as an observer in MDCG working groups.

The MPP association will continue to engage with key stakeholders to communicate industry positions on the MDR/IVDR and on upcoming implementing and delegated acts.

MPP stakeholder interaction and publication of the MPP White Paper

Since its foundation in 2017, the Medtech & Pharma Platform (MPP) association has established its presence at the European level as the only association focusing specifically on combined products at the intersection of medicinal products and medical devices. Notably, the MPP has introduced itself to European Union institutions, competent authorities and trade associations, with the goal to advocate for a robust and appropriate regulatory framework for combined products.

In order to pursue its objectives, the MPP formed a Working Group for combined products. The first accomplishment of the MPP Working Group is the MPP White Paper, which includes a focus on areas that the association has identified as priorities. The focus areas of the paper include the Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR), amendments to the Medicinal Products Directive (MPD) affecting combined products, and additional regulatory challenges for combined products such as digital health, post-market safety and labelling.

The White Paper will represent the starting point for all future dialogues with key stakeholders.

New members and contact details

The MPP association includes senior professionals coming from leading pharmaceutical and medtech companies, namely:

• Merck Sharp & Dohme
• Novartis
• Sanofi
• Ypsomed
• Swiss Medtech
• SFL Regulatory Affairs & Scientific Communication

If you are interested in becoming a member of MPP, please contact association@medtech-pharma.com.

5^th anniversary of the annual event

The MPP annual event, which celebrates its 5^th anniversary this year will take place at the Congress Center Basel on 16-17 October 2018, will focus on “Global perspectives and trends at the intersection of pharma and medtech”.

During six sessions over two days, current topics such as the EU MDR and IVDR, digital health, innovative technologies, combined products development and data management will be discussed. Internationally acknowledged experts will present insights and offer ample opportunities for further discussion.

In addition, the keynote session will feature Michael Doherty, Head of Product Development at Foundation Medicine, Charles Bridges, Global Chief Technology Officer at Actelion, and Matthew May from the European Patients’ Forum, who will focus on innovations at the interface of pharma and medtech.

SFL will be present at the MPP with a booth and Karin Schulze, SFL’s Head of Regulatory Affairs & Medical Devices, will give a presentation on clinical evaluation under the MDR on 16 October 2018.

If you wish to register for the MPP 2018, please contact office@medtech-pharma.com.

Recent RDAF developments

In July 2018, the Rare Disease Action Forum (RDAF) adopted a position paper on the ongoing revision of the Swiss Invalidity Insurance (IV) to relevant members of the Swiss Parliament, where the topic is currently being discussed. The revision will have a great impact on the capacity of patients with rare diseases in Switzerland to access treatment and care.

The RDAF is also excited to announce that Roche Switzerland, Prof. Dr med. Philipp Latzin from Inselspital in Bern, the Swiss Society for Porphyria and Dipharma Switzerland joined the forum, which now hosts a total of 19 members. With its increased membership, the RDAF reinforces its contribution towards the development of sustainable solutions to improve the situation of patients with rare diseases in Switzerland.

Upcoming RDAF event on value assessment for orphan drugs

On 31 October 2018, the RDAF will host an event on “Value assessment of orphan drugs in Switzerland and the EU” in Basel. The discussion will focus on exchanging knowledge on the different value assessment models in Switzerland, Germany, Austria, and France.

The program features experts from authorities, leading companies in the field of rare diseases, patient organizations, national and international industry associations, as well as independent experts in the area of rare diseases. If you wish to attend the event, please register through this form.

EMA portal for orphan drugs submissions

Since 19 September 2018, the EMA’s IRIS online portal has become the mandatory submission system for activities relating to orphan medicines. While the system is currently dedicated only to orphan designations, EMA plans to broaden the scope of the portal and include other regulatory and scientific procedures in the future.

SFL can assist you with advice on orphan drugs development, preparation and submissions of orphan drug designations to EMA via the new portal.

ISPOR is the leading scientific non-profit organization for health economics and outcomes research (HEOR) that organizes the ISPOR Europe 2018 conference in Barcelona on 10-14 November 2018. The event, focusing on “New Perspectives for Improving 21st Century Health Systems”, will feature three plenary sessions and over 2,500 presentations from international experts.

SFL’s presentations

SFL’s Senior Manager Market Access and HEOR, Daniel Dröschel, will present two posters, which will be published in the journal “Value in Health” together with the related abstracts.

The first presentation will take place on Monday 12 November 2018 and is entitled “Impact of Medical Devices Regulation on future HTA’s and reimbursement decisions in Germany, France and Switzerland – what is blooming here?”. Featuring in Session II, Daniel will discuss the challenges posed by the new EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR) on health technology assessment (HTA), with an eye to digital health products. The analysis will show how the assessment of authorities will differ when products are classified differently and what the impact on existing technologies will be.

On Tuesday 13 November 2018, Daniel will present “An analysis of healthcare systems’ readiness for cell and gene therapies in Switzerland – bright future or dire straits?”. Focusing on the Swiss market, Daniel will evaluate the readiness of the regulatory and reimbursement system to cope with the specific requirements of cell and gene therapies, which frequently come with high costs for the payers.

If you wish to meet Daniel during the conference, please contact office@sfl-services.com.

In January 2018, the European Commission published a proposal for a Regulation on health technology assessment (the systematic evaluation of clinical, social, economic and ethical aspects of medical technologies). After more than 20 years of voluntary cooperation among Member States, the Commission takes a step further and proposes to make cooperation in certain areas mandatory.  However, the proposal establishes common rules and procedures only for the clinical part of HTA (the relative safety and clinical effectiveness of a health technology as compared with existing technologies) leaving the non-clinical part (social, economic and ethical issues) under the jurisdiction of the EU Member States.

Areas of cooperation
The proposal establishes a Coordination Group on HTA composed of representatives from national HTA authorities and bodies, which will be responsible for overseeing four pillars of joint work:

• Joint clinical assessments are a key task of the Coordination Group. The outcomes of these assessments will be used in all Member States as part of their national HTA processes. Medical technologies that fall under certain conditions under the scope are medicinal products which undergo the EU’s central marketing authorization procedure and certain high risk medical devices and in vitro diagnostics
• Joint scientific consultations are a tool for health technology developers, such as pharma and medtech companies, to consult HTA authorities on the required type of data and evidence for HTA submission
• Identification of emerging health technologies by the Coordination Group each year on new technologies that would become the focus of the joint work
• Voluntary cooperation is foreseen for areas outside the mandatory cooperation, such as on non-clinical aspects of medical technologies.

Member States’ reactions and next steps
Following its publication, the HTA proposal received a broad range of feedback from stakeholders and Member States. Notably, some Member States, including Germany, France and Poland, questioned the legitimacy of the proposal, arguing that the mandatory uptake of joint clinical assessments in national HTAs would go against the principle of subsidiarity.

This notwithstanding, the HTA proposal is now being discussed by the co-legislators of the EU, i.e. the European Parliament and the Council of the European Union. In the Parliament, the responsible Committee (Environment, Public Health and Food Safety – ENVI; rapporteur: Cabezón Ruiz from the S&D) is currently debating the proposal, and a first position of the Parliament is planned to be adopted by early October. The Council is also starting discussions which are expected to enter into a decisive phase in the second half of 2018 under the Austrian Presidency.

As the Commission considers it very important that the legislative proposal will be adopted in early 2019, a lot of debates will be needed during the next month to come to a proposal that is acceptable for both the Parliament and the Council.

SFL is closely monitoring the legislative process of the HTA proposal and advises clients on this important health policy dossier.

Clinical trials and data protection are two critical legislations for the entire healthcare sector as well as for patients’ access to medicines.

Discussion on how different levels of divergence between legislation in post-Brexit UK and EU-27 can impact disclosure and exchange of data in clinical trials is anchored around several core clinical trial activities. These include, for example: collection of clinical data from trial subjects (triggering the relevance of discussing matters such as informed consent forms, rights of the trial subjects and lawfulness of processing), disclosure of information (at different stages in the process of approval of medicines and subsequent potential EU-UK cooperation for purposes of clinical trials unified database), and transfers of data outside the EU (from the EU or to the EU), be it at company level or in the context of obtaining EU and/or UK approval of new medicines.

Potential Brexit scenarios

Despite the many shades of Brexit (from hard to soft or even Brexit-in-name-only, from immediate to open-end transition) and the posturing of the negotiators on both sides, it is considered very likely that the post-Brexit UK will have at least some sort of aligned legislation and policies with the EU in the fields of public health and data protection and privacy.

The UK publicly declared, in various instances, that they are positive about leaving the EU but also very keen in maintaining close cooperation with the EU. However, more than 60 conservative MPs publicly communicated their position that the UK should significantly distance itself from the EU and any EU legislation. On the EU side, it was made clear that a non-member cannot have the same EU privileges while not assuming corresponding obligations.

On paper, the situation is far from being clear. Certain progress has been recorded in drafting the Withdrawal Agreement, but the areas which should settle clear rules or answers are, to date, left open.

Clinical trials data and data protection

Regarding clinical trials data, it seems that the UK will keep the EU acquis which precedes the 30^th of March 2019, at least during the so-called transition period (that also still needs to be agreed). This would mean maintaining the EU level of protection on clinical trials data, both from a regulatory and an intellectual property point of view. If no Withdrawal Agreement can be achieved, the UK would be legally free to create variations in these standards after the withdrawal date. However, business partnerships are often a more stringent determinant.

With respect to data protection, an adequacy decision from the EU – unilaterally taken – would pave the way for smooth data flows between the EU and the countries on the adequacy list. However, it remains to be seen whether the US Cloud Act will influence the UK’s data protection policy. If this is the case, the pursuit of an adequacy decision of the EU Commission would be seriously hampered.

Further references on this topic

SFL recently published two articles touching upon the topics discussed above. If you are interested in more detailed information you can download the articles on ‘Disclosure of Clinical Trials Data’ and ‘Privacy Law in Clinical Trials Data Exchange’.

SFL can help you define the regulatory pathway for conducting clinical trials and complying with EU and UK data protection requirements.

Europe’s new Medical Devices Regulation (MDR), applicable as of May 2020, will bring substantial changes to the way medical device manufacturers can bring their products to the market. Considerable changes pertain to requirements for device classification, clinical evaluation reports, compilation of technical documentation and CE certificates.

Clinical evaluation reports

Under the MDR, stricter criteria for equivalent devices are specified for the clinical evaluation reports (CERs) for all devices. The MDR indicates that a formal CER is part of the technical documentation and needs to be updated through the entire life cycle of the device (annually for high risk products, and every two to five years for others). The MDR requires more efforts to demonstrate product safety and performance. A greater volume and more robust clinical data will therefore need to be produced along with a more rigorous interpretation of the equivalence of devices  .

Technical documentation

The most important change in the technical documentation is that it should incorporate a subpart dedicated to the post-marketing surveillance (PMS) of the device in the form of a PMS plan and a PMS report for class I devices or a Periodic Safety Update Report (PSUR) for devices other than Class I.

CE certificates

Manufacturers will be required to fully comply with the MDR’s requirements in order not only to obtain a new CE certificate but also to renew the old one(s). Notably, the MDR specifies that legacy medical devices (that have been on the market under the Medical Devices Directive (MDD)) need to have their compliance reassessed by a Notified Body and to be CE marked anew.

Specifically, manufacturers’ technical documentation will need to comply with the MDR by the 26^th of May 2020 if they want to obtain or renew a CE certificate or to be issued a Declaration of Conformity. However, as indicated in Article 120 of the MDR, after the 26^th of May 2020, medical devices can still be placed on the market under the provision of the MDD, provided the certificate was issued prior to this date, that the manufacturer continues to comply with either one of the directives and that no significant changes are made in the design and intended purpose of the device. Manufacturers of such devices must also meet other requirements, which are detailed in Article 120 of the MDR. The certificates issued in accordance with MDD after the 25^th of May 2017 remain valid until reaching their expiry date; but, in any case, they become void on the 27^th of May 2024 at the latest.

SFL can support you to ensure business continuity during the transition period for the MDR, with the classification / reclassification of medical devices in accordance with the new MDR rules, preparation of a fully compliant CER, the preparation of the technical documentation summary and PMS/PSUR.

The two-year anniversary of the launch of the PRIority MEdicines scheme (PRIME) by the European Medicines Agency (EMA) was an opportunity to reap the harvest of this initiative established to support the development of medicines that address unmet medical needs. In general, the PRIME scheme provides EMA early and enhanced scientific and regulatory support to enable the generation of better data and more robust evidence on benefits and risks of medicines that are of major public health interest.

Criteria for eligibility and requests accepted

A request for PRIME eligibility should demonstrate the availability of adequate non-clinical and exploratory clinical data to justify a potential major public health interest prior to initiation of confirmatory clinical studies. It is particularly advantageous for applicants from the academic sector and micro-, small- and medium-sized enterprises (SMEs) who are eligible for the scheme at an even earlier stage of development, based on convincing non-clinical and very early clinical data (proof of principle).

As of May 2018, 177 requests for eligibility to PRIME were assessed and 36 (21%) of them were accepted. The requests came from a wide range of therapeutic areas, with the majority pertaining to oncology and hematology. The medicines accepted for the scheme reflect the focus on therapeutic areas with scarce treatment options: 83% concern rare diseases and 44% are intended for treatment of pediatric patients (a summary of the first-year evaluation was provided in the July 2017 SFL Newsletter).

The latest additions to the list of products granted eligibility to PRIME are intended for treatment of chikungunya, hematopoietic stem cell transplant patients, the rare monogenic disease, X-linked myotubular myopathy as well as mantle cell lymphoma (CAR-T therapy).

SFL offers support in preparation for the PRIME eligibility assessment and assistance in all interactions with EMA.

MPP association

The MPP association is pleased to welcome Novartis, MSD and Ypsomed, key players in the development of innovative combined products, as members. With the new members, the MPP working group will continue to ensure and facilitate market access for safe, innovative and well-established combined products, as well as promoting joint work on a balanced and feasible regulatory and political framework.

In this regard, the MPP actively communicates industry positions, in cooperation with other industry associations, on the regulatory framework affecting combined products to key decision makers.

Companies interested to actively shape the regulatory framework for combined products and who want to learn about MPP activities and membership opportunities are invited to contact association@medtech-pharma.com.

The 2018 MPP annual event

• The MPP annual event will celebrate its 5^th anniversary on the 16^th and 17^th of October 2018 in Basel, Switzerland. As the leading conference in the sector of products/solutions that combine medtech and pharma components, the MPP annual event has gained increasing interest since its initiation and attracts more stakeholders from the medtech and pharma industries each year.

This year’s event will be dedicated to “Global perspectives and trends at the intersection of pharma and medtech”. The advanced program, available on the MPP website, features six sessions that will explore the following topics:

• the EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR)
• digital health
• revolutionary technologies
• challenges and opportunities for combined products
• data transparency
• eHealth and data management

International speakers will offer cutting-edge discussions on the above topics from a global perspective. In addition, Dr. Lukas Engelberger, Member of the Executive Council and Head of Public Health Department of the Canton Basel-City, will give the welcome speech to the attendees of the MPP annual event.

The annual event includes also an exhibition where innovative technologies will be displayed, allowing for further knowledge exchange among participants, and a gala dinner that will offer networking opportunities in a relaxed atmosphere.

If you wish to register as an exhibitor or as a participant for the upcoming annual event, please get in touch with office@medtech-pharma.com

Multistakeholder workshop

On the 23^rd of May 2018, the RDAF held a multistakeholder workshop on the revision of the Swiss invalidity insurance (IV) in Bern. Swiss parliamentarians, representatives from patient organizations, medical professionals and industry members took part in the workshop entitled “The revision of the invalidity insurance and its meaning for people with rare diseases”.

The IV covers the costs of necessary medical treatments and care for indications included on the list of congenital defects. This coverage runs until the age of 20. As 75% of rare diseases affect children and 80% of rare diseases are of genetic origin, people with such diseases are greatly affected by the current revision.

Participants therefore discussed whether and how the revision of the IV could contribute to improving the lives of people with rare diseases in the country. The aim of the workshop was to discuss current issues of the revision, such as how to improve access to diagnosis and care as well as responsibility for societal solidarity. In this context, the RDAF members have developed a position paper on the revision on the IV.

New members

In addition, the RDAF welcomed three new members: Swedish Orphan Biovitrum, a pharmaceutical company specialized in the area of rare diseases; ProRaris, the Swiss umbrella patient organization; and the Swiss Foundation for Research on Muscle Diseases (SSEM/FSRMM). In total, the Forum now hosts fifteen members from different stakeholders in the area of rare diseases, including industry, patient organizations, healthcare organizations, physicians and foundations for research. With its increased membership, the RDAF reinforces its contribution towards the development of sustainable solutions that improve the situation of patients with rare diseases in Switzerland.

For more information, please get in touch with the RDAF secretariat, run by SFL, at info@rda-forum.org

Regulating products that “blur historical lines”

SFL is pleased to announce the publication of chapter 6, ‘Combination Products, Borderline Products, and Companion Diagnostics’, in the first edition of ‘An Overview of FDA Regulated Products: From Drugs and Medical Devices to Food and Tobacco’.

The chapter, written by SFL’s CEO, provides a concise and practical overview of key regulatory concepts governing the review and approval of combination and borderline products and delineates how in vitro diagnostics are regulated in the US and EU territories. Further, the content illustrates the complexities of designating products that “blur the historical lines separating traditional drugs, biologics and medical devices” to a given regulatory pathway. The unique challenges associated with regulation of these products (so-called borderline products) can impact several aspects of the product lifecycle, including preclinical and clinical development, manufacturing, quality control and post-market surveillance; this chapter provides succinct and accessible information on how to navigate these complex regulatory landscapes.

SFL will give a 1-hour free webinar on reimbursement mechanisms for drugs and devices in Switzerland and Germany on the 10^th of July 2018, 3:00 pm CET.

Objective and target audience

The webinar will provide an overview of the key elements of market access, pricing and reimbursement in the two countries. The presented key aspects will be relevant for both experienced professionals as well as newcomers in the field, and include:

• Healthcare system landscape and regulatory requirements
• Reimbursement pathways and Health Technology Assessments
• Alternative funding (Integrated care; Early access)
• Fees and pricing

You can register for the webinar via this link

SFL is proud to have been named a Great Place to Work® (GPTW) in Switzerland. During a ceremony in Zurich on the 16^th of May 2018, the independent global organization GPTW has named SFL one of the best employers in Switzerland in the category small companies (20-49 employees).

“A milestone fostering our efforts”

“We are honored to be recognized as one of the best workplaces in Switzerland by one of the most prestigious organizations in the field” said the CEO of SFL, Shayesteh Fürst-Ladani. “I would like to thank all of our team members for their trust and support in achieving this milestone through their daily commitment and dedication. For years now, we have strived to create a working environment that promotes our core values of integrity, fairness and respect in all our activities. Each member of our international and multi-disciplinary team is unique, and our goal has always been to make them feel valued while endorsing their different personalities. This award fosters our efforts and encourages us to keep working in this direction.”

SFL earned this important award based on a survey that employees completed anonymously in 2017 on the degrees of trust, credibility, respect, pride and camaraderie they experience n the workplace.

Healthcare in the pediatric population suffers from two significant limitations: lack of authorized medicines and widespread off-label use. The EU Pediatric Regulation entered into force in 2007 with the aim to improve the development of medicinal products for pediatric use, address the lack of age-appropriate formulations and generate more data on efficacy, safety and dosing for the pediatric population.

The Pediatric Regulation established a system of obligations, rewards and incentives to promote regular research, development and authorization of medicines that meet children’s specific therapeutic needs. Pediatric investigation plans (PIPs) have been introduced to screen every product for its potential use in children. As a reward for industry, a six-month extension of the Supplementary Protection Certificate (SPC) has been set up for medicinal products developed in compliance with the PIP obligation. For new orphan medicinal products, 2 additional years of market exclusivity can even be granted if compliance with an agreed PIP can be demonstrated. Scientific advice from the EMA for pediatric-related questions is provided free of charge.

Internationally, it has been observed that legal systems with pediatric-specific legislation have a significantly higher number of new pediatric medicines than those without. In the 2007-2016 period, more than 260 new medicines for use in children were authorized in the EU (new marketing authorizations and new indications). Of these 260 medicines, more than 40 were granted the SPC reward, and 7 orphan medicines obtained the additional market exclusivity reward. During this same period, the European Network of Pediatric Research at the European Medicines Agency (Enpr-EMA) was established and further expanded with the inclusion of American, Canadian and Japanese networks.

To further improve the implementation of the Pediatric Regulation, EMA and the European Commission are organizing a multi-stakeholder workshop on the state of pediatric medicines in the EU on 20 March 2018. A concrete action plan to address challenges associated with medicine development for children in Europe will be discussed among patients, academia, healthcare professionals and industry. One major challenge to be addressed will be the international harmonization of regulatory frameworks for the development of medicines for children.

SFL provides assistance in defining pediatric development strategy, as well as preparing PIPs and negotiating clients’ interests with key stakeholders.

The European Court of Justice (ECJ) has just shed light on two critical topics affecting the healthcare industry: i) classification of software as a medical device; ii) what is considered non-redactable commercially confidential information.

Software as a medical device

Although software was listed in the definition of medical devices in Directive 93/42/EEC, it was not clear which criteria a software had to fulfil in order to be classified as a medical device; and until recently, no harmonized legal definition existed.

In the decision Snitem vs. France, the ECJ provides clarification on the basis for which a software can be defined as a medical device. In doing so, the ECJ has transformed what has largely been considered a guideline, that could be followed or not, into codified case law. Consequently, for a software to be classified as a medical device, it must now fulfil two conditions: i) an intended use for one or more medical purposes; ii) not achieving its principal intended action by pharmacological, immunological or metabolic means, in or on the human body.

Implications of the new ruling go as far as potentially overruling national procedures for medical device certification. As a major consequence, national authorities might no longer be able to issue separate certificates for software that is used to support prescription of medicinal products. Previously, it happened that such certificates were issued on top of the EU CE mark certification (e.g. in France).

More information on the classification of software as a medical device under the Medical Device Regulation (EU) 2017/745 shall be provided in our next Newsletter.

Commercially confidential information (CCI)

With respect to CCI, the ECJ clearly prioritized the EU’s rule that citizens should have access to EU documents. This is best illustrated by three decisions given on February 5^th 2018 (PTC Therapeutics vs. EMA case T-718/15, Pari Pharma vs. EMA case T-235/15 and MSD Animal Health Innovation vs. EMA case T-729/15), for which the court balanced the principles of public access against the exception to protect commercial and intellectual property interests (as per Regulation (EC) 1049/2001).

In a nutshell, these decisions highlighted that no presumption of confidentiality applies to clinical study reports. The ECJ underlined that study reports are submitted to the EMA in order to satisfy a pre-defined regulatory scheme; thus, they are not reflective of a company’s business strategy.

Consequently, applicants need to proactively avoid inclusion of information that they consider commercially confidential when preparing their MAA dossier, because EMA will only redact very specific information (e.g. information that could compromise privacy rights; also, information like the active substance, the formulation and manufacturing and test procedures; or the names of manufacturers or suppliers of the active substance or the excipients).

Both rulings highlight the importance of critical evaluation, impact assessment and in-depth training on new legislation, such as the MDR and CCI EU policy. SFL has a long track record of providing intelligence on these matters to clients.

As of 2017, the Medtech & Pharma Platform (MPP) Association has advanced its activities into political advocacy work, complementing the MPP annual event and training courses. The Association’s mission is to represent the medtech and pharmaceutical industries in their joint efforts for product development and innovation. Acting with an international mindset, the MPP Association shall initially focus on the European regulatory framework for combined products and digital healthcare applications.

From Q2/2018, a dedicated Regulatory Policy Working Group will begin to engage in the upcoming delegated and implementing acts of the Medical Devices Regulation 2017/745 and the Medicinal Product Directive 2001/83, both of which affect combined products.

In addition to its policy work, the MPP Association pursues its goal of increased interaction between the pharmaceutical and medtech industries through its annual event, which is dedicated to enhancing partnerships in this cross-sectoral field.

The international annual event has gained increasing interest since its start, with more than 230 participants from 11 countries who attended the event in 2017, representing the medical technology and pharmaceutical industries in a balanced way.

On October 16^th and 17^th 2018, the MPP annual event will celebrate its 5^th anniversary with cutting-edge discussions on the latest developments concerning the two industries. Major topics that will be discussed this year include digital health, companion diagnostics, user experience, use of real world data and the EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR).

Internationally acknowledged speakers will present innovative technologies; many of which will be displayed in the exhibition hall to allow further participant and exhibitor engagement.

Along with its annual event, the MPP Association aims to boost knowledge exchange by offering expert training sessions throughout the year for a broad range of topics regarding industry, regulatory and technical developments. For example, in February, a full-day training on the new MDR provided a comprehensive overview on the new requirements for medical devices in Europe. Following the strong demand, a second presentation of this course will be held on April 12^th 2018.

For more information on the Association’s membership and policy work, please contact association@medtech-pharma.com. For any queries related to the MPP annual event or training courses, please get in touch with office@medtech-pharma.com.

The Rare Disease Action Forum (RDAF) is a multi-stakeholder platform with the aim to develop and implement solutions to improve access to diagnosis and treatment for patients with rare diseases in Switzerland.

Since its foundation in February 2016, the forum has gained an increasing number of members who represent companies active in the field of rare diseases. Additionally, by opening its membership to leading national patient organizations, healthcare professionals and research institutes in 2017, the RDAF has reinforced its multi-stakeholder approach. SFL was a key driver in initiating and setting up the RDAF and is currently running the secretariat.

One of RDAF’s key activities is organizing multi-stakeholder workshops to promote the exchange of views between experts from pharmaceutical companies, patient organizations, health insurers, physicians and political decision makers.

One of this year’s workshops will focus on the revision of the invalidity insurance (IV). The event is intended to raise awareness among key decision makers about the importance of the IV law for patients with rare diseases. The workshop will take place on May 23rd in Bern, with speakers ranging from politicians, KOLs, patient organization representatives and health care professionals.

A second workshop in Q4/2018 will be dedicated to the key theme of “how to make the benefit assessment in the Article 71 KVV reimbursement process fit for the purpose of assessing the benefit of orphan medicinal products”.

The RDAF attended also the “Swiss Rare Disease Day” that was organized by ProRaris on March 3^rd. The global “Rare Disease Day” aims to raise awareness among the general public and decision makers about rare diseases. The campaign started 2008 as a European event and has progressively become a world phenomenon with hundreds of events organized around the end of February.

Current members of RDAF: Alexion, Amicus, Curatis, Santhera, Sanofi Genzyme SFL, Shire, Pfizer, Vertex, BLACKSWAN Foundation, Children’s Research Center (CRC) of the Children’s Hospital Zurich – Eleonore Foundation, Prof. Andrea Superti-Furga from CHUV’s department of genetic medicine.

If you are interested to become member of the RDAF and to attend the workshops, please contact the secretariat run by SFL at info@rda-forum.org

SFL has reinforced its expertise in the medtech area and welcomes Dr. Karin Schulze as Head of Medical Devices.

Dr. Schulze was formerly leading the Medical Devices Division of the Swiss Association for Quality and Management Systems (SQS). In view of the new Medical Devices Regulations (MDR and IVDR), the medical device sector will be significantly perturbed in the upcoming years. The changes will require considerable investments for medtech companies to comply with the new requirements.

Under Karin’s leadership, the SFL team will support clients manufacturing medical devices, IVDs, and combination products to ensure continuous marketing of their products under the MDR/IVDR.

In addition, we are pleased to inform our clients that Ms. Robin Conrad, Senior Consultant, is supporting SFL clients with US regulatory strategy, as well as acting as US Agent and facilitating US FDA interactions. She has worked in both large and small pharma and biotech organizations, covering strategic, operational and compliance related activities.

The 4th international Medtech & Pharma Platform (MPP) conference, held on 26-27 October 2017, attracted participants representing pharma and medech companies, regulatory agencies, academic organizations, government institutions and service companies. International speakers discussed regulatory trends, innovative technologies, experience design, connectivity in relation to health data, and accessibility of medical products in emerging markets. In the exhibition hall, exhibitors from different sectors showcased their products, while 1-on-1 partnering meetings allowed participants to create lasting connections. The balance of delegates from medtech and pharma companies complemented the cross-sectoral character of the conference.

In her closing speech, the CEO of SFL and President of the MPP highlighted the future directions of the MPP and invited companies active in the field of combined products to become members of the MPP association, founded in February 2017. In the coming months, the MPP will be setting up working groups concerning the new EU Medical Devices Regulations (MDR and IVDR), to ensure that the interests of key stakeholders and MPP members are conveyed in the upcoming delegated and implementing acts.

Save the date for the next MPP conference on 16 – 17 October 2018 in Basel!

The adoption of the MDR and IVDR triggered an early revision of the MedDo by the Swiss Federal Council in October 2017. The MedDo has been adapted to include key points from the EU Regulations, applying as of 26 November 2017 (e.g. point on re-designation of Notified Bodies).

The complete revision of the MedDo and the new Ordinance for in vitro diagnostics, that are yet to come, will take into account all the provisions of the MDR and IVDR. Their entry into force is scheduled in the first half of 2020.

The Rare Disease Action Forum (RDAF) is an association that aims to improve patient access to diagnosis and treatment, and raise awareness of rare diseases in Switzerland.

In 2017, two multi-stakeholder workshops were held. The most recent one took place in November 2017, where guest speakers discussed the legislative developments in the Swiss Invalidity Insurance framework and the European Reference Networks from the Swiss perspective.

The RDAF is pleased to welcome three new members as of 2018. Membership is now open to patient and non-profit organizations, as well as healthcare institutions and professionals.

This year, the SFL team gave speeches and attended key conferences in the US, Europe and especially in Asia, such as GPKOL in South Korea and BIO Asia in Japan, where we presented our expertise in European regulatory affairs and policies in the area of orphan drugs, advanced therapies and medical devices.

In addition, the CEO of SFL became a lecturer on “Medical Affairs in Medicines Development” at IFAPP/King’s College and gave lectures about global regulatory frameworks for medical devices, IVDs and combination products.

Furthermore, she gave lectures on regulatory strategy in clinical development of innovative drugs at George Washington University, as well as an interview to the Swiss Embassy on the Japanese medical engineering market.

With 2017 almost behind us and heading for 2018, it is a great time to reflect on some of the main developments that have shaped the healthcare industry’s environment and review how SFL’s activities and services help our partners to stay ahead of the upcoming challenges.

We wish you a joyful and relaxing holiday season and success in the coming year.

I would like to thank all our clients and partners for their trust in SFL. As always, SFL is committed to the highest quality and professionalism, which we combine with the skills and experience of our multi-disciplinary team to help our clients in their daily business challenges.

The SFL team looks forward to working with you again in 2018.

Antimicrobial resistance (AMR) has become a rising global threat with the potential to cause mortality rates of 10 million per year by 2050. AMR cannot be tackled effectively by one country or one sector alone, and therefore requires a comprehensive, interdisciplinary and transnational approach.

The EU is in a good position to coordinate this approach, and in June 2017, the European Commission in fact published “A European One Health Action Plan against Antimicrobial Resistance (AMR)”. The Plan is built on three pillars:

• Making the EU a best practice region, which aims at enhancing surveillance of AMR and data sharing across the EU, as well as increasing awareness on the issue;
• Boosting research, development and innovation on AMR, which includes developing alternative products and new economic models;
• Shaping the global agenda, whose goal is to make the EU a reference model for developing countries and the rest of the world.

The efforts by the European Commission have been promptly followed by a series of initiatives from other EU bodies and specialized agencies on AMR. Some of these include a workshop by the European Parliament, a stakeholder meeting by EMA, and several calls for tenders by EU specialized agencies to improve control measures and surveillance.

The European pharmaceutical industry is very supportive of this proactive, multi-sectoral approach involving all key stakeholders, and welcomes further alignment between Member States in their measures to prevent and monitor AMR. The role of the private sector is crucial to develop new therapeutics, yet antimicrobial innovation is still not adequately incentivized. Long-term customized solutions are needed to compensate for the absence of financial benefits for these products.

Among the envisaged solutions, the European pharmaceutical industry agrees that a European priority pathogens list, in line with the one by the WHO, would help determine common priorities and incentivize research in these areas. At the same time, both “push” and “pull” mechanisms would encourage knowledge advancement and R&D sharing, as well as create incentives to counterbalance financial investments. Finally, participation of regulatory authorities in dialogues with the private sector would help adapt the regulatory framework.

The SFL team can help you stay updated on EU policies and initiatives on AMR, and can provide you with advice on how to take advantage of opportunities available at the EU level in the field of AMR.

This article gives an overview of some of the latest updates concerning the implementation of the EU Clinical Trials Regulation No. 536/2014 (CTR):

• EU portal and Database: the CTR’s entry into application is conditional to the portal and related IT infrastructures being up and running. Recently, the EMA’s Management Board announced that, due to technical difficulties in the implementation of IT systems, the entry into application would be postponed from October 2018 to a yet undisclosed date in 2019. More information is to be expected from the EMA in October 2017.

• Training: the finalization of EMA’s training environment on the new EU portal, which will be offered to various stakeholders, is expected for the end of 2017 / early 2018.

• Implementation measures and guidelines for 2017 (on EU level):
  • • Commission Delegated Act specifying principles of and guidelines for Good Manufacturing Practice (GMP) for investigational medicinal products and arrangements for inspections (art. 63 CTR): final versionwas published on 16 September 2017 in the Official Journal of the European Union.
    • Commission guidelines on GMP for investigational medicinal products (art. 63(1) CTR): guidelines are expected in the second semester of 2017.
    • Commission Implementing Regulation on the detailed arrangements for Good Clinical Practice (GCP) inspection procedures (art. 78(7) CTR): final version published on 25 March 2017 in the Official Journal of the European Union.
    • EMA Draft Guideline for the notification of serious breaches of the CTR or the clinical trial protocol (art. 52 CTR): based on the public consultation on the draft guideline, which was closed on 22 August 2017, the EMA will finalize and adopt the document.

• National implementation of CTR: efforts of implementation at the national level have been observed in various EU Member States, such as France and Belgium. In France, three legal texts were adopted in 2016 with the aim of adapting the national legislation and notably resulted in the integration of all 39 French Ethics Committees. In addition, both countries launched pilot projects. Initiated in 2015, the French Health Agency’s (ANSM’s) voluntary pilot project has been running for more than 18 months. In Belgium, the first tests of its pilot project are expected to take place between October and December 2017. The delay of the portal implementation gives more time to EU Members to align national processes and infrastructures with the CTR.

The CTR will bring important changes for industry actors and it is thus important to not only monitor its implementation but also to actively prepare for it. In this context, SFL’s experienced team can provide policy advice and regulatory support to facilitate the transition to the new legal regime and IT systems.

A new initiative to replace the existing tool for parallel scientific advice by the EMA and Health Technology Assessment Bodies (HTABs) came into play in July 2017. The initiative provides a single gateway for parallel consultation requests and builds on previous pilots on HTA regulatory collaboration led by EMA, European Network for Health Technology Assessment (EUnetHTA) and the European Commission. Medicine developers were previously required to contact Member States’ HTA bodies individually.

The new joint platform for parallel consultation provides developers of medicines with simultaneous, coordinated advice on evidence generation plans. The aim is to allow medicine developers to obtain feedback from regulators and HTABs on their plans regarding marketing authorization, health technology assessment, and reimbursement simultaneously. The consultations may be requested for any medicinal product for use in humans and at any stage of the product lifecycle.

Closer interactions between regulators and HTA bodies are expected to improve their coordination, offer a streamlined procedure for the applicants and lead to more robust outcomes. Early dialogue can facilitate discussion on evidence generation required after the launch of a medicine to allow the continuous assessment of the benefit-risk balance and long-term effectiveness of the medicine. Patient representatives and healthcare professionals also participate in the procedure on a routine basis so that their views and experiences are incorporated into discussions.

Common templates for simultaneously notifying EMA and EUnetHTA of the intent to participate in a parallel consultation have been published, and further procedural steps are coordinated by EUnetHTA’s Early Dialogue Secretariat. The consultation can take two different pathways: ‘consolidated consultation’ includes the full participation of the EUnetHTA Early Dialogue Working Party plus up to three additional HTABs, whereas in ‘individual consultation’, HTABs participate based on their own national priorities. Some HTA bodies charge fees for their participation in the consultation, and EMA charges the same fees as for its standard scientific advice.

Based on a long-standing experience in interaction with regulatory authorities, and multiple successful projects conducted in collaboration with both the EMA and the HTAs, SFL offers assistance in preparation of documents and support in all stages of EMA-EUnetHTA parallel consultation procedures.

In July 2017, the European Commission launched its public consultation on Health and Care in the Digital Single Market. The Digital Single Market is of key importance for the life science sector as the consequences of its implementation will be far-reaching. It may particularly result in the improvement of healthcare through the sharing, in real time, of real world data for efficient pharmacovigilance, prompt assessment of performance of products placed on the market or EU-wide identification of infectious threats. It may also influence the advancement of science through cross-border sharing of scientific research expertise or via a timely transfer of knowledge from the laboratory to the clinical setting.

The consultation addresses issues central to the Digital Single Market, including secure access to health data and cross-border sharing (i.e. through exchange of sensitive patient data collected in the course of multinational studies), the use of digital services and how the General Data Protection Regulation (GDPR) will affect this initiative. It aims at evaluating the impact of a Digital Single Market, based on input from interested stakeholders, in order to determine the necessity of policy. Consequently, the target group of the consultation are, among others, health and social care professionals and organizations, manufacturers and service providers in the health industry, public authorities, patient organizations, hospitals and citizens. Responses may be submitted in any EU language through the online questionnaire until 12 October 2017.

According to the Mid-Term Review on the implementation of the Digital Single Market Strategy, digital technologies should ensure that citizens can transfer their basic medical information, electronically, when receiving treatment in another Member State and use e-prescriptions to get their medication dispensed. Through telemedicine and mobile health applications, a transition from a hospital-based to a patient-centered and integrated health care model is envisaged. The consultation further emphasizes the significance of the newly-adopted EU Regulations on IVDs (the IVDR) and medical devices (the MDR), to the extent that the two regulations include a reclassification of health-related mobile apps. In particular, a robust Digital Single Market will be partially achieved through authorization of such mobile apps, a large part of which will most probably require the involvement of notified bodies in order to be put on the market.

Our experienced team can provide regulatory support on key themes, such as issues of compliance with the GDPR, and support you in the area of eHealth and mHealth.

The time for being in full compliance with the GDPR (25 May 2015) is fast approaching. The implications for organizations operating in the life science and healthcare sectors are particularly relevant, as they often collect and/or use large amounts of sensitive health-related data in respect of living individuals, such as patients and clinical trial subjects. Lack of compliance could be costly; infringement can bring fines of up to 4% of annual global revenue or €20 million (whichever is the greater) and damage corporate reputation.

The more significant changes likely to impact stakeholders in these sectors are summarized below. The topic of sensitive personal data categories is not included here but will be discussed in our next newsletter.

The GDPR applies to organizations established in the European Economic Area (EEA) as well as to organizations that process personal data and either: (i) offer goods or services to individuals within the EEA and/or (ii) monitor the behavior of data subjects within the EEA.

For those in the life science and healthcare sectors, particular regard needs to be taken to the changes in the definitions of “personal data” and “sensitive personal data”: Both of these have been expanded under the GDPR, with the former now, explicitly, including factors specific to the genetic identity of a person and the latter including genetic data, biometric data and data concerning the health of a natural person. Additionally, the definition of “consent” has been strengthened and will be more difficult to obtain and rely upon as a basis for data processing by those in the healthcare area. Valid consent will require clear, affirmative action, and this consent must be freely given, specific, informed, voluntary, unambiguous and, in the case of sensitive personal data, explicit. The other grounds for processing this type of personal information remain largely unchanged from the existing Directive. Note that the GDPR grants Member States the right to introduce additional conditions, including restrictions, regarding the processing of genetic data or data concerning health; so, even if an organization is compliant with the GDPR, local country laws must be taken into account.

All data subjects now have the right to: (i) be forgotten, (ii) amend their information, (iii) data portability and (iv) withdraw their consent to the collection and processing of their personal data.

What does this mean for an organization? In the event a data subject, patient or clinical trial participant opts to exercise his right to be forgotten, the organization which collected the personal information must, without undue delay, find and delete any data associated with that individual within their organization and within any company that the organization has shared the data with (e.g. data analysts, doctors, hospitals, CROs, and all of their emails, file shares etc.).

However, if the patient data can be anonymized, it can be retained for scientific purposes; this applies as long as that data cannot be re-attributed to the individual by ANY possible means.

All organizations that collect and process sensitive personal information must appoint a Data Protection Officer (DPO) and, if they do not have a physical presence in the EEA, must appoint a representative in one of the EU countries to act as main point of contact for questions arising from the data protection authorities and the data subjects.

The DPO can be an employee of the organization or an external consultant but, in either case, must have expert knowledge of data protection law and practices in order to perform the tasks attributed to the DPO.

Life science and healthcare related businesses should take steps now to ensure they are able to comply with the new requirements of the GDPR.

The SFL team is ready to support you on your road to compliance with the GDPR.

To accelerate the development of medicines that target an unmet medical need, the widely publicized EMA PRIority MEdicines (PRIME) scheme was launched in April 2016 and represents a step towards a more influential and pro-active role for the EMA.

PRIME was developed in line with the European Commission’s priorities and EMA’s 2020 strategy. It is a voluntary scheme based on enhanced interaction with developers of promising medicines and is somewhat based on the FDA Priority Review scheme, which was launched in 2007. Early dialogue and support of development plans are intended to bring these medicines to patients earlier, without compromising high evaluation standards or patient safety.

In a workshop held in May 2017, EMA gathered relevant stakeholders to reflect on the first 12 months of the scheme’s implementation. In the first year, 96 PRIME eligibility assessments were processed. The requests covered a wide range of product types and therapeutic areas. Of the 20 eligible products, 12 were advanced therapies, 5 chemical-based medicines, 2 biologics and 1 vaccine. 12 of the granted requests represent orphan medicines and 1 in 3 eligible products targets a disease for which no treatment exists. The main reasons for denial of requests were insufficiently robust data (in 70% of cases), inadequate justification of therapeutic advantage (40%) and development of the therapy already being too far advanced for early engagement (20%).

Regarding therapeutic areas, most PRIME-eligible medicines are developed for oncology and hematologic diseases, followed by medicines used in neurology, gastroenterology, immunology, endocrinology and psychiatry. The nature of unmet needs dictates that PRIME is usually more relevant for rare diseases and neglected tropical diseases. EMA considers these figures as proof of the PRIME concept and will continue apace.

The procedure particularly benefits SMEs and applicants from the academic sector. Compared to big pharma companies, they can apply for PRIME at an earlier stage of development and request a fee waiver for scientific advice.

The experienced team at SFL can assist you in both the preparation of PRIME eligibility assessments and in performing a gap analysis to reduce the risk of rejection.

The new regulations on medical devices (MDR) and in vitro diagnostic medical devices (IVDR) introduce new classification rules and extension of concepts, creating a binding legal Regulation on medical technology products for the first time. The Regulations took ten years of fraught political process to adopt, with the result being highly complex measures to be implemented.

In the MDR, the definition of “medical device” now includes certain devices with no intended medical purpose and devices manufactured utilizing non-viable tissues/cells of human origin. In addition, classification rules are explicitly formulated for: nanomaterials, medicinal products administered via inhalation, substance-based products and active therapeutic devices with a diagnostic function. The scope of the IVDR has also grown, and now covers companion diagnostics.

The MDR & IVDR will have a significant impact on the industry, notably due to:

• The mandatory appointment of a person responsible for regulatory compliance, in each company
• Increasing number of audits, as a responsibility of notified bodies (NBs), have been enhanced (e.g. one audit per year mandatory for certain classes of devices)
• Unique Device Identifier to be applied on alldevices
• A significantly higher bar for pre- and post-market data, especially for high risk class devices and implants
• Potential delays in the conformity assessment procedure, where involvement of expert panels is required
• Increased obligations pertinent to post-market surveillance, especially for higher risk devices whose manufacturers will need to prepare periodic safety update reports

NBs will have increased responsibilities towards all economic operators (manufacturer, authorized representative, importer, distributor). A re-certification procedure is imposed for NBs, as well as for all devices; since there is no “grandfathering” rule, it is highly likely that many NBs will not be re-certified. If your NB is not re-certified, the certificates they issued will not be valid anymore and, as a manufacturer, you have to contract another NB.

For the MDR and IVDR, product manufacturers will need to comply with the new Regulations by May 2020 and May 2022, respectively. Certificates issued by NBs under the current legislation during the transition period will continue to be valid until maximum 2024. However, requirements in the MDR and IVDR, related to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices, shall apply as of the application date (namely 2020 and 2022, respectively).

There are many emerging and critical needs for manufacturers with the new MDR/IVDR. SFL can assist you with customized training on the Regulations and provide strategic advice on developing your products in compliance with the new requirements.

Dr. Conxita Barajas-Diaz has joined SFL as Head of Drug Safety and Pharmacovigilance. Dr. Barajas-Diaz brings many years of experience in drug safety, having worked on all functional levels with both European and US pharmaceutical companies and in consultancy. She is a highly experienced EU Qualified Person for Pharmacovigilance (EU QPPV) for medicinal products and has been involved in the oversight of vigilance activities for medical devices and advanced therapy medicinal products.

Dr. Barajas-Diaz is an associate professor at Barcelona University and University of Alcalá in Madrid, where she initiated postgraduate studies in Pharmacovigilance (PV) and is a coordinator of seminars in PV for the pharmaceutical industry. Together with the Spanish Health Authorities, she participates in elaboration of Good Pharmacovigilance Practices for the pharmaceutical industry.

Dr. Barajas-Diaz will support SFL clients with their PV requirements, including acting as EU QPPV and PV auditor, and lead the SFL internal PV System. She will be providing expertise and support in a range of PV topics, including benefit/risk assessments, risk management planning and mitigation, signal detection and training. Along with the multidisciplinary SFL team, the appointment of Dr. Barajas-Diaz fosters SFL’s expertise in strategic management, the writing of periodic evaluation reports (PBRERs), medical reviews, audits and quality topics in PV.

For assistance on projects including drug safety and PV topics, please contact the SFL team. 

SFL is pleased to announce the creation of a new company SFL Regulatory Services GmbH in Vienna, Austria. The Vienna office has been established in order to continue and expand SFL’s EU activities and interactions with the EMA. SFL’s already established UK entity will continue to serve as a future contact point to the MHRA. The SFL team will continue supporting clients from offices in Basel, Barcelona, Brussels, London and Vienna.

The EMA guideline on the role of pharmacokinetic (PK) studies in pediatric drug development has been in force since 2007, when the Pediatric Regulation was implemented. The goal of this guideline is to promote a more effective use of medicines in pediatric patients by assisting applicants in the development of medicinal products for the pediatric population, particularly for very young patients. During the last decade, many applications for pediatric indications have been submitted to the EMA and the national regulatory agencies. Numerous Pediatric Investigation Plans (PIPs) have been approved under this procedure. Based on the wealth of information and experience gathered through the procedure, and along with scientific developments in the last decade, a revision of the pediatric PK guideline has been proposed by EMA.

The revision will mainly target optimization of the study design and use of current PK modeling methods to support pediatric drug development. Due to the difficulty of demonstrating efficacy and safety in pediatric patients in clinical studies, PK data obtained in adults needs to be presented and used in an optimal manner. The revision will, therefore, highlight the appropriate methods for scaling PK from adults to children and between different pediatric subpopulations. Further changes relate to dose finding and dose selection. Considerations on dosage adaptation, individualized dosing, pediatric age categories and simulation-based approaches to optimize study design are identified for update in the revision of the guideline.

The concept paper on revision of the guideline is currently open for public consultation, and the deadline for submission of comments is 31 July 2017. Following the receipt of comments and consolidation, the draft guideline itself will be released for 6 months external consultation in Q4 2018. Interested stakeholders affected by the revision include the pharmaceutical industry, regulatory agencies, pediatricians and other healthcare professionals, medical societies and academia. The revision will have a significant impact on applications for pediatric drug development and the design, conduct and analysis of studies in PIP proposals.

To stay on top of the latest guideline revisions and for assistance in the development and preparation of PIP submissions, contact the SFL team.

Industry stakeholders, patient organizations, public health authorities and medical professionals from the field of rare diseases met at the Rare Disease Action Forum’s (RDAF) multi-stakeholder meeting in May. They discussed access to therapies for children and young people with rare diseases, and the Swiss Federal Council’s proposal for revision of the Swiss Invalidity Insurance (IV/AI) framework.

The proposed revision of IV/AI was presented from the perspective of patient organizations, with a focus on relevant aspects for children with rare diseases. One of the issues discussed included the process to update the list of congenital defects (GGL). This list is said to result in some shortfalls, notably when it comes to the procedure of inclusion or exclusion of a congenital defect.

Participants were also updated on the Swiss National Concept for rare diseases, whose four implementation pillars were said to be progressing well. Notably, it was mentioned that a Swiss structure for the coordination of rare diseases (KOSEK) would be set up this year, which was done on 22 June 2017. In addition, the topic of Swiss participation in the EU European Reference Networks (ERN) for rare diseases, which were launched in March 2017, was discussed.

Participants were presented with the view of a hospital’s tariff management department, where the billing of healthcare services provided to address rare conditions can be challenging. Finally, two university professors and medical doctors presented their experience in treating patients with rare diseases, under both the reimbursement scheme of the IV/AI and under health insurance.

The purpose of the RDAF is to serve as a multi-stakeholder platform to exchange ideas and define actions on how to raise awareness of rare disease and improve access to innovative therapies for patients with rare diseases in Switzerland. If you are interested to become member of RDAF please contact its secretariat, which is run by SFL.

Formal Brexit negotiations between the UK and the EU started on 19 June, yet the veil of uncertainty brought upon the medtech and pharma industries will remain for as long as it takes to reach a final agreement.

The EU27 agreed its negotiation priorities unanimously, and within a matter of minutes, on 29 April 2017. Among other aspects, the directive for the EU’s negotiation emphasized the priority of safeguarding rights of EU and UK citizens and settling the so-called Divorce Bill before further negotiations concerning trade can begin. In addition to the time lost for the UK general election, this agreed sequence o