CH – First approvals by Swissmedic of products under new regulatory pathways
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.
EU - COVID-19 regulatory responses and future implications for regulatory procedures
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.
EU - New MDCG documents provide clarification on MDR implementation
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.
CH – Consultation opens on revision of Swiss genetic legislation for human tests
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).
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 engages with experts in multi-stakeholder workshop
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.
MPP – New activities increase engagement with members
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.
CH – Swissmedic streamlines review of medicines for serious communicable diseases
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.
EU – EMA changes to the organizational structure of the Human Medicines Division come into effect
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.
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.
EU – New Scientific Advice pilot program supporting innovative medicines
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.
CH/EU – Medical devices to be affected by delay in the EU-Switzerland MRA
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).
EU – Recommendations on the use of big data in the regulatory process
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.
EU/US – EMA and FDA reports on 2019 NAS/NDE and orphan drug approvals
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.
EU – “Shaping Europe’s Digital Future” initiative launches with focus on data and AI
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.
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.
EU –Regulations and guidelines update for devices and combination products
The release of new risk management, cybersecurity and clinical evaluation guidelines addresses outstanding uncertainties for medical devices and software in the MDR & 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.
EU – Latest news from the European Commission on MDR implementation
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.
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).
EU/US – Using real-world evidence to support regulatory assessments
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.
SFL Christmas Newsletter – December 2019
Thank you from SFL’s CEO
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 - Stakeholder meeting on Regulatory Science Strategy 2025
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.
CH - Revised Swiss Therapeutic Products Act - 1 year in force
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.
EU - Implementation of MDR/IVDR for devices and combination products
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.
CH - Paving the way for entry into the Swiss pharma market
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.
MPP - Successful 2019 MPP annual conference
The 6th 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.
SFL - SFL expansion continues in 2019
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.
Charity – Support for SOS Children’s Villages
SFL is happy to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages.
Save the date – SFL webinar
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 Newsletter – September 2019
SFL to host expert webinar on Market Access and Supply Chain in Switzerland
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.
MPP increases membership base and expands activities
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 email@example.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.
Commissioner-candidates for DG SANTE & DG GROW
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.
Implementation of the MDR – are the stakeholders ready?
Continued challenges with MDR raise concerns about Notified Body capacity and devices shortages in the EU
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.
Scientific and technical collaborations between EMA and the FDA
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/FDA - EMA and FDA report to improve early access to new drugs
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.
Presence of SFL at upcoming conferences and events
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.
Combination products - SFL continues to strengthen the team
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.
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 combination and borderline products
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.
Brexit - Implications for data protection and clinical trials
SFL publication assesses the impact of different Brexit scenarios in the context of data exchanges in clinical trials.
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.
Orphan Drugs - Improving patient access in Switzerland
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 - A model addressing future healthcare needs?
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 - Expert trainings and conference drive medtech and pharma collaboration
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 6th 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 firstname.lastname@example.org 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.
SFL Newsletter – March 2019
EU – Legislators agree on proposal for Regulation on SPC for medicines
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.
EU – Medicines required to comply with new safety features obligation
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.
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.
US – Acceptance of data from clinical investigations for medical devices
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 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.
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.
EMA – Path from big data to evaluation and supervision of medicines
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.
DE- CH – Changes in the German and Swiss healthcare legislation
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.
Switzerland – Changes ahead for reimbursement of medical devices
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.
SFL – Update on association work
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.
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 email@example.com.
SFL – Celebration of 10th anniversary
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 10th anniversary celebrations can be found here.
SFL Christmas Newsletter – December 2018
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 - Evaluation of the orphan and pediatric regulations
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.
ECJ - Two recent rulings impact the life sciences 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.
SFL - New offices in Basel and Lausanne
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.
MPP - Annual event and association
The Medtech & Pharma Platform (MPP) association celebrated this year the 5th 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.
EMA - Use of patient disease registries for regulatory purposes
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.
RDAF - Strengthening of multistakeholder contribution in the area of rare diseases
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.
SFL - Commitment to knowledge sharing
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).
Charity - Support for SOS Children’s Villages
SFL is happy to continue its financial support for the independent, non-governmental, international development charity SOS Children’s Villages.
Save the date - MDR training
The MPP training on “Overview of the Medical Devices Regulation and Impact on Industry” will take place in Basel on 18 March 2019.
SFL - Best wishes from the CEO
Thank you to all our partners and clients for your ongoing trust in our support of your business endeavors. This year SFL expanded its expertise in GDPR Compliance, Brexit Support, Commercial Operations and Supply Chain Management and Distribution. We look forward to integrating these areas into our core strengths of Regulatory and Medical Affairs, Public Affairs, Quality Assurance, Pharmacovigilance and Market Access to provide you with comprehensive tailored solutions to achieve your goals in 2019.
SFL Newsletter – October 2018
EU CTR– Entry into application delayed and consequences of Brexit for implementation in the UK
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.
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.
Switzerland – Revision of the Therapeutic Products Act (HMG) due to enter into force in 2019
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.
QMS and pharmacovigilance-related changes: Pharmacovigilance: Pharmacovigilance plan, GVP, reporting duties
AMBV revision: establishment licenses, GMP certificates and RP requirements
New forms and templates
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.
EMA – Pharmacogenomics guideline effective as of September 2018
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.
EC – The draft Guidelines on GCP for ATMPs are now open for consultation
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.
MDR/IVDR implementation – News from the EU MDCG meeting with relevant stakeholders
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 – Fostering medtech and pharma cooperation through the association and the annual event
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:
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.
Rare diseases – update on the RDAF and recent developments at EU level
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
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.
Market access – Meet SFL at ISPOR Europe 2018 in Barcelona
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 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.
Health technology assessment – The proposed EU Regulation
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.
Brexit – Data protection and disclosure of clinical trial data
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 30th 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.
SFL can help you define the regulatory pathway for conducting clinical trials and complying with EU and UK data protection requirements.
Medical devices – The new requirements introduced by the MDR
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 .
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.
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 26th 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 26th 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 25th of May 2017 remain valid until reaching their expiry date; but, in any case, they become void on the 27th 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.
PRIME – Two-year experience
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 – Global trends for pharma and medtech companies
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 firstname.lastname@example.org.
The 2018 MPP annual event
The MPP annual event will celebrate its 5th anniversary on the 16th and 17th 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)
challenges and opportunities for combined products
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 email@example.com
RDAF – Successful multistakeholder workshop and growing membership base
On the 23rd 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.
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 firstname.lastname@example.org
SFL – Publication on combination and borderline products in ‘An Overview of FDA Regulated Products’
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 – Webinar on reimbursement in Switzerland and Germany
SFL will give a 1-hour free webinar on reimbursement mechanisms for drugs and devices in Switzerland and Germany on the 10th 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)
SFL is proud to have been named a Great Place to Work® (GPTW) in Switzerland. During a ceremony in Zurich on the 16th 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.
First decade of the Pediatric Regulation in the EU
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.
European Court of Justice – Landmark rulings relevant for the healthcare industry
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 5th 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.
Medtech & Pharma Platform – The key forum for combined products
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 16th and 17th 2018, the MPP annual event will celebrate its 5th 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 12th 2018.
RDAF – Sustainable solutions for patients with rare diseases in Switzerland
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 3rd. 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 email@example.com
SFL Christmas Newsletter – December 2017
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.
SFL is expanding its leadership role in providing medtech and US support
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.
Medtech & Pharma Platform
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!
Switzerland revised its Medical Devices Ordinance (MedDo)
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.
RDAF: breakthrough for the rare disease multi-stakeholder platform
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.
Presence at conferences and academia
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.
Thank you and best wishes from the CEO
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.
SFL Newsletter – October 2017
Current strategy and industry position on AMR
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.
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.
Update on the EU Clinical Trials Regulation
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 aligned procedure from EMA and HTA bodies
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.
The Digital Single Market and the life sciences sector
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 EU General Data Protection Regulation (GDPR)
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.
SFL Newsletter – July 2017
One year EMA’s PRIME scheme; progress towards meeting unmet patient needs
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.
MDR/IVDR: a new era for medical technologies
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.
Head of Drug Safety & Pharmacovigilance joins SFL
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 opens new affiliate in Vienna, Austria
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.
EMA’s new pediatric PK guideline – concept paper open for public consultation
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.
RDAF: Swiss Invalidity Insurance (IV/AI) and rare diseases
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 finally underway but uncertainty for medtech and pharma industries remains
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