SFL Policy Insights & Newsletters

EU Portal and Database

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

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

Implementation documents

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

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

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

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

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

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

Implementation in the UK – The future relationship with the EU

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

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

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

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

Key areas affected by the revision

Regulatory changes:

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

Reimbursement and marketing-related changes:

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

Administrative changes:

• New forms and templates
• Fees

Publication of new Swissmedic guidelines and Swissmedic information days

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

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

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

Content of the EMA guideline

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

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

SFL can assist you with impact analysis of the relevant guidelines for the use of genomic biomarkers in drug development.

Advanced Therapy Medicinal Products (ATMPs) are complex and innovative products that may pose specific challenges to the design and conduct of clinical trials. Manufacturing constraints, short shelf-life, mode of application, long-term effects of the product as well as preclinical data generation may require adaptation to specific characteristics of ATMPs.

Focus areas of the guidelines and consultation period

To tackle these issues, a targeted stakeholder consultation on the draft Guidelines on Good Clinical Practice (GCP) for ATMPs is currently open until 31 October. The final Guidelines will be a document that focuses on ATMP specificities only and applies in addition to GCP Guidelines of the International Council for Harmonization (ICH).

In particular, the Guidelines focus on the clinical trial design, content of the protocol and investigator’s brochure, quality of the investigational ATMPs, protection of clinical trial subjects, safety reporting and long-term follow-up. The comments received during the consultation period will be considered by the European Commission in the finalization of the Guidelines.

SFL’s experienced team can assist you with impact assessments complying with the requirements specific to ATMPs.

On 24 September 2018, the Medical Device Coordination Group (MDGC) under the lead of the European Commission DG GROW held its second meeting, this time also hosting several key stakeholders. On behalf of the ‘Medtech & Pharma Platform’ (MPP) association, Shayesteh Fürst-Ladani, President of MPP, participated in the meeting, together with the other relevant European industry associations.

The meeting agenda included an update on the status of MDR/IVDR implementation and related main topics such as the notified body designation process, Joint Research Centers, Eudamed and the implementation of the Unique Device Identification (UDI).

Delegation of European industry associations presented their perspective and concerns

The joint delegation of European industry associations, including MPP, was invited to present their perspective in particular regarding Article 117 of MDR, which was communicated as a joint industry letter of 26 July to the European Commission DG GROW/DG SANTE. MPP was cosignatory to this joint industry letter.

MDCG working groups – Call to stakeholders will be launched soon

Following the Transparency obligations of the European Commission, the MDCG will soon publish a call to stakeholders for expressions of interest to participate as an observer in MDCG working groups.

The MPP association will continue to engage with key stakeholders to communicate industry positions on the MDR/IVDR and on upcoming implementing and delegated acts.

MPP stakeholder interaction and publication of the MPP White Paper

Since its foundation in 2017, the Medtech & Pharma Platform (MPP) association has established its presence at the European level as the only association focusing specifically on combined products at the intersection of medicinal products and medical devices. Notably, the MPP has introduced itself to European Union institutions, competent authorities and trade associations, with the goal to advocate for a robust and appropriate regulatory framework for combined products.

In order to pursue its objectives, the MPP formed a Working Group for combined products. The first accomplishment of the MPP Working Group is the MPP White Paper, which includes a focus on areas that the association has identified as priorities. The focus areas of the paper include the Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR), amendments to the Medicinal Products Directive (MPD) affecting combined products, and additional regulatory challenges for combined products such as digital health, post-market safety and labelling.

The White Paper will represent the starting point for all future dialogues with key stakeholders.

New members and contact details

The MPP association includes senior professionals coming from leading pharmaceutical and medtech companies, namely:

• Merck Sharp & Dohme
• Novartis
• Sanofi
• Ypsomed
• Swiss Medtech
• SFL Regulatory Affairs & Scientific Communication

If you are interested in becoming a member of MPP, please contact association@medtech-pharma.com.

5^th anniversary of the annual event

The MPP annual event, which celebrates its 5^th anniversary this year will take place at the Congress Center Basel on 16-17 October 2018, will focus on “Global perspectives and trends at the intersection of pharma and medtech”.

During six sessions over two days, current topics such as the EU MDR and IVDR, digital health, innovative technologies, combined products development and data management will be discussed. Internationally acknowledged experts will present insights and offer ample opportunities for further discussion.

In addition, the keynote session will feature Michael Doherty, Head of Product Development at Foundation Medicine, Charles Bridges, Global Chief Technology Officer at Actelion, and Matthew May from the European Patients’ Forum, who will focus on innovations at the interface of pharma and medtech.

SFL will be present at the MPP with a booth and Karin Schulze, SFL’s Head of Regulatory Affairs & Medical Devices, will give a presentation on clinical evaluation under the MDR on 16 October 2018.

If you wish to register for the MPP 2018, please contact office@medtech-pharma.com.

Recent RDAF developments

In July 2018, the Rare Disease Action Forum (RDAF) adopted a position paper on the ongoing revision of the Swiss Invalidity Insurance (IV) to relevant members of the Swiss Parliament, where the topic is currently being discussed. The revision will have a great impact on the capacity of patients with rare diseases in Switzerland to access treatment and care.

The RDAF is also excited to announce that Roche Switzerland, Prof. Dr med. Philipp Latzin from Inselspital in Bern, the Swiss Society for Porphyria and Dipharma Switzerland joined the forum, which now hosts a total of 19 members. With its increased membership, the RDAF reinforces its contribution towards the development of sustainable solutions to improve the situation of patients with rare diseases in Switzerland.

Upcoming RDAF event on value assessment for orphan drugs

On 31 October 2018, the RDAF will host an event on “Value assessment of orphan drugs in Switzerland and the EU” in Basel. The discussion will focus on exchanging knowledge on the different value assessment models in Switzerland, Germany, Austria, and France.

The program features experts from authorities, leading companies in the field of rare diseases, patient organizations, national and international industry associations, as well as independent experts in the area of rare diseases. If you wish to attend the event, please register through this form.

EMA portal for orphan drugs submissions

Since 19 September 2018, the EMA’s IRIS online portal has become the mandatory submission system for activities relating to orphan medicines. While the system is currently dedicated only to orphan designations, EMA plans to broaden the scope of the portal and include other regulatory and scientific procedures in the future.

SFL can assist you with advice on orphan drugs development, preparation and submissions of orphan drug designations to EMA via the new portal.

ISPOR is the leading scientific non-profit organization for health economics and outcomes research (HEOR) that organizes the ISPOR Europe 2018 conference in Barcelona on 10-14 November 2018. The event, focusing on “New Perspectives for Improving 21st Century Health Systems”, will feature three plenary sessions and over 2,500 presentations from international experts.

SFL’s presentations

SFL’s Senior Manager Market Access and HEOR, Daniel Dröschel, will present two posters, which will be published in the journal “Value in Health” together with the related abstracts.

The first presentation will take place on Monday 12 November 2018 and is entitled “Impact of Medical Devices Regulation on future HTA’s and reimbursement decisions in Germany, France and Switzerland – what is blooming here?”. Featuring in Session II, Daniel will discuss the challenges posed by the new EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR) on health technology assessment (HTA), with an eye to digital health products. The analysis will show how the assessment of authorities will differ when products are classified differently and what the impact on existing technologies will be.

On Tuesday 13 November 2018, Daniel will present “An analysis of healthcare systems’ readiness for cell and gene therapies in Switzerland – bright future or dire straits?”. Focusing on the Swiss market, Daniel will evaluate the readiness of the regulatory and reimbursement system to cope with the specific requirements of cell and gene therapies, which frequently come with high costs for the payers.

If you wish to meet Daniel during the conference, please contact office@sfl-services.com.

In January 2018, the European Commission published a proposal for a Regulation on health technology assessment (the systematic evaluation of clinical, social, economic and ethical aspects of medical technologies). After more than 20 years of voluntary cooperation among Member States, the Commission takes a step further and proposes to make cooperation in certain areas mandatory.  However, the proposal establishes common rules and procedures only for the clinical part of HTA (the relative safety and clinical effectiveness of a health technology as compared with existing technologies) leaving the non-clinical part (social, economic and ethical issues) under the jurisdiction of the EU Member States.

Areas of cooperation
The proposal establishes a Coordination Group on HTA composed of representatives from national HTA authorities and bodies, which will be responsible for overseeing four pillars of joint work:

• Joint clinical assessments are a key task of the Coordination Group. The outcomes of these assessments will be used in all Member States as part of their national HTA processes. Medical technologies that fall under certain conditions under the scope are medicinal products which undergo the EU’s central marketing authorization procedure and certain high risk medical devices and in vitro diagnostics
• Joint scientific consultations are a tool for health technology developers, such as pharma and medtech companies, to consult HTA authorities on the required type of data and evidence for HTA submission
• Identification of emerging health technologies by the Coordination Group each year on new technologies that would become the focus of the joint work
• Voluntary cooperation is foreseen for areas outside the mandatory cooperation, such as on non-clinical aspects of medical technologies.

Member States’ reactions and next steps
Following its publication, the HTA proposal received a broad range of feedback from stakeholders and Member States. Notably, some Member States, including Germany, France and Poland, questioned the legitimacy of the proposal, arguing that the mandatory uptake of joint clinical assessments in national HTAs would go against the principle of subsidiarity.

This notwithstanding, the HTA proposal is now being discussed by the co-legislators of the EU, i.e. the European Parliament and the Council of the European Union. In the Parliament, the responsible Committee (Environment, Public Health and Food Safety – ENVI; rapporteur: Cabezón Ruiz from the S&D) is currently debating the proposal, and a first position of the Parliament is planned to be adopted by early October. The Council is also starting discussions which are expected to enter into a decisive phase in the second half of 2018 under the Austrian Presidency.

As the Commission considers it very important that the legislative proposal will be adopted in early 2019, a lot of debates will be needed during the next month to come to a proposal that is acceptable for both the Parliament and the Council.

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

Clinical trials and data protection are two critical legislations for the entire healthcare sector as well as for patients’ access to medicines.

Discussion on how different levels of divergence between legislation in post-Brexit UK and EU-27 can impact disclosure and exchange of data in clinical trials is anchored around several core clinical trial activities. These include, for example: collection of clinical data from trial subjects (triggering the relevance of discussing matters such as informed consent forms, rights of the trial subjects and lawfulness of processing), disclosure of information (at different stages in the process of approval of medicines and subsequent potential EU-UK cooperation for purposes of clinical trials unified database), and transfers of data outside the EU (from the EU or to the EU), be it at company level or in the context of obtaining EU and/or UK approval of new medicines.

Potential Brexit scenarios

Despite the many shades of Brexit (from hard to soft or even Brexit-in-name-only, from immediate to open-end transition) and the posturing of the negotiators on both sides, it is considered very likely that the post-Brexit UK will have at least some sort of aligned legislation and policies with the EU in the fields of public health and data protection and privacy.

The UK publicly declared, in various instances, that they are positive about leaving the EU but also very keen in maintaining close cooperation with the EU. However, more than 60 conservative MPs publicly communicated their position that the UK should significantly distance itself from the EU and any EU legislation. On the EU side, it was made clear that a non-member cannot have the same EU privileges while not assuming corresponding obligations.

On paper, the situation is far from being clear. Certain progress has been recorded in drafting the Withdrawal Agreement, but the areas which should settle clear rules or answers are, to date, left open.

Clinical trials data and data protection

Regarding clinical trials data, it seems that the UK will keep the EU acquis which precedes the 30^th of March 2019, at least during the so-called transition period (that also still needs to be agreed). This would mean maintaining the EU level of protection on clinical trials data, both from a regulatory and an intellectual property point of view. If no Withdrawal Agreement can be achieved, the UK would be legally free to create variations in these standards after the withdrawal date. However, business partnerships are often a more stringent determinant.

With respect to data protection, an adequacy decision from the EU – unilaterally taken – would pave the way for smooth data flows between the EU and the countries on the adequacy list. However, it remains to be seen whether the US Cloud Act will influence the UK’s data protection policy. If this is the case, the pursuit of an adequacy decision of the EU Commission would be seriously hampered.

Further references on this topic

SFL recently published two articles touching upon the topics discussed above. If you are interested in more detailed information you can download the articles on ‘Disclosure of Clinical Trials Data’ and ‘Privacy Law in Clinical Trials Data Exchange’.

SFL can help you define the regulatory pathway for conducting clinical trials and complying with EU and UK data protection requirements.

Europe’s new Medical Devices Regulation (MDR), applicable as of May 2020, will bring substantial changes to the way medical device manufacturers can bring their products to the market. Considerable changes pertain to requirements for device classification, clinical evaluation reports, compilation of technical documentation and CE certificates.

Clinical evaluation reports

Under the MDR, stricter criteria for equivalent devices are specified for the clinical evaluation reports (CERs) for all devices. The MDR indicates that a formal CER is part of the technical documentation and needs to be updated through the entire life cycle of the device (annually for high risk products, and every two to five years for others). The MDR requires more efforts to demonstrate product safety and performance. A greater volume and more robust clinical data will therefore need to be produced along with a more rigorous interpretation of the equivalence of devices  .

Technical documentation

The most important change in the technical documentation is that it should incorporate a subpart dedicated to the post-marketing surveillance (PMS) of the device in the form of a PMS plan and a PMS report for class I devices or a Periodic Safety Update Report (PSUR) for devices other than Class I.

CE certificates

Manufacturers will be required to fully comply with the MDR’s requirements in order not only to obtain a new CE certificate but also to renew the old one(s). Notably, the MDR specifies that legacy medical devices (that have been on the market under the Medical Devices Directive (MDD)) need to have their compliance reassessed by a Notified Body and to be CE marked anew.

Specifically, manufacturers’ technical documentation will need to comply with the MDR by the 26^th of May 2020 if they want to obtain or renew a CE certificate or to be issued a Declaration of Conformity. However, as indicated in Article 120 of the MDR, after the 26^th of May 2020, medical devices can still be placed on the market under the provision of the MDD, provided the certificate was issued prior to this date, that the manufacturer continues to comply with either one of the directives and that no significant changes are made in the design and intended purpose of the device. Manufacturers of such devices must also meet other requirements, which are detailed in Article 120 of the MDR. The certificates issued in accordance with MDD after the 25^th of May 2017 remain valid until reaching their expiry date; but, in any case, they become void on the 27^th of May 2024 at the latest.

SFL can support you to ensure business continuity during the transition period for the MDR, with the classification / reclassification of medical devices in accordance with the new MDR rules, preparation of a fully compliant CER, the preparation of the technical documentation summary and PMS/PSUR.

The two-year anniversary of the launch of the PRIority MEdicines scheme (PRIME) by the European Medicines Agency (EMA) was an opportunity to reap the harvest of this initiative established to support the development of medicines that address unmet medical needs. In general, the PRIME scheme provides EMA early and enhanced scientific and regulatory support to enable the generation of better data and more robust evidence on benefits and risks of medicines that are of major public health interest.

Criteria for eligibility and requests accepted

A request for PRIME eligibility should demonstrate the availability of adequate non-clinical and exploratory clinical data to justify a potential major public health interest prior to initiation of confirmatory clinical studies. It is particularly advantageous for applicants from the academic sector and micro-, small- and medium-sized enterprises (SMEs) who are eligible for the scheme at an even earlier stage of development, based on convincing non-clinical and very early clinical data (proof of principle).

As of May 2018, 177 requests for eligibility to PRIME were assessed and 36 (21%) of them were accepted. The requests came from a wide range of therapeutic areas, with the majority pertaining to oncology and hematology. The medicines accepted for the scheme reflect the focus on therapeutic areas with scarce treatment options: 83% concern rare diseases and 44% are intended for treatment of pediatric patients (a summary of the first-year evaluation was provided in the July 2017 SFL Newsletter).

The latest additions to the list of products granted eligibility to PRIME are intended for treatment of chikungunya, hematopoietic stem cell transplant patients, the rare monogenic disease, X-linked myotubular myopathy as well as mantle cell lymphoma (CAR-T therapy).

SFL offers support in preparation for the PRIME eligibility assessment and assistance in all interactions with EMA.

MPP association

The MPP association is pleased to welcome Novartis, MSD and Ypsomed, key players in the development of innovative combined products, as members. With the new members, the MPP working group will continue to ensure and facilitate market access for safe, innovative and well-established combined products, as well as promoting joint work on a balanced and feasible regulatory and political framework.

In this regard, the MPP actively communicates industry positions, in cooperation with other industry associations, on the regulatory framework affecting combined products to key decision makers.

Companies interested to actively shape the regulatory framework for combined products and who want to learn about MPP activities and membership opportunities are invited to contact association@medtech-pharma.com.

The 2018 MPP annual event

• The MPP annual event will celebrate its 5^th anniversary on the 16^th and 17^th of October 2018 in Basel, Switzerland. As the leading conference in the sector of products/solutions that combine medtech and pharma components, the MPP annual event has gained increasing interest since its initiation and attracts more stakeholders from the medtech and pharma industries each year.

This year’s event will be dedicated to “Global perspectives and trends at the intersection of pharma and medtech”. The advanced program, available on the MPP website, features six sessions that will explore the following topics:

• the EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR)
• digital health
• revolutionary technologies
• challenges and opportunities for combined products
• data transparency
• eHealth and data management

International speakers will offer cutting-edge discussions on the above topics from a global perspective. In addition, Dr. Lukas Engelberger, Member of the Executive Council and Head of Public Health Department of the Canton Basel-City, will give the welcome speech to the attendees of the MPP annual event.

The annual event includes also an exhibition where innovative technologies will be displayed, allowing for further knowledge exchange among participants, and a gala dinner that will offer networking opportunities in a relaxed atmosphere.

If you wish to register as an exhibitor or as a participant for the upcoming annual event, please get in touch with office@medtech-pharma.com

Multistakeholder workshop

On the 23^rd of May 2018, the RDAF held a multistakeholder workshop on the revision of the Swiss invalidity insurance (IV) in Bern. Swiss parliamentarians, representatives from patient organizations, medical professionals and industry members took part in the workshop entitled “The revision of the invalidity insurance and its meaning for people with rare diseases”.

The IV covers the costs of necessary medical treatments and care for indications included on the list of congenital defects. This coverage runs until the age of 20. As 75% of rare diseases affect children and 80% of rare diseases are of genetic origin, people with such diseases are greatly affected by the current revision.

Participants therefore discussed whether and how the revision of the IV could contribute to improving the lives of people with rare diseases in the country. The aim of the workshop was to discuss current issues of the revision, such as how to improve access to diagnosis and care as well as responsibility for societal solidarity. In this context, the RDAF members have developed a position paper on the revision on the IV.

New members

In addition, the RDAF welcomed three new members: Swedish Orphan Biovitrum, a pharmaceutical company specialized in the area of rare diseases; ProRaris, the Swiss umbrella patient organization; and the Swiss Foundation for Research on Muscle Diseases (SSEM/FSRMM). In total, the Forum now hosts fifteen members from different stakeholders in the area of rare diseases, including industry, patient organizations, healthcare organizations, physicians and foundations for research. With its increased membership, the RDAF reinforces its contribution towards the development of sustainable solutions that improve the situation of patients with rare diseases in Switzerland.

For more information, please get in touch with the RDAF secretariat, run by SFL, at info@rda-forum.org

Regulating products that “blur historical lines”

SFL is pleased to announce the publication of chapter 6, ‘Combination Products, Borderline Products, and Companion Diagnostics’, in the first edition of ‘An Overview of FDA Regulated Products: From Drugs and Medical Devices to Food and Tobacco’.

The chapter, written by SFL’s CEO, provides a concise and practical overview of key regulatory concepts governing the review and approval of combination and borderline products and delineates how in vitro diagnostics are regulated in the US and EU territories. Further, the content illustrates the complexities of designating products that “blur the historical lines separating traditional drugs, biologics and medical devices” to a given regulatory pathway. The unique challenges associated with regulation of these products (so-called borderline products) can impact several aspects of the product lifecycle, including preclinical and clinical development, manufacturing, quality control and post-market surveillance; this chapter provides succinct and accessible information on how to navigate these complex regulatory landscapes.

SFL will give a 1-hour free webinar on reimbursement mechanisms for drugs and devices in Switzerland and Germany on the 10^th of July 2018, 3:00 pm CET.

Objective and target audience

The webinar will provide an overview of the key elements of market access, pricing and reimbursement in the two countries. The presented key aspects will be relevant for both experienced professionals as well as newcomers in the field, and include:

• Healthcare system landscape and regulatory requirements
• Reimbursement pathways and Health Technology Assessments
• Alternative funding (Integrated care; Early access)
• Fees and pricing

You can register for the webinar via this link

SFL is proud to have been named a Great Place to Work® (GPTW) in Switzerland. During a ceremony in Zurich on the 16^th of May 2018, the independent global organization GPTW has named SFL one of the best employers in Switzerland in the category small companies (20-49 employees).

“A milestone fostering our efforts”

“We are honored to be recognized as one of the best workplaces in Switzerland by one of the most prestigious organizations in the field” said the CEO of SFL, Shayesteh Fürst-Ladani. “I would like to thank all of our team members for their trust and support in achieving this milestone through their daily commitment and dedication. For years now, we have strived to create a working environment that promotes our core values of integrity, fairness and respect in all our activities. Each member of our international and multi-disciplinary team is unique, and our goal has always been to make them feel valued while endorsing their different personalities. This award fosters our efforts and encourages us to keep working in this direction.”

SFL earned this important award based on a survey that employees completed anonymously in 2017 on the degrees of trust, credibility, respect, pride and camaraderie they experience n the workplace.

Healthcare in the pediatric population suffers from two significant limitations: lack of authorized medicines and widespread off-label use. The EU Pediatric Regulation entered into force in 2007 with the aim to improve the development of medicinal products for pediatric use, address the lack of age-appropriate formulations and generate more data on efficacy, safety and dosing for the pediatric population.

The Pediatric Regulation established a system of obligations, rewards and incentives to promote regular research, development and authorization of medicines that meet children’s specific therapeutic needs. Pediatric investigation plans (PIPs) have been introduced to screen every product for its potential use in children. As a reward for industry, a six-month extension of the Supplementary Protection Certificate (SPC) has been set up for medicinal products developed in compliance with the PIP obligation. For new orphan medicinal products, 2 additional years of market exclusivity can even be granted if compliance with an agreed PIP can be demonstrated. Scientific advice from the EMA for pediatric-related questions is provided free of charge.

Internationally, it has been observed that legal systems with pediatric-specific legislation have a significantly higher number of new pediatric medicines than those without. In the 2007-2016 period, more than 260 new medicines for use in children were authorized in the EU (new marketing authorizations and new indications). Of these 260 medicines, more than 40 were granted the SPC reward, and 7 orphan medicines obtained the additional market exclusivity reward. During this same period, the European Network of Pediatric Research at the European Medicines Agency (Enpr-EMA) was established and further expanded with the inclusion of American, Canadian and Japanese networks.

To further improve the implementation of the Pediatric Regulation, EMA and the European Commission are organizing a multi-stakeholder workshop on the state of pediatric medicines in the EU on 20 March 2018. A concrete action plan to address challenges associated with medicine development for children in Europe will be discussed among patients, academia, healthcare professionals and industry. One major challenge to be addressed will be the international harmonization of regulatory frameworks for the development of medicines for children.

SFL provides assistance in defining pediatric development strategy, as well as preparing PIPs and negotiating clients’ interests with key stakeholders.

The European Court of Justice (ECJ) has just shed light on two critical topics affecting the healthcare industry: i) classification of software as a medical device; ii) what is considered non-redactable commercially confidential information.

Software as a medical device

Although software was listed in the definition of medical devices in Directive 93/42/EEC, it was not clear which criteria a software had to fulfil in order to be classified as a medical device; and until recently, no harmonized legal definition existed.

In the decision Snitem vs. France, the ECJ provides clarification on the basis for which a software can be defined as a medical device. In doing so, the ECJ has transformed what has largely been considered a guideline, that could be followed or not, into codified case law. Consequently, for a software to be classified as a medical device, it must now fulfil two conditions: i) an intended use for one or more medical purposes; ii) not achieving its principal intended action by pharmacological, immunological or metabolic means, in or on the human body.

Implications of the new ruling go as far as potentially overruling national procedures for medical device certification. As a major consequence, national authorities might no longer be able to issue separate certificates for software that is used to support prescription of medicinal products. Previously, it happened that such certificates were issued on top of the EU CE mark certification (e.g. in France).

More information on the classification of software as a medical device under the Medical Device Regulation (EU) 2017/745 shall be provided in our next Newsletter.

Commercially confidential information (CCI)

With respect to CCI, the ECJ clearly prioritized the EU’s rule that citizens should have access to EU documents. This is best illustrated by three decisions given on February 5^th 2018 (PTC Therapeutics vs. EMA case T-718/15, Pari Pharma vs. EMA case T-235/15 and MSD Animal Health Innovation vs. EMA case T-729/15), for which the court balanced the principles of public access against the exception to protect commercial and intellectual property interests (as per Regulation (EC) 1049/2001).

In a nutshell, these decisions highlighted that no presumption of confidentiality applies to clinical study reports. The ECJ underlined that study reports are submitted to the EMA in order to satisfy a pre-defined regulatory scheme; thus, they are not reflective of a company’s business strategy.

Consequently, applicants need to proactively avoid inclusion of information that they consider commercially confidential when preparing their MAA dossier, because EMA will only redact very specific information (e.g. information that could compromise privacy rights; also, information like the active substance, the formulation and manufacturing and test procedures; or the names of manufacturers or suppliers of the active substance or the excipients).

Both rulings highlight the importance of critical evaluation, impact assessment and in-depth training on new legislation, such as the MDR and CCI EU policy. SFL has a long track record of providing intelligence on these matters to clients.

As of 2017, the Medtech & Pharma Platform (MPP) Association has advanced its activities into political advocacy work, complementing the MPP annual event and training courses. The Association’s mission is to represent the medtech and pharmaceutical industries in their joint efforts for product development and innovation. Acting with an international mindset, the MPP Association shall initially focus on the European regulatory framework for combined products and digital healthcare applications.

From Q2/2018, a dedicated Regulatory Policy Working Group will begin to engage in the upcoming delegated and implementing acts of the Medical Devices Regulation 2017/745 and the Medicinal Product Directive 2001/83, both of which affect combined products.

In addition to its policy work, the MPP Association pursues its goal of increased interaction between the pharmaceutical and medtech industries through its annual event, which is dedicated to enhancing partnerships in this cross-sectoral field.

The international annual event has gained increasing interest since its start, with more than 230 participants from 11 countries who attended the event in 2017, representing the medical technology and pharmaceutical industries in a balanced way.

On October 16^th and 17^th 2018, the MPP annual event will celebrate its 5^th anniversary with cutting-edge discussions on the latest developments concerning the two industries. Major topics that will be discussed this year include digital health, companion diagnostics, user experience, use of real world data and the EU Medical Devices and In Vitro Diagnostics Regulations (MDR and IVDR).

Internationally acknowledged speakers will present innovative technologies; many of which will be displayed in the exhibition hall to allow further participant and exhibitor engagement.

Along with its annual event, the MPP Association aims to boost knowledge exchange by offering expert training sessions throughout the year for a broad range of topics regarding industry, regulatory and technical developments. For example, in February, a full-day training on the new MDR provided a comprehensive overview on the new requirements for medical devices in Europe. Following the strong demand, a second presentation of this course will be held on April 12^th 2018.

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

The Rare Disease Action Forum (RDAF) is a multi-stakeholder platform with the aim to develop and implement solutions to improve access to diagnosis and treatment for patients with rare diseases in Switzerland.

Since its foundation in February 2016, the forum has gained an increasing number of members who represent companies active in the field of rare diseases. Additionally, by opening its membership to leading national patient organizations, healthcare professionals and research institutes in 2017, the RDAF has reinforced its multi-stakeholder approach. SFL was a key driver in initiating and setting up the RDAF and is currently running the secretariat.

One of RDAF’s key activities is organizing multi-stakeholder workshops to promote the exchange of views between experts from pharmaceutical companies, patient organizations, health insurers, physicians and political decision makers.

One of this year’s workshops will focus on the revision of the invalidity insurance (IV). The event is intended to raise awareness among key decision makers about the importance of the IV law for patients with rare diseases. The workshop will take place on May 23rd in Bern, with speakers ranging from politicians, KOLs, patient organization representatives and health care professionals.

A second workshop in Q4/2018 will be dedicated to the key theme of “how to make the benefit assessment in the Article 71 KVV reimbursement process fit for the purpose of assessing the benefit of orphan medicinal products”.

The RDAF attended also the “Swiss Rare Disease Day” that was organized by ProRaris on March 3^rd. The global “Rare Disease Day” aims to raise awareness among the general public and decision makers about rare diseases. The campaign started 2008 as a European event and has progressively become a world phenomenon with hundreds of events organized around the end of February.

Current members of RDAF: Alexion, Amicus, Curatis, Santhera, Sanofi Genzyme SFL, Shire, Pfizer, Vertex, BLACKSWAN Foundation, Children’s Research Center (CRC) of the Children’s Hospital Zurich – Eleonore Foundation, Prof. Andrea Superti-Furga from CHUV’s department of genetic medicine.

If you are interested to become member of the RDAF and to attend the workshops, please contact the secretariat run by SFL at info@rda-forum.org

Antimicrobial resistance (AMR) has become a rising global threat with the potential to cause mortality rates of 10 million per year by 2050. AMR cannot be tackled effectively by one country or one sector alone, and therefore requires a comprehensive, interdisciplinary and transnational approach.

The EU is in a good position to coordinate this approach, and in June 2017, the European Commission in fact published “A European One Health Action Plan against Antimicrobial Resistance (AMR)”. The Plan is built on three pillars:

• Making the EU a best practice region, which aims at enhancing surveillance of AMR and data sharing across the EU, as well as increasing awareness on the issue;
• Boosting research, development and innovation on AMR, which includes developing alternative products and new economic models;
• Shaping the global agenda, whose goal is to make the EU a reference model for developing countries and the rest of the world.

The efforts by the European Commission have been promptly followed by a series of initiatives from other EU bodies and specialized agencies on AMR. Some of these include a workshop by the European Parliament, a stakeholder meeting by EMA, and several calls for tenders by EU specialized agencies to improve control measures and surveillance.

The European pharmaceutical industry is very supportive of this proactive, multi-sectoral approach involving all key stakeholders, and welcomes further alignment between Member States in their measures to prevent and monitor AMR. The role of the private sector is crucial to develop new therapeutics, yet antimicrobial innovation is still not adequately incentivized. Long-term customized solutions are needed to compensate for the absence of financial benefits for these products.

Among the envisaged solutions, the European pharmaceutical industry agrees that a European priority pathogens list, in line with the one by the WHO, would help determine common priorities and incentivize research in these areas. At the same time, both “push” and “pull” mechanisms would encourage knowledge advancement and R&D sharing, as well as create incentives to counterbalance financial investments. Finally, participation of regulatory authorities in dialogues with the private sector would help adapt the regulatory framework.

The SFL team can help you stay updated on EU policies and initiatives on AMR, and can provide you with advice on how to take advantage of opportunities available at the EU level in the field of AMR.

This article gives an overview of some of the latest updates concerning the implementation of the EU Clinical Trials Regulation No. 536/2014 (CTR):

• EU portal and Database: the CTR’s entry into application is conditional to the portal and related IT infrastructures being up and running. Recently, the EMA’s Management Board announced that, due to technical difficulties in the implementation of IT systems, the entry into application would be postponed from October 2018 to a yet undisclosed date in 2019. More information is to be expected from the EMA in October 2017.

• Training: the finalization of EMA’s training environment on the new EU portal, which will be offered to various stakeholders, is expected for the end of 2017 / early 2018.

• Implementation measures and guidelines for 2017 (on EU level):
  • • Commission Delegated Act specifying principles of and guidelines for Good Manufacturing Practice (GMP) for investigational medicinal products and arrangements for inspections (art. 63 CTR): final versionwas published on 16 September 2017 in the Official Journal of the European Union.
    • Commission guidelines on GMP for investigational medicinal products (art. 63(1) CTR): guidelines are expected in the second semester of 2017.
    • Commission Implementing Regulation on the detailed arrangements for Good Clinical Practice (GCP) inspection procedures (art. 78(7) CTR): final version published on 25 March 2017 in the Official Journal of the European Union.
    • EMA Draft Guideline for the notification of serious breaches of the CTR or the clinical trial protocol (art. 52 CTR): based on the public consultation on the draft guideline, which was closed on 22 August 2017, the EMA will finalize and adopt the document.

• National implementation of CTR: efforts of implementation at the national level have been observed in various EU Member States, such as France and Belgium. In France, three legal texts were adopted in 2016 with the aim of adapting the national legislation and notably resulted in the integration of all 39 French Ethics Committees. In addition, both countries launched pilot projects. Initiated in 2015, the French Health Agency’s (ANSM’s) voluntary pilot project has been running for more than 18 months. In Belgium, the first tests of its pilot project are expected to take place between October and December 2017. The delay of the portal implementation gives more time to EU Members to align national processes and infrastructures with the CTR.

The CTR will bring important changes for industry actors and it is thus important to not only monitor its implementation but also to actively prepare for it. In this context, SFL’s experienced team can provide policy advice and regulatory support to facilitate the transition to the new legal regime and IT systems.

A new initiative to replace the existing tool for parallel scientific advice by the EMA and Health Technology Assessment Bodies (HTABs) came into play in July 2017. The initiative provides a single gateway for parallel consultation requests and builds on previous pilots on HTA regulatory collaboration led by EMA, European Network for Health Technology Assessment (EUnetHTA) and the European Commission. Medicine developers were previously required to contact Member States’ HTA bodies individually.

The new joint platform for parallel consultation provides developers of medicines with simultaneous, coordinated advice on evidence generation plans. The aim is to allow medicine developers to obtain feedback from regulators and HTABs on their plans regarding marketing authorization, health technology assessment, and reimbursement simultaneously. The consultations may be requested for any medicinal product for use in humans and at any stage of the product lifecycle.

Closer interactions between regulators and HTA bodies are expected to improve their coordination, offer a streamlined procedure for the applicants and lead to more robust outcomes. Early dialogue can facilitate discussion on evidence generation required after the launch of a medicine to allow the continuous assessment of the benefit-risk balance and long-term effectiveness of the medicine. Patient representatives and healthcare professionals also participate in the procedure on a routine basis so that their views and experiences are incorporated into discussions.

Common templates for simultaneously notifying EMA and EUnetHTA of the intent to participate in a parallel consultation have been published, and further procedural steps are coordinated by EUnetHTA’s Early Dialogue Secretariat. The consultation can take two different pathways: ‘consolidated consultation’ includes the full participation of the EUnetHTA Early Dialogue Working Party plus up to three additional HTABs, whereas in ‘individual consultation’, HTABs participate based on their own national priorities. Some HTA bodies charge fees for their participation in the consultation, and EMA charges the same fees as for its standard scientific advice.

Based on a long-standing experience in interaction with regulatory authorities, and multiple successful projects conducted in collaboration with both the EMA and the HTAs, SFL offers assistance in preparation of documents and support in all stages of EMA-EUnetHTA parallel consultation procedures.

In July 2017, the European Commission launched its public consultation on Health and Care in the Digital Single Market. The Digital Single Market is of key importance for the life science sector as the consequences of its implementation will be far-reaching. It may particularly result in the improvement of healthcare through the sharing, in real time, of real world data for efficient pharmacovigilance, prompt assessment of performance of products placed on the market or EU-wide identification of infectious threats. It may also influence the advancement of science through cross-border sharing of scientific research expertise or via a timely transfer of knowledge from the laboratory to the clinical setting.

The consultation addresses issues central to the Digital Single Market, including secure access to health data and cross-border sharing (i.e. through exchange of sensitive patient data collected in the course of multinational studies), the use of digital services and how the General Data Protection Regulation (GDPR) will affect this initiative. It aims at evaluating the impact of a Digital Single Market, based on input from interested stakeholders, in order to determine the necessity of policy. Consequently, the target group of the consultation are, among others, health and social care professionals and organizations, manufacturers and service providers in the health industry, public authorities, patient organizations, hospitals and citizens. Responses may be submitted in any EU language through the online questionnaire until 12 October 2017.

According to the Mid-Term Review on the implementation of the Digital Single Market Strategy, digital technologies should ensure that citizens can transfer their basic medical information, electronically, when receiving treatment in another Member State and use e-prescriptions to get their medication dispensed. Through telemedicine and mobile health applications, a transition from a hospital-based to a patient-centered and integrated health care model is envisaged. The consultation further emphasizes the significance of the newly-adopted EU Regulations on IVDs (the IVDR) and medical devices (the MDR), to the extent that the two regulations include a reclassification of health-related mobile apps. In particular, a robust Digital Single Market will be partially achieved through authorization of such mobile apps, a large part of which will most probably require the involvement of notified bodies in order to be put on the market.

Our experienced team can provide regulatory support on key themes, such as issues of compliance with the GDPR, and support you in the area of eHealth and mHealth.

The time for being in full compliance with the GDPR (25 May 2015) is fast approaching. The implications for organizations operating in the life science and healthcare sectors are particularly relevant, as they often collect and/or use large amounts of sensitive health-related data in respect of living individuals, such as patients and clinical trial subjects. Lack of compliance could be costly; infringement can bring fines of up to 4% of annual global revenue or €20 million (whichever is the greater) and damage corporate reputation.

The more significant changes likely to impact stakeholders in these sectors are summarized below. The topic of sensitive personal data categories is not included here but will be discussed in our next newsletter.

The GDPR applies to organizations established in the European Economic Area (EEA) as well as to organizations that process personal data and either: (i) offer goods or services to individuals within the EEA and/or (ii) monitor the behavior of data subjects within the EEA.

For those in the life science and healthcare sectors, particular regard needs to be taken to the changes in the definitions of “personal data” and “sensitive personal data”: Both of these have been expanded under the GDPR, with the former now, explicitly, including factors specific to the genetic identity of a person and the latter including genetic data, biometric data and data concerning the health of a natural person. Additionally, the definition of “consent” has been strengthened and will be more difficult to obtain and rely upon as a basis for data processing by those in the healthcare area. Valid consent will require clear, affirmative action, and this consent must be freely given, specific, informed, voluntary, unambiguous and, in the case of sensitive personal data, explicit. The other grounds for processing this type of personal information remain largely unchanged from the existing Directive. Note that the GDPR grants Member States the right to introduce additional conditions, including restrictions, regarding the processing of genetic data or data concerning health; so, even if an organization is compliant with the GDPR, local country laws must be taken into account.

All data subjects now have the right to: (i) be forgotten, (ii) amend their information, (iii) data portability and (iv) withdraw their consent to the collection and processing of their personal data.

What does this mean for an organization? In the event a data subject, patient or clinical trial participant opts to exercise his right to be forgotten, the organization which collected the personal information must, without undue delay, find and delete any data associated with that individual within their organization and within any company that the organization has shared the data with (e.g. data analysts, doctors, hospitals, CROs, and all of their emails, file shares etc.).

However, if the patient data can be anonymized, it can be retained for scientific purposes; this applies as long as that data cannot be re-attributed to the individual by ANY possible means.

All organizations that collect and process sensitive personal information must appoint a Data Protection Officer (DPO) and, if they do not have a physical presence in the EEA, must appoint a representative in one of the EU countries to act as main point of contact for questions arising from the data protection authorities and the data subjects.

The DPO can be an employee of the organization or an external consultant but, in either case, must have expert knowledge of data protection law and practices in order to perform the tasks attributed to the DPO.

Life science and healthcare related businesses should take steps now to ensure they are able to comply with the new requirements of the GDPR.

The SFL team is ready to support you on your road to compliance with the GDPR.