SFL Newsletter - March 2017

International Rare Disease Day in Switzerland; “Collaboration is crucial!”

On 4 March 2017, ProRaris and Lausanne’s hospital center (CHUV) joined forces to organize the 7th International Rare Disease Day in Switzerland. Rare Disease Day offers an important opportunity to address some of the main challenges currently limiting the effective management of rare diseases: lack of awareness and prioritization.

The event brought together patients, their relatives and experts in public health, scientific research and the health industry to discuss the importance of reference centers for provision of specialized diagnosis and care. With SFL acting as the secretariat of the RDAF (Rare Disease Action Forum), a SFL representative attended the event.

Speakers Prof. Jean-Blaise Wasserfallen, medical director of CHUV and Anne-Francoise Auberson, president of ProRaris, outlined major developments and accomplishments in Switzerland in the last year. Both emphasized the need for further initiatives related to the rare disease environment. In line with the meeting’s focus, Prof. Wasserfallen highlighted the importance of interdisciplinary and interinstitutional collaboration.

Presentations focused on four collaborative projects, which served as examples of successful multi-stakeholder approaches: an internet portal and helpline (Portail Romand), Reference Center for Osteogenesis Imperfecta (SVOI), the Rheumatology Department for children and the Reference Center for muscle diseases at CHUV.

Round tables were held to discuss specific challenges that the rare disease patient community faces. The first round table of the day was dedicated to the “bench to bedside” loop for orphan drugs, and highlighted the roles of different stakeholders in the process. An interesting discussion reflected on the experiences of patients, the pharmaceutical industry and the Swiss public health institution. It was concluded that further steps in accelerating access to rare disease treatments require closer integration and collaboration of all interest groups.

The topic of the second panel discussion was the relationship between rare disease patients, industry and health insurance providers. It underlined the need for holistic and homogenous procedures for rare disease practices in Switzerland. In the last section of the conference, an update on the status of the national concept for rare diseases was given by Ms. Esther Neiditsch of the Federal Office of Public Health and Agnes Nienhaus of medical universities’ association Unimedsuisse. The latter association is responsible for the development of a National Coordination Platform for Rare diseases.

Overall, the discussions at the 7th International Rare Disease Day encouraged all stakeholders to engage and collaborate in creating incentives to improve diagnosis, provision of care, and development of new medicines and technologies.

The EU In-Vitro Diagnostic Regulation – eventually adoption is near

The In Vitro Diagnostic Regulation (IVDR) moved closer to its final adoption during March. Given that the European Commission published its original proposal in September 2012, the IVDR (along with the Medical Devices Regulation [MDR]) has been one of the longest running legislative procedures in the history of the European Union.

The latest version of the legislation was published by the Council of the European Union at the end of February 2017. This text, legally consistent and fully translated into all EU languages, was in preparation for the last six months.

Following publication, the Council voted to formally approve the text on 7 March 2017. The European Parliament’s Environment, Health and Food Safety Committee voted to adopt the IVDR text itself on 21 March. Now, just the formality of the plenary vote of the whole Parliament in 4 April remains to enact the IVDR.

In terms of implementation timelines, there are still some steps to go for the legislation. The IVDR is expected to be published in the Official Journal of the European Union in May 2017. Consequently, the new Regulation could enter into force in June 2017, together with the MDR. Five years after entry into force (i.e. June 2022), most provisions of the IVDR will enter into application. The MDR will be fully applicable by June 2020 following a three-year transition period.

Compared to the June 2016 version, there are no major changes concerning the likely final text of the IVDR. The regulatory assessment process remains largely the same as proposed in 2016, as are the rights and responsibilities of the key regulatory and market stakeholders. Nevertheless, there are a few changes that IVD manufacturers should be aware of.

Compared to the 2016 version, these changes mainly concern the transitional period and provisions. Starting from the date of application, the requirements in the IVDR will apply to all devices on the market or put into service. Even though manufacturers can use the transitional period to place devices on the market according to the old In Vitro Diagnostic Directive (IVDD), they will need to comply with some requirements of the new IVDR from when the IVDR becomes applicable.

Other minor changes comprise more specific definitions and technical clarifications, such as timelines for publishing documents on the different databases.

To further clarify and specify some details in the regulation and make it work in practice, a series of delegated and implementing acts is expected to be adopted by the Commission in the coming years. In such a detailed legislation, it will be important to follow developments closely even after the Regulation enters into application.  

The SFL team can help you to follow the next steps in the adoption and implementation of the IVDR and MDR and assess the impact on your products and development plan.

ECJ Decision on TÜV Rheinland liability for defective certified products

In the context of defective[1] breast implants produced by a French company, which later went bankrupt and could no longer be held liable, the European Court of Justice (ECJ) had to establish if the Notified Body[2] appointed to certify the medical devices for compliance with EU standards, TÜV Rheinland, could be directly held liable by end users.

The ECJ had to determine what legal obligations incurred to these Notified Bodies, and whether end users enjoyed correlative rights.

The ECJ outlined what the Notified Body must[3] and may do. The Notified Body must be “alert” when faced with evidence that a medical device might not comply with the requirements laid down in Medical Devices Directive 93/42/EEC (MDD) and mustact with all due diligence” when engaged in a procedure relating to the EC declaration of conformity. The Notified Body must, therefore, do something; the final concrete action is, however, left at the discretion of the respective Notified Body. In terms of surveillance, a Notified Body may “carry out unannounced inspections, to examine devices and/or to examine the manufacturer’s business records”.

Put simply, the ECJ answered “no” to end users enjoying correlative rights. The ECJ reiterated its position that a directive which imposes surveillance obligations on Notified Bodies does not confer correlative rights on end users. Also, end users are not conferred rights despite one of the objectives of the directive being to protect injured parties.

This is “especially [true] if the directive does not contain any express rule granting such rights”.  

Nonetheless, the court underlined that the legislation on liability for defective products does not preclude Member States from recurring to other systems of (non-)contractual liability, for instance based on fault. The impact of the Decision is somewhat limited as the MDD is due to be replaced by new MDR in mid 2020.

This jurisprudence pushed for the introduction of enhanced responsibilities on behalf of both manufacturers and the Notified Bodies through the IVDR and MDR, as well as for the introduction of a Unique Device Identification (UDI), for a precise track of devices and their manufacturers.

To keep track of requirements for certification of medical devices, please consult SFL team.

[1] Due to use of substandard industrial-grade silicone.

[2] The “notified body” in question is TÜV Rheinland AG (“TÜV”, in the following), an independent German company that certifies products and processes for their compliance with statutory specifications and other relevant performance benchmarks and standards. See http://www.tuv.com/en/corporate/home.jsp

[3] See paragraph 41 of the judgment, according to which the notified body is under an obligation to “Analyze the application for examination of the design dossier lodged by the manufacturer, which must describe the design, manufacture and performance of the product in question and […] ascertain whether the application of the quality system contemplated by the manufacturer ensures that the products fulfil the relevant requirements under that directive. Moreover, […] the notified body must satisfy itself that the manufacturer duly fulfils the obligations imposed by the approved quality system.”

Changes afoot on EMA’s policy on access to documents

In recent years, there has been an apparent need for an updated policy on transparency of information and access to documents underlying the European Medicines Agency’s (EMA) granting of marketing authorizations.

The growing demand of important stakeholders and the general public for more information and greater transparency can create tension with IP rights and marketing authorization holders (MAHs). This is underlined by several legal proceedings raised against the EMA regarding the provision of data considered to be “commercially confidential”. Since October 2016, upon marketing authorization application (MAA) submission, the EMA publishes Clinical Study Reports (CSRs) as part of a drive for transparency.

In February 2017, the EMA published a proposed revision to its original policy on access to documents of 2010 for public consultation. The policy is in accordance with Regulation (EC) No 1049/2001, which grants citizens a right to access EU documents. Stakeholders can submit comments until 18 May 2017.

To enhance the EMA’s capabilities in creating transparency, in addition to EU official documents, the proposal (ref.: EMA/729522/2016) aims to include corporate documents in the range of documents to be disclosed.

According to the EMA’s proposal, the policy shall be reviewed within 3 years or at an earlier stage if considered necessary. Supplementary documents to the policy comprise a new table with the access rules related to corporate documents (ref.: EMA/183710/2016), and a revised table outlining the rules pertaining to access to documents concerning medicinal products for human and veterinary use (ref.: EMA/127362/2006).

The new version of the policy increases the scope of the information that shall be proactively published on the EMA website. This includes information about the medicinal products and regulatory procedures for which EMA is responsible as well as agendas and minutes of the scientific committees’ meetings, and, in relation to EMA, its reports, funding and financial management, and other corporate documents.

A modification proposed by the new version of the policy is to change the previous classification of documents from “public” and “confidential” to “releasable” and “non-releasable”. As part of this re-classification, substance changes propose a detailed assessment of the level of information to be disclosed to requesters.

The proposal underlines that “EMA reserves to classify documents for internal purposes such as for internal security reasons or to manage access to its databases according to separate procedures and criteria.”

As for the timing of disclosure of documents, this will only occur once the application for the marketing authorization has a certain outcome: be it the moment of availability of the Commission Decision (including situations when there is an ongoing assessment by scientific committees of EMA – such as the Committee on Advanced Therapies, the Pediatric Committee or the Pharmacovigilance Risk Assessment Committee), or the moment of the scientific committee opinion (if there is no Commission Decision concerning the marketing authorization). Until such time, the documents are “non-releasable”.

For an assessment of your documents prepared for a MAA, please contact SFL team.

Stay up to date with Medtech & Pharma Platform training courses

Medtech & Pharma Platform offers high-level and strategic training to support you in achieving your working objectives. In the medtech field, the European regulatory environment is due to change significantly in the coming years. The next Medtech & Pharma Platform courses will take place in Basel in April 2017:

  • `An overview of the current MDD and future MDR requirements’ on 25 April 2017
  • `An overview of the current IVDD and future IVDR requirements’ on 26 April 2017

Course leaders will provide a comprehensive overview of the regulatory system and requirements for medical devices and in-vitro diagnostics in Europe.

More information on the trainings and the registration process are detailed on the flyer.

Procedures to amend EU legislation continue to evolve

Comitology refers to committees of experts (largely representatives of member state governments) meant to take technical decisions on EU matters. It is a method of keeping Directives and Regulations up to date over time (such as responding to technological developments, assessments by the European Commission or EU agencies, legal judgements) without re-opening the legislation for revision in full. The European Commission has made its proposal to amend the relevant legislation (182/2011) on how this process works.

Comitology works as follows: the Commission devises draft implementing acts, which are submitted to Appeal Committees for voting. The vote’s outcome may be in favour or against the adoption of the draft act or be a ‘no opinion’ vote. In the latter case, for sensitive topics, such as new pharmaceutical products, glyphosate or genetically modified organisms (GMOs), the Commission must refer the matter to an Appeal Committee. The Commission must only make the final decision on such matters when the appeal committee is unable to decide.  

The European Commission believes that Member States are often unwilling to take responsibility for a decision. Subsequently, the decision-making process is left, on purpose, to the Commission’s latitude. Thus, the proposed changes aim to increase transparency and accountability, so that Member States can no longer “hide behind Brussels”[1] on delicate topics.

Hence, four changes are proposed:

  1. Change the voting rules for the Appeal Committee, so that only votes in favour or against can be considered for calculating the qualified majority needed to take a decision. Abstentions or absences will amount to “non-participating” Member States. For a vote to be valid, a simple majority of the Member States has to be present.
  2. Further refer the draft act to the Appeal Committee at ministerial level, enabling sensitive issues to be settled at a higher ministerial level.
  3. Make public the vote of individual Member States’ representatives at Appeal Committee level
  4. Foresee the right to refer the matter to the Council for a non-binding opinion, but useful in providing the political orientation of the Union.

This proposal is now to be transmitted to the Parliament and the Council in the ordinary legislative procedure.

Various stakeholders wrote a joint letter to the Commission, arguing that science-based decisions should remain central to the comitology system, and the latter should not be shifted to political decision-making. The comitology procedure should not be used to amend, add or delete political aspects of the text. However, in reality, technical content can sometimes be political (e.g. the definition of Endocrine Disruptors under the REACH Regulation or the approval of glyphosate).

[1] Commission President, Juncker, in his State of the Union speech, February 2017


SFL Newsletter - September 2016
Successful 3rd Medtech & Pharma Platform 2016

The 3rd edition of the annual Medtech & Pharma Platform congress, co-organized by SFL and Medical Cluster, attracted over 220 participants and 35 exhibitors, representing pharma and medtech companies, regulatory agencies, academic organizations, government institutions, service companies and patients’ organizations.

The conference focused on ‘innovative drug-device combinations and diagnostics’ and was generously supported by the Canton Basel City. Dr Engelberger, member of the Executive Council and Head of Public Health Department of the Canton Basel-City, emphasized the importance of cooperation between pharma and medtech companies to better address patients’ needs as well as to maintain a prosperous life-science sector in light of increasing global competition. This is also in the utmost interest of Basel-City as a world-leading life science hub.

The platform’s utility in uniting several companies and stakeholders in the life-science sector is highlighted by over 200 pre-booked 1-on-1 partnering meetings and numerous stimulating discussions during the conference. As a result, the platform has become a successful method in fostering cross-sector cooperation.

The various sessions covered the latest developments in ‘cooperation between Medtech & Pharma’, the ‘new EU Medical Devices Regulation’, ‘Companion Diagnostics’, the ‘view of Regulatory Agencies’, ‘e-Health’, and ‘m-Health’. As a hallmark for all companies that develop or produce medical devices in Switzerland, Ms. Cordula Landgraf from Swissmedic described the implementation of the new EU Medical Devices Regulation into Swiss law. As an insight from within the EU, Mrs. Elizabeth Baker from the UK MHRA explained her agency’s approach to harmonizing regulations on combination products. SFL as co-organizer of the event is glad that representatives also from the Austrian and Belgian Competent Authorities accepted the invitation to detail their experiences in assessing combination products, notably for clinical trials.

During her closing speech, Ms. Shayesteh Fürst-Ladani, CEO of SFL, emphasized the importance for medtech and pharma industries to work hand in hand in order to foster innovation. She also announced next year’s event, which will take place on 26-27 October 2017 in Basel.

Update on e-Health and m-Health

Current trends in e- and m-Health were extensively discussed at the 2016 Medtech-Pharma Platform.

The session focused on e-Health and the management of patient data in and outside the Cloud. The speakers emphasized on several occasions the importance to have a patient-centered innovation. The necessity of patient adherence for the success of treatment was also a recurring feature of the discussions.

A session on m-Health and the evolution from healthcare provider to patient-centric care discussed the use of mobile-apps in clinical trials. An additional conferred topic was allowing cloud-based connections between different actors involved in insulin treatment with emphasis on access, simplicity, motivation and support as the drivers of adherence to treatment.

Overall, these presentations and lively panel discussions provided a broad overview of these trending topics, reminding the audience of the challenges ahead while also detailing the solutions already developed.

Insights on the New In-Vitro Diagnostic Regulation

The new In Vitro Diagnostic (IVD) Regulation (IVDR) is expected to be published within the next months in the Official Journal of the EU. The IVDR brings important changes in the regulatory assessment process. As opposed to the current situation, the IVDR requires the involvement of a Notified Body (NB) for IVDs of all risk classes except class A (unless sterile). The IVDR also specifies the involvement of reference laboratories and Competent Authorities, and defines their interactions with NBs during the conformity assessment process as well as for post-marketing activities.

The IVDR requires provision of 'sufficient clinical evidence' supporting the intended purpose of an IVD. Collection and analysis of clinical evidence are described as a continuous process during the product life cycle, requiring a performance evaluation plan and the issuing of performance evaluation reports during the pre-market phase. This process continues in the post-market phase. 

Furthermore, the IVDR includes for first time a definition of companion diagnostics (CDx) and classifies them as class C or D IVDs. Accordingly, CDx must also obtain an opinion by EMA or a national regulatory authority (depending on the assessing agency), in addition to an assessment by a NB. 

In-house tests/lab-developed tests (LDTs) are described in the regulation as an IVD that is manufactured and used within health institutions. These LDTs are exempted from several requirements of the IVDR, except if manufactured on an industrial scale.

Complemented with multiple delegated and implementing acts, the IVDR is expected to apply early 2022 (i.e. 5 years after expected publication early 2017). A complex set of transition rules and exceptions are in place to enable current products to stay on the market for longer than 2022.

A more detailed overview about the IVDR and how it may affect products that are already marketed or in development can be provided by the SFL Team.

Director Drug Safety Appointed at SFL

Ms. Sam Temple-Scotton joined SFL as Director of Drug Safety. Sam brings many years of experience in the implementation of both Vigilance and Pharmacovigilance (PV) systems for pharmaceutical and medical device product portfolios. Having held the role of EU Qualified Person for Pharmacovigilance (EU QPPV), Sam has been involved with the development of the PV System Master File (PSMF), and systems oversight to support the requirements of the Pharmacovigilance Regulation. She has also developed subject matter expertise in a number of specialist PV areas, including the PV requirements related to digital and social media, inspection and CAPA management and data integration after merger and acquisition.

Sam’s appointment coupled with the multidisciplinary nature of the established SFL Team fosters SFL’s full PV systems support, including QPPV services, implementation and development of the PSMF, inspection support, audit and gap analysis and training. Moreover, strong in-house medical writing expertise means that SFL can also cover individual outsourced projects, such as writing of periodic safety reports (PADER, PBRER) and the development of Risk Management Plans.

Expansion of Regulatory Affairs at SFL

Ms. Beatrice Oberle-Rolle joined SFL as Director of Regulatory Affairs for early development projects. Together with Ms. Serena Baldissera, Director Regulatory Affairs for lifecycle projects, the SFL regulatory team uses a multidisciplinary approach to provide state-of-the-art, innovative and customized regulatory solutions for our clients. These solutions range from regulatory strategy and advice on the development of healthcare products, to hands-on operational support during product registration and post-marketing activities for drugs, devices, IVDs, combination products and ATMPs in various therapeutic areas.

In Switzerland, our Swissmedic establishment license allows SFL to act as applicant for MAA filings on clients' behalf, to ensure regulatory success.

The team’s regulatory experience covers the EU, Switzerland, Japan, US and Canada as well as other global regions such as APAC, MENA and LATAM, allowing us to offer regulatory solutions tailored to our clients' needs.

Upcoming Training Courses

The next training courses organized by the Medtech-Pharma Platform will take place at SFL offices in November 2016:

  • 'An overview of the current MDD and future MDR requirements'
    14 November 2016
  • 'An overview of the current IVDD and future IVDR requirements'
    15 November 2016

These training courses will provide a comprehensive overview to the current regulatory system and requirements in Europe, regarding medical devices and in vitro diagnostics, from a current and future regulatory perspective.

More information on the trainings and the registration process are detailed on the flyer.


Devices – EU Regulations: what you need to know

On 15 June 2016, the Council's Permanent Representatives Committee endorsed the agreement reached with the European Parliament on 25 May on the new medical devices and in vitro diagnostics (IVDs) regulations. The regulations introduce new requirements and stakeholders such as:

  • Subjecting some high-risk devices such as Class III and implants to additional checks by an expert group (Medical Device Coordination Group (MDCG))
  • Conducting risk-based classification of IVDs from A (lowest risk) to D (highest risk), where Notified Bodies will need to perform conformity assessment for all IVDs except for Class A
  • Introducing a new definition for companion diagnostics (CDx) classified as second highest Class C where involvement of the European Medicines Agency (EMA) or a national competent authority to assess suitability of IVD is required
  • Introducing requirements for drug & device combination products
  • Nominating of a qualified person responsible for compliance with the new regulations
  • Increasing traceability for patients such as implementation of UDI (unique device identification) and implant cards
  • Increasing transparency requirements for publishing clinical trials data in the central EU database within a year after finalization of the trial
  • Broadening and up-classifying devices such as those containing nanomaterial and apheresis machines as Class III medical devices
  • Strengthening the system with tighter controls and surveillance over placing devices/IVDs on the market, including unannounced audits throughout the supply chain
  • Increasing requirements for clinical performance studies for IVDs

The MDR/IVDR are expected to be published in the Official Journal of the European Union by the end of 2016/early 2017 with a three-years transition period for medical devices and five years for IVDs. By the end of these periods, companies will have to comply fully with the new legislation.

To ensure continued marketability of their products, manufacturers will need to receive a reassessment and certification by their chosen Notified Body according to the new rules before the end of the transition period.

It is recommended that companies execute gap analysis, especially if their products will undergo up-classification, to ensure timely conformity assessment slots by the Notified Bodies in light of further consolidations of Notified Bodies which are expected during the transitional period.

The SFL team has extensive knowledge of current and future regulatory frameworks for medical devices, IVDs, CDx and combination products, and supports organizations with impact assessment to ensure compliance with the new requirements.

Rare Diseases – Update from the RDAF Meeting

Experts in field of rare diseases met in April at the meeting of the Rare Disease Action Forum (RDAF) to discuss challenges and opportunities with patient access to diagnosis and treatment for rare diseases in Switzerland. In additio