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.

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.


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 version was 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
    1. One year EMA’s PRIME scheme; progress towards meeting unmet patient needs
    2. MDR/IVDR: a new era for medical technologies
    3. Head of Drug Safety & Pharmacovigilance joins SFL
    4. SFL opens new affiliate in Vienna, Austria
    5. EMA’s new pediatric PK guideline – concept paper open for public consultation
    6. RDAF: Swiss Invalidity Insurance (IV/AI) and rare diseases
    7. Formal Brexit negotiations finally underway but uncertainty for medtech and pharma industries remains
    8. EU chemicals agency decides that bisphenol A (BPA) is a hormone disruptor
    9. The Medtech & Pharma Platform 2017; building bridges between stakeholders in life science

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