Proposed Regulations – NB view

1. Proposed Regulations – NB view Gert Bos Head of Regulatory and Clinical Affairs – BSI President – TEAM-NB gert.bos@bsigroup.com IMDA Quality & Regulatory Forum, 25-10-2012

2. Guide to the Presentation • BSI – slides: • TEAM-NB slides:

3. Legal form • More details captured in Regulation than Directives • combining MDD and AIMDD makes sense • IVDD is not too different………… • Appropriate legal instrument that imposes clear and detailed rules which become applicable in a uniform manner and at the same time throughout the Union • divergent transposition of directives by MS has led to different levels of health and safety protection and created obstacles to the internal market which can only be avoided by a Regulation • important simplification effect allowing economic operators to conduct their business based on one regulatory framework, rather than a 'patchwork' of 27+ national laws • more harmonized implementation on designation, ERs • BUT…. what about approval of clinical trials, market surveillance & enforcement, vigilance actions, detailed instructions to and oversight on NBs…….. • detailed implementing legislation – need for transparent stakeholder involvement

4. Notified Bodies, Certificates and the Regulation • Well described transitioning: • Designations under AIMD, MDD, IVD become void at the date of application of the regulation • EC Certificates issued before the regulation enters into force remain valid until expiration date • EC Certificates issued after the regulation enters into force shall become void two years after the application of the regulation • Certificates against the new regulations can be issued by notified bodies designated under the new regulations before the date of application of the regulation

5. Scope • Ready to assess scope additions – waiting for NBOG codes • Products utilizing non-viable human tissues or cells unless they are covered by the Advanced Therapy Medicinal Products (ATMP) – e.g. syringes prefilled with human collagen • Certain products with no medical purpose, but, similar devices in characteristics and profiles – e.g. non-corrective contact lenses, implants aesthetic purposes • High-risk devices manufactured and used within a single health institution • Must meet the majority of the proposal’s requirements • Genetic tests providing information about the predisposition to a medical condition or a disease and tests providing information to predict treatment response or reactions • Considered as in vitro diagnostic medical devices (e.g. companion diagnostics) • cope Exclusions - no major impact ? • Products containing viable biological substances • Food covered by other EU regulations (slimming products) – devices now excluded from food regulations • EC empowered to confirm regulatory status of product(s) – improvement

6. Reclassifications – no surprises • Provides mechanism to change classification – anticipate future up classification based on ‘media-level’ • Brings AIMD and accessories are class III • Identifies spinal disk replacement implants and implantable devices that contact the spinal column are class III • Devices incorporating nanomaterial are class III • Devices intended for aphaeresis are class III • Devices intended to be ingested, inhaled or administered rectally or vaginally and are wholly or partially absorbed by or dispersed in the human body are class III • New risk-rule based classification system for IVD • GHTF principles; replaces the current Annex II listing of IVD Directive 98/79/EC • Four classes of risk: A (lowest risk), B, C and D (highest risk) • Concept of batch testing clarified

7. Standards and Common Technical Specifications • Presumption of conformity using harmonized standards increased to clearly include process / conformity assessment standards • QMS, risk management, clinical investigation, clinical evaluation and post –market clinical follow-up • Unclear future of harmonization • ……….. • Allows the possibility for the EC to mandate common technical specifications (CTS) • Not too happy with COEN balloon on comparative analysis • Will need coordinated action in transparent way

8. Qualified Person and Authorised Rep – realistic requirements • Manufacturers will be required to have a qualified person available within their organization, who has medical device expertise • Either education requirements plus two years medical device RA / QA experience or five years medical device RA / QA experience • Protected when properly fulfilling responsibilities • Responsibilities include • Statements re clinical investigation devices ER compliance and protection of subjects • Conformity of devices confirmed before batch release • Technical documentation and declarations of conformity are current and maintained • Reporting obligations are met • EU Representatives shall also have qualified person • Expert knowledge of EU medical device regulations • Similar to manufacturer QP qualifications

9. Electronic System on Registration of Devices and Economic Operators • The EC will set up and manage an electronic system • Manufacturers will submit information for the database • Importers will submit information • All changes updated within one week • Accuracy confirmed at least every 24 months (??) • Data shall be publically available • Fees may be collected • Reliability, transparency, IT security, privacy protection, ….

10. Transparency • Summary of Safety and Clinical Performance • For all class III and implantable devices • Submitted to Notified Body for review • Notified Body will validate • Must be understandable by users • More detail vigilance reports centrally available?

11. Notified Bodies • National authorities responsible for notified bodies • Separate from notified bodies • Sufficient resources • Consult with competent authority for medical devices as appropriate • Peer review every two years, Commission invited to participate • Significant new requirements regarding the designation, competence, scope, monitoring and maintenance of notified bodies • Requirement to issue certificates and status in database • Procedure for changing notified bodies • Current notified bodies will need to apply for and achieve designation under the new regulation • National Authority shall notify to the EC, MS and MDCG • Scopes of NB’s will be competence specific

12. Conformity Assessment • Annex VIII Full Quality Assurance • Introduction of a minimum frequency for unannounced visits (taking account of device risks / types) – prevention of hostile environment • Tests to be carried out by notified bodies – sample checks – big debates • Notified body shall rotate the members of the audit team (no more than three years per lead auditor)

13. Scrutiny of Certain Conformity Assessments – ….. to PMA or NOT • Notified bodies shall notify the Commission and MDCG of new applications for class III devices and estimate for certification date • Within 28 days the MDCG may request submission of a preliminary summary • NB 5 days to inform manufacturer • Up to 60 days after receiving the summary to request further information • Within 30 days request further information (stop the clock on 60 days) • Further requests possible • NB shall address concerns received back from the MSCG and justify any CE decisions • Summary and outcome made public • Do authorities have resources? Will they outsource? Quality of review?

14. Unannounced Visits • Notified body shall randomly perform unannounced factory inspections and if appropriate suppliers / subcontractors • Could replace a periodic surveillance assessment ? • Notified body shall establish a plan for unannounced factory inspections which shall not be disclosed to the manufacturer • Within the context of unannounced factory inspections the notified body shall check an adequate sample of devices from production to verify compliance with technical file • Notified body could take samples from the market and verify compliance with technical file

15. Budgetary Implications: Finding the Money – biggest change of all?? • The Commission, the Member States or and the designated EU reference laboratories will charge fees for various activities • The Commission will use implementing acts to set the level and structure of fees • The Commission • Fees for the registration of medical devices in the central database • Fees for the issue of scientific advice provided at the request of a manufacturer or notified body • The Member States • Fees for the designation and monitoring of notified bodies • Transfer a portion to the Commission to finance the 'joint assessments' and the scrutiny mechanism for high risk devices • EU Reference Laboratories • Fees for scientific opinions provided to notified bodies and manufacturers

16. Clinical Evaluation & Clinical Investigation • Regulation combines and incorporates current guidance's on clinical evaluation and clinical investigation • Significant requirements on clinical • General requirements – sponsor responsibilities • Application • Registration • Electronic system • Post market clinical investigation requirements • Substantial modification • Sponsor information obligations regarding suspension / termination • Event reporting

17. TEAM-NB • To improve communications with • the EC Commission, • Industry, • Competent Authorities and • User Groups • To promote high technical and ethical standards • Members are Notified Bodies under any or all of the 3 medical devices directives: • 90/385/EEC - AIMD • 93/42/EEC - MDD • 98/79/EC - IVD

18. Code of Conduct • Mandatory to sign for TEAM-NB members • Available on website • Changes and additions: • Extension to IVD • Unannounced visits • Product Verification • Supervisory Structure • Peer assessment

19. Detailed content CoC V3 • Implementation, enforcement and monitoring of the Code of Conduct • Qualification and Assignment of Notified Body Assessment Personnel • Minimum time for Notified Body assessments • Unannounced visits • Sampling of class IIa and IIb technical files • Design Dossier Reviews • Rules for subcontracting • Rules for Certification Decisions

20. Quality of Notified Body work • Code of Conduct addresses where NBs diverge • Detailed requirements with less room to interpret • Result must be more consistent • Requires consistency in oversight => cross-inspections Integrity Independence Competence Time spent Interpretation Quality

21. Statement towards ‘Daily Telegraph’ • TEAM-NB members are committed to ensure the safety of Medical Devices on the EU market • TEAM-NB members abide by regulatory and ethical aspects by law as well as on voluntary basis • TEAM-NB members agree to be submitted to a strong and harmonized assessment and surveillance system by member states and commission • TEAM-NB members are fully aware of their responsibility to ensure certification of medical devices complies with the Directives

22. For further information