This document outlines the M5 amendment of the EU Directive 93/42/EEC regarding medical devices, detailing the revision, implementation, and key changes, including clinical requirements and technical file sampling. It emphasizes necessary compliance timelines, alterations in document retention, and the need for updated clinical evaluations and post-market surveillance processes. By March 2010, all manufacturers and notified bodies must ensure full adherence to the revised directive.

1. M5 Amendment of EU Directive 93/42/EEC - regulatory update Jan van Lochem – Gert Bos – Suzanne Halliday 5 November 2009 HKTDC Hong Kong International Medical Devices and Supplies Fair 2009 Seminar “Regulatory update on medical devices in Asia and EU” For more information on healthcare standards visit: http://shop.bsigroup.com/healthcarestandards

2. Content 1. Revision of the EU medical device directive 2. Implementation of the revised directive 3. Key changes 4. Changes to clinical requirements 5. Introduction of technical file sampling 6. Impact revision on technical or design dossiers

3. 1. Revision of the EU medical device directive

4. History “The Commission shall, no later than 5 years from the date of implementation…..submit a report .....and if necessary make appropriate proposals” 93/42 Article 11.4 It was decided that the review should: Cover all aspects Be open to all stakeholders

5. Main Findings of Report Directives provide appropriate legal framework and, in general, work well Areas needing improvements: Conformity assessment Designation & control NoBos Clinical data & PMS Member State resources devoted to implementation Most areas of improvement could be addressed by guidance

6. 2. Implementation of the revised directive

7. Timescales for Implementing 2007/47/EC - 5th (M5) amendment of 93/42/EEC http://ec.europa.eu/enterprise/medical_devices/revision_mdd_en.htm MS required to transpose ‘M5’ into National Laws by 21 December 2008 Manufacturers and NoBo may start to implement Directive fully enforced in all MS by 21 March 2010 Manufacturers and Notified Bodies must be in compliance

8. Q&A around amended MDD Do certificates change after 21 March 2010 2007/47 is amending directive, not stand-alone one Existing certificates remain valid; no need to re-issue them on 21 March 2010 No need to refer to M5 or 2007/47 on certificates Do Notified Bodies audit to M5 before March 2010 Raise observations / OFIs rather than non-conformities to cover the additional requirements Show M4 or M5 as audit basis in Notified Body documents and reports

9. Q&A around amended MDD Can Manufacturers use Essential Requirement Checklists including M5 requirements now? Yes; but they must agree with their Notified Body which versions of their procedures are “official” up to 21 March 2010 Is there a requirement to have had an M5 compliance audit before 21 March 2010? No; except where a change in classification requires a different conformity route or additional review by NB After 21 March 2010 all audits must be to 93/42/EEC as amended by 2007/47/EC ie M5

10. State of play certificate changes EC Certificates DO NOT need updating to refer to 2007/47/EC NO assessment required to 2007/47/EC before March 2010 to maintain EC QA Certificates (Annex II, V & VI) NO requirement to review and update EC Design Dossier Examination Certificates before March 2010 NEW certificate needed in some reclassifications Evolving guidance, further clarifications expected before March 2010

11. 3. Key changes

12. Key MDD Changes Software in definition, single use devices defined Classification changes, PPE, MD Alternative labelling (draft directive) Clinical evaluation Single authorized rep Improved communication / Confidentiality Essential requirements Quality system & PMS Techfile sampling

13. Essential requirements ER 6a: - always clinical evaluation ER 7.1: - biophysical modelling introduced ER 7.4: - major rewording combination products ER 7.4: - consultation on changes ER 7.5: - carcinogenic, mutagenic, toxic for reproduction, phthalates (67/548/EEC) ER 12.1a - Validation of software ER 13.3 - Authorized representative ER 13.3 - Single use consistency ER 13.6 - risks re-use IFU, latest revision IFU

14. Impact on QA Assessments - General 2007/47 makes some changes to the assessment under the QA modules, eg: Documentation of control of subcontractors Procedure for clinical evaluation Pro-active post market surveillance BSI already emphasises these points as they are both explicit in ISO 13485 , and active PMS was already identified in ISO 14971 and NB-rec on PMS

15. Impact on QA Assessments - General Surveillance audit focuses more on clinical follow-up data, PMS, update risk management file More audit time expected due to introduction of Technical File sampling class IIa and IIb devices

16. All Annexes Document Retention Times What it Says The manufacturer or his authorised representative must, for a period ending at least five years, and in the case of implantable devices at least 15 years, after the last product has been manufactured, keep (records) at the disposal of the national authorities What it Does Increases document retention time (in line with ISO 13485) Distinguishes implants from other products Appears to be unrelated to product lifetime

17. Confidentiality Not treated as confidential: Name manufacturer / authorized rep Certificate info including issuance, modifications, suspensions, withdrawals

18. 4. Changes to clinical requirements

19. Key MDD Changes – clinical Clearer Definitions (Annex X) Clinical Data – safety / performance data (literature, market information, clinical investigation) Clinical Evaluation – review of any type of clinical data Clinical Investigation – clinical study involving human subjects Clinical Evaluation of Clinical Data is required for CE Marking Alignment with MEDDEV 2.7.1 and ISO 14155

20. Key MDD changes – clinical data

21. Annex X – Clinical Evaluation Clinical evaluation for all medical devices Where demonstration of conformity based on clinical data is not deemed appropriate, compliance to ERs must be justified through risk management output, performance evaluation, bench testing and preclinical evaluation. Reason duly substantiated. For implants and class III medical devices: clinical evaluation unless……. Clinical evaluation in technical file (or full reference) Clinical evaluation and documentation must be actively updated based on PMS data

22. Clinical investigations Data relating to clinical investigation in Europe in European database Any interruption, modification, refusal of clinical investigation in EU member states communicated to other Member States in the EU

23. 5. Introduction of technical file sampling

24. Key MDD changes TF sampling IIa and IIb Devices What it Says For devices in Class IIa the notified body shall assess …… the technical documentation … for at least one representative sample for each device subcategory …. For devices in Class IIb the notified body shall assess ….. The technical documentation … for at least one representative sample for each generic device group … What it Does Sets out different sampling regimes for Class IIa and Class IIb Derived from GMDN terminology (BS EN ISO 15445:2000) GMDN definitions are reproduced in Article 1

25. Key MDD Changes – Definitions ‘device subcategory’ means a set of devices having common areas of intended use or common technology (class IIa) ‘generic device group’ means a set of devices having the same or similar intended uses or commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics (class IIb) Critical for sampling of IIa and IIb technical documentation

26. GMDN – a method of grouping devices

27. Technical Documentation Sampling by Notified Bodies Incorporated in audit plan Notified Bodies, extra audit time Already a MEDDEV 2.10 “requirement” Adds similar sampling under Annex V and VI Defines sampling regimes NBOG Guidance 2009-4 (July 2009) applicable

28. BSI approach to sampling Sampling regimes will be based on rationale agreed with manufacturer BSI objective is to deliver required increased scrutiny in a pragmatic and practical way Class IIa Based on “subcategories” identified in manufacturer scope on certificate Use of NBOG guidance 2009-3 on product categories Class IIb Manufacturer starts from GMDN generic device group definitions BSI, in agreement with manufacturer, rationalises down to representative samples

29. Class IIa – Device subcategory

30. Latest NBOG Guidance on TF sampling, reduced sampling numbers For Class IIb devices: sample of generic device groups, referenced by different GMDN preferred terms, to following plan: Up to 2 groups: a sample from each group Up to 10 groups: a sample from 3 (was 6) of these groups Up to 20 groups: a sample from 5 (was 7) of these groups Up to 30 groups: from 7 (was 8) groups a sample N > 30 groups: from N/10 + 5 groups a sample

31. Sampling –BSI approach Class IIa devices: a sample of each group over a 5 year period. Class IIb devices: determine sample plan for a 5 year period. The Sampling plan updated periodically, at least each 3 years.

32. Depth of Assessment of Technical Files Not full Design Dossier review, but it will cover “essentials” No differentiation between Class IIa and IIb Guidance from NBOG indicates that assessment of each set of technical documentation should consist of review of: classification validity of essential requirements checklist risk management pre-clinical data (studies in animal models, biocompatibility, nanotechnology etc.) clinical data (Note NoBo review as per MEDDEV 2.7.1) declaration of conformity, and other technical documentation based on risk

33. Sampling conclusions Major new requirement for Annex V: involvement NB in review of technical documentation Sampling regime Depth review based on NBOG guidance NBs need to agree sampling regimes with manufacturers as soon as possible Major new requirement for both NoBo and manufacturers

34. 6. Impact revision on technical or design dossiers

35. 2007/47/EC Impact on Technical Documentation Notified Bodies, Manufacturers - Full Compliance Required by 21 March 2010 Transition started December 2008 New ER’s & Clinical Evaluation Requirements Proactive Review of Amendments by Manufacturer Impact on Technical Documentation & DoC Confirmation Amendments Have Been Considered and if Appropriate Addressed By Product or Manufacturers’ Full Scope, as Appropriate

36. Design Examination or Type Examination Certificates Manufacturer updates DoC to reference 2007/47/EC amendments when satisfied that product complies NB will review compliance with modified Directive during Design Dossier renewals / changes and audits after 21 March 2010 Irrespective manufacturer is responsible for ensuring full compliance with 2007/47/EC amendments from 21 March 2010

37. 2007/47/EC Clarifications on Technical Documentation Annex II Technical Documentation A statement indicating whether or not the device is manufactured utilizing tissues of animal origin as referred to in Commission Directive 2003/32/EC Annex II, V & VI Technical Documentation The solutions adopted as referred to in Annex I Section I (2), the preclinical evaluation, the clinical evaluation referred to in Annex X Annex X Confirm that plan for post market clinical follow-up exists and is acted upon and justification for no post market clinical follow-up is documented

38. Summary March 2010 full compliance required No effect on classification? 5 year sampling plans agreed with Notified Body Labelling checked and updated Devices already on the market Devices in stock Updated technical documentation Update declarations of conformity

39. What is next? In June 2008, EC started recast Significant revision of legal framework proposed Converge on global model Harmonize on national differences, reduce fragmentation Strengthen clinical requirements Harmonization quality and oversight Notified Bodies Adapt to new technologies Involve possible EMEA for high risk devices EC preparing next steps, talking to stakeholders

40. Relevant links Website European Commission (new 28 October 2009): http://ec.europa.eu/enterprise/sectors/medicaldevices/index_en.htm Website NBOG: http://www.nbog.eu/

41. For more information on healthcare standards visit: http://shop.bsigroup.com/healthcarestandards

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