New European Rules governing medical devices vigilance and combination products

1. New European Rules governing medical devices vigilance and combination products Lincoln Tsang May 2008

2. Topics • Review of rules governing medical devices sector • Changes made in the new law • New framework governing novel combination products

3. European regulatory landscape • Directives on devices adopted in 1990, 1993 and 1998 constitute the basic regulatory framework to harmonise practices in Member States • Placing on the market is linked to the need to undertake conformity assessment with essential requirements • Risk assessment • Risk management • Risk/benefit analysis • Standards

4. Reviews • Medical Devices Experts Group (June 2002) • Functioning of the Medical Devices Directive • Commission Communication to Council of Ministers and European Parliament (May 2003) • Enhancing the implementation of the New Approach Directives • Commission Communication to Council of Ministers and European Parliament (July 2003) • Medical devices

5. Conclusion of Sector-specific Reviews • The basic framework remains appropriate • Room for improvement in a number of areas, including • Conformity assessment • Proper implementation of provisions on clinical data and quality assurance • Post-market Surveillance • Vigilance • Co-operation between Member States • International dimension

6. What happened during the legislative process? • EP negotiated 141 amendments • definition of single use • proposal from Commission on “reprocessing of devices” • specific labelling requiring for SUD and devices containing DEHP • Council negotiated 90 amendments • 17 out of 23 articles are changed • 9 out of 12 annexes of MDD modified • Mixture of cosmetic changes and substantial major changes • Alignment of AMIDD with MDD

7. Major changes to the regulatory framework • Refinement made: • clinical evaluation • classification and the corresponding conformity assessment • uniform application of rules and demarcation • reclassification issues • principle of design for patient safety

8. Why clinical trials and monitoring? • Failure ex vivo to mimic clinical evaluation • Proof of concept • Modifications • New purpose • User issues • Efficacy • Safety for humans • Pharmacoeconomic considerations

9. An example- treatment of abdominal aortic aneurysms • Design • Stress testing • Fatigue testing X Fractures in vivo X Endoleaks

10. Clinical evaluation • In principle clinical evaluation is necessary for every device • In principle for Class III device and implantable devices a clinical investigation has to be performed • Documentation of clinical evaluation now part of the technical documentation • Notified bodies are required to assess clinical evaluation as part of conformity assessments (subject to classification of the device) • Principles of clinical evaluation clarified

11. Clinical data in new law (amendment made to Annex X) • Information about safety and/or performance generated from use of device • Clinical investigations • Clinical investigations or other studies reported in literature or similar device (where equivalence to the device in question can be demonstrated) • Published and/or unpublished reports on other clinical experience of either the device or similar device

12. Continuous monitoring • Clinical evaluation must be kept up to date • Implementation of post-market clinical follow up (PMCF) as part of PMS unless justification for absence • Exchange of information as regards clinical investigations between CAs • information on approval or non-approvals of clinical studies • information on termination of clinical trials • information on adverse events

13. Essential requirements • Inclusion of design for patient safety • Consideration of • ergonomic features • mental, physical and health conditions of patients and users (home use devices for disabled and elderly patients) • Electronic labelling possible in the future (requires implementation) • Specific labelling requirements for SUD (risks on reuse)

14. Read across to Machinery Directive • Machinery Directive excluded medical devices • Where the relevant hazard exists, devices which are also machinery…must also meet the essential health and safety requirements set out in Annex I of [Machinery Directive] to the extent that those essential health and safety requirements are more specific than MDD • lex specialis applies if Machinery Directive is more specific (moving parts, assembling of devices at point of care)

15. Special labelling requirements • Devices intended to administer and/or remove medicines, body fluids or other substances to or from the body or devices intended for transport or storage of such body fluids or substances contain Phthalates • Devices including treatment of children or pregnant or nursing women, justification for use substances which are classified as carcinogenic, mutagenic or toxic to reproduction in technical documentation and instructions for use residual risks based upon precautionary principle • EP wanted to place prohibition of all dangerous substances

16. Device Vigilance • Most significant • Changes made in amending Directive • basic framework not changed • collect, record, report • Parallel changes made to MEDDEV 2.12-1 (Device Vigilance) • 2.5 years consultation with CAs, Commission, industry and other interested parties • agreed position of best practice in interpretation • definitions • process • GHTF

17. Reporting timescales • Serious public health threat • immediately but not later than 2 calendar days after awareness by the manufacturer • Death or unanticipated serious deterioration in state of health • immediately after the manufacturer established a link between the device and the event but not later than 10 elapsed calendar days following the date of awareness of the event • Immediately means without delay that could not be justified

18. Definitions • Serious deterioration in state of health (expanded) • life threatening illness or deterioration in state of health • permanent impairment of a body function or permanent damage to a body structure • a condition required medical or surgical intervention to prevent • any indirect harm as a consequence of an incorrect diagnostic or IVD test results when used within IFU • foetal distress, foetal death or any congenital abnormality or birth defects • Serious public health threat • any event type resulting in imminent risk of death, serious injury, or serious illness that may require prompt remedial action

19. Field safety corrective action • Replaced definition for recall • action taken by manufacturer to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device already on the market • action notified via a field safety notice • In assessing need for FSCA, use methodology described in harmonised standard EN ISO 14971 last edition

20. FSCA • Return of device to supplier • Device modification • Device exchange • Device destruction • Retrofit by purchaser of manufacturer’s modification or design change • Advice given by manufacturer regarding use of the device

21. Exemption rules • Previous exemption rules 1-6 replaced by “conditions where under the vigilance system a report is usually not required”. • Summary reporting might be allowed for incidents described in FSNs and for common and well documented incidents (cfr old exemption rules 7 & 8)

22. Enforcement • National competence • effective • dissuasive • proportionate • Co-ordination and centralisation of information exchange • May be based upon consumer protection and/or general product safety regulation

23. Challenges ahead: ancillary component to a device • Novel drug/device combination products • EMEA guidance on quality, safety and effectiveness of medicinal substance • Advanced therapy medicinal products • gene therapy • cell therapy • tissue engineered • specific risk management guidance