Introduction: EU Commission working with clinicians

1. Clinical Evaluation Requirements from Notified Bodies are increasing!Dr. John O Dwyer Sept 13th 2012john.odwyer@nsai.ie

2. Introduction:EU Commission working with clinicians • RECAST & the PIP and metal on metal sagas has expedited the need for more clinician involvement. • Existing drafts of new legislation encourage more clinical stakeholder involvement. • Clinical Investigation Working Group (CIE) is interested in how clinicians report registries & monitor vigilance trends • Clinician input into guidance documents recommended re clinical safety data & specific guidance into clinical risks

3. Introduction:EU Commission working with clinicians • Cooperation with clinical societies, patients groups & other stakeholders (e.g. cardiology, arthroplasty registers, Joint Actions; Best practice) • Increasing clinical expertise and scientific knowledge with regulation of cardiology devices • Opportunity also to share with clinicians the NEW MED device regulatory framework • Desire for Vigilance incl. PMCF & registries to be shared with clinicians for their comments.

4. EU Commission working with clinicians EU Society of Cardiologists: • Very interested in med device regulation • Large network involving 1600 cardiologists. • 53 member countries with strong international collaborations & Links with FDA • 5 large sub-specialities: & Transparency is essential. • Angioplasty, electrophysiology, heart failure, imaging devices • Desire to be more involved in regulating high risk devices, PMS, registries and common databases

5. EUDAMED Clinical Investigation Module • Draft CI Notification Form (EUDAMED-friendly) • 30 countries have entered data (May 2012) • 300 clinical investigation in systems • Unique protocol number for a clinical investigation especially important for a multi-centre trial

6. RECAST & Clinical Reviews • New definitions on MEDDEVS and GHTF documents • Ref to term ‘state of the art’ in medicine • Proposals to further highlight PMCF importance • Increase transparency in system • Healthcare professionals to get access to final clinical investigation reports. • Summary of safety and performance data available to healthcare professionals • Increasing requirements for clinical reviews

7. RECAST & Clinical Reviews • EU commission to create a Medical advisory board in clinical specialities • Resource requirements of NBs with regard to clinical expertise & competency under review • Competent authority competencies & resources • NB need to have in-house ability to make clinical review decisions > appropriate clinilcal expertise. • Appropriate use of external clinical experts by NBs. • Consistency among NBswith clinical competencies & clinical reviews.

8. CIE group working with Pharma • Discuss with pharma colleagues mutual issues – e.g. parallel reviews • Joint problems with combination products. • Pharma sector is now following a risk based approach. • Opportunity to Discuss ICH and ISO 14155 • Co-operation between medicine agencies and med device regulators. • Increasing clinical review collaborations among all regulatory stakeholders

9. Clinical review requirements increasing • Detailed Critical evaluation required of relevant literature (Equivalence) & clinical studies • Clinical Investigations req’d for high risk devices • Clinical evaluation must be actively updated with Post Market Surveillance (PMS) • Use of MEDDEVs clinical guidance documents

10. Clinical review requirements increasing • Post Market Clinical Follow up (PMCF) - must be justified and documented • Where demonstration of conformity based on clinical data is not deemed appropriate, ER compliance must be through risk management, performance evaluation, bench testing & preclinical evaluation. • PMCF data used to update Clinical Evaluation Report for the product family

11. Quality System Requirements • Procedures ensure suitably qualified persons • Clinical evaluation integration into QMS as continuous process • Procedures for clinical evaluation, investigation & PMS/PMCF • Document control of procedures, reports and qualifications.

12. Clinical Investigations • Strict adherence to ISO 14155 • Clinical Investigation Plan, Protocol, Ethics, investigator responsibilities etc. – clearly identified • Does data adequately comply with ERs • Does data support device lifetime? > PMCF • Is conclusion based on Equivalence? > PMCF

13. Post market Surveillance/ PMCF Clinical Evaluation Conclusion ‘Benefit outweighs risk’ PMCF/PMS Continued evidence of Compliance with ERs New or emerging risks identified Evidence of performance & safety in ‘real world pop’

14. Device amendments & Design Changes • ‘State of the art’ is essential with design • Clinical evaluation must be kept up-to-date to ensure there is recognition of: • ‘State of the art’ • PMS/PMCF data • predicate device performance history • FDA/EU advisory notices etc.

15. Notified Body clinical review competency • Clinical expertise to identify and estimate the clinical risks and benefits associated with the use of the specific device under review • Clinical expertise to recognise whether further input from ‘external’ qualified medical practitioners with practicing experience in the pathology of the condition being treated and alternative treatments? • Qualified staff based on NBOG product category

16. Notified Body clinical review competency • Knowledge & experience in the review of clinical data from literature reviews • Knowledge in design, planning, conduct and interpretation of clinical investigations • Clinical competence ideally per MEDDEVs – ‘knowledgeable in ongoing patient mgt for the intended device under review’

17. Clinical Evaluations Clinical Literature Reviews Clinical Investigations (per Meddev 2.7.1) (per ISO 14155) Clinical Evaluation Report (CER) (per Meddev 2.7.1) > CER incorporates data from both literature review and clinical investigation

18. Clinical Evaluation Report (CER) • CER prepared as per MEDDEV 2.7.1 Rev 3 (2009) • A Dynamic ‘stand alone’ document - for NBs & CAs • Appendix E & F - adhere to with preparing a CER • Competency in preparation & Overview by a clinical expert, knowledgeable in the application of use of the device and the patient management

19. Thank YouDr. John O Dwyer Sept 13th 2012john.odwyer@nsai.iehttp://www.nsaiinc.com/services/MedicalDevice/