Requirements on clinical data in Europe

Transcription

1 Requirements on clinical data in Europe Dr. Bassil Akra Director Global Clinical Affairs TÜV SÜD Product Service

2 Current Medical Device Directives Applicable Directives Active Implantable Medical Devices AIMDD 90/385/EEC accepted: ; adopted: ; end of transition: Medical Devices MDD 93/42/EEC accepted: ; adopted: ; end of transition: In Vitro Diagnostics IVDMDD 98/79/EC accepted: ; published: ; adopted: ; end of transition: TÜV SÜD Product Service Slide 2

3 Where are we heading to? 2007/47EG Rec. 2013/ /2013 MEDDEV MDD AIMD IVDD TÜV SÜD Product Service Slide 3

4 Current Requirements for Clinical Data Dir. 2007/47/EC Which medical devices require a clinical evaluation? ALL Medical Devices regardless of Classification Annex I: Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex X One focus of the new regulations will be clinical evaluation TÜV SÜD Product Service Slide 4

5 Clinical Evaluation according to current MEDDEV Rev. 3 Clinical Evaluation The assessment and analysis of clinical data pertaining to a medical device to verify the clinical safety and performance of the device when used as intended by the manufacturer. TÜV SÜD Product Service Slide 5

6 EU Regulations Proposal Clinical Evaluation Article 4: Placing on the market and putting into service A device shall meet the general safety and performance requirements which apply to it, taking into account its intended purpose. Demonstration of conformity with the general safety and performance requirements shall include a clinical evaluation in accordance with Artilce 49. TÜV SÜD Product Service Slide 6

7 Current Requirements for Clinical Data Dir. 2007/47/EC - CLINICAL DATA The safety and/or performance information that is generated from the use of a device SOURCE OF CLINICAL DATA Studies reported in scientific literature of a similar device (EQUIVALENCY) Published and/or unpublished reports Clinical investigation(s) of the device concerned TÜV SÜD Product Service Slide 7

8 EU Regulations Proposal Clinical Evaluation Article 49: Clinical Evaluation Manufacturers shall conduct a clinical evaluation in accordance with the principles set out in this Article and Part A of Annex XIII. A clinical evaluation shall follow a defined and methodologically sound procedure based on either of the following: A critical evaluation of the relevant scientific literature A critical evaluation of the results of all clinical investigations A critical evaluation of the combined clinical data TÜV SÜD Product Service Slide 8

9 Equivalence Approach based on current available literature Same intended use (Clinical condition/disease, Severity, Application Site, Patient Population, Critical Performance Parameter) + Technical and biological equivalence + No clinically significant difference regarding safety and performance TÜV SÜD Product Service Slide 9

10 Clinical Evaluation Example 1 Which route should you follow for the device under consideration? New Device Example of available competitors TÜV SÜD Product Service Slide 10

11 Clinical Evaluation Example 2 Which route should you follow for the device under consideration? A New Device B Example of available competitors TÜV SÜD Product Service Slide 11

12 Clinical Evaluation RISK MANAGEMENT PROCESS Which route should you follow for the device under consideration? IDEA RISK IDENTIFICATION METHODS RISK MITIGATION METHODS RESIDUAL RISKS ACCEPTABILITY TÜV SÜD Product Service Slide 12

13 Clinical Evaluation according to MEDDEV Rev. 3 Determination of Scope Stage 1 Identification of Clinical Data Generate additional clinical Data NO Clinical Evaluation Report YES Stage 2 Appraisal of individual data sets Sufficient? Stage 3 Analysis of relevant data TÜV SÜD Product Service Slide 13

14 Clinical Investigation Route MEDDEV 2.7/4 When should a clinical investigation be undertaken? Decision Tree General Classification Rules Class III Implants, Most Cardiovascular Devices Class IIb Energy/Substance Delivering, Ionizing Radiation Emitting, Long Term Surgically Invasive Devices Class IIa Most Active & Short Term Surgically Invasive Class I Wheelchairs, Surgical Instruments TÜV SÜD Product Service Slide 14

15 Current Clinical Investigation Route Requirements MEDDEV 2.7/4 When should a clinical investigation be undertaken? The Conformity Assessment process for active implantable medical devices as well as for class III and implantable medical devices requires that a clinical investigation is undertaken unless it is duly justified to rely on existing data. Section 1.2 of Annex 7 of directive 90/385/EEC Section I.1a of Annex X of directive 93/42/EEC TÜV SÜD Product Service Slide 15

16 Current Clinical Investigation Route Requirements MEDDEV 2.7/4 When should a clinical investigation be undertaken? Depending on clinical claims, risk management outcome and on the results of the clinical evaluation, clinical investigations may also have to be performed for nonimplantable medical devices of classes I, IIa and IIb. Additional clinical investigations may be feasible to corroborate the existing clinical evidence with regard to aspects of clinical performance, safety, benefit/risk-ratio or to determine relative effectiveness and safety with suitable comparators. TÜV SÜD Product Service Slide 16

17 EU Regulations Proposal Clinical Investigations Requirements Preamble (46) in the proposed regulation Clinical data of Class III medical devices and Implantable medical devices should be, as a general rule, based on clinical investigations to be carried out under the responsibility of a sponsor. Preamble (47) in the proposed regulation Clinical investigations in line with major international guidance in this field, such as the international standard ISO 14155:2011. TÜV SÜD Product Service Slide 17

18 Clinical Investigation Route Clinical Investigation Sponsor Favorable opinion of ethics committee Investigation site CIP Annex A normative Insurance CIB Annex B normative Informed consent form Qualified investigators Approval of Competent Authority TÜV SÜD Product Service Slide 18

19 EU Regulations Proposal - Clinical Investigations Requirements Preamble (48) in the proposed regulation An electronic system should be set up at Union level to ensure that every clinical investigation is registered in a publicly accessible database. No personal data of subjects participating in a clinical investigation should be recorded in the electronic system. Preamble (51) in the proposed regulation This Regulation should only cover clinical investigations which pursue regulatory purposes laid down in this Regulation. TÜV SÜD Product Service Slide 19

20 Already there Three Annexes: I. Product Assessment II. Quality System Assessment III. Unannounced Audit TÜV SÜD Product Service Slide 20

21 Annex I Product assessment Notified Bodies should: Review All relevant preclinical data Clinical evaluation Post-market clinical follow-up undertaken or planned Verify the clinical evaluation is up-to-date Assess the need for and appropriateness of a post- market clinical follow-up plan TÜV SÜD Product Service April 2014 Slide 21

22 EU Regulations Proposal - Resource Requirements Manufacturers have to perform qualified clinical evaluations Designating authorities have to employ qualified staff Notified Bodies have to employ qualified staff TÜV SÜD Product Service Slide 22

23 EU Regulations Proposal - Resource Requirements At all times and for each conformity assessment procedure and each kind or category of products in relation to which it has been notified, a notified body shall have within its organization the necessary administrative, technical and scientific personnel with technical knowledge and sufficient appropriate experience relating to medical devices and the corresponding technologies to perform the conformity assessment tasks, including the assessment of clinical data. TÜV SÜD Product Service Slide 23

24 EU Regulations Proposal - Resource Requirements Medical Science Neurology Electrical Engineering Chemical Engineering Radiology Add value by know-how Cardiology Biological Science Computer Science Environmental Science Surgery Orthopedic Mechanical Engineering General Medicine TÜV SÜD Product Service Slide Slide 24 24

25 EU Regulations Proposal - Resource Requirements Notified bodies shall have available personnel with clinical expertise. This personnel shall be integrated in the notified body s decision-making process in a steady way in order to: Identify when specialist input is required Appropriately train external clinical experts Be able to discuss and challenge the clinical data contained in the CER Be able to ascertain the comparability and consistency of the clinical Assessments conducted by clinical experts Be able to make an objective judgment TÜV SÜD Product Service April 2014 New Clinical Data Requirements in the EU Slide 25

26 PMCF Requirements according to current MEDDEV 2.12/2 Rev. 2 Why PMCF? Rare complications or problems become apparent after wide-spread or long term use of the device An appropriate PMS Plan is key to identifying and investigating residual risks associated with the use of medical devices placed on the market To confirm the safety and performance throughout the expected lifetime of the device, the continued acceptability of identified risks and to detect emerging risks on the basis of factual evidence TÜV SÜD Product Service Slide 26

27 PMCF Requirements according to current MEDDEV 2.12/2 Rev. 2 PMCF is mandatory per example, for: Innovative Products Significant changes High product related risks High risk anatomical locations/target populations Emergence of new information on safety or performance Where CE marking was based on equivalence Unanswered questions of long-term safety and performance TÜV SÜD Product Service Slide 27

28 EU Regulations Proposal PMCF Requirements Why PMCF? To confirm the safety and performance throughout the expected lifetime of the device, the continued acceptability of identified risks and to detect emerging risks on the basis of factual evidence Systematic registries for Class IIb and Class III devices TÜV SÜD Product Service Slide 28

29 EU Regulations Proposal Scrutiny Procedure Proposal Commission Proposed Scrutiny Procedure (Article 44, Page 66) Medical Devices Directives revision proposal Consider Manufacturer Submission Notified Body Notified Body Review Notified Body Prereport Notified Body Approval Board CE Commission Scrutiny? Scrutiny Start Medical Devices Coordination Group MDCG T= 28 Days MDCG final comment MDCG Scrutiny T= 60 Days TÜV SÜD Product Service Slide 29

30 EU Regulations Proposal Scrutiny Procedure Proposal Parliament Manufacturer Submission SNB SNB Evaluation SNB Approval Board CE Follow Commission Scrutiny? MDCG T= 20 Days If scrutiny Opinion Appeal procedure Evaluation of CER, PMCF and other relevant doc T= 30 Days* *Clock Stop System TÜV SÜD Product Service Slide 30

31 Summary: what to expect in the future? Involve external clinical experts if deemed necessary Challenge the comparability and consistency of the clinical data Notified bodies will Discuss and challenge the clinical data contained in the CER TÜV SÜD Product Service New Clinical Data Requirements in the EU Slide 31

32 Questions? Dr. Bassil Akra Director - Global Clinical Affairs For enquiries, me at: bassil.akra@tuev-sued.de Global website: Stay informed and updated with our Healthcare & Medical Device newsletter: TÜV TÜV SÜD SÜD Product Service Lighting Services Slide 32