PRIPREMA KLINIČKE DOKUMENTACIJE ZA MEDICINSKO SREDSTVO U POSTUPKU DOBIJANJA CE ZNAKA. Zoran Spasić, dipl. maš. inž.

Transcription

1 PRIPREMA KLINIČKE DOKUMENTACIJE ZA MEDICINSKO SREDSTVO U POSTUPKU DOBIJANJA CE ZNAKA Zoran Spasić, dipl. maš. inž.

2 2

3 SADRŽAJ Termini i definicije Regulatorni zahtevi Smernice Praktičan pristup 3

4 Priprema kliničke dokumentacije za medicinsko sredstvo u postupku dobijanja CE znaka TERMINI I DEFINICIJE 4

5 TERMINI I DEFINICIJE ISO 13485: clinical evaluation 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 MEDDEV 2.7/1 rev.4 Clinical data: the safety and/or performance information that is generated from the clinical use of a device. Clinical data are sourced from: clinical investigation(s) of the device concerned; or clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated. 5

6 TERMINI I DEFINICIJE MEDDEV 2.7/1 rev.4 Clinical evaluation: a methodologically sound ongoing procedure to collect, appraise and analyse clinical data pertaining to a medical device and to evaluate whether there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer s Instructions for Use. Note: In exceptional cases where an instruction for use is not required, the collection, analysis and assessment are conducted taking into account generally recognised modalities of use. 6

7 Priprema kliničke dokumentacije za medicinsko sredstvo u postupku dobijanja ce znaka REGULATORNI ZAHTEVI 7

8 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX I, ESSENTIAL REQUIREMENTS, I. GENERAL REQUIREMENTS 1. The devices must be designed and manufactured in such a way that, when used under the conditions and for the purposes intended, they will not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their intended use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety. MEDDEV 2.7/1 rev.4 Clinical evaluation: Guide for manufacturers and notified bodies EN ISO 14971:2012 Medical devices application of risk management to medical devices... 8

9 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX I, ESSENTIAL REQUIREMENTS, I. GENERAL REQUIREMENTS 3. The devices must achieve the performances intended by the manufacturer and be designed, manufactured and packaged in such a way that they are suitable for one or more of the functions referred to in Article 1 (2) (a), as specified by the manufacturer. Article 1, Definitions, scope For the purposes of this Directive, the following definitions shall apply: (a) medical device means any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of: diagnosis, prevention, monitoring, treatment or alleviation of disease, diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap, investigation, replacement or modification of the anatomy or of a physiological process, control of conception, and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means; 9

10 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX I, ESSENTIAL REQUIREMENTS, I. GENERAL REQUIREMENTS 6. Any undesirable side-effect must constitute an acceptable risk when weighed against the performances intended. MEDDEV 2.7/1 rev.4 Clinical evaluation: Guide for manufacturers and notified bodies EN ISO 14971:2012 Medical devices application of risk management to medical devices 6a. Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex X. 10

11 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX X, CLINICAL EVALUATION, I. GENERAL PROVISIONS As a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in Sections 1 and 3 of Annex I, under the normal conditions of use of the device, and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio referred to in Section 6 of Annex I, must be based on clinical data. The evaluation of this data, hereinafter referred to as clinical evaluation, where appropriate taking account of any relevant harmonised standards, must follow a defined and methodologically sound procedure based on:... 11

12 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX X, CLINICAL EVALUATION, I. GENERAL PROVISIONS Either a critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where: there is demonstration of equivalence of the device to the device to which the data relates, and the data adequately demonstrate compliance with the relevant essential requirements Or a critical evaluation of the results of all clinical investigations made Or a critical evaluation of the combined clinical data provided in and

13 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX X, CLINICAL EVALUATION, I. GENERAL PROVISIONS b The clinical evaluation and its outcome shall be documented. This documentation shall be included and/or fully referenced in the technical documentation of the device. Recommendation NB-MED/2.5.1/Rec5 Technical documentation 1.1c The clinical evaluation and its documentation must be actively updated with data obtained from the postmarket surveillance Where post-market clinical follow-up as part of the post-market surveillance plan for the device is not deemed necessary, this must be duly justified and documented. NB-MED/2.12/Rec1 Post-Marketing Surveillance (PMS) MEDDEV 2.12/2 rev2, Post Market Clinical Follow-Up Studies - A Guide for Manufacturers and Notified Bodies... 13

14 REGULATORNI ZAHTEVI 93/42/EEC, ANNEX X, CLINICAL EVALUATION, I. GENERAL PROVISIONS d Where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended and the claims of the manufacturer. Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated

15 Priprema kliničke dokumentacije za medicinsko sredstvo u postupku dobijanja ce znaka SMERNICE 15

16 SMERNICE MEDDEV 2.7/1 rev.4 Clinical evaluation: Guide for manufacturers and notified bodies Effective date 06/ pages Recommendation NB-MED/2.7/Rec3 Evaluation of clinical data... Warning!!! Effective date 29/03/2010 Recommendation NB-MED/2.12/Rec1 Post-Marketing Surveillance (PMS)... itd. Warning!!! Effective date 29/03/

17 SMERNICE MEDDEV 2.7/1 REV.4 CONTENTS 1. Introduction 2. Scope 3. References 4. Definitions 5. Abbreviations 6. General principles of clinical evaluation 6.1. What is clinical evaluation? 6.2. When is clinical evaluation undertaken and why is it important? Clinical evaluation undertaken for the development of a medical device Clinical evaluation for initial CE-marking Updating the clinical evaluation 6.3. How is a clinical evaluation performed? 6.4. Who should perform the clinical evaluation? 17

18 SMERNICE MEDDEV 2.7/1 REV.4 CONTENTS Contd. 7. Definition of the scope of the clinical evaluation (Stage 0) 8. Identification of pertinent data (Stage 1) 8.1. Data generated and held by the manufacturer 8.2. Data retrieved from literature 9. Appraisal of pertinent data (Stage 2) 9.1. General considerations 9.2. The appraisal plan 9.3. Conduct of the appraisal How to evaluate methodological quality and scientific validity How to determine the relevance of a data set for the clinical evaluation How to weight the contribution of each data set 10. Analysis of the clinical data (Stage 3) General considerations Specific considerations Where demonstration of conformity based on clinical data is not deemed appropriate 18

19 SMERNICE MEDDEV 2.7/1 REV.4 CONTENTS Contd. Appendices. A1. Demonstration of equivalence A2. When should additional clinical investigations be carried out? A3. Device description - typical contents A4. Sources of literature A5. Literature search and literature review protocol, key elements A5.1. Background to the literature search and the literature review A5.2. Objective A5.3. Methods A6. Appraisal of clinical data - examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety A7. Analysis of the clinical data - compliance to specific Essential Requirements A7.1. Conformity assessment with requirement on safety (MDD ER1 / AIMDD ER1) A7.2. Conformity assessment with requirement on acceptable benefit/risk profile (MDD ER1 / AIMDD ER1) A7.3. Conformity assessment with requirement on performance (MDD ER3 / AIMDD ER2) A7.4. Conformity assessment with requirement on acceptability of undesirable side-effects (MDD ER6 / AIMDD ER5) 19

20 SMERNICE MEDDEV 2.7/1 REV.4 CONTENTS Contd. Appendices. A8. Devices for unmet medical needs - aspects to consider A9. Clinical evaluation report - proposed table of contents, examples of contents A10. Proposed checklist for the release of the clinical evaluation report A11. Information on declarations of interests A12. Activities of notified bodies A12.1. Notified body assessment of clinical evaluation by conformity assessment route A12.2. Examination of a design dossier (Annex II.4; Annex 2.4) or of a type examination dossier (Annex III; Annex 3) A12.3. Evaluation as part of quality system related procedures A12.4. Notified body specific procedures and expertise 20

21 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT Can the report be read and understood by a third party, does it provide sufficient detail for understanding the data that are available, all assumptions made and all conclusions reached? Kratko, jasno, nedvosmisleno! If clinical data have been generated and are held by the manufacturer, are all data mentioned and adequately summarised in the report? Izvor(i) podataka! Reklamacije, literatura, kongresi, povratna sprega sa kupcem, regulatorni organi, kontrola kvaliteta, validacije, PMS/PMCF,... 21

22 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT If equivalence is claimed, is demonstration of equivalence included in the report? MEDDEV 2.7/1 rev.4 Annex A1. Demonstration of equivalence does the report disclose all the differences between the device under evaluation and the equivalent device? does it explain why the differences are not expected to affect the clinical performance and clinical safety of the device? If the product is already in the market in Europe or elsewhere, has the latest PMS/ PMCF data been taken into consideration and has it been summarised and referenced in the report? PMS Post Market Surveillance MEDDEV 2.12/2 rev2, Post Market Clinical Follow-Up Studies - A Guide for Manufacturers and Notified Bodies 22

23 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT In respect to current knowledge/ the state of the art, has the report been updated? is current knowledge/ the state of the art summarised in the report and is it adequately substantiated by literature? does the content of the report fully correspond to current knowledge/ the state of the art? does the report explain why the benefit/risk profile and the undesirable side-effects are acceptable in relation to current knowledge/ the state of the art? MEDDEV 2.7/1 rev.4 Clause 8.2 Data retrieved from literature 23

24 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT If the report covers several models/ sizes/ settings and/or different clinical situations, is there sufficient clinical evidence and are the report s conclusions correct for all the devices? all its sizes, models and settings? (including the smallest/ largest size, highest/ lowest dose, etc.) every medical indication? (as described in the IFU/ not excluded with contraindications in the IFU) the entire target population? (from pre term infants to old age, for males and females, etc., if not restricted in the IFU) every form, stage and severity of the medical condition, as applicable?... 24

25 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT all intended users? (including lay persons, if not excluded in the IFU, and any unusual user group) the whole duration of product use, including the maximal number of repeated exposure? (as allowed by the IFU) if there are any discrepancies as to the above, are they identified in the report s conclusions? 25

26 SMERNICE MEDDEV 2.7/1 REV.4 A10. PROPOSED CHECKLIST FOR THE RELEASE OF THE CLINICAL EVALUATION REPORT Is conformity to each of the relevant Essential Requirements (AIMDD ER1,2,5 / MDD ER1,3,6 ) clearly stated and are all discrepancies identified in the report s conclusions? Do the information materials supplied by the manufacturer correspond with the contents of the report and are all discrepancies identified in the report s conclusions? Do the report s conclusions identify all residual risks and uncertainties or unanswered questions that should be addressed with PMS/ PMCF studies? Is the report dated? Is the qualification of the evaluators included in the report and correct? Does the manufacturer hold a CV and declaration of interests of each of the evaluators and are these up-to-date? MEDDEV 2.7/1 rev.4 Annex A11. Information on declarations of interests 26

27 Priprema kliničke dokumentacije za medicinsko sredstvo u postupku dobijanja ce znaka PRAKTIČAN PRISTUP 27

28 PRAKTIČAN PRISTUP... Plan Temeljno proučite 93/42/EEC Essential Requirements, MEDDEV 2.7/1 rev.4,... Formirajte tim Preispitajte analizu rizika, Medical Device File/Technical File/, IfU, promotivne materijale, rezultate PMS/PMCFU, rezultate Literature Screening-a, reklamacije, izveštaje u vezi sa vigilancom,... Do Odgovorite na svaki zahtev......utvrđen u MEDDEV 2.7/1 rev.4 A9. Clinical evaluation report - proposed table of contents, examples of contents na isti način kao kada utvrđujete npr. EN ISO 13485:2016 Poslovnik o kvalitet 28

29 PRAKTIČAN PRISTUP... Check Act Proverite Clinical Evaluation Report koristeći MEDDEV 2.7/1 rev.4 A10. Proposed checklist for the release of the clinical evaluation report kao što biste proverili svaki element npr. EN ISO 13485:2016 Upravljajte dokumentima i izmenama u životnom ciklusu Clinical Evaluation Report Upravljajte komptetntnošću Tima 29

30 30