Medical Regulation (Europe) PDF

Chapter 10 Regulation (Europe) Lecture Series: Artificial Organs Content 2 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 4 Declaration of Conformity Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation CNN (2012) 3 Artifici...

Chapter 10 Regulation (Europe) Lecture Series: Artificial Organs Content 2 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 4 Declaration of Conformity Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation CNN (2012) 3 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) – 05.2017: European Parliament and Council Of Europe pass the Regulation (EU) 2017/745 on medical devices (MDR) – Does apply to medical devices and accessories for human use – Does not apply to – Medication – In-vitro diagnostic devices – Cosmetics – Devices with living tissue from human or animals – … 4 Artificial Organs - Regulation (Europe) European Parliament Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) – Medical Device Regulation (MDR) replaces Medical Device Directive (MDD) – MPDG replaces Medizinproduktegesetz (MDG) – All notifed Bodies need to be recertified according to MDR – All medical products need to be recertified according to MDR – Transition period till 05/2024 5 Artificial Organs - Regulation (Europe) Medical Device Regulation (MDR) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 5 6 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 51 and 52 7 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 53 8 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 10 9 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) - Excerpts (Article 10) European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 10 10 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medical Device Regulation (MDR) Medical Device Regulation (MDR) Except Special approval and samples for clinical trials – Medical Device Regulation (MDR) replaces Medical Device Directive (MDD) Every medical product must be conform with the MDR before placing it on the market (CE-mark) – MPDG replaces Medizinproduktegesetz (MDG) Manufacturer defines product, classification and conformity assessment procedure – All notifed Bodies need to be recertified according to MDR Conformity is assessed and certified by a Notified Body according to the chosen procedure (in most procedures) – All medical products need to be recertified according to MDR Manufacturer declares conformity of the product and affix a CE-mark on the product – Transition period till 05/2024 Some specifics are regulated in national laws Medizinprodukterecht Durchführungsgesetz (MPDG) 11 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Content MDR 2017/745 - Chapters – – – – – – – – – – 12 Chapter 1: Scope and definitions Chapter 2: CE marking Chapter 3: Product Traceability Chapter 4: Notified Bodies Chapter 5: Classification & Conformity Chapter 6: Clinical Evaluation Chapter 7: Post-market surveillance Chapter 8: Member State cooperation Chapter 9: Data protection Chapter 10: Final provisions Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Content MDR 2017/745 - Annexes – – – – – – – – – – – – – – – – 13 Annex I: General Requirements Annex II: Technical Documentation Annex III: Post-market surveillance Annex IV: Declaration of Conformity Annex V: CE-marking Annex VI: Registration and UDI Annex VII: Req. for Notified Bodies Annex VIII: Classification rules Annex IX: Conf. Ass. QM & TD Annex X: Conf. Ass. Type Examination Annex XI: Conf. Ass. Product verification Annex XII: Certificates Annex XIII: Custom-made devices Annex XIV: Clinical Evaluation Annex XV: Clinical Investigation Annex XVI & XVII: Other Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Legal Situation Medizinprodukterecht Durchführungsgesetz (MPDG) – BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) is responsible authority in Germany: Surveillance of medical products on the market (Vigilance) Approval and monitoring of clinical trials in Germany – ZLG (Zentralstelle der Länder für Gesundheitsschutz) certifies and monitors Notified Bodies in Germany – Notified Bodies are private enterprises that are certified by ZLG – Currently 36 Notified Bodies in Europe (8 in Germany) are certified for MDR (58 formerly under MDD) Notified Bodies certified for MDR in Germany, as of today 14 Artificial Organs - Regulation (Europe) Content 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 4 Declaration of Conformity 15 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Product Definition & Classification Open Questions: – Is it a Medical Device? European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Article 2 16 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Product Definition & Classification Open Questions: (Article 2) – Is it a Medical Device? – Definition of Intended Purpose, e.g. patient-cohort, duration of application, invasiveness, … European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpt from Article 2 (above) and Annex VIII (below) 17 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Product Definition & Classification Open Questions: – Is it a Medical Device? – Definition of Intended Purpose, e.g. patient-cohort, duration of application, invasiveness, … – Classification of the product (22 rules) in class I, IIa, IIb, or III European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex VIII, Chapter III 18 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Product Definition & Classification Open Questions: – Is it a Medical Device? – Definition of Intended Purpose, e.g. patient-cohort, duration of application, invasiveness, … – Classification of the product (22 rules) in class I, IIa, IIb, or III Class I Wheelchair Stethoscopes Scalpel Surgical clamps Syringe Class IIa CT machine Oxygenators Implantable plates Class IIb Condoms Pacemakers Heart valves Class III Ventricular Assist Devices Risk 19 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Product Definition & Classification Open Questions: – Is it a Medical Device? – Definition of Intended Purpose, e.g. patient-cohort, duration of application, invasiveness, … – Classification of the product (22 rules) in class I, IIa, IIb, or III MDR Annex IX – Definition of Regulatory Strategy (e.g. choosing a Conformity Assessment Procedure, eventually choosing and contacting a Notified Body) Different Regulatory Strategies dependent on product classification Johner Institute 20 Artificial Organs - Regulation (Europe) Content 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 3.1 Quality Management 3.2 Technical Documentation 4 21 Declaration of Conformity Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Conformity Assessment Procedure Procedure according to Annex IX – Assessment procedure based on quality management system and technical documentation – Documented fulfillment of all „General obligations for manufactures“ (Article 10) – Assessment of quality management system by Notified Body – Assessment of technical documentation by Notified Body 22 Artificial Organs - Regulation (Europe) Content 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 3.1 Quality Management 3.2 Technical Documentation 4 23 Declaration of Conformity Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System Definition of Quality Management System – A quality management system (QMS) is a collection of business processes focused on consistently meeting customer requirements and enhancing their satisfaction. Wikipedia – For manufacturer of medical products, a quality management according to DIN EN ISO 13485 is recommended – DIN EN ISO 13485 also includes processes that ensure conformity with MDR DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from Introduction, subchapter 0.3 24 Artificial Organs - Regulation (Europe) ISO 9001 Medical Regulation (Europe) – Quality Management System Comparison: ISO 13485 vs. ISO 9001 – ISO 13485 is based on ISO 9001 – Additional specifics of ISO 13485: – – – – – – Medical device file Cleanliness of product Installation activities (production) Servicing activities Particular requirements for sterile medical devices Particular requirements for validation of processes for sterilization and sterile barrier system DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from Introduction, subchapter 0.4 25 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Content – Foreword – Introduction – – – – – – – – Chapter 1: Scope Chapter 2: Normative references Chapter 3: Terms and definitions Chapter 4: Quality management system Chapter 5: Management responsibility Chapter 6: Resource management Chapter 7: Product realization Chapter 8: Measurement, analysis and improvement – Annex A: Comparison to ISO 9001:2008 – Annex B: Correspondence to ISO 9001:2015 DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from Introduction, subchapter 0.4 26 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 4 27 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 – Main Aspects: Chapter 4 Documentation of the QMS must include: – – – – 28 Documented quality policy and quality objectives A quality manual Documents and Records of all required processes Documents and Records of all processes needed to maintain and improve the QMS Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 5 29 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 5 30 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 – Main Aspects: Chapter 5 Definition of Quality Police and commitment! – – – – – 31 Quality policy is top management responsibility Commitment of top management Quality management representative Training and internal communication Management reviews and internal audits Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 32 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 33 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 34 Artificial Organs - Regulation (Europe) e.g. using the V-Model Medical Regulation (Europe) – Quality Management System Product development – The V-model – A structured process for the development of products. – Example: – URS: A pen that is easy to write with – DRS: The ink flow of the pen shall be 100 - 120 mg/km – Verification: Test reveals ink flow is 107 +/- 4 mg/km – Validation: Test with probands reveal 90% are satisfied with the easiness to write User Requirement Specification (URS) Design Requirement Specification (DRS) Test Test Validation (vs. URS) Verification (vs. DRS) Prototyping A variation of a V-Model for the development of products 35 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 – Main Aspects: Chapter 7 (part 1/2) Plan and document development – – – – – – 36 Customer related requirements (URS) Verification and Validation Documentation of design evolution Documentation of design reviews and decision Traceability of design improvements Design and development file for each product Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 37 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 38 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 39 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 40 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 - Excerpts DIN EN ISO 13485, 2016: Medizinprodukte - Qualitätsmanagementsysteme Anforderungen für regulatorische Zwecke. Excerpt from chapter 7 41 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System DIN EN ISO 13485 – Main Aspects: Chapter 7 (part 2/2) Plan and document development – – – – – – Customer related requirements (URS) Verification and Validation Documentation of design evolution Documentation of design reviews and decision Traceability of design improvements Design and development file for each product – Controlled purchasing with verification of purchased articles and supplier – Control and validation of all production processes with continuously monitoring of the process quality – A production record of every product/batch – Control of all measurement equipment and infrastructure 42 Artificial Organs - Regulation (Europe) Content 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 3.1 Quality Management 3.2 Technical Documentation 4 43 Declaration of Conformity Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex II 44 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex II 45 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex II 46 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex II 47 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 – Technical Documentation (Annex II) Technical Documentation shall contain: – Device Description & Specification – Labels, Packaging, Instructions for Use – Design & Manufacturing Information – General Safety & Performance Requirements – Benefit Risk Analysis & Risk Management – Product Verification & Validation (incl. Clinical Evaluation) European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Chapters of Annex II 48 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 – Excerpts (Risk Management) European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex I 49 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation DIN EN ISO 14971 – Content – Foreword – Introduction – – – – – – – – – – Chapter 1: Scope Chapter 2: Normative references Chapter 3: Terms and definitions Chapter 4: General requirements for risk management system Chapter 5: Risk analysis Chapter 6: Risk evaluation Chapter 7: Risk control Chapter 8: Evaluation of overall residual risk Chapter 9: Risk management review Chapter 10: Production and post-production activities – Annex A: Rationale for requirements – Annex B: Risk management process for medical devices – Annex C: Fundamental risk concepts 50 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation DIN EN ISO 14971 – Risk assessment consists of a risk analysis together with an evaluation of the risk – Risk management is the extension to a risk control and an evaluation of the residual risks. Also insights gained during production and post-production (market surveillance) needs to be taken into account. – Risk management is a living document throughout the entire life-cycle of the product. – For product design as well as for production processes DIN EN ISO 14971, 2019: Medizinprodukte - Anwendung des Risikomanagements auf Medizinprodukte. Figure 1. 51 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation DIN EN ISO 14971 – Hazards need to be identified that can lead to a hazardous situation with a certain probability – A hazardous situation can lead to a harm with a certain probability. – The severity of the harm needs to be estimated – The risk is the combination of occurrence probability and severity of the harm DIN EN ISO 14971, 2019: Medizinprodukte - Anwendung des Risikomanagements auf Medizinprodukte. Annex C, Figure C.1. 52 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation DIN EN ISO 14971 – Hazards need to be identified that can lead to a hazardous situation with a certain probability – A hazardous situation can lead to a harm with a certain probability. – The severity of the harm needs to be estimated – The risk is the combination of occurrence probability and severity of the harm – For risk evaluation, it is practical to classify probability and severity into categories with a previous definition of the acceptable risk Example of categorization of occurrence and severity for risk evaluation Oriel STAT A MATRIX 53 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 – Excerpts (Clinical Evaluation) European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex XV 54 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MPDG – Excerpts (Clinical Evaluation) Bundesrepublik Deutschland (04.2020): Medizinprodukterecht Durchführungsgesetz - MPDG. Excerpts 55 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Quality Management System Necessary documentation for clinical trial (Excerpts) Application to BfArM (Main Aspects): – – – – – – – – – Clinical investigator Plan of clinical trial Product description Pre-clinical evaluation Evaluation of foreseeable risks Insurance of probands Plan for further treatment of probands Risk analysis and evaluation Statement of the Ethic commission Approval of BfArM – Manufacturer has responsibility for corrective measures 56 Artificial Organs - Regulation (Europe) Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) Content 1 Legal Situation 2 Product Definition & Classification 3 Conformity Assessment Procedure 4 Declaration of Conformity 57 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation MDR 2017/745 - Excerpts European Union (05.2017): Medical Device Regulation. MDR, 2017/745 Excerpts from Annex XII 58 Artificial Organs - Regulation (Europe) Medical Regulation (Europe) – Technical Documentation Declaration of Conformity – Notified Body certifies conformity with MDR (according to MDR, Annex XII) – Manufacturer declares conformity (according to MDR, Annex IV) – Manufacture affixes CE-marking (according to MDR, Annex V) Registration number of Notified Body 59 Artificial Organs - Regulation (Europe)