LOOKING FOR CLARITY IN A CHANGING ENVIRONMENT TO ENSURE COMPLIANCE INDUSTRY PERSPECTIVE ANNEKE HURKENS SR DIRECTOR CORPORATE CLINICAL QUALITY & COMPLIANCE MANON GIELKENS SR REGULATORY AFFAIRS SPECIALIST
CONTENT Introduction Upcoming revision of ISO 14155 Clinical investigation of medical devices for human subjects Good clinical practice The impact of the GDPR for Global Trials General Data Protection Regulation / Algemene Verordening Gegevensbescherming Changes with the Medical Device Regulation Verordening Medische Hulpmiddelen Conclusion 2
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MEDTRONIC IN THE NETHERLANDS European Operations Center (EOC) - Heerlen International Distribution Center - Heerlen C-Mill, Service & Repair - Heerlen CardioVascular Operations - Kerkrade Medtronic Trading NL B.V. Sales Office Eindhoven Bakken Research Center (BRC) - Maastricht 4
BAKKEN RESEARCH CENTER (BRC) MAASTRICHT, THE NETHERLANDS 2018 New created Center of Excellence in VALUE-BASED HEALTHCARE 5
AN INTERNATIONAL COMPANY CONDUCTING GLOBAL TRIALS Most of our Medtronic clinical research studies are being conducted in multiple countries, with each their own regulation around Clinical Trials 6
COMPLEXITY WHEN GOING ACROSS THE BORDER Imagine the complexity for Global Clinical Trials 7
GLOBAL TRIALS: MULTIPLE REVIEWS BY MULTIPLE REGIONS WITH EACH THEIR OWN FOCUS AREA Authorities Ethical review bodies 8
STANDARDIZATION TO FACILITATE COMPLIANT GLOBAL RESEARCH AND GLOBAL ACCEPTANCE OF WORLDWIDE DATA Patient Safety Scientific Soundness Data Integrity 9
UPCOMING REVISION OF ISO 14155 CLINICAL INVESTIGATION OF MEDICAL DEVICES FOR HUMAN SUBJECTS GOOD CLINICAL PRACTICE
ISO 14155 Revision NEN/NC 301085 Clinical Investigation ISO/TC 194 WG4 Standards and Regulations 11
ISO:"International Organization for Standardization." Standardization is the process to develop agreements among stakeholders on specific aspects of a product, service or process Standards and Regulations 12
Main stakeholders Industry Associations Public administrations Academia Societal organizations Certification bodies Representatives of Ethics Committees are relevant stakeholders for the NEN/NC 301085 Clinical Investigation Standards and Regulations 13
China FDA EU MDR ICH GCP ISO 14155 Japan GCPs IMDRF US FDA regulations Standards and Regulations 14
HIGH LEVEL OVERVIEW OF CHANGES COMPARED TO 2011 VERSION Standards and Regulations 15
Summary of main revisions
Structure of ISO/DIS 14155:2018 Light blue boxes are new sections Standards and Regulations 17
Summary of GCP principles Added on request of several Asian countries Principles were originally spread throughout the ISO standard in several clauses Facilitate cross-reference in national regulation to GCP principles Standards and Regulations 18
Annex G Ethics Committee responsibilities ANNEX G The contents of this annex are intended to provide guidance on best practices for the operation of ECs involved in the review of clinical investigations of medical devices. ECs should also follow the requirements outlined in national or local regulations [see 5.6.1]. 5.6.1 If national or regional EC requirements are less strict than the requirements of this standard, the sponsor shall apply the requirements of this standard to the greatest extent possible, irrespective of any lesser requirements, and shall record such efforts (see Annex G). Standards and Regulations 19
5.8 Informed Consent Elements specific for medical device trials h) Information on the role of sponsor's representative (e.g. monitor, product specialist, field engineer etc.) in the clinical investigation. c 1) description of anticipated adverse device effects; Standards and Regulations 20
THE IMPACT OF THE GDPR FOR GLOBAL TRIALS
ALGEMENE VERORDENING GEGEVENSBESCHERMING GENERAL DATA PROTECTION REGULATION Eén Europese regelgeving in plaats van 28 verschillende wetgevingen. Maar 28 verschillende interpretaties van de wetgeving wat betreft het Patient Informed Consent document + verschillende interpretaties per locale Ethische Commissie 22
CHANGES WITH THE MEDICAL DEVICE REGULATION
EU MEDICAL DEVICE REGULATION (EU) 2017/745 AANLEIDING http://www.theguardian.com/world/2012/jan/14/pip-implants-scandal-march-replacements http://www.dailymail.co.uk/health/article-2117368/i-warned-dangers-metal-hips-15-years-ago-a-whistleblower-reveals-realscandal-danger-joints.html 24
EU MEDICAL DEVICE REGULATION (EU) 2017/745 TEXT PUBLISHED MAY 05, 2017 Chapter I Scope and definitions Article 1 Subject matter and scope 1. This Regulation lays down rules concerning the placing on the market, making available on the market or putting into service of medical devices for human use and accessories for such devices in the Union. This Regulation also applies to clinical investigations concerning such medical devices and accessories conducted in the Union. 2. This Regulation shall also apply, as from the date of application of common specifications adopted pursuant to Article 9, to the groups of products without an intended medical purpose that are listed in Annex XVI, taking into account the state of the art, and in particular existing harmonized standards for analogous devices with a medical purpose, based on similar technology. 101 Recitals (MDD: 22 Recitals) 123 Articles (MDD: 23 Articles) 17 Annexes (MDD: 12 Annexes) 25
MEDICAL DEVICE REGULATION (EU) 2017/745 VERANDERINGEN VOOR STUDIES New key provisions: 1. EU legal representative of sponsor is required if located outside EU 2. CA notification for post-market interventional studies 3. Optional single study application for studies conducted in several Member States 4. At least 1 lay person for EC review Study Conduct I. Clear timelines for clinical application assessment by CAs a. Pre-market: up to 120-day review (worst-case scenario) II. b. Post-market interventional: 30-day notification timeline Clear timelines and process for closure notification and final report a. Closure notification: within 15-days (24 hours in case of termination/halt on safety grounds) b. Final Report: within 1 year (3 months in case of early termination) accompanied by a Summary Final Report c. Commission shall issue guideline on content and structure of the summary III. SAE reporting a. Pre-market: (potentially) device and/or procedure related SAEs b. Post-market: Vigilance reporting requirements (unless SAE has a causal relationship with investigational procedure in interventional studies) IV. Eudamed database a. CA clinical application, SAE reports, Final Clinical Investigation Report (publicly available) 26
EU MEDICAL DEVICE REGULATION (EU) 2017/745 WANNEER EEN STUDIE Uitzonderingen Nieuwe risico s Nieuwe claims (S/P) Klasse III en implantaten Klinische evaluatie Nieuwe therapie of technologie Nieuwe design features Nieuwe populatie Nieuwe doeleinden * Zie Artikel 61 en bijlage XIV
CONNECTIE TUSSEN PROCESSEN: KLINISCH ONDERZOEK EN KLINISCHE EVALUATIE = Clinical Investigation = Clinical Evaluation Process = Risk Management process = Output deliverables 28
MEDICAL DEVICE REGULATION (EU) 2017/745 PROCEDURE EN TIJDSLIJN Aanvraag Eudamed Besluit = Valideringsdatum (als positief advies van EC) = toestemming onderzoek IIA, IIB 10 DAGEN (+5) 45 DAGEN (+20 voor raadpleging deskundigen) NOTIFICATIE TOESTEMMING Onderzoek niet onder toepassingsgebied/ onvolledig 10 DAGEN (+20) Sponsor dient opmerkingen in /vult documentatie aan Acceptatie (5 dagen (+5)) Lidstaat & sponsor geen overeenstemming => aanvraag verworpen Opmerkingen sponsor niet op tijd => aanvraag vervallen
ROL VAN DE ETHISCHE COMMISSIE BIJ DE BEOORDELING Artikel 62: Klinische onderzoeken worden onderworpen aan een wetenschappelijke en ethische toetsing. De ethische toetsing wordt verricht door een ethische commissie overeenkomstig het nationale recht. De lidstaten zien erop toe dat de procedures voor toetsing door ethische commissies verenigbaar zijn met de procedures in deze verordening voor de beoordeling van de aanvraag tot machtiging voor een klinisch onderzoek.
DE STAND VAN ZAKEN
CLARITY: DUIDELIJKHEID IN TAKEN EN VERANTWOORDELIJKHEDEN
CONCLUSION
HOW TO ACHIEVE CLARITY IN A COMPLEX AND CHANGING ENVIRONMENT TO ENSURE COMPLIANCE Our common goal: Safe products for our patients Standardization / Harmonization: - Importance of NEN work, including all stakeholders - Importance of the acceptance of ISO 14155 standard -Importance of International collaboration Bring clarity in Roles and Responsibilities for all stakeholders. - No duplication of effort and no gaps - Communication /transparency on expectations 34
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