LOOKING FOR CLARITYIN A CHANGING ENVIRONMENT

TO ENSURE COMPLIANCE

INDUSTRY PERSPECTIVE

ANNEKE HURKENSSR DIRECTOR CORPORATE CLINICAL QUALITY & COMPLIANCE

MANON GIELKENSSR REGULATORY AFFAIRS SPECIALIST

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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

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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

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BAKKEN RESEARCH CENTER (BRC)MAASTRICHT, THE NETHERLANDS

2018

New created Center of Excellence inVALUE-BASED HEALTHCARE

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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

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COMPLEXITY WHEN GOING ACROSS THE BORDER

Imagine the complexity for Global Clinical Trials ………

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GLOBAL TRIALS: MULTIPLE REVIEWS BY MULTIPLE REGIONSWITH EACH THEIR OWN FOCUS AREA

Authorities

Ethical reviewbodies

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STANDARDIZATIONTO FACILITATE COMPLIANT GLOBAL RESEARCH AND GLOBAL ACCEPTANCE OF WORLDWIDE DATA

Patient Safety Scientific Soundness Data Integrity

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

Standards and Regulations 12

“Standardization is the process to develop agreements among stakeholders on specific aspects of a product, service or process”

ISO:"International Organization for Standardization."

Standards and Regulations 13

• Industry• Associations• Public administrations• Academia• Societal organizations• Certification bodies

Main stakeholders

Representatives of Ethics Committees are relevant stakeholders for the NEN/NC 301085 Clinical Investigation

Standards and Regulations 14

ISO 14155ICH – GCP

US FDA regulations

Japan GCPs

IMDRF

EU MDRChina FDA

Standards and Regulations 15

HIGH LEVEL OVERVIEW OF

CHANGES COMPARED TO 2011 VERSION

Summary of main revisions

Standards and Regulations 17

Structure of ISO/DIS 14155:2018 Light blue boxes are new sections

Summary of GCP principles

Standards and Regulations 18

• Added on request of several Asian countries

• Principles were originally spread throughout the ISO standard in several clauses

• Facilitate cross-reference in national regulationto “GCP principles”

Annex G –Ethics Committee responsibilities

Standards and Regulations 19

ANNEX GThe 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 outlinedin 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).

5.8 – Informed Consent

Standards and Regulations 20

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;

Elements specific for medical device trials

THE IMPACT OF THE GDPR FOR GLOBAL TRIALS

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ALGEMENE VERORDENING GEGEVENSBESCHERMINGGENERAL DATA PROTECTION REGULATION

§ Eén Europese regelgeving in plaats van 28 verschillende wetgevingen.

§ Maar 28 verschillende interpretaties van de wetgeving wat betreft het PatientInformed Consent document

§ + verschillende interpretaties per localeEthische Commissie

CHANGES WITH THE MEDICAL DEVICE REGULATION

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EU MEDICAL DEVICE REGULATION (EU) 2017/745AANLEIDING

http://www.dailymail.co.uk/health/article-2117368/I-warned-dangers-metal-hips-15-YEARS-ago-A-whistleblower-reveals-real-scandal-danger-joints.html

http://www.theguardian.com/world/2012/jan/14/pip-implants-scandal-march-replacements

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EU MEDICAL DEVICE REGULATION (EU) 2017/745TEXT PUBLISHED MAY 05, 2017

101 Recitals (MDD: 22 Recitals)123 Articles (MDD: 23 Articles) 17 Annexes (MDD: 12 Annexes)

Chapter I Scope and definitions Article 1 Subject matter and scope

1. This Regulation lays down rules concerning the placing on themarket, making available on the market or putting into service ofmedical devices for human use and accessories for such devices in theUnion. This Regulation also applies to clinical investigations concerningsuch medical devices and accessories conducted in the Union.2. This Regulation shall also apply, as from the date of application ofcommon specifications adopted pursuant to Article 9, to the groups ofproducts without an intended medical purpose that are listed in AnnexXVI, taking into account the state of the art, and in particular existingharmonized standards for analogous devices with a medical purpose,based on similar technology.

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MEDICAL DEVICE REGULATION (EU) 2017/745VERANDERINGEN VOOR STUDIES

New key provisions:1. EU legal representative of sponsor is required if located outside EU2. CA notification for post-market interventional studies3. Optional single study application for studies conducted in several Member States4. At least 1 lay person for EC review

Study ConductI. Clear timelines for clinical application assessment by CAs

a. Pre-market: up to 120-day review (worst-case scenario)

b. Post-market interventional: 30-day notification timeline

II. Clear timelines and process for closure notification and final reporta. 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 reportinga. 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)

EU MEDICAL DEVICE REGULATION (EU) 2017/745WANNEER EEN STUDIE

Klinischeevaluatie

KlasseIII en

implan-taten Nieuwe

therapieof tech-nologie

Nieuwedesign

features

Nieuwedoel-

einden

Nieuwepopula-

tie

Nieuweclaims (S/P)

Nieuwerisico’s

* Zie Artikel 61 en bijlage XIV

Uitzonderingen

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CONNECTIE TUSSEN PROCESSEN: KLINISCH ONDERZOEK EN KLINISCHE EVALUATIE

= Clinical Investigation

= Clinical Evaluation Process

= Risk Management process

= Output deliverables

PROCEDURE EN TIJDSLIJN

AanvraagEudamed

Besluit

NOTIFICATIE TOESTEMMING10 DAGEN (+5) 45 DAGEN (+20 voor raadpleging deskundigen)

= Valideringsdatum (als positief advies van EC) = toestemmingonderzoek IIA, IIB

10 DAGEN (+20)

Onderzoek niet ondertoepassingsgebied/ onvolledig

Sponsor dient opmerkingen in /vult documentatieaan

Acceptatie (5 dagen (+5))

Lidstaat & sponsor geen overeenstemming => aanvraag verworpen

Opmerkingen sponsor niet op tijd => aanvraag vervallen

MEDICAL DEVICE REGULATION (EU) 2017/745

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.

ROL VAN DE ETHISCHE COMMISSIE BIJ DE BEOORDELING

DE STAND VAN ZAKEN

CLARITY: DUIDELIJKHEID IN TAKEN ENVERANTWOORDELIJKHEDEN

CONCLUSION

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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

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