intro to mdr (-the quick version) helene quie, ceo, qmed … · 2020. 6. 11. · ce marking of...

©2019 Qmed Consulting

Intro to MDR (-the quick version)Helene Quie, CEO, Qmed Consulting


Overview of the MDR – Timelines

2018 2019 2020 2021 2022 2023 2024 2025MDR only

MDR only and require MDR compliant QMS

Existing devices with valid MDD certificates Sell out

No new devices until QMS is compliant MDR only

Class I devices except IS and IM

Class IR devices

All other devices

QMS

The grace period

EU MDR DOA26MAY2020

Last MDD certificate

valid26MAY2024

Last MDD product

26MAY2025

NEWEU MDR DOA26MAY2021


Structure of MDR – 10 chapters

• Chapter I (Art. 1-3): Scope and definition• Chapter II (Art. 5-24): Making available on the market and putting into service of

devices, obligations of economic operators, reprocessing, CE marking, free movement• Chapter III (Art. 25-34) Identification and traceability of devices, registration of devices

and of economic operators, summary of safety and clinical performance (SSCP), European database on medical devices

• Chapter IV (Art. 35-50): Notified bodies• Chapter V (Art. 51-60): Classification and conformity assessment, consultations,

scrutiny• Chapter VI (Art. 61-82): Clinical evaluation & clinical investigation• Chapter VII (Art. 83-100): Post-market surveillance (PMS), post market clinical

follow up (PMCF), vigilance, market surveillance, trends, periodic safety update report (PSUR)

• Chapter VIII (Art. 101-108): Cooperation between member states, expert laboratories, medical device coordination group, expert panels, device registers

• Chapter IX (Art. 109-113): Confidentiality, data protection, funding, penalties• Chapter X (Art. 114-123): Final provisions

Overview of the MDR – Structure


General safety &Performance requirements

Technical documentation

Technical documentation

on PMS

EU declaration of conformity

CE marking of conformity

Overview of the MDR – Structure

Information to be submitted upon

registration of devices & economic operators

Requirements to be met by notified bodies

Classification rules

Conformity assessment based on QMS & assessment of TD

Conformity assessment based on type examination

Conformity assessment based on product

conformity verification

Certificates issued by a notified body

Procedure for custom-made device

Clinical evaluation and post-market clinical

follow-up

Clinical investigations

List of groups of products without an

intended medical purpose

Correlation table

I

II

III

VI

V

XV

VII

XVI

XIV

XIII

XVII

XII

XI

X

VIII

VI

IX


What type of processes and documentation do I need to get in place for which type of devices?

Overview

Process and documentation Required for which type of device

Clinical Evaluation Plan (CEP) All devices throughout lifecycle

Clinical Evaluation Report (CER) All devices throughout lifecycle

Incidences, FSCA, FSN, Trends All devices throughout lifecycle

Post-Market Surveillance Plan (PMSP) All devices throughout lifecycle

Post-Market Safety Report (PMSR) Class I devices

Periodic Safety Update Report (PSUR) Class IIa, IIb and III devices, annual or biannually

Summary and Safety Clinical Progress (SSCP) report Class III and implantable devices, annually

Post-Market Clinical Follow-up Plan (PMCFP) Class III and implantable, annual or justification for other devices

Post-Market Clinical Follow Report (PMCFR) Class III and implantable, annual or justification for other devices

Consultation, scrutiny Special processes: Class III, class III implants or class IIb active devices (not needed for legacy devices?)


Equivalence

Are you still allowed to and can you demonstrate equivalence?

According to MEDDEV 2.7/1 rev4 “Clinical data retrieved from literature must be related to a device for which equivalence to the device under evaluation has been demonstrated”

According to MDR “These characteristics shall be similar to such an extent that there would be no clinically significant difference in the clinical performance and safety of the device”, “..be based on proper scientific justification”, “..have sufficient levels of access to the data on devices to which Manufacturer is claiming equivalence..” and “..results are described in CER , which is part of the TD”.

Clinical Equivalence

Technical Equivalence

Biological Equivalence

In case no equivalence can be demonstrated clinical investigations need to be performed


Aims are:• Confirmation of conformity with relevant GSPR under normal condition and intended use of device• the evaluation of the undesired side effects• the evaluation acceptable benefit /risk ratio …(annex I)

shall be based on:• clinical data providing sufficient clinical evidence,• including relevant data of Annex III (PMS/PMCF)

Clinical evaluation

What does Clinical Data

and Sufficient Evidence mean?


Clinical evidence - for discussion

Sufficient Amount

• Intended use• All indications• All target groups• Clinical Claims• Safety• Performance• Contra indication• Device of concern (relevance)• Equivalent device• Statistical evidence, power,

etc.• SOTA• Timeframe

Sufficient Quality

• Type of data sets• Type of investigation/study• Feasibility• Pivotal ….• Case report• Statistical considerations• Statistical evidence, power ,

etc.• Ethical considerations• Quality, Monitoring• Legal/Regulatory

considerations• Actuality of data set - SOTA

ISO 14155


Major elements of PMS and other regular updates


Chapter VI & Annex XV: Clinical Investigation

Clinical Investigation

Consider

Claims

Clinical Risks

ISO 14155:2011

Declaration of Helsinki

Member state

requirement

Eudamed

Single submission


• Verify the performance and clinical safety• Verify intended benefits for the patient,

• when used in intended purpose,• in target population,• in accordance with instruction for use

• Determine undesired side effects• Rights, safety and well being of subjects• Scientifically valid, reliable and robust• Subject to scientific and ethical review (national law)• Protect vulnerable populations• Informed consent required• Sponsor in EU or legal representative in EU• Design, conduct, record & report aspects - Art. 62-81, Annex XV• Requirements for investigator and personnel

Art. 62 - General requirements regarding Clinical Investigations (CI)


Chapter I: General Requirements1. Ethical considerationEvery step in the CI, from- first consideration of the need and- justification of the study- to the publication of the results,shall be carried out in accordance with recognized ethical principles.

Annex XV - Clinical Investigation (CI)

Aspects of EN ISO 14155


Chapter I: General Requirements2. Methods• appropriate plan (CIP) in accordance with the

CEP• reflecting latest scientific and technical

knowledge,• …confirm the manufacturer´s claims regarding

safety, performance and benefit /risk,• adequate number of patients,• design,• statistical methods,• procedures,• research methodologies,• clinical investigation plan (CIP),• technical and functional features,• endpoints,• competence and experience of investigator,• clinical investigation report (CIR)

Annex XV Clinical Investigation (CI)

Before MDR a lot was regulated in

MS level


Chapter II:Documentation regarding the application for Clinical Investigations1. Application form: 17 detailed content and requirements2. Investigator Brochure (IB)3. CIP, Synopsis (see next slide)4. Other information (see next slide)

Annex XV Clinical Investigation (CI)

Compare to Annex of ISO 14155 however, regulation

are mandatory


The CIP should identify and were needed justify at minimum

Protocol content

• Single Identification Number• Sponsor and Principle Investigator,

Qualification and Agreements• Synopsis• Device description, comparator,

comedication• Risk and clinical benefits• Objectives and hypotheses• Study population, number of

subjects• Inclusion/exclusion criteria• Rational and justification of the

chosen study design including use of control groups

• Selection of sites and investigators• Statistical consideration

Protocol content

• Monitoring plan• Data management• Duration of patient follow-up• Data to be collected• Analysis plan• Safety reporting• Procedures/criteria for early study

termination• Ethical considerations, Informed

Consent process• Methods of quality control of data

where appropriate• Amendments• Policy on CIR• Other statements …………..


Consideration for clinical Investigation


Other sponsor’s obligations:• Keep available for the competent national authorities any

documentation necessary to provide evidence for the application• Have an agreement in place to ensure SAE are reported to the

sponsor in a timely manner• Retention of documents 10 years after end of the CI or at least 10

years last device has been placed on market (15 years for implants)• Complete the follow up of investigation subjects• Provide evidence to assure that the investigation is being conducted

in line with Good Clinical Practice e.g. by internal or external auditing/inspection

• Appoint an independent monitor to ensure conduction of the investigation (acc. CIP, GCP)

• Prepare a clinical investigation report (CIR) and Summary (SCIR)

Annex XV Clinical Investigation


There are six aspects to ensure the rights, safety and well being of subjects.

Art. 72 Conduct a Clinical Investigation

Sponsor and the investigator shall ensures: CI is conducted according to CIP

Procedure for Emergency Situation

Member States involvement

Monitoring :Consider: Objectives and methodology

of CI, Deviation of the intervention / normal practice

All CI information: recorded, processed, handled, and

stored as applicable that it can be accurately reported,

interpreted and verified

Technical and organisational measures to protect information and personal data


• Electronic registration of clinical investigation (CI) in EU• Single identification number for CI• Entry pointfor submissions, notification, CIRand Summary of CIR, data processing• Exchange of Information betweenMember States and Commission• Reporting of SAE and product deficiencies• Protection of personal data• Protection of commercial information• Effective supervision of the conduct of CI• No personal data of subjects shall be publicly available

Art. 73 Electronic system on Clinical Investigation (EUDAMED)


In summary how will you see the changes:• Most aspects of MEDDEV 2.7/1 rev 4 and ISO 14155 are integrated in

MDR (reference to MDR instead)• Many other countries accept / expect compliance to ISO 14155 (FDA for

example)• Definition of Sponsor available• Clinical data sourcing and evaluation during life cycle of medical devices

(pre and post-market studies and activites)• Clinical Investigation is a data source of clinicalFor some devices clinical

investigation are expected• Chapter VI and Annex XV for Clinical Investigation (details follow in Part

II)• Coming centralised processes• Increased need for Clinical Data using different methods


Qmed Consulting A/S Ørnevej 2 • 4600 KøgeTEL.: +45 56 64 10 10

Mail: [email protected]

www.qmed-consulting.com

Thank you

intro to mdr (-the quick version) helene quie, ceo, qmed … · 2020. 6. 11. · ce marking of...

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