The European Medical Device Regulation (MDR)Updates and developments

December 2020 – Chemical Watch Expo 2020

Dr. Isabelle Lang-Zwosta

Agenda

• Transition to the MDR – what does that mean

• What‘s important to know

• How to get started

• Transition strategy – from MDD to MDR

• General Safety and Performance Requirements – Focus on substances

• Additional Requirements – REACH and SCIP

• Summary

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Transition MDD to MDR

2017 2018 2019 2020 2021 2022 2023 2024 2025

May 25th

entry into

force

May 26th

date of

application

May 27th

expiry date

of MDD

certificates

Grace periodMay 27th

no MDD

devices

on EU

market

Grace period for existing MDD CE devices (NB re-certification by May 2020), allows devices to be placed on the

market with a valid certifcate based on MDD (extends certificate) until May 2024

BUT: requirements for market and post-market surveillance (PMS), vigilance, registration of economic operators

and devices and NB (accredited for IVDR), no significant design or intended purpose changes are allowed

No grandfathering provisions – all MDs must be certified to meet MDR (May 2020/24)

NB Notified Body

Sell-offMDR transition period

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NEW:

May 26th

date of

application

3

From MDD to MDR – important changes

REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT

AND OF THE COUNCIL of 5 April 2017

on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No

1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

• Broader scope for definition of medical devices

• More stringent requirements for clinical data including clinical evaluation consultation procedure (e.g.

for some class IIb and class III devices)

• Requirements on UDI (unique device identification) in order to increase traceability and effectiveness of

post-market safety related activities

• Setup European database EUDAMED to increase transparency of device information to public and

regulatory bodies

• More and stringent requirements for post-market surveillance and vigilance

• New responsibilities, roles and obligations of manufacturers and economic operators

• Additional requirements for materials used for the manufacturing of medical devices

No grandfathering provisions – all MDs must be certified to meet MDR (May 2021)

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What‘s important to know

Post-market surveillance and vigilance

PMS Post-market surveillance

PSUR Periodic safety update report

PMPF Post-market performance follow up

SSP Summary of safety + performance

PMS System

All

Class I

IIa, IIb, III

• Serious incident reporting within 15 days (2

days public health threat/10 days death or unanticiated

deterioration of persons health status)

• Field safety corrective action (FSCA)

• Trend reporting (statistically significant increase in

frequency or severity of non-serious inicidents)

Vigilance

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EUDAMED and UDI

https://ec.europa.eu/growth/sectors/medical-devices/new-regulations/eudamed_en

EO Economic Operators

UDI Unique device identification

EUDAMED

Electronic System on NotifiedBodies andCertificates

Electronic System on Vigilance and

Post-Market Surveillance

Electronic System on Market

Surveillance

Electronic System on Clinical

Investigations

Electronic system on registration of economic operators (Art. 27) (manufacturer, importer, authorized representative, distributor)

UDI Database (Art. 25) (incl. Basic UDI-DI) Unique Device Identification System

Device Identifier

(static)

Production Identifier

(variable)

Restricted site Public site

European database on medical devices (EUDAMED) for constant traceability (Art. 30)

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New regulatory functions at manufacturer

Person responsible for regulatory compliance

PRRC

Responsible for ensuring:

Conformity of devices, batch release

Technical documentation kept and is up-to-date

PMS and vigilance reporting obligations are fulfilled

Certain aspects of interventional studies

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Distributor- Register complaints

- Assist with CAPA

- Safeguard storage

conditions

- EUDAMED

Customer

/ User

Verify complianceVerify compliance

Manufacturer- Name on device

- CE certificate +

DoC

- GSPR

- UDI

- PRRC

- EUDAMED

Importer- Name on device

- Register of

complaints

- Safeguard storage

conditions

- Assist with CAPA

- EUDAMED

Economic operators

EUAR

AR Authorized representative CAPA Corrective and preventive actions

DoC Declaration of conformity GSPR General safety and performance requirements

PRRC Person responsible for regulatory compliance UDI Unique device identification

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Update Technical Documentation

Device description,

specifications

Label, instruction for

use

Design & manufacturing

General safety& performance

Benefit-riskanalysis, riskmanagement

Productverifcation &

validation

Summary ofsafety &

performance(SSP)

Post-marketsurveillance

plan

Annex II

Periodic safety

update report

(PSUR)

Post-market

surveillance report

Annex III

Pre-market Post-market

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Time critical actions and potential pain points

Setup post-market surveillance procedures (May 2021)

Clinical evidence requiring clinical data

Install / update QMS (ISO 13485)

Verify definition and classification of MD

Notified Body cooperation (limited capacities)

UDI system (label format, barcode)

Update of Technical Documentation

Set up and maintain EUDAMED

Expenditure of time

Depends on organization

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Setup transitionplan and plan

resources

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How to get started

CA Conformity assessment

PMS Post-market surveillance

QMS Quality management system

TD Technical Documentation

UDI Unique device identification

2020/21

Fine-tuning for

routine

Internal

audits

Life cycle

manage-

ment

Manage-

ment

review

MDR implementation strategy

2018 / 2019 / 2020

Plan & implement

Per-

formance

evaluation

Intended

purpose,

risk class,

CA

Notified

Body

coo-

peration

EUDAMED

& UDI

PMS &

Vigilance

Update

TD

New

regulatory

functions Economic

operators

Prioritise!

Define gaps and time-critical

tasks and products

Portfolio

assess-

ment

Reg.

strategy

QMS

update

Status TD

New roles

and

processes

Risk

manage-

ment

2017 / 2018

Gap

analysis

and

transition

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Product Portfolio and Market Assessment

Parameter Product x Product y Product z

(MDR relevant) markets

Sales figures over the last years

Expiration date of certificate for MDD

conformity

Intended purpose

New MDR class

Conformity assessment route under MDR

Eligible for grace period?

Rough estimate on TD status

Estimate time for update of TD

Assessment for renewal of certificate

TD Technical Documentation© by knoell 14

Transition strategy MDD - MDR

From gap assessment to transition plan

Gap

Analysis

MDR vs.

MDD

Product

requirements• Classification

• Identify conformity

assessment procedure

QMS requirements• Identify relevant gaps

• Requirements acc.

conformity assessment

procedure

e.g. Annex I• Define gaps to MDR

(product specific)

e.g. regulatory

functions and

requirements• PRRC

• PSUR

Project

management• Transition/

project plan

• Team meetings

Implementation• Tech Doc Review

• QMS Audits

CE

Conformity

by Notified

Body

PRRC Person Responsible for Regulatory Compliance

PSUR Periodic Safety Update Report © by knoell 16

From gap assessment to transition plan

Transition plan can be derived from gap assessment

• MDR vs. MDD comparison – specific review of changes and new topics

• Product classification / define conformity assessment route

• Get in touch with Notified Body (NB)

• Analysis of requirements based on gap assessment

• Transfer into work packages (incl. review and approval) transfer into project/transition plan (Gantt chart)

incl. time lines and responsibilities

• Project management (responsible project leader) team meetings and update of Gantt chart

• Update project plan schedule conformity assessment process internal and with NB

• Submission of technical documentation for review at NB

• Completion of conformity assessment process

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Team work

• Involve Top Management

• Stakeholder management

• Centrally managed process: determine chrononogical order of document update and

process implementation

• Include members from different departments/areas

• Regular update meetings for management and all-company

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General Safety and Performance Requirements (GSPR) Focus on substances

GSPR 10 – Chemical, physical and biological properties

Main difference to EU Medical Device Directive: Requirements for specific substances of concern

(SPR 10.4)

Applicable for invasive devices and devices administering/storing substances

● May only contain CMR and ED substances above 0.1 % w/w if duly justified

In addition, special guidelines and requirements are implemented for:

● Phthalates

● Particles and nanomaterials

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• Analyse and estimate potential patient exposure to the substance

• Analyse possible alternative substances, materials and/or designs

• Justify why presence is considered appropriate

• Adapt Labelling

CMR Carcinogenic, Mutagenic, Toxic for Reproduction

ED Endocrine Disruptor 20

*Source: ISO/DIS 15223-1:2020

Please keep in mind copyright restrictions for use of symbols

Contains hazardous substances*

Contains nanomaterials*

Additional Requirements – REACH

REACH Evaluation

Substances of potential concern are evaluated by ECHA or EU Member states

for further regulatory actions.

Substances of Very High Concern

(SVHCs) (according to Article 57):

a. Carcinogenic category 1 or 2

b. Mutagenic category 1 or 2

c. Toxic for reproduction category 1 or 2

d. Persistent, bioaccumulative and toxic

(PBT)

e. Very persistent and very bioaccumulative

(vPvB)

f. Equivalent level of concern to those

listed in points (a) to (e) (e.g. endocrine

disrupting properties, skin sensitizer,

etc…)

~ 1300

substances of

potential concern

~ 270

substances with

identified

concern

© by knoellECHA: European Chemicals Agency

22

REACH Authorisation

Authorisation process aims to ensure that substances of very high concern (SVHCs) are

progressively replaced by less dangerous substances or technologies.

Usage of substances on the Authorisation list (Annex XIV) is prohibited after the sunset date

unless:

● An exemption applies

● Concentration in mixture/article: < 0.1 % w/w

● Authorisation for specific use has been granted (time limited)

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Authorisations for a defined use of the substance will only be granted for a limited period of time, a

transition phase, before the substance or the technology can be substituted

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REACH Authorisation

● After inclusion on Authorisation list, substance will

be phased out (sunset date) around 32 months

later.

● Latest application date is 18 months before the

sunset date.

Source: https://echa.europa.eu/substances-of-potential-concern

Source: ECHA, 2020. Integrated regulatory strategy- Annual report

https://echa.europa.eu/documents/10162/27467748/irs_annual_report_2019_en.pdf/bd23e8c

b-a55a-24af-4be3-7a29828ebb09

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Exemptions from REACH Authorisation

for Medical Devices (MDs) and In-vitro Diagnostics (IVDs)

Exemptions specific to intrinsic properties

What does this mean?

● MDR (EU 2017/745) and IVDR (EU 2017/746) cover only Human Health

● SVHC based on human health hazards are exempted from authorisation requirements

● Environmental hazards still fall under the scope of REACH

● SVHC based on environmental hazards are not exempted from authorisation requirements (e.g.

PBT; vPvB, endocrine disrupting properties)

Use in medical devices, within the scope of Directives 90/385/EEC, 93/42/EEC or 98/79/EC in the

case of substances that are subject to authorisation only because of hazards to human health (Art.

60(2) and 62 (6) REACH)

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REACH Authorisation

Nothing for now and then

Requirements for granting an authorisation:

● No suitable alternatives are (immediately) available

● Risk is adequately controlled or

● Benefits outweigh the risk (socio-economic analysis)

(Monetised)

risk

Cost of

substitution

or non-use

SEA

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Not an easy job!

● Time and capacity consuming

● Company-specific data (e.g. sales; business-case) required

● Expensive

● Timeframe: > 2 years

● Decision making >13 months

Source: ECHA, 2017. How to apply for authorisation

https://echa.europa.eu/documents/10162/13637/apply_for_authorisation_en.pdf/bd1c2842-4c90-7a1a-3e48-f5eaf3954676

REACH Authorisation

Nothing for now and then

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No general exemption for the MD and IVD sector

Blanket exemption for all MDs and IVDs from REACH restrictions

related on Human Health hazards (CMR) are currently under

discussion

REACH Restrictions

Restrictions are an instrument to protect human health and the

environment from unacceptable risks posed by chemicals.

A restriction may apply to any substance on its own, in a mixture or

in an article, including those that do not require registration, for

example, substances manufactured or imported below < 1 t/y or

certain polymers. Use

prohibited

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Exemplary Substances relevant for MDs and IVDs

Substance name Description EC No.CAS

No.

Entry

No.Sunset date

Latest application

date

Intrinsic property(ies) referred to in

Article 57

4-Nonylphenol, branched and

linear, ethoxylated

substances with a linear and/or

branched alkyl chain with a

carbon number of 9 covalently

bound in position 4 to phenol,

ethoxylated covering UVCB-

and well-defined substances,

polymers and homologues,

which include any of the

individual isomers and/or

combinations thereof

- - 43 04/01/2021 04/07/2019Endocrine disrupting properties (Article 57(f) -

environment)

Source: https://echa.europa.eu/de/authorisation-list

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SubstanceNumber of received

applications (applicants)

Number of

users

RAC and SEAC

opinions per use²

RAC and SEAC opinions per use

and per applicant³

Commission decisions per use

and per applicant4

4-(1, 1, 3, 3-

tetramethylbutyl)phenol,

ethoxylated

50 (69) 79 6 8

4-Nonyphenol, branched and

linear, ethoxylated5 (6) 6

4- (1, 1, 3, 3-tetramethylbutyl)

phenol, ethoxylated; 4-

Nonylphenol, branched and

linear, ethoxylated

6 (22) 21

Exemplary Substances relevant for MDs and IVDs

Source: https://echa.europa.eu/de/received-applications

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Exemplary Substances relevant for MDs and IVDs

Substances on Candidate list (recommended for inclusion into Annex XIV):

Substance name Description EC No.CAS

No.

Entry

No.Sunset date

Latest application

date

Intrinsic property(ies) referred to

in Article 57

4,4'-isopropylidenediphenol

(Bisphenol A; BPA)201-245-8 80-05-7 18 months after latest application date

Date of inclusion plus 24

months

Toxic for Reproduction (category 1B);

Endocrine disrupting properties (Article 57(f)

-human health and environment)

Amendments on entries in Annex XIV:

Substance name Description EC No.CAS

No.

Entry

No.Sunset date

Latest application

date

Intrinsic property(ies) referred to

in Article 57

Bis(2-ethylhexyl)

phthalate(DEHP)204-211-0 117-81-7

36 months after entry into force for

uses:

medical devices regulated by

Directive 90/385/EEC, Directive

93/42/EEC or Directive 98/79/EC;

immediate packaging of medicinal

products covered under Regulation

(EC) No 726/2004, Directive

2001/82/EC, and/or Directive

2001/83/EC;

18 months after entry

into force

Toxic for reproduction (category 1B)

Endocrine disrupting properties (Article

57(f) -human health)

Endocrine disrupting properties (Article

57(f) -environment)

Source: https://echa.europa.eu/documents/10162/13640/axiv_amend_recommendation_phthalates_july2019_en.pdf/1889866a-bec3-fe16-6322-67c16a13b09d

Source: https://echa.europa.eu/documents/10162/13640/9th_axiv_recommendation_October2019_en.pdf/d4d55dea-cc36-8f57-0d9f-33b8e64c4f07

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Substances on the candidate list:

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Additional Requirements – SCIP

SCIP notification under EU waste Framework Directive

New requirement to notify ECHA about Candidate List substances in articles

● As from 5 January 2021 any company supplying articles containing Substances of Very High Concern

(SVHCs) on the REACH Candidate List in a concentration above 0.1% weight (w/w) on the EU market has

to submit information to the ECHA to be collected into the SCIP (Substances of Concern in Products)

database.

● What is an article?

An object which during production is given a special shape, surface or design which determines its function to

a greater degree than does its chemical composition (Art 3(3) REACH)

Note: this also includes packaging!

© by knoellArticle 9(1)(i) of Directive (EU) 2018/851 amending Directive 2008/98/EC on waste (Waste Framework Directive, WFD), https://echa.europa.eu/scip-

database https://echa.europa.eu/documents/10162/23036412/articles_en.pdf 33

SCIP notification under EU waste Framework Directive

A medical device is subject to a SCIP notification obligation if that medical device itself or one of its

components:

● fulfils the REACH definition of article, and

● contains a substance of very high concern (SVHC) on the Candidate List in a concentration above 0.1%

w/w.

The assessment on whether a medical device itself or one (or more) of its components, can be considered

an article under REACH needs to be done on a case-by-case basis after identifying the function of the

object.

The assessment on whether a medical device itself or one (or more) of its components, can be

considered an article under REACH needs to be done on a case-by-case basis after identifying the

function of the object.

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Summary

Summary

• Planning is key in order to keep your products on the market and to bring new products to the market

• Make sure you are aware of your role as economic operator

• Know your devices and their exact composition – supplier qualification

• Be realistic with the quantity and quality of your clinical data

• Prepare for Post-Market activities

• Make the transition a TEAM approach and work with qualified partners

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Nashville (TN)

knoell in

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knoell in Europe

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Contact us

Knoell Medical Devices, LLCNashville (TN), USA

Dr. Isabelle Lang-ZwostaGlobal Regulatory AffairsE-Mail: ilang@knoell.com Tel: +1 615 374 1242

General E-Mail: MedDev@knoell.com

www.knoell.com 38