the european medical device regulation (mdr) updates and ......1223/2009 and repealing council...
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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
© by knoell CMR: carcinogenic, mutagenic, toxic for reproduction 28
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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Contact us
Knoell Medical Devices, LLCNashville (TN), USA
Dr. Isabelle Lang-ZwostaGlobal Regulatory AffairsE-Mail: [email protected] Tel: +1 615 374 1242
General E-Mail: [email protected]
www.knoell.com 38