2021 01 22 - DIAGNED IVDR webinar handouts

DIAGNED
IVDR workshop:
IVDR: bent u er klaar voor?

Anja Wiersma
Januari 22, 2021

Introduction
Anja Wiersma:

• Education

– University Degree: Medical Biology at University of Groningen
– PhD: Thesis on Neuropharmacology/physiology/behaviour topic.

• Work Experience

– Organon NV (International)
• 4 year basic research (Dept. of Endocrinology-Pharmacology)
• 4 year Strategic Portfolio Manager Gynaecology (dept. of Strategy and Business Development)

– KEMA Quality BV, Medical 6.5 years (now DEKRA Certification BV)
• QMS auditor: ISO 9001; ISO 13485
• Notified Body auditor for medical device and In Vitro Diagnostic Medical Devices (IVD’s)
• Certification Manager IVDD and ISO 13485 (including under CMDCAS)

– Eurotrol BV: IVD manufacturer (1-1-2013 tot 1-08-2015)
• Parttime QA/RA Director; member of MT

DIAGNED IVDR workshop: 22-01-2021 2

Introduction 3

Anja Wiersma:

• Current position

– mi-CE consultancy: (CEO and senior consultant)
- Medical Devices
- In vitro Diagnostic device
- Clinical Evaluation
- CE marking

- Consultancy for medical devices manufacturers and or subcontractors of them
- Contractor for several Notified Bodies

– RAPS Netherlands Chapter:
• Chair of the board
• Email contact: rachapternedvl.gmail.com

– REC (Raps European Council)
• Member of the council

DIAGNED IVDR workshop: 22-01-2021

Introduction and AIM: 4

• Who is: In Vitro Medical Device manufacturer?

– 1) Already products on the market under IVDD?
• List A
• List B
• Self-testing?
• Self-declared products?

– 2) what are the product classification under the IVDR?
• Up - Classification ?
• Unknown?

– 3) in development of IVD under the IVDR

DIAGNED IVDR workshop: 22-01-2021

Introduction and AIM: 5

• Who is a distributor/ local company of a “big manufacturer” ?
4 ) IVD under the IVDD
– List A products?
– List B Products?
– self-test?
– Self-declared products?

5) what are the product classification under the IVDR?
• Up - Classification ?
• Unknown?

• Who is and or becomes a EU Representative? :

– Is?
– Becomes?
– Unknown?

• Who becomes an importer?

– Unknown?

• Who is critical subcontractor?
• Other?

DIAGNED IVDR workshop: 22-01-2021

IVDR – General Overview

AIM
•• UUnndderesrtasntdainngdtihnegnoewf trehqeuiCreEmmenatsrokfinthge pIVrDoRcoefstshefCoErmIanrkvinitgrporocess for In

dViitarogMnoedsitciacl Dmeveicdeisc:afolcdues vonictehse.Economic operators process

- Tools, strategic stepsà what do you have to do after this workshop

• Tools, strategic steps?

- Answering your questions

• Understanding the timelines and actions to be started after this workshop

DIAGNED IVDR workshop: 22-01-2021 6

Questions?

And which questions do you want to get an answer to? 7

- TD content and how NoBo’s review it : Standard text?
- Registration documentation: eudamed
- Country affiliate as marketing and Sales organisation: requirements
- Local customization process (legal manufacturer? Of not?)
- Requirements for PMS/ vigilance?
- Impact for business partners in the complete chain
- Consequences of new requirements as importer/distributor
- Economic operators requirements
- Notified body alignment , technical doc update, labelling changesà translation

requirements?

- NEW Questionsà chat for an interactive session

DIAGNED IVDR workshop: 22-01-2021

Questions?

And which questions do you want to get an answer to?

• IVDD instruments in het veld en IVDR reagents, die door de manufacturer niet gevalideerd zijn

op de IVDD legacy instrumenten, hoe kan dit door de gebruiker alsnog als IVD worden gebruikt
op deze IVDD legacy instrumenten? Het ganse installed base kan onmogelijk worden vervangen
op korte tijd door IVDR instrumenten...

• Registratieverplichtingen, verificatieverplichtingen levering van 3e-partijen.

• Zijn er mogelijkheden om deze richtlijnen te omzeilen door de gebruiker?

• IVDR in relatie tot LDT

• IVD

• UDI eisen

• ‘’ Verschillen tussen de verschillende economic operators. Verantwoordelijkheden voor de EC
Rep"

• UDI en Basic-UDI en het verschil

• Algemeen kennis niveau op peilen houden

• Wat zijn de gevolgen van IVDR voor leveranciers en voor klanten? In welke gevallen hoeft er niet
aan IVDR gehouden te worden en in welke gevallen wel?

• Tijdslijn en vertraging EC

• Hoe wordt er gecontroleerd vanuit de inspectie en of accreditatie op de implementatie

- NEW Questionsà chat for an interactive session 8
DIAGNED IVDR workshop: 22-01-2021

Interaction:

DIAGNED IVDR workshop: 22-01-2021 10

IVDs: CE-markering

DIAGNED IVDR workshop: 22-01-2021 11

Medical device / IVD products

On the MARKET ASAP!!!!!

• However, you have to comply to the law:

EUROPE Medical Device Directive (MDD) (93/42/EEC)
Active Implantable Medical Device Directive (AIMD) (90/385/EEC)
Medical Device Regulation (MDR) (EU 2017/745)

In Vitro Medical Device Directive (IVDD) (98/79/EC)
In Vitro Medical Device Regulation (IVDR) (EU 2017/746)

• Medical device/ IVD’s:

•Notified bodies voor Europa:
•FDA (USA)

– PMA
– 510 (K)

DIAGNED IVDR workshop: 22-01-2021 12

Europe:
CE

• EU countries: total of 27 members (member states)

IJsland EC“ onformitee uropeenne

“ = “European Conformity”

• European Free Trade Association (EFTA): Switzerland, Liechtenstein, Norway, 13
Iceland

• BREXIT update: Switzerland MRA and Turkey under debate

DIAGNED IVDR workshop: 22-01-2021

IVDD
Classifications

• Notified Body control:
Annex II

– List A: à Common Technical Specifications

• Batch release/control

– List B: see list

– All Self-testing (example home pregnancy tests, home cholesterol test)

• (annex III.6)

• All others are self-certifiable (= 90% of the market) FOR NOW!!!!

• Potential inspection by CA

DIAGNED IVDR workshop: 22-01-2021 14

Your product

• Notified bodies voor Europa

– 68 NoBoà currently 53; expected to be reduced to 30?
– IVDs à currently 21 : expected to be reduced to 5-10?

• Example : NB0086 UK
NB2797
BSI
BSI Netherlands

DEKRA Certification GmbH NB0124 Germany
DEKRA Certification BV NB0344 the Netherlands

• Every year NoBo executes audit.
• Un-announced audits!

See NANDO site 15
http://ec.europa.eu/enterprise/newapproach/nando/index.cfm

DIAGNED IVDR workshop: 22-01-2021

General MDD/MDR
IVDD/IVDR

• Your products should comply to the LAW before getting an approval:

• 2 STEPS needed for getting the approval:
– 1) Technical Dossier analysis:

• off-site

– 2) proper working Quality Management system of the manufacturer

• Short off-site review of the Quality Manual and objectives
• On-site examinationà CE audit.

If both steps are accepted à CE approval

Allowed to place the product ON THE MARKET

DIAGNED IVDR workshop: 22-01-2021 16

General IVDD/IVDR 17

• TD review by the NoBo is also risk based:
– Depending on the classification
– Type of the product:
– High risk à extensive review

• Quality Management System:

– Audit IVDD, Annex VII, IV
– IVDR Annex IX, XI
– Or EN ISO 13485:2016

AIM: Product is produced identical compared to the approval:
Manufacturer is in complete control

DIAGNED IVDR workshop: 22-01-2021

IVDD à IVDR 18
A HUGE CHANGE FOR
INDUSTRY AND REGULATORS

RULES-BASED AP:

DIAGNED IVDR workshop: 22-01-2021

IVDR vs MDR:
The small little sweet brother?

DIAGNED IVDR workshop: 22-01-2021 19

IVDD/ IVDR comparison

DIAGNED IVDR workshop: 22-01-2021 20

IVDR
Regulation No: EU 2017/746

TOTAL 157 pages !! (compared to 37 pgs IVDD) • Chapter I – Introductory provisions incl. Scope and Definitions
101 Whereas … = Why • Chapter II – Placing on the market, putting into service, CE
10 Chapters of 113 Articles = What
XV Annexes = How Marking, Economic Operators, Free movement

• Chapter III – Identification and Traceability of Devices
• Chapter IV – Notified Bodies
• Chapter V – Classification and Conformity Assessment
• Chapter VI – Clinical Evidence, Performance Evaluation and

Performance Studies

• Chapter VII – Post-Market Surveillance, Vigilance and Market

Surveillance

• Chapter VIII – Cooperation between Member States
• Chapter IX – Confidentiality, Data Protection, Funding and

Penalties

• Chapter X – Final Provisions

DIAGNED IVDR workshop: 22-01-2021

IVDR
Regulation No: EU 2017/746

TOTAL 157 pages !! (compared to 37 pgs. IVDD) • Annex I – General safety and performance requirements

101 Whereas … = Why • Annex II – Technical Documentation
10 Chapters of 113 Articles = What • Annex III – Technical Documentation on PMS
XV Annexes = How • Annex IV – EU Declaration of Conformity

• Annex V – CE Marking of Conformity
• Annex VI – European UDI System

• Annex VII – Requirements to be met by Notified Bodies
• Annex VIII – Classification Rules
• Annex IX – Conformity Assessment – QMS and Technical Documentation

• Annex X – Conformity Assessment – Type Examination
• Annex XI – Conformity Assessment – Production Quality Assurance

Verification
• Annex XII – Certificates issued by a Notified Body
• Annex XIII – Performance Evaluation, Performance Studies and Post-

Market Performance Follow-up
• Annex XIV – Interventional Clinical Performance Studies and certain other

Performance Studies
• Annex XV – Correlation Table 98/78/EC and Regulation

DIAGNED IVDR workshop: 22-01-2021

IVDR
EU 2017/746

Implementing and delegating acts (total of +/- 80) (both MDR and IVDR)

1) NBOG codes for NB to apply for designation

DIAGNED IVDR workshop: 22-01-2021

New IVDR

HOT TOPICS

- IVDR Timelines
- Changes to the classification

- Requirements for a person responsible for regulatory compliance
- Increased clinical (performance) data

- Increased post market surveillance

- Requirements for Economic Operators/ Distributors/Importers/AR

- IN-HOUSE testing
- Unique Device Identifier / EUDAMED
- Liability Insurance
- Others??

- Designation of NOTIFIED BODIES
- à possible lack of resources

NO GRANDFATHERING Erik Vollebregt (Axon2) 4

DIAGNED IVDR workshop: 22-01-2021

Transition period for IVDR

Articles 110 and 113 – IVDR

IVDR transition period (5 years)

26th May: IVDR entry into force Referenc 26th May: IVDR date of application
e labs?
26th May:
Expert IVDD certs
panels? invalid

NB available ? conditions

2017 2018 2019 2020 2021 2022 2023 2024

Placing on the market under IVDD or IVDR Placing on market under IVDR

Article 110 Transitional provisions or IVDD (not for TÜV SÜD Product Service
Article 112 Repeal CDx) GmbH
Article 113 Entry into force and date of application Andreas Stange

TÜV SÜD Product Service GmbH DIAGNED IVDR workshop: 22-01-2021 Slide 25

New IVDR 26
Classification IVDR

• Classification under the IVDDà list based

• Classification under the IVDRà risk based with
rule-based approach
– A huge change for the Industry and regulators

• Newly covered products and special cases in IVDR
– Software
– Companion diagnostics
– In-house exemption / lab-developed tests
– Distance sales and diagnostic labs

DIAGNED IVDR workshop: 22-01-2021

Classification commercial IVD:
IVDR Quantum Leap

CE- IVD’s

LDT/ in- No involvement on in- Involvement of CA:
house house developed test article 5.5
under the IVDD Only allowed when
developed no CE-IVD is
tests Own requirements available

ISO 15189: Internal
validation and use

DIAGNED IVDR workshop: 22-01-2021 27

Classification shift

Significant up-classification 28

DIAGNED IVDR workshop: 22-01-2021

Classification
7 RULES (Annex VIII)

DIAGNED IVDR workshop: 22-01-2021

Classification shift
Situation in the Netherland

IVD manufacturer: all range IVD products: 30
IVDD 4% notified body à
IVDR 92 % notified body

DIAGNED IVDR workshop: 22-01-2021

Classification shift
MDCG Guidance

DIAGNED IVDR workshop: 22-01-2021 31

‘health institution’ means an In-house exemption/”LDT”
organisation whose primary “Home Brews” (article 5.4, and 5.5)

purpose is the care or
treatment of patients or the
promotion of public health

With the exception of the relevant general safety and performance requirements
set out in Annex I, the requirements of this Regulation shall not apply to devices manufactured and
used only within health institutions, provided that the following conditions are met:
•(a) the device is not transferred to another legal entity,…
•(b) manufacture and use of the devices occur under appropriate quality management systems;
•(c) the laboratory of the health institution is compliant with standard EN ISO 15189 …
•(d) the health institution justifies in its documentation that the target patient group’s specific needs
cannot be met by an equivalent device available on the market,
•(e) the health institution provides information upon request on the use of such devices
•(f)
•(g) as regards class D devices in accordance with the rules set out in Annex VIII, the health institution
draws up documentation, …to enable the competent authority to ascertain that the general safety and
performance requirements are met; …
•(h)
•(i) the health institution reviews experience gained from clinical use of the devices and takes all
necessary corrective actions.

DIAGNED IVDR workshop: 22-01-2021 32

IVDR
Conformity assessment routes

DIAGNED IVDR workshop: 22-01-2021 33

IVDR 34

HOT TOPICS

Increased clinical (performance) data requirements
- IVDs:

- 80% -90% under notified body control
- NO GRANDFATHERING (List A and List B: self-tests)

- own clinical performance data!

- Now required clinical performance data

- New clinical performance trials:

- Informed consent
- Left over samples
- Invasive clinical performance à CCMO; METC

- Increased post market surveillance requirements

- Class C, D
- Annual PMS plan and PSUR report
- Annual Clinical Evaluation Plan and report
- IN EUDAMED (Class III)

- In House Developed test: Lab Developed test (HOME BREWS)

- ISO 15189 required for test lab
DIAGNED IVDR workshop: 22-01-2021

IVDR Actively updated
Performance Evaluation throughout life

Performance cycle of the
Evaluation Report device

DIAGNED IVDR workshop: 22-01-2021 35

IVDR
Performance Evaluation

Lab results with Scientific Literature
manufacturer
results in house Scientific Validity

Analytical performance Sc
Va R
An
Pe R

Clinical Performance

Cl Scientific peer reviewed
Clinical Performance Pe R Literature data
And published experience
Validation studies.
And/or with own assay data

DIAGNED IVDR workshop: 22-01-2021 36

Designation process: 5-December-2020

Notified Bodies MDR and IVDR

IVDR

DIAGNED IVDR workshop: 22-01-2021 37

IVDR
Implementation

MDCG guidance
Common Specifications (implementing acts):
CTS current List A (IVDD)à CS Class D

DIAGNED IVDR workshop: 22-01-2021 39

IVDR
Performance Evaluation

Implementation

https://ec.europa.eu/health/md_sector/new_regulation
s/guidance_en

MDR

DIAGNED IVDR workshop: 22-01-2021 40

https://ec.europa.eu/health/md_sector/new_regulations/guidance_en

IVDR
Regulation No: EU 2017/746

TOTAL 157 pages !! (compared to 37 pgs IVDD) • Chapter I – Introductory provisions incl. Scope and Definitions
101 Whereas … = Why • Chapter II – Placing on the market, putting into service, CE
10 Chapters of 113 Articles = What
XV Annexes = How Marking, Economic Operators, Free movement

• Chapter III – Identification and Traceability of Devices
• Chapter IV – Notified Bodies
• Chapter V – Classification and Conformity Assessment
• Chapter VI – Clinical Evidence, Performance Evaluation and

Performance Studies

• Chapter VII – Post-Market Surveillance, Vigilance and Market

Surveillance

• Chapter VIII – Cooperation between Member States
• Chapter IX – Confidentiality, Data Protection, Funding and

Penalties

• Chapter X – Final Provisions

DIAGNED IVDR workshop: 22-01-2021

IVDR
Regulation No: EU 2017/746

TOTAL 157 pages !! (compared to 37 pgs. IVDD) • Annex I – General safety and performance requirements

101 Whereas … = Why • Annex II – Technical Documentation
10 Chapters of 113 Articles = What • Annex III – Technical Documentation on PMS
XV Annexes = How • Annex IV – EU Declaration of Conformity

• Annex V – CE Marking of Conformity
• Annex VI – European UDI System

• Annex VII – Requirements to be met by Notified Bodies
• Annex VIII – Classification Rules
• Annex IX – Conformity Assessment – QMS and Technical Documentation

• Annex X – Conformity Assessment – Type Examination
• Annex XI – Conformity Assessment – Production Quality Assurance

Verification
• Annex XII – Certificates issued by a Notified Body
• Annex XIII – Performance Evaluation, Performance Studies and Post-

Market Performance Follow-up
• Annex XIV – Interventional Clinical Performance Studies and certain other

Performance Studies
• Annex XV – Correlation Table 98/78/EC and Regulation

DIAGNED IVDR workshop: 22-01-2021

Economic Operator

Definition Art 2 (28)
•“Economic Operator” means a manufacturer, and
authorised representative, and importer or an
distributor

•What is the difference between IVDD and IVDR?

DIAGNED IVDR workshop: 22-01-2021 43

Economic Operators : IVDD vs IVDR

Economic Manufacturer Economic
Operators in Authorized Operators in
Representative
IVD Regulation IVD Directive

Importer Importer Distributor

Distributor

User User User User

DIAGNED IVDR workshop: 22-01-2021 44

Economic Operators

DIAGNED IVDR workshop: 22-01-2021 45

Economic Operator
Manufacturer

Definition:
•‘manufacturer’ means the natural or legal person who
manufactures or fully refurbishes a device or has a device
designed, manufactured or fully refurbished, and markets that
device under his name or trademark.

• See article 10 : specific See Art. 10.8 – 10.13

DIAGNED IVDR workshop: 22-01-2021 46

Supply Chain/
Economic Operators IVDR

Supplier Verify Compliance Verify Compliance

Supplier Manufact Importer Distributo End-Users
Subccotonrtra urer servic r
of 30
contract e
manufact DcoonpwSsreunourlvsstpiatdpreliaemrs
consulta urers Key
Upsnttrseam Key Etc

conSturapcpt liers nts .
R&D

DIAGNED IVDR workshop: 22-01-2021 47

Economic Operator
Manufacturer

Manufacturer’s general Obligations (art 10)

• Shall ensure that design and manufacture of devices is in accordance with the requirements
• Risk Management
• Conduct Performance Evaluation
• Technical Documentation
• Follow applicable conformity assessment procedures
• UDI
• Keep Technical Documentation etc… available to competent authorities
• Registered in Eudamed SRN tc.

48

Economic Operator
Manufacturer

Manufacturer’s general Obligations (art 10)
• Appoint Authorized Representative (if not in EU)
• Quality Management System
• Post-Marketing Surveillance system
• Provide IFU and labels with the device
• Bring nonconforming products into conformity or do recall or withdrawal
• Inform competent authorities of this nonconformity and Field Safety Corrective

Actions (FSCA)
• System for reporting of incidents and FSCA
• Person Responsible for Regulatory Compliance
• Etc..

49

QMS Article 10
Manufacturer

Manufacturer’s general Obligations (art 10)
- Financial compensation

50

Economic Operator
AUTHORIZED REPRESENTATIVE

‘authorised representative’ means any natural or legal person
established within the Union who has received and accepted a written
mandate from a manufacturer, located outside the European Union, to
act on his behalf in relation to specified tasks with regard to the latter's
obligations under this Regulation;
See article 11 and Article 12.

51

Economic Operator
AUTHORIZED REPRESENTATIVE

See article 11 and Article 12.

52