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IVDR White Paper 03.06.2020final

The document provides an overview of the new In Vitro Diagnostic Regulation (IVDR) that replaces the In Vitro Diagnostic Directive. The IVDR introduces stricter requirements for IVD devices, including a new risk-based classification system, increased clinical evidence requirements, and more stringent oversight of notified bodies and manufacturers. It has a transition period until 2022 when full compliance will be required. The IVDR aims to improve regulation of IVD devices to better protect public health in the rapidly advancing field of medical diagnostics.

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100% found this document useful (1 vote)
150 views11 pages

IVDR White Paper 03.06.2020final

The document provides an overview of the new In Vitro Diagnostic Regulation (IVDR) that replaces the In Vitro Diagnostic Directive. The IVDR introduces stricter requirements for IVD devices, including a new risk-based classification system, increased clinical evidence requirements, and more stringent oversight of notified bodies and manufacturers. It has a transition period until 2022 when full compliance will be required. The IVDR aims to improve regulation of IVD devices to better protect public health in the rapidly advancing field of medical diagnostics.

Uploaded by

Steven King
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Guide to the In Vitro Diagnostic

Medical Devices Regulation


(EU) 2017/746
By: Asaf Azulay, Rebecca Feldman, June 2020

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Background

The In Vitro Diagnostic Directive (IVDD 98/79/EC) As a result, the In Vitro Diagnostic Regulation
was introduced two decades ago to define the (2017/746) or “IVDR” was developed to employ a
requirements for marketing IVD products in the stricter oversight that will encompass many more
European Union. Under the directive, the majority products. The requirements are now a regulation,
of IVD products were self-certified and not subject rather than a directive, which means that it is legally
to oversight by a Notified Body, and some IVDs binding in EU countries. IVDR is longer and
were not even addressed in this directive. expands the scope of compliance to cover more
Innovation in life-sciences developed rapidly and it products as well as define requirements for Notified
became clear to European regulators that the IVDD Bodies. The IVDR follows a life-cycle approach,
was largely inadequate in the fast-changing world demonstrated by The IVDR is about 4
of medical diagnostics technology. incorporating the times longer than the
IVDD it replaces. It
MEDDEV guidances
Over the years, several flaws in the system of contains 10 chapters
and introduces many that are comprised of
Notified Bodies (NBs) were exposed and it became
new concepts and articles (113 in total)
clear that the system needed an overhaul. In and 15 annexes.
requirements.
addition, the IVDD lacked alignment with
international guidelines regarding IVDs.

In Vitro Diagnostic (IVD)


Definition*
‘In vitro diagnostic medical device’ means any
medical device which uses reagents and their
products, calibrators, control materials, kits,
instruments, apparatus, equipment, software
and/or system to examine bodily specimens,
such as blood, saliva, urine or tissue, derived
from the human body.

*A full definition can be found in Article 2(2) of


the IVDR

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The IVDR Transition Period

The IVDR officially came into force in 25 May 2017 transition period, IVDs may be put on the market
with a five-year transition period to full under the IVDD or the IVDR. By 27 May 2024, all
implementation, meaning that it only fully applies CE certificates under the IVDD will become void, if
from 26 May 2022. The timeline for this transition not before.
is outlined in Article 110 of the IVDR. During the

25 May 2017 26 May 2022 26 May 2024 27 May 2025


25 May 2024
Devices that conform IVDR enforced, mo All new IVDs placed on Any IVDD devices
with IVDR may be placed Existing IVDD certiicates
more IVDD certificates the market must remaining must be
on the market expire
issued conform with IVDR taken off the market

The IVDR also outlines new requirements


for NBs including stricter supervision by
What are the major IVDR changes?
competent authorities in Europe and
currently few NBs have been designated to
There are many changes in the IVDR and it is the the IVDR. This, as well as the increased
responsibility of the manufacturer to ensure its requirement for NB assessment of IVDs will
products are in compliance. We will outline the lead to a greater demand for NB services.
Plan accordingly!
major changes here and go into more detail later:
A list of Notified Bodies can be found on the
IVDR uses a risk-based approach to NANDO website.
classification: Classes A, B, C, and D. (Chapter
reviewed by a Notified Body will apply to IVD
V & Annex VIII of the IVDR describe the
classes B, C and D. Manufacturers of these
classification system). This classification is
devices will be subject to unannounced audits
based on the Global Harmonization Task Force
by the NB. (Annexes II, III, IX, X, & XI).
(GHTF) classification system bringing the EU
More stringent requirements for the designation
regulations into alignment with global
of Notified Bodies are introduced, including
classification of IVDs. As a result of this new
increased control and monitoring by the
classification system, the majority of IVDs will
competent authorities and the European
now require the involvement of a Notified Body
Commission.
in Europe.
The IVDR also covers software that is
The requirement for a quality management
incorporated into IVD instruments, such as
system and technical documentation to be
24 Imber st., Petach Tikva 4951158. | [email protected]| www.li-med.com|| |+972-54-8028817
Software as a Medical Device (SaMD) and Responsible for Regulatory Compliance
apps. (PRRC) are detailed. (Articles 10-16).
There is an increased requirement for clinical The European Commission will set up a new
and performance studies (Chapter VI & EUDAMED database to enable transparency by
Annexes XIII & XIV). maintaining records of device traceability,
The requirements for vigilance and post-market clinical investigations, vigilance and
surveillance are stricter (Chapter VII & Annex surveillance. Its functions and information
III). required to be submitted are outlined in the
Product traceability throughout the supply-chain IVDR. (Article 30). This database is scheduled
and labelling identification have received a to go online in May 2022.
greater focus with the introduction of the UDI
Navigating these changes can be challenging,
system. (Articles 24-27).
Li-Med’s regulatory professionals can help steer
The requirements for Economic Operators (EO)
you in the right direction.
including Authorized Representatives (AR),
importers, distributors and the Person

How are IVDs classified?

The IVDR introduces a new classification scheme the highest classification will apply to the device.
for IVDs based on GHTF IVD Classification Class A non-sterile devices will be self-certified by
Guidance that is more resilient to changes in manufacturers, excluding sterile devices. Class B,
technology and medicine. Instead of the IVDD’s list- C and D devices require conformity assessment by
based classification, the IVDR’s rule-based a Notified Body.
classification system divides IVDs into four classes
It is highly likely that even if your product was self-
based on their risk profiles. The device classes certified under the IVDD, it will be up-classified under
the IVDR an require NB involvement.
increase with risk, Class A being the lowest risk and
Class D being the highest risk. Classification is
Manufacturers will need to re-assess their product
determined by the intended purpose and considers
to determine which rules apply and justify the
the risks to both the individual and public health.
classification. The following flow chart illustrates
Article 47 of the IVDR discusses the classification,
the application of the classification rules. For an
and the rules themselves are laid out in Annex VIII.
accurate classification of the IVD, please refer to
All seven rules must be consulted to determine the
the IVDR Annex VIII.
device classification the applicable rule leading to

24 Imber st., Petach Tikva 4951158. | [email protected]| www.li-med.com|| |+972-54-8028817


24 Imber st., Petach Tikva 4951158. | [email protected]| www.li-med.com|| |+972-54-8028817
What route to Conformity Assessment applies to my IVD?

The IVDR lays out several routes for conformity The manufacturer may have some choice in the
assessment depending on the risk class of the IVD route to conformity assessment. The following
which are descried in Annexes IX, X and XI. The table outlines the available routes depending on the
routes to conformity assessment are based on: device class. (The exact requirements are detailed
in the IVDR):
Quality management system and technical
documentation (Annex IX) NBs performing conformity assessment will
request an EU reference lab to verify the
EU Type-examination (includes technical performance claimed by the manufacturer.
documentation) (Annex X)
Production quality assurance (Annex XI)

IVD Class (per Conformity assessment options NB involvement Notes


Annex VIII)
Class A Prepare Technical None (self-declared) Class A sterile IVDs – NB assess QMS or
Documentation (Annexes II and Production QA of sterile aspects
III)
EU Declaration of conformity
Class B QMS (Annex IX excl. chapter II) NB Audit and
and assessment –
Technical Documentation (Annex sampling of
IX 4.4-4.8) technical
documentation per
category device
Option 1 Option 2
Class C QMS (Annex IX EU Type NB Audit and Companion
excl. chapter II) Examination assessment – For diagnostics require
and (Annex X) Option 1: Review of Competent Authority Near-patient testing
Technical and technical consultation and self-testing IVDs
Documentation Production documentation of require technical
(Annex IX 4.4- Quality per generic device documentation
4.8a Assurance group assessment by NB
(Annex XI)
Class D QMS EU Type NB Audit and Performance
and Examination assessment verification by
Technical (Annex X) reference laboratory
Documentation and
(Annex IX) Production
Quality
Assurance
(Annex XI)

Determining the classification of your IVDs and deciding which conformity assessment route to take is a key
factor in compliance with the IVDR. Li-Med can assist in this process to ensure a smooth transition.

24 Imber st., Petach Tikva 4951158. | [email protected]| www.li-med.com|| |+972-54-8028817


What Technical Documentation will I need to present to the Notified Body?

Annex II details the technical documentation a The GSPR in Annex I is similar to the Essential
manufacturer will need to prepare for a Class B, C Requirements in the IVDD but includes many more
or D product that will be reviewed by a Notified requirements and greater detail. Among others, the
Body. Even though Class A products will not have GSPR includes requirements for performance
their technical documentation reviewed by a NB characteristics, risk
before they are placed on the market, the management, and The GSPR are a core
component of the IVDR
manufacturer must still compile this information. specific devices such and provide the criteria
for safety and
Technical documentation must include: as electronic
performance applicable
Device specification, including intended programmable to all aspects of IVDs,
throughout their life-
purpose, method of operation, etc. systems, self-testing
cycle.
Labels and instructions for use and near-patient
Design and manufacturing information testing.
General safety and performance requirements
Preparing the technical documentation can place
(GSPR) (Annex I)
demands on manufacturers; Li-Med’s experts can
Benefit-risk analysis and Risk Management
help in easing the burden.
Product verification and validation
Performance Evaluation Report (PER) which
includes clinical evidence

What Clinical and Performance studies do I need to perform?

Chapter VI discusses the requirements for clinical The Performance Evaluation must demonstrate
evidence, performance evaluation and the following elements regarding the IVD:
performance studies, the details of which are
Scientific validity
described in Annexes XIII-XIV. The requirement for
Analytical performance
clinical evidence and post-market performance
Clinical performance
follow-up are new for IVDs. As mentioned
previously, a Performance Evaluation Report Much of this information can be obtained from

(PER) must be included in scientific literature, but manufacturers must


The Notified Body
will review the the technical determine if it is adequate and perform necessary
information in the
PER and may documentation. tests to fill in the gaps.
request additional
testing The performance evaluation is an on-going process
with the purpose of evaluating the IVD throughout

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its life-cycle, and will constantly need updating by
assessing and analyzing post-market performance
follow-up data. The PER of Class C and D IVDs
must be updated annually. The PER of Class A and
B devices can be updated as needed but it is a good
idea to annually review the data to determine if it
needs updating.

Information from performance studies is required to


be uploaded to the EUDAMED database. The PER
Arranging the clinical and performance studies and
is in line with the FDA requirements so if you have
preparing the performance evaluation report can be
an IVD marketed in the US, this documentation
daunting; Li-Med’s experts can help in determining
should be easy to compile.
and arranging the testing.

What are the new requirements for vigilance and Post-Market Surveillance?

The requirements for post-market surveillance, Actions (applies to Class A and B and may be
vigilance and market surveillance are outlined in updated as needed)
Chapter VII. Manufacturers must gather and Periodic Safety Update Report which includes
analyze data about post-market activities as part of the same information as the Post-Market
the life-cycle approach to continuously review the Surveillance Report as well as benefit-risk
benefit-risk analysis of their products. Annex III analysis, sales volumes, user population
describes the technical documentation for Post- characteristics, and use frequency. (Applies to
Market Surveillance required for each product. It Class C and D and must be updated annually)
includes:
Requirements regarding vigilance and incident
Post-Market Surveillance Plan which describes reporting are much stricter in the IVDR than the
the system for gathering, recording and IVDD. The timeframes for reporting serious
analyzing relevant quality, safety and incidents are laid out in Article 82 and there are new
performance data regarding the IVD throughout requirements regarding vigilance reporting if there
its life-time. is a significant increase in frequency or severity of
Post-Market Surveillance Report which incidents. Requirements regarding reporting of and
summarizes the results and conclusions of the Field Safety Corrective Actions (FSCA) as well as
analysis of the Post-Market Surveillance data analysis of vigilance information are described in
and include any Corrective and Preventative detail. There is a new requirement to submit
vigilance reports to the EUDAMED database.

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What is the UDI system?

The Unique Device against falsification of devices. Each device will be


Identifier (UDI) system designated with a device identifier (UDI-DI), and
is introduced in each batch or production lot will receive a
Chapter III to enable production identifier (UDI-PI). The Basic UDI-DI of
consistent and a device must be listed on the IVD Declaration of
universal identification of medical devices Conformity as well as the CE certificates. There are
throughout their distribution and use. It is similar to a number of designated entities which assign the
the FDA’s UDI system and its purpose is to facilitate UDIs, and the UDIs must be entered into the
device traceability. The idea is to increase the EUDAMED database.
effectiveness of Post-Market Surveillance and
improve monitoring by competent authorities. The
use of UDIs for traceability should also help protect

What are Economic Operators and the PRRC?

Economic Operators (EO) include manufacturers, authorities in the case


It is the manufacturer’s
authorized representatives (AR), importers and of investigations, and responsibility to ensure
distributors whose obligations are described in the ensure that the the EOs meet their
obligations.
IVDR. The Person Responsible for Regulatory manufacturer has
Compliance (PRRC) has the role of ensuring the appropriate conformity
regulatory compliance of the manufacturer or AR. assessment (with the use of its own PRRC). EOs
The PRRC must have appropriate experience and must register with the EUDAMED database and
education and bears a huge responsibility. Small obtain an SRN. Chapter II defines the roles and
companies can outsource the role of the PRRC. In responsibilities of each EO and the PRRC.
the case of a non-EU based manufacturer, an AR
Li-Med’s regulatory and quality assurance
must be contracted and will assume legal liability for
expertise and experience allow us to offer our
defective devices alongside the manufacturer. This
services as an outsourced PRRC
means that the AR must be involved in market
surveillance, cooperate with the competent

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How should I prepare for the new IVDR?

3. Prepare a plan of action


Now that you know where your gaps are,
prepare a transition plan for your products,
according to the IVDR transition timeline. You
will need to consider how long your IVDD CE
certificates will remain valid and if it makes
sense to try to renew them or transition to the
It may seem as if May 2022, when the IVDR enters
IVDR sooner. Once you decide when to
into force, is a long way off, but the transition will
transition to the IVDR, determine what
take time and you should start planning for it now.
additional tests your device will require. Since
Here is how:
many more IVDs will require additional testing
1. Determine the class of your IVD products and NB oversight, there will be a lot of demand
First of all, use the rules in Annex VIII to re- for NB resources and reference labs, so plan
classify your device according to the IVDR. accordingly.
Once you know the device class, you will be 4. Fill those gaps
able to determine what routes of conformity Once your plan is in place, assign
assessment are available to you and what you responsibilities and resources to deal with the
need to do to achieve this. workload to fill the gaps. Determine if you will
2. Conduct an IVDR Gap Assessment need to hire extra staff or external consulting
Once you have determined your IVD class, a help. If you do not have a QMS in compliance
Gap assessment will help you find what you with ISO 13485 in place, get one ASAP. Start
need to do to achieve compliance with the gathering the necessary technical
IVDR. It is possible that you will find that you documentation and plan your clinical and
have not much to do. If your IVD has FDA performance studies.
510(k) clearance, you will already have most of 5. Get your EOs (and PRRC) on board
the clinical and performance data needed for Make sure your EOs and PRRCs are aware of
the PER. If you have a Quality Management their new responsibilities according to the IVDR.
System in place that complies with ISO 13485, Discuss with your importers, distributors and
you will not need many changes to comply with AR how they are preparing for the IVDR. Draw
Annex IX. Compare the Essential up new contracts and find new suppliers if
Requirements from the IVDD with the GSPR of needed. It is the manufacturer’s responsibility
the IVDR and determine what additional tests to make sure that the EOs assume these new
and documentation you need. obligations.
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Conclusion

The IVDR was introduced to address the some products, it is not financially beneficial to
shortcomings of the IVDD, which has become make the transition and it is better to scrap them.
increasingly inadequate in world with rapidly
While the task of moving to the IVDR may seem
advancing medical diagnostics technology. It
daunting, it is important to understand the
brings regulations regarding IVDs closer in line with
reasoning behind it. Safety of the individual and the
international regulations, such as the FDA, and
public should always be the number one priority in
guidances. The IVDR is a regulation and therefore
healthcare and medicine. Remember that when
EU member states must apply it in their national
you or a family member receive medical care, you
law.
want it to be at the highest standard. Make sure
IVD manufacturers will have to seriously consider your IVD meets the standards you would expect for
the implications of the IVDR and the new yourself and your loved ones.
obligations placed on them. They may find that for

Li-Med can help

Li-Med supports medical device and IVD manufacturers overcome regulatory hurdles.

We can help with:

IVDD to IVDR Gap Assessment


IVD classification and conformity assessment
Technical Documentation and PER preparation
Quality Management (ISO 13485:2016 and QSR)
PRRC services

Contact us at [email protected] for further information.

24 Imber st., Petach Tikva 4951158. | [email protected]| www.li-med.com|| |+972-54-8028817

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