Overview of the In Vitro Diagnostic Regulation (IVDR) Compliance

1. What is the IVDR EU 2017/746 ?

In Vitro Diagnostic Regulation (IVDR) is an EU Regulation which lays down the criteria for safety, performance and quality of devices used to examine biological samples from humans, such as blood, tissue or urine samples. This new regulation has been replacing the previous In Vitro Diagnostic Directive (IVDD) since May 2022. The IVDR increases the standards of safety, performance, transparency and post market surveillance.

The In Vitro Diagnostic Regulation ensures patient safety and uniformity in the regulation throughout the EU MDR Consultant. Moreover, the IVDR includes a risk classification system, higher standards of clinical evidence, as well as greater involvement of Notified Bodies.

2. The Importance of IVDR Compliance for IVD Manufacturers

Without adhering to the IVDR Compliance you will not be able to sell your products on the EU market. The EU market is one of the largest markets in the world. The regulation prevents patients from faulty or misleading diagnostic devices.

Here are the reasons why you should comply with the IVDR regulation:

Market access: You have to adhere to the IVDR to sell your products in the EU.

Risk mitigation: By complying with the IVDR you will reduce risks of fines, expensive. Harm to your brand reputation.

Credibility & Trust: IVDR compliance builds the trust of physicians and patients.

Global alignment: In vitro diagnostic regulation is similar to other regulations in the world, making it easy to sell products globally.

To sum it all up, adhering to the IVDR compliance is not just a legal thing. It is mandatory to succeed.

3. Major Differences Between IVDD And IVDR

The In Vitro Diagnostic Regulations have a better regulated approach compared to the previous in vitro diagnostic directive. These include:

The above changes reflect a bigger movement towards managing, evidential based in vitro diagnostic testing.

4. Which Devices Come Under The Scope Of The IVDR?

All devices that are used to test human specimens for medical purposes come under the scope of the IVDR regulation. These include:

In depth In Vitro Diagnostic Devices: blood glucose meters, pregnancy test kits, laboratory reagents

Self testing Devices: HIV and COVID-19 test kits

Companion Diagnostics: This Test is used to determine whether someone qualifies for treatment

Genetic Tests and Screening Devices

Software: if the software controls or influences the working of the IVD.

The manufacturers need to consider the intended use and the risk factor in order to group their devices as per the IVDR, which has a wider and more comprehensive scope than that of the In Vitro Diagnostic Device Directive.

5. Summary of Main Alterations to the Regulation of In Vitro Diagnostic Regulations.

Some regulatory procedures exist for In Vitro Diagnostic Regulations. These regulations provide people with certain time and give them more clarity so that they can continue marketing their In Vitro Diagnostic devices in the EU market. These regulations are intended to help people to get more clarity on how they can continue marketing In Vitro devices in the EU market.

6. Classification of IVDs according to IVDR

IVDs according to IVDR are classified in four different groups.These groups include:

Group A: IVDs whose classification involves the risk associated with their use. These IVDs include laboratory devices and sample containers.

Group B: IVDs which involve risk as pregnancy tests and CRP tests.

Group C includes IVDs which have high risks such as tests for infectious diseases like Hepatitis B.

Group D includes IVDs with higher risks than those in other groups such as HIV tests or blood types which are done when individuals are getting blood transfusions.

The process of classifying these IVDs is dependent on the intended use of the IVDs, the risks they pose to the health of patients or the general public and the importance of information they provide. This type of classification is consistent with the global standards of device classification and ensures that these devices are evaluated taking the risks associated with them into consideration.

7. Role and Significance of Notified Bodies

Notified Bodies have an entirely new and vital role to play in terms of conformity assessment of IVDs under the IVDR regime. This represents a complete change of paradigm from the IVDD regime (Directive 98/79/EC), wherein self certification of IVDs was the norm. Under IVDR, all IVDs categorized as Class B, C, and D are required to undergo conformity assessment by a Notified Body, except in certain very limited cases of Class A devices.

Regulatory Background

Whereas, according to Article 48(10) of Regulation EU (2017/746)

The manufacturers of Class A medical devices that aren’t meant for assessing the performance must declare compliance of their devices with the regulation by providing the EU Declaration of Conformity according to Article 17 after compiling the documentation as stipulated in Annexes II and III.

8. IVDR Compliance Plan

To achieve compliance with IVDR, it's important to plan. You'll have to upgrade your quality system and generate many documents. Here is a plan for achieving IVDR compliance:

1. Perform Gap Assessment: Check systems, technical file, quality management system, claims related to products. Make a comparison with IVDR requirements. This action allows identifying gaps in such areas as Technical Documentation, Post Market Surveillance, Classification and conformity assessment. This step doesn't relate to any Annex but helps to identify gaps in relation to Annex II Annex III, Annex VIII and conformity assessment Annexes IX, X, XI.

2. Reclassify Devices: Every IVD should be reclassified according to risk classes A, B, C or D according to their intended use and risk to the patient. That is an essential change from list based classification under In Vitro Diagnostic Device Directive regulation.

• Annex VIII – Provides information regarding the classification rules.

• Article 47 – Introduces the risk based classification approach.

Devices Classes B-D require a Notified Body; only Class A non sterile can self declare. 

Update the technical documentation: Technical file needs to be updated in accordance with the new requirements and structure. 

• Annex II – Specifies the required content of technical documentation.

• Annex III – PMS documentation requirements (e.g. PMS Plan, PMS Report, PSUR)

Verify that documentation reflects safety, performance and benefit risk balance.

Upgrade the Quality Management System : Make sure that your Quality Management System is in line with ISO 13485:2016 requirements. And also it includes responsibilities for IVDR.

• Article 10(8) – Imposes the obligation for manufacturers to establish and maintain compliant QMS.

• Annex IX / XI – QMS assessment is a part of conformity procedures including Notified Bodies.

NBs will check your QMS during the process of conformity assessment.

Choose Notified Body: Choose and contract a Notified Body (NB), which has designation appropriate for your type of device.

• Article 48 – Specifies the situation when the involvement of NB is necessary.

• Annex IX / X / XI – Routes of observance assessment depending on the classification and documentation strategy.

The early engagement is very important because of the limited number of NBs' resources.

Acquire Data for Performance Evaluation: There are three pillars of the evidence based performance evaluation: 

Scientific Validity Report

Analytical Performance Specifications

Clinical Performance

• Annex XIII – Specifies requirements for the performance evaluation and Performance Evaluation Report (PER).

It is a core evidence requirement according to IVDR.

Prepare PMS and Vigilance Plans: You'll have to perform proactive monitoring and analysis of device performance after its placing on the market.

• Annex III – Specifies structure of PMS plan and PSUR requirements.

• Articles 78 to 81 – Provide the information regarding PMS requirements depending on the classification (e.g., PMS Reports for Class A/B and PSUR for Class C/D). 

PMS is no longer optional, it's mandatory, structured and risk based.

Appoint Economic Operators: If your company is not based in the EU, appoint an EU Authorised Representative (EC REP) and specify responsibilities of your importers and distributors.

• Article 11 – EU Licensed  Representative

• Article 13 – Importer commitments 

You'll have to guarantee the monitorability and compliance through your supply chain.

UDI and labelling Compliance: It is important to comply with the requirements of the UDI and labeling. To do this update your device labels and packaging in accordance with the GSPR and UDI requirements.

• Annex I, Section 20 – Specifies requirements for labels and information.

• Annex VI – Specifies the structure and application of UDI (Unique Device Identifier).

UDI provides traceability and should be registered in EUDAMED.

Submit for Conformity Assessment: After preparation of all the necessary documentation submit your application to the Notified Body.

• Annex IX, X, XI – Depending on your conformity assessment route.

CE marking must be done after reviewing and approval of the NB for Class B, C, and D.

Although there are some Class A contaminated devices which can be self certified, others require thorough assessment by NB.

9. Performance Evaluation Requirements

The performance evaluation is mandatory under IVDR for all classes of IVDs and is elaborated in Annex XIII, Article 56,57,58.

• Scientific validity report: Relation of the analyte with the clinical condition (for example gene mutation and disease risk)

• Analytical Performance specifications: Refers to the ability of the test in detecting/measuring the analyte intended by the test.

• Clinical Performance: It is about how well the test works in a clinical setup.

Manufacturers need to prepare a Performance Evaluation Report supported by continuous data from Post Market Performance Follow Up Activities.

10. Technical Documentation under the Regulation on In Vitro Diagnostic

The regulation on IVDR provides that the technical documentation should be more complete and structured than under the directive. The format of this documentation is defined. It is set out in Annex II. Of the EU regulation No. 2017/746.

Key elements are:

• device description and specifications,

• design and manufacturing information,

• labelling and IFU samples,

• risk management documentation,

• performance evaluation documentation,

• PMS and PMPF plans,

• UDI assignment and traceability,

• declarations of  observance  and certificates,

For review by the Notified Body and Competent Authorities, this document should be current and accessible. To obtain permissions in time, it is important to have a clear structure and enough information. It is important to keep current documents. Proper structure and completeness are essential for getting approvals, from the Notified Body and Competent Authorities.

11. Post Market Surveillance and Vigilance Responsibilities

A PMS system that is functional and risk based should be established by all manufacturers according to the IVDR.

The following are key PMS components:

• Post Market Surveillance Plan (Annex III Part B)

• Periodic Safety Update Report (PSUR) – mandatory for Class C & D

• Reporting trends in minor adverse events and potential adverse events

• Reporting adverse incidents to Competent Authorities

• Field Safety Corrective Actions and Field Safety Notice

These procedures guarantee continuous adherence to IVDR and patients’ safety throughout the lifespan of a device.

12. Timeline and deadlines of IVDR

A new set of regulations concerning the In Vitro Diagnostic Devices took effect on May 26 2022. Though, some companies producing In Vitro Diagnostic Devices have been granted additional time in preparation before compliance. The additional time depends on which type of In Vitro Diagnostic Device Directive is manufactured by such companies. And if they hold appropriate certificate documents according to the regulation of In Vitro Diagnostic Device Directive.

Key dates to know:

13. Language & Labelling Requirements under IVDR

Labelling (Chapter III, Section 20.2) and language requirements (Article 37) are more strict under the IVDR to support patient safety and traceability across the EU.

 Labelling must include:

• UDI DI and UDI PI codes in compliance with Annex VI.

• Name/trade name of the device.

• Manufacturer’s name, registered trade name/mark, and address (plus an Authorized Representative’s details if applicable).

• Importer’s contact information (if device is placed on the EU market by an importer).

• Lot number or serial number for Monitoring.

• Date of manufacture or expiry date where applicable.

• Special storage or handling conditions if required. 

• Sterile indicator and method of sanitation if applicable. 

• Warnings or limitations that are necessary for safe use.

• Intended purpose of the device.

• Symbols as per harmonized standards (EN ISO 15223-1), ensuring clarity without translation where possible.

Language considerations: Article 37  Language requirements

• Translation into official EU languages: All instructions for use IFU, labels, and safety information must be provided in the official languages of the EU Member State where the device is made available to the user or patient.

• Clear and understandable: The language used must be clear and easily understood by the intended user, whether a layperson or healthcare professional.

14. EUDAMED Requirements

The European Database on Medical Devices is the main EU IT system developed with the purpose of ensuring transparency and improving coordination of information concerning medical devices and in vitro diagnostic devices. EUDAMED is the main platform that includes the manufacturer, the Authorized Representative, importer, distributor, Notified Body, and Competent Authorities. All of them register, exchange and control the information. That is all according to the IVDR regulation. 

Core Requirements in In Vitro Diagnostic Regulation (IVDR)

EUDAMED requirements are mainly described in Articles 25 to 34 of the IVDR - Regulation EU (2017/746) and annexes to them. The main requirements include:

Actor Registration

• Registration under EUDAMED is mandatory for importers, manufacturers, and authorized representatives.

• Every individual actor gets assigned a Single Registration Number for identifying purposes.

• Reference: Article 28.

UDI Database

• The data on Unique Device Identification has to be entered into the EUDAMED database.

• Manufacturers should register the Unique Device Identification Device Identifier and the details of the device for the Unique Device Identification.

• Reference: Articles 24 to 27, Annex VI.

Device Registration

• Certificates from Notified Bodies must be entered into the EUDAMED database. 

• Information such as device identification, risk classification, intended use, information about the manufacturer, and certificates is an example of information. 

• Reference: Article 26.

Certificates and Information on Notified Bodies

• Certificates from Notified Bodies must be entered into the EUDAMED database. 

• This provides for transparency and traceability of conformity assessments.

• Reference: Article 51(5).

Clinical/Performance Study Data

• A module dedicated for registration of clinical and performance studies of IVDs is available on EUDAMED.

• It covers applications, authorizations, variations, and outcomes.

• Reference: Articles 57 to 77.

Post Market Surveillance & Vigilance

• Trend reports, PSUR, field safety corrective actions, and serious incidents have to be submitted to EUDAMED by manufacturers.

• Commission and Competent Authorities use this data for safety assessment and monitoring.

• Reference: Articles 82 to 87.

Authorities' Market Surveillance Activities

• Competent Authorities register their market surveillance activities, such as inspections and audits, in EUDAMED.

• Reference: Article 93 to 100.