The EU Regulation on In-Vitro Diagnostic medical devices 2017/746, also known as the EU IVDR, was published in the Official Journal of the European Union (OJEU) on 26 May 2017, and was set to begin to apply 5 years later from 26 May 2022. The new and improved legislation presents a major overhaul to the previous IVD Directive 98/79/EC (IVDD) and ended an era of relatively lax regulation of certain IVDs. Nevertheless, in doing so, it presents a major challenge for the industry to overcome.
What are the major changes introduced by the EU IVDR? #
There are several changes which have been introduced by the new regulation which may qualify as “major” for IVD manufacturers accustomed to the previous IVDD, including the following:
- New classification system and rules.
- Quality Management System requirements.
- Importer and distributor obligations.
- Person Responsible for Regulatory Compliance.
- Post-Market Surveillance.
- General Safety and Performance Requirements.
- Technical Documentation.
- Reference Laboratories.
Let’s discuss these further below.
New EU IVDR Classification System and Rules #
EU IVDR 2017/746 introduces a classification system similar to that in the EU medical device regulation 2017/745 (MDR), with IVD devices taking on the following distinct classifications:
Using Annex VIII of the EU IVDR, manufacturers must identify and select the most appropriate classification for their device. This decision should be duly justified within a rationale in the Device Description and Specification section of your technical documentation. The Rules themselves are quite descriptive, with Class B being used as a ‘catch-all’ for certain devices which otherwise do not fall under any other rule.
Once the classification has been settled, the manufacturer must then identify the appropriate conformity assessment route applicable to their device (Article 48). Devices falling into the Class B, Class C, Class D classifications, as well as Class A products provided sterile, will require the intervention of a Notified Body as part of their conformity assessment process in order to obtain their CE mark. As many manufacturers will find, there has been a significant increase in the number of products now requiring Notified Body assessment.
If you’re having trouble classifying your device, you can use the helpful guidance provided by the EU Medical Device Coordination Group (MDCG), MDCG 2020-16.
Quality Management System #
The EU IVDR specifically requires manufacturers of IVD products to operate a Quality Management System (QMS) as indicated in Article 10 which discusses the obligations of manufacturers. Paragraph 8 of Article 10 highlights those areas which will need to be addressed in the QMS as a minimum. There are additional provisions throughout the IVDR which may be classification-specific, including those found in Annexes IX to XI, however, the QMS requirements in Article 10 will need to be met by all classifications. The extent of the QMS is expected to be based on the overall risk the device poses.
Importer and Distributor Obligations #
The IVDR has upped the ante on the obligations of importers and distributors in Articles 13 and 14, respectively. As a manufacturer, you must ensure that your supply chain is aware of these new obligations, especially those entities placing your products on the EU market. Importers are now considered to be part of the liability chain in case of defective products and therefore have increased obligations. We’ve dedicated a whole article to the obligations of importers.
Person Responsible for Regulatory Compliance #
Manufacturers are expected to have at least one person within their organisation who shall be appointed as the Person Responsible for Regulatory Compliance (PRRC). They shall be in charge of ensuring that the manufacturer is meeting its obligations as stipulated in the IVDR. In order to qualify as a PRRC, that person will need to meet the qualifications as identified in Article 15. Read our in-depth article on PRRC for more information.
Post-Market Surveillance #
Manufacturers of IVDs were always expected to have in place a system for post-market surveillance (PMS), even under the IVDD. However, the IVDR is far clearer in what these expectations are and what documentation shall be required in order to demonstrate compliance. In essence, a PMS system includes:
- PMS Procedure [QMS-level].
- PMS Plan.
- PMS Report [Class A and B].
- Periodic Safety Update Report [Class C and D].
- Post-Market Performance Follow-up (PMPF) Plan.
- PMPF Evaluation Report.
Post-market surveillance is indeed a major part of compliance with the EU IVDR and it will require an appropriate solution in order to maintain it. Especially for higher-risk devices, PMS will be fundamental in acquiring clinical data and may be a make or break in your conformity assessment process with a Notified Body. Exhibiting a strong and robust PMS system will give a good impression and is key to regulatory success.
PMS is governed by Section 1 of Chapter VII, as well as Annex III and XIII of the IVDR.
The major change within vigilance expectations is that the reporting timelines have been altered such that serious incidents are reported as soon as possible, but within 15 days unless it is a serious public health threat (within 2 days) or has caused death / serious deterioration in a person’s health (within 10 days). Unlike its predecessor, the requirements for vigilance reporting are all neatly contained within the Regulation (Chapter VII, Section 2 for reference) making MEDDEV 2.12/1 rev.8 somewhat redundant.
General Safety and Performance Requirements #
The EU IVDR replaces the Essential Requirements from the IVDD with the General Safety and Performance Requirements (GSPR) in Annex I; although the concept is the same. The manufacturer is required to provide demonstratable evidence for how they have met each of the GSPRs, providing an appropriate rationale when the requirement is not applicable. An industry-standard approach is the development of a GSPR checklist which provides the reviewer with a clear identification of which requirements apply, which do not, and how the manufacturer demonstrates conformity.
EU IVDR Technical Documentation #
Annexes II and III of the EU IVDR provide a clear indication of the documentation expected to be held for IVD devices which should include:
- Device description and specification.
- Information supplied by the manufacturer.
- Design and manufacturing information.
- General Safety and Performance Requirements.
- Benefit-risk analysis and risk management.
- Product verification and validation, including:
- Preclinical testing.
- Performance evaluation plan and report (PEP/PER).
- Post-Market Performance Follow-up.
- Post-Market Surveillance.
Although each IVD product must consider the above sections, the extent of the documentation should be related to the overall risk the IVD product is posing. For example, although Class A IVDs are still expected to have a PER, this will look significantly different to one prepared for a Class D device.
Furthermore, we would suggest grouping together devices with similar intended purposes within the same technical documentation. This is especially true for low-risk devices such as sample receptacles.
EU IVDR Reference Laboratories #
Article 100 of the EU IVDR introduces a new concept as part of the assessment of certain devices: the EU Reference Laboratories (EURL). These are planned to be third-party entities designated by the Commission to carry out the tasks indicated in Article 100(2), including the assessment of Class D IVDs. At the time of writing, little else is known about these entities and none have yet been designated.
We cannot forget about the introduction of EUDAMED, which stands for European Database on Medical Devices. This database is well integrated into the obligations and requirements set in the EU IVDR such as registration of the manufacturer and devices. The database will consist of 6 modules, including:
- Actors registration.
- UDI/Devices registration.
- Notified Bodies and Certificates.
- Clinical Investigations and performance studies.
- Vigilance and post-market surveillance.
- Market Surveillance.
Following a successful registration application for your organisation in EUDAMED, you will be provided with a Single Registration Number (SRN) which is a unique code for your company which will be used to link to your registered devices, importers, and EU authorised representative in order to improve traceability.
EUDAMED is not yet fully functional. Following a number of delays, it is set to become fully functional in 2024.
EU IVDR Transitional Provisions #
As discussed above, manufacturers of devices falling into the Class B, C, D and sterile Class A products must now also apply for Notified Body assessment; a decision which has led to controversy in the industry, with an estimated 90% of existing Directive products now requiring intervention from a Notified Body.
In order to lessen the load, the European Commission introduced a stepped approach to the transitional provisions indicated in an amendment of Article 110 of the EU IVDR. Whilst the IVDR began to apply from 26 May 2022, those devices which now require NB intervention were provided additional grace to meet their requirements, depending on their new classification. Therefore, the following transition dates will now apply:
- Class D: 26 May 2025
- Class C: 26 May 2026
- Class B: 26 May 2027
- Class A (sterile): 26 May 2027
This means that until the appropriate date identified above, the IVD can continue to comply with the EU IVD Directive. The key thing here is that these dates will only apply to those IVDs which did not previously require NB involvement. This means that List A, List B, and Self-Test IVDs which required NB assessment under the IVD Directive will not be eligible for these transitional provisions.
Article 110 is clear in saying that if a product is covered by a valid certificate issued under the IVD Directive, then the manufacturer will have until the end of the validity date on that certificate to meet the requirements of the IVDR. Such IVD products which are allowed to remain compliant with the IVDD due to the provisions laid down in Article 110, are known as “legacy” products.
With all that said, devices which were grouped under the “General IVD” definition under the IVD Directive, and which do not require NB intervention under the IVDR (simple Class A) will need to be compliant with the EU IVDR from 26 May 2022 to continue being placed legally on the EU market.
Terms and Conditions #
There are, of course, Terms and Conditions tied to these transitional provisions. Legacy products (i.e. Directive-compliant devices allowed to stay on the market under the conditions of Article 110) are required to meet the IVD Regulation’s requirements for the following topics from 26 May 2022:
- Post-Market Surveillance. [Chapter VII, Section 1]
- Market Surveillance. [Chapter VII, Section 3]
- Vigilance. [Chapter VII, Section 2]
- Registration of Economic Operators and Devices. [Article 28 and 26]
The issue being faced by IVD manufacturers is that there are only a handful of Notified Bodies currently designated to carry out assessments under the EU IVD Regulation, making conformity assessments a rather tedious and drawn-out process. Even though the transitional provisions are generous, we do recommend that you transition your products to the EU IVDR and contact a Notified Body as soon as possible.
How we can help #
We understand that the EU IVDR is not the easiest text to follow and comply with. There are advantages in both cost and time in outsourcing your regulatory compliance. Our team can help you on various fronts, including:
- IVDR Qualification and Classification.
- IVDR Regulatory Strategy.
- EU IVDR Technical Documentation.
- IVDD-IVDR Gap Analysis.
- Quality Management System Setup/Audit.
- General Consulting.
- EUDAMED Consulting.
Get in touch today, for a free consultation and learn how we can help you further.