CE marking for in vitro diagnostic devices under the IVDR

Since 2017 in vitro diagnostic devices (IVD) are governed in the EU by Regulation (EU) No. 2017/746 (IVDR). Any new IVD placed on the EU market from 26 May 2022 must be developed, manufactured and maintained in accordance with this regulation to be CE marked. If you are unsure about the conformity assessment process for CE-marking under the IVDR, read on.

Key takeaways

  • New IVDs must be CE-marked in accordance with Regulation (EU) No. 2017/746 (IVDR)
  • The requirements have significantly increased from those in the former Directive 98/79/EC (IVDD) and, due to the new classification approach, in far more cases a Notified Body needs to be involved in the conformity assessment.
  • The conformity assessment process involving a Notified Body can be very lengthy. Start the process as early as possible.
  • Affixing the CE mark is not necessarily the last step before selling your device. You still need to ensure registration and labelling translations for the country of interest.

Content

How the IVDR has changed the conformity assessment of IVDs

The new Regulation (EU) No. 2017/746 on in vitro diagnostic devices (IVDR) entered into application on 26 May 2022. Since then, new IVDs and IVDs CE-marked under the former Directive 98/79/EC (IVDD) that do not qualify as “legacy” devices (according to the conditions in IVDR Article 110), can only be placed on the EU market if they are CE-marked under the IVDR.

CE-marking under the IVDR is a significant hurdle compared to the IVDD.

The most significant difference in the IVDR is the new IVD classification based on the intended purpose and inherent risks, analogous to that of non-IVD medical devices, which replaces the list-based categorization in the IVDD. There are now 4 device risk classes, where Class A is the lowest risk class and Class D is the highest.

Most IVDs used to have no categorization under the IVDD, i.e. not in either List A or List B, and could be self-declared by the manufacturer. This has dramatically changed with the IVDR. Many of those self-declared devices fall now into Class B or above, thus requiring the involvement of a Notified Body in the CE conformity assessment. Notified Bodies are independent, third-party companies officially designated by national competent authorities to carry out the conformity assessment process under a given EU harmonized legislation, like the IVDR for IVDs. And Notified Bodies designated under the IVDR are scarce.

The level of compliance requirements increases with the IVD risk class. However, and this is also new under the IVDR, all IVD manufacturers irrespective of the device risk class must:

  • have a Quality Management System (QMS) according to IVDR Article 10, 
  • appoint a Person Responsible for Regulatory Compliance (PRRC) fulfilling the requirements in IVDR Article 15, and 
  • compile a technical documentation with the structure and contents in Annex II and Annex III, as evidence of fulfilment of the General Safety and Performance Requirements (GSPRs) set forth in Annex I of the IVDR.

EU Reference Laboratories are another new requirement introduced by the IVDR. These laboratories are designated by the EU Commission to support Notified Bodies by verifying the performance of Class D IVDs. The number of such laboratories available is also low, contributing to the already lengthy certification timelines of Notified Bodies.

Conformity assessment routes for IVDs

Once the manufacturer has determined the risk class, by following the classification rules in IVDR Annex VIII, it must determine the relevant conformity assessment procedure, as outlined in Article 48 of the IVDR.

Devices intended for performance studies that are not yet CE-marked, or CE-marked for a different intended purpose than the one being investigated, do not bear a CE mark and do not need to undergo a conformity assessment procedure, although specific requirements apply before the investigational device can be used, per Articles 57 through 77 of the IVDR.

Also, in-house IVDs, i.e. those manufactured and used solely within healthcare institutions, do not require CE marking but are subject to strict conditions, per IVDR Article 5.5.

The below table summarizes the applicable conformity assessment routes based on the device classification.

Classification

Conformity Assessment Options

Class A
(non-sterile)

EU Declaration of Conformity (per Annex IV), upon compilation of the technical documentation in accordance with Annexes II and III (without Notified Body involvement)

Class A sterile

Technical documentation in accordance with Annexes II and III. AND Annex IX, chapters I and III. (Notified Body involvement limited to sterility aspects)

OR

Technical documentation in accordance with Annexes II and III AND Annex XI (Notified Body involvement limited to sterility aspects)

Class B

Annex IX, chapters I and III AND Technical documentation assessment (of at least 1 representative device per generic group), per section 4 of Annex IX.

Class B for self-testing or near-patient testing

Annex IX, chapters I and III AND Technical documentation assessment, per sections 4 and 5.1 of Annex IX.

Class C

Annex IX, chapters I and III AND Technical documentation assessment (of at least 1 representative device per generic group), per section 4 of Annex IX.

OR

Annex X AND Annex XI (except section 5).

Class C for self-testing or near-patient testing

Annex IX, chapters I and III AND Technical documentation assessment, per sections 4 and 5.1 of Annex IX.

OR

Annex X AND Annex XI (except section 5).

Class C for companion diagnostics

Annex IX, chapters I and III AND Technical documentation assessment, per sections 4 and 5.2 of Annex IX AND
Notified Body consultation with pharmaceutical competent authorities, per section 5.2 of Annex IX.

OR

Annex X AND Annex XI (except section 5) AND Notified Body consultation with pharmaceutical competent authorities, per section 3(k) of Annex X.

Class D

Annex IX, chapters I and III AND Technical documentation assessment, per section 4 (incl. verification by EU Reference Lab).

OR

Annex X (incl. verification by EU Reference Lab, per section 3) AND Annex XI.

Class D for self-testing or near-patient testing

Annex IX, chapters I and III AND Technical documentation assessment, per sections 4 (incl. verification by EU Reference Lab) and 5.1 of Annex IX.

OR

Annex X (incl. verification by EU Reference Lab, per section 3) AND Annex XI.

Class D companion diagnostics

Annex IX, chapters I and III AND Technical documentation assessment, per sections 4 (incl. verification by EU Reference Lab) and 5.2 of Annex IX AND Notified Body consultation with pharmaceutical competent authorities, per section 5.2 of Annex IX.

OR

Annex X (incl. verification by EU Reference Lab, per section 3) AND Annex XI AND Notified Body consultation with pharmaceutical competent authorities, per section 3(k) of Annex X.

In addition, for Class D devices where no common specifications are available and it is the first certification for that type of device, the Notified Body shall consult relevant experts regarding the performance evaluation report.

Conformity assessment carried out by the manufacturer

For Class A IVDs that are not sterile, the manufacturer has sole responsibility for the conformity assessment and a Notified Body is not involved in the process. This is why these devices only bear a CE mark, without a 4-digit Notified Body identification number.

A successful conformity assessment by the manufacturer presupposes that the product and its related processes (i.e. the manufacturer’s QMS) meet all applicable requirements in the IVDR. Written evidence of conformity must be available for each product (such as technical documentation and batch records) and duly maintained throughout the device lifecycle. This means reviewing all impacted documents upon device changes, changes in processes and changes in regulations, official guidelines or harmonised standards that affect device conformity.

Before releasing a product to market, the manufacturer must declare conformity in the EU Declaration of Conformity. By signing the EU Declaration of Conformity for an IVD, the manufacturer is attesting that the device and its related process (i.e. the QMS) comply with the applicable requirements in the IVDR. A manufacturer should only sign if such compliance is true and can be demonstrated.

In addition, Class A devices placed in an EEA country or Turkey must be registered via the UDI module in EUDAMED or, in some cases, still through the national competent authority. Registration in EUDAMED is incumbent upon the manufacturer, irrespective of the country where it is located. Registration with national competent authorities, wherever still applicable, is usually required from local manufacturers or EU authorised representatives located in that country.

Note also that the information supplied with the device (labels, instructions for use) must be available in the required languages of the countries where the CE-marked device is intended to be sold.

Conformity assessment carried out by a Notified Body

Manufacturers can choose a Notified Body amongst those accredited under the IVDR that have the relevant product group within their scope. Information on the Notified Bodies can be found in NANDO (New Approach Notified and Designated Organisations).

A formal submission for CE mark certification must be filed by the manufacturer to the selected Notified Body. It is not possible to apply to various Notified Bodies simultaneously and it is difficult to change Notified Bodies once the certification process has started. And the certification process with a Notified Body can be extremely lengthy. As shown in the European Commission’s Notified Bodies Survey on certifications and applications (MDR/IVDR), 85% of the IVDR certifications for products take over 13 months, 14% take over 19 months.

Notified Bodies issue different types of certificates depending on the conformity assessment procedure:

  • For the manufacturer’s quality management system: the EU QMS certificate (under Annex IX) or EU production quality assurance certificate (under Annex XI).
  • For the device: the EU technical documentation assessment certificate (under Annex IX) or EU type-examination certificate (under Annex X).

Annual surveillance audits are conducted by the Notified Body and unannounced audits can be decided by the Notified Body in-between surveillance audits.

After the successful conformity assessment, the manufacturer can affix the CE mark on the products and issue a EU Declaration of Conformity in accordance with IVDR Annex IV, attesting that the products conform to the regulation, which entails conformity with all product and product-related processes required by the IVDR.

Note that under the former Directive for medical devices (Dir. 98/79/EC, IVDD), the certificates issued by the Notified Body were named “EC” instead of “EU” and the Declaration of Conformity was named “EC” instead of “EU”, in alignment with the legislation coding.

The Notified Body audits the manufacturer’s quality management system according to the IVDR (where a pre-existing certification to the harmonised standard ISO 13485 provides presumption of conformity) and, depending on the risk class, the audit also includes a review of the technical documentation or design dossier. The purpose of the review is to ensure that sufficient design controls are in place, and that the established processes to create and maintain a technical documentation/design dossier are adequate.

Devices that were assessed with the involvement of a Notified Body are to be marked with a CE mark followed by the identification number of the responsible Notified Body.

The EU Declaration of Conformity is a legal document that must be structured per IVDR Annex IV; all information must be correct and clearly identify the devices.

How Decomplix can help

Decomplix provides expert assessment of your situation and a complete roadmap to obtaining a CE mark for your IVD or your medical device. You can learn more about our services here.

Further reading

More articles