Development and Approval of Companion Diagnostics (CDx) – Impact of the EU Biotech Act and the MDR/IVDR Revision

Companion Diagnostics ("CDx") play a central role in modern healthcare. Particularly in the field of personalised medicine, which is of significant importance in areas such as oncology and rare diseases, CDx ensure the success of pharmaceutical therapy. Through their use in examining human samples, it is possible, for instance, to determine whether a patient carries the biomarkers that the proposed medicinal product is intended to target. Under Regulation (EU) 2017/746 on in vitro diagnostic medical devices ("IVDR"), a CDx is defined as an in vitro diagnostic medical device “which is essential for the safe and effective use of a corresponding medicinal product to:

a) identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or
b) identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product (Art. 2 no. 7 IVDR).

In practice, CDx and the corresponding medicinal product are precisely coordinated with one another. CDx are regularly incorporated into the clinical trial of the medicinal product under Regulation (EU) 536/2014 ("CTR") or even developed in parallel. Unlike in other jurisdictions, however, the development and authorisation procedures are regulated separately, which poses considerable challenges for CDx manufacturers and sponsors of clinical trials. As early as 2024, efforts to harmonise these procedures at the European level were initiated through the COMBINE programme. On 16 December 2025, the European Commission published two proposals aimed at strengthening the European biotechnology sector („EU Biotech Act“) and amending Regulation (EU) 2017/745 on medical devices and the IVDR („MDR/IVDR Revision“; see our article Revision of the MDR and IVDR: European Commission Presents Reform Proposal for Simplification), which also contain significant changes affecting the development and approval of CDx.

I. Current Regulatory Framework

In the EU, the development and approval of CDx is carried out separately from the corresponding medicinal product. Demonstration of compliance with the general safety and performance requirements for the CDx, i.e. confirmation of analytical performance or clinical performance, takes place by means of so-called performance studies (Art. 57 et seq. IVDR). CDx performance studies require, in particular, authorisation from the competent authority and invariably involve the relevant ethics committees. Exceptions exist only for performance studies using left-over specimens (e.g. residual material from other studies, provided this is covered by the subject's informed consent). 

In order to affix the CE marking under the IVDR, a conformity assessment involving a Notified Body is necessary, as CDx fall into at least the second-highest risk class C (Annex VIII rule 3 lit. f) IVDR; MDCG 2020-16 rev.4, p. 22). The Notified Body must also obtain a scientific opinion on the suitability of the CDx from the national medicines authority or the EMA. A link to the corresponding medicinal product is established only to the extent that the International Nonproprietary Name (INN) is listed in the CDx's instructions for use. 

In many cases, only parallel development of the CDx and the medicinal product is possible. However, there is no uniform procedure for combined studies involving (not yet authorised) CDx used as assays in clinical trials of medicinal products due to the different regulatory frameworks and competences. Clinical trials for the medicinal product and the CDx may be conducted simultaneously, but they proceed through two separate regulatory processes, typically involving different sponsors. Sponsors have so far been dependent on a patchwork of individual member state regulations (MDCG 2022-10, question 10). 

II. Revision of the IVDR

New Definition of CDx

The Commission's proposal first includes a clarifying expansion of the CDx definition. As it has already been the practice, in vitro diagnostic medical devices shall now also expressly qualify as CDx where they are intended for the safe and effective use of multiple medicinal products (Art. 2 no. 7 IVDR). Accordingly, the Commission's proposal provides that, as an alternative to the INN of the corresponding medicinal product, the relevant class of corresponding medicinal products may also be indicated in the CDx's instructions for use (Annex I Sec. 20.4.1 lit. c) viii) IVDR). Products used for monitoring treatment with a medicinal product in order to ensure that the concentration of the relevant substances in the human body remains within the therapeutic window (so-called complementary diagnostics, e.g. blood glucose monitoring) shall, however, continue not to be qualified as CDx.

Facilitation of CDx Performance Studies

Furthermore, the Commission's proposal provides for simplifications in respect of CDx performance studies that do not entail any additional risks for subjects. Performance studies involving only routine blood sampling from non-vulnerable study participants shall no longer be subject to the additional requirements under Art. 58 to 76 IVDR and, in particular, shall no longer require authorisation from the competent authority. For such performance studies, only notification obligations vis-à-vis the authorities and the general requirements in conjunction with the respective national law shall apply. For CDx performance studies using exclusively left-over specimens, even this notification obligation of the sponsor is to be dispensed with (Art. 58 para. 1 lit. c), 2 IVDR; Recital (50) MDR/IVDR Revision).

Primacy of Pharmaceutical Law for Combined Studies

Moreover, the Commission's proposal sets the course for a genuine co-development of CDx and the corresponding medicinal products. For the first time, the Commission's proposal introduces the concept of a combined study. Combined studies are defined as clinical trials involving medicinal products within the meaning of the CTR that are combined with performance studies for in vitro diagnostic medical devices (including CDx) (Art. 2 no. 75 IVDR). Within the framework of these combined studies, sponsors of performance studies requiring authorisation shall have the option of a single application and assessment procedure. As an alternative to the current separate application process under the IVDR (in the affected member states) and the CTR (via the EU portal CTIS), sponsors shall be enabled to submit a single application for a combined study. In such cases, a primacy of pharmaceutical law shall apply, and a coordinated assessment shall take place exclusively in accordance with the provisions of the CTR (Art. 75a IVDR; Recital (43) MDR/IVDR Revision). 

Consultation of Medicines Authorities

Finally, the Commission's proposal emphasises that the consultation of the medicines authority, as currently provided for, shall only be required for novel CDx. For established CDx, a renewed assessment is to be waived. In this context, the European Commission also clarifies that the medicines authority shall not repeat the medical device regulatory assessment carried out by the Notified Bodies (Art. 48 para. 10b IVDR, Annex IX Sec. 5.2 lit. c), g) IVDR respectively Annex X Sec. 3 lit. k) IVDR; Recital (49) MDR/IVDR Revision). 

III. EU Biotech Act

Coordinated Assessment Procedure for Combined Studies

The EU Biotech Act establishes the legal prerequisites for implementing the unified assessment mechanism for combined studies. To this end, an identical definition of combined studies is to be codified in pharmaceutical law as well (Art. 2 no. 44 CTR). The Commission's proposal then sets out substantive details regarding the procedure for the coordinated assessment. The sponsor's single application is first to be transmitted via the EU portal to all affected member states. The assessment of the application is then carried out under the lead of a reporting member state and also encompasses the assessments of the competent authorities and the ethics committees. Objections raised by affected member states during and after the assessment are to be limited to specific grounds. The final decision on the authorisation of the combined study, however, is to remain with each affected member state individually. The European Commission is empowered to amend or supplement the relevant provisions of the CTR with regard to the conduct of combined studies by means of delegated acts (Art. 14c CTR; Recital (135) EU Biotech Act).

Combined Studies Involving AI

In the examination of human samples, analytical software is regularly employed which, depending on its intended purpose, may itself constitute a CDx. In practice, such software-based CDx increasingly utilise artificial intelligence. Examples include machine learning for the localisation of granular biomarkers, pattern recognition in identifying suitable or unsuitable patients, or linking vast datasets with patient data to create comprehensive suitability profiles. The Commission's proposal also provides for the described coordinated assessment for the authorisation of combined studies involving such AI-based CDx. Corresponding guidelines on the handling of AI are to be developed by the EMA, the newly established Clinical Trials Coordination and Advisory Group (CTAG), the MDCG and the Artificial Intelligence Board (Art. 27e para. 3, 4 CTR).

IV. Conclusion and Outlook

On a global scale, the market for personalised medicine and CDx is experiencing strong growth. In the EU, however, the rigid regulatory requirements for CDx manufacturers and sponsors of clinical trials have posed considerable challenges in recent years to the practical implementation of research and development projects. The simplifications introduced through the EU Biotech Act and the MDR/IVDR Revision are therefore welcome from an industry perspective. Nevertheless, both Commission proposals merely mark the beginning of the respective legislative processes. The opinions of the European Parliament and the Council are still pending. It remains to be seen how quickly the European legislator will be able to translate these plans into action.