Introduction

Assays used in clinical trials vary widely in complexity and regulatory status.. They may be fully developed and marketed as in vitro diagnostic medical devices (IVDs), including companion diagnostics (CDx), that clearly fall within the scope of the EU In Vitro Diagnostic Regulation (IVDR) and/or the UK Medical Devices Regulations 2002 (UK MDR). Alternatively, they may be bespoke assays created specifically for use in a given clinical trial or in connection with an investigational medicinal product (IMP).

Importantly, however, the fact that an assay has been developed specifically for a clinical trial does not exempt it from IVD regulation. If an assay meets the definition of an IVD and is placed on the EU or UK market, the applicable regulatory regime will apply.

The MHRA has emphasised that assays used for identification, selection, stratification, and monitoring of clinical trial participants will likely fall within the IVD framework, and similarly EU guidance refers to the use of assay for medical management decisions, though interestingly excludes stratification.

It is equally important to note that use of an assay within a clinical trial does not, in itself, mean the device has not been placed on the EU or UK market. The same supply rules apply as outside the clinical trial context.. These considerations require determination on a case-by-case basis, with analysis of the intended purpose and the supply circumstances.

The clinical trial sponsor, rather than the legal manufacturer, bears responsibility for determining the regulatory status of an assay used in a clinical trial and to ensure regulatory compliance. Additionally, where sponsors assign a medical purpose or use to a CE/UKCA‑marked IVD outside its intended purpose, they may assume the role of an IVD manufacturer under the relevant legislation.

This article outlines the regulatory position in the EU and the UK, identifies areas of alignment and divergence, and sets out key considerations for clinical trial sponsors and IVD manufacturers.

EU Position

The EU Clinical Trials Regulation (EU CTR) and the IVDR acknowledge the need for interoperable databases for clinical trials involving medicinal products and IVDs. However, the two regimes do not contain explicit legislative provisions on how the rules interface where an IVD is used within a clinical trial.

Practical guidance is provided through the MDCG 2022‑10 Q&A document, which clarifies the responsibilities of clinical trial sponsors and the conditions under which IVDs may be used in an EU clinical trial.  

This guidance is clear that any IVD used in the clinical trial must comply with the IVDR. Specifically, the IVD must either:

1. Be CE‑marked for the intended purpose used in the clinical trial,
2. Qualify as an in‑house IVD under Article 5(5) IVDR, or
3. Be subject to a performance study conducted in parallel with the clinical trial under the IVDR.

Each of these pathways requires careful assessment:

• CE-marked IVDs must be used strictly within the scope of their intended purpose. If an IVD is CE‑marked but used for a new or different intended purpose within the trial, it may no longer be considered compliant.
• In-house IVDs are permitted only where the health institution manufacturing and using them meets extensive Article 5(5) requirements, many of which are complex and operationally demanding. Some EU Member States also impose additional national requirements, requiring further local assessment. Note that the European Commission’s recent proposals on amending the MDR and IVDR include easing of some of the in-house exemption requirements – read about this in more detail in our blog on the proposals.
• Performance studies must comply with regulatory requirements, including Annexes XIII and XIV of the IVDR, as applicable, and may impose significant regulatory and practical burdens, making them an onerous option for many sponsors.

Furthermore, Article 6.2 of the IVDR (and the MDR) sets out that any natural or legal person offering diagnostic or therapeutic services through distance sales to patients in the EU must use devices that comply with the regulations. Importantly, the in-house exemption under Article 5(5) is only applicable to health institutions within the EU.

Failure to comply with IVDR requirements may lead to regulatory sanctions. More critically, a non-compliant IVD risks compromising Good Clinical Practice (GCP) standards and data integrity, and regulators may decline to accept trial data where the validity or reliability of an assay cannot be demonstrated.

UK Position

The UK clinical trials regime is undergoing significant transformation, with the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 expected to apply from 28 April 2026. Additionally, the UK MDR is undergoing staged reform with the aim of aligning more closely with international best practice and ensuring a proportionate, risk‑based approach for Great Britain (GB). Note, however, that the EU IVDR continues to apply in Northern Ireland.

The MHRA’s recent guidance, supported by a recent webinar, outlines how IVDs should be handled within GB clinical trial applications. Sponsors must provide information on every IVD used in a trial in the covering letter sent as part of the trial application, including:

• whether the IVD is CE or UKCA‑marked for its intended purpose (CE marks remain recognised in GB until at least June 2030, with the possibility of indefinite recognition being implemented).
• details of the IVD and its manufacturer; and
• justification for use where the IVD is not marked.

The MHRA therefore requires sponsors to provide upfront information enabling the MHRA to assess the suitability of any IVDs used in clinical trials as part of the incoming reforms. Where an IVD is not CE‑ or UKCA‑marked for use in the clinical trial, the MHRA permits several pathways:

1. Use of the health institution exemption under Article 33 UK MDR. Conditions must be met, but these are currently considerably less burdensome than Article 5(5) IVDR. This includes that the IVD must be used on the same premises or in the immediate vicinity of the health institution.
2. If the IVD is not marked and the exemption above does not apply, an analytical performance study should be conducted in relation to the IVD, and the analytical performance summary report(s) for the IVD should be submitted with the clinical trial application, demonstrating evidence of device performance.
3. Where no analytic performance study has been conducted at the point of application,, a Tabular Summary and a completed checklist should be submitted to the MHRA, which describes the analytical methods, including acceptance limits and parameters for performing validation.

The MHRA’s approach therefore appears less onerous than the EU’s, especially since it does not require a parallel performance study, but requires certain information to be supplied to enable the MHRA to assess whether the IVD is suitable and safe to use in the clinical trial, which could significantly reduce regulatory burden. That said, this guidance is new and untested in practice, and sponsors should monitor how it is applied.

Furthermore, if a trial involves sites in both GB and Northern Ireland, it seems that IVDR requirements apply instead of or in addition to the MHRA’s approach. This creates a dual‑compliance scenario requiring careful planning.

There remains uncertainty as to whether data generated under the UK’s more flexible framework will be accepted by EU regulators, particularly where the IVD was not CE-marked or subject to a performance study. This is an area that will need to be tested in practice.

Key Considerations for Sponsors and Manufacturers

When planning a clinical trial involving any assay that may qualify as an IVD, sponsors and manufacturers should address the following::

• Determine whether the assay for use in a clinical trial meets the definition of an IVD under the relevant regulatory regime, whether it is CE or UKCA marked, and whether it is being used in accordance with its intended purpose.
• Where an assay meets the definition of an IVD and is not marked accordingly, or is used outside of its intended purpose, determine which other compliance options are available and can feasibly be met.
• The clinical trial sponsor should also determine whether it is assigning a medical purpose to the assay and if so, whether they are attaining the role of legal manufacturer of an IVD.
• Determine which jurisdictional rules apply to the IVD, based on the location of the clinical trial site(s).
• If a performance / analytical study is required, it must be determined which entity is responsible for its conducted. If it is the trial sponsor, it should be clarified whether the legal manufacturer will support the study and/or provide the sponsor with particular documentation, including parts of the technical documentation and clinical evaluation documents.
• The regulatory requirements for the type of performance study required should be determined. 
• It must be considered whether the IVD is being placed on the relevant market (which seems likely in the context of a commercial clinical trial), and if so, who the actors in the supply chain are and their obligations under the relevant regulatory regime.
• It should be determined whether a UK Responsible Person or EU Authorised Representative needs to be appointed by the legal manufacturer.
• It should be determined which regulatory authorities, along with notified bodies, will be involved in the authorisation of both the clinical trial and the use of the IVD in that context. For example, EMA involvement is required for the conformity assessment of CDx.
• Contracts must be reviewed and tightened to ensure these reflect each relevant party’s respective obligations and commitments, and include suitable contractual indemnities and liabilities.
• The sponsor must ensure it is aware of potential repercussions should a non-compliant IVD be used in its clinical trial, including the possibility that this may invalidate certain data, meaning there is a risk regulatory authorities would reject this.
• The legal manufacturer must ensure its regulatory vigilance obligations can be met.

Each of these factors requires careful, case-by-case consideration. Our European regulatory team regularly advises clients on navigating the applicable framework, supporting strategic decision-making and ensuring that commercial arrangements adequately protect their interests. If you would like to discuss any of the issues raised in this article, please do not hesitate to get in touch.