Over the holidays, the European Commission released amendments to the IVDR that could materially change how clinical trial biomarker testing is delivered in Europe.
It’s a dense update, but for sponsors running enrolment-critical biomarker strategies, there are some genuinely meaningful implications, particularly around who can develop and run diagnostic-grade assays, under what conditions, and with what level of regulatory risk.
The extended in-house device exemption for LDTs
The most significant change, in my view, is the formal extension of the in-house device exemption to laboratory-developed tests (LDTs) used exclusively in clinical trials, provided the laboratory is established in the EU. That may sound technical, but operationally it brings long-overdue regulatory clarity. EU-established labs now have a far more defensible position when developing and running diagnostic-grade assays for enrolment and treatment decisions. That clarity translates directly into reduced regulatory risk and greater sponsor confidence.
Operational changes impacting biomarker testing workflows
There are several other changes that are particularly relevant from an operational perspective:
- The requirement to demonstrate that no equivalent commercial test exists for in-house IVDs has been removed. This significantly reduces friction for protocol-specific assays already validated in experienced laboratories, without forcing unnecessary revalidation of CE-marked alternatives.
- LDTs can now be transferred between health institutions within the EU where justified, in the interest of public health or patient safety. This better reflects how multi-site and multi-vendor clinical trial models actually operate.
- The framework clearly favours ISO 15189 as the recognised quality standard for laboratories benefiting from reduced documentation expectations.
The role of ISO 15189 and GLP compliance under the amended framework
That last point is worth diving into a bit further, as this is something I often discuss with Sponsors and internal stakeholders alike.
Most CRO laboratories are GLP or GCLP-accredited, not ISO 15189-accredited, and the amended IVDR recognises that reality, but with conditions. GLP-only laboratories can still rely on the in-house exemption, provided they maintain robust documentation demonstrating compliance with the IVDR General Safety and Performance Requirements (GSPR). In other words, the question is no longer whether GLP labs can support diagnostic-grade testing, but whether they have the right systems, traceability, and risk documentation in place to bridge that gap.
From a sponsor perspective, this is critical. Enrolment-critical assays typically sit outside traditional exploratory bioanalysis: they require faster turnaround times, tighter change control, and a regulatory mindset aligned with patient safety rather than purely pharmacodynamic interpretation. CROs that understand this and have already built the appropriate GSPR-aligned documentation frameworks into their GLP operations are far better positioned to support these strategies without introducing avoidable regulatory risk.
Implications for sponsors working with EU-established laboratories
One further consequence worth stating explicitly: these clarifications apply only to laboratories established in the EU. Is this reasonable or necessary? Probably not. Does it, on its own, mandate a shift in trial location or CRO footprint? Also no. However, the fact that regulatory clarity is now explicitly anchored to EU-established laboratories may create a degree of comfort for sponsors who still perceive diagnostic testing under IVDR as a higher-risk area. In practice, that comfort can matter. Where enrolment-critical biomarker results are concerned, sponsors tend to favour options that minimise interpretive or jurisdictional ambiguity, even when the underlying science and quality systems are equivalent. The result may end up being a subtle preference for partners operating within a framework that regulators have clearly defined, at least for now.
In conclusion, I don’t think these amendments solve every IVDR challenge, but they do provide something the industry has been missing: a coherent and workable pathway for developing and running fit-for-purpose diagnostic assays within clinical trials.
If you are looking to partner with a CRO that understands both the letter of the regulation and the realities of applying it in a clinical trial setting, Synexa can help you to navigate the new IVDR landscape with confidence.
