Precision medicine works when the right biomarker test reaches the right patient in time.
In Europe, the regulatory plumbing is making that harder than it should be.
At the 16th Clinical Biomarkers & CDx Summit in London in March 2026, I discussed lessons from MDx CRO’s experience across 40+ combined IVD/clinical and CDx programs in Europe. One case captured the problem particularly well.
A pharma sponsor ran the same protocol involving a CE-marked companion diagnostic used on leftover tumour samples, with the diagnostic component intended to be exploratory. The same study was discussed with three national competent authorities. One authority indicated that no submission was required. A second considered a full Performance Study Application (PSA) mandatory. A third did not provide a clear position within the consultation window because there was no formal process for this type of query, but indicated that a Performance Study Notification (PSN) could be required.
Same device. Same samples. Same study context. Three incompatible answers.
A regulatory affairs director in the audience asked the sharpest question: “If one Member State requires the full PSA route, should we follow that stricter position across the more permissive countries as well, just to keep the programme harmonised?” It was half a joke. It was also exactly the problem.
This type of divergence can cost sponsors months. In one case, the diagnostic component alone contributed to a 4-6 month delay. EFPIA data has also shown that 43% of companies surveyed expected 6-12 month IVDR-related delays to clinical trials using IVDs.
The root cause I see most consistently is that pharma teams still treat the IVDR performance study as the diagnostic partner’s problem, rather than as a core part of the clinical development programme. Under Article 2(57) of the IVDR, the sponsor is the entity taking responsibility for the initiation, management, and financing of the performance study. In practical terms, that means IVDR strategy cannot sit outside the master trial plan.
The most expensive mistake is late engagement. In one case I have seen, the sponsor had not properly addressed IVDR requirements until three months before first-patient-in. The result was a nine-month delay and substantial avoidable cost, in the range of €800K-€1.2M.
What is Actually Changing
Things are moving in the right direction. MDCG 2025-5, published in June 2025, introduced a decision tree for PSA/PSN classification and clarified “interventional” in the IVDR context. This should help reduce divergent NCA interpretation, although it remains guidance and national implementation may still vary.
The December 2025 Commission package, including the Biotech Act and related targeted MDR/IVDR amendments, also points toward a more integrated application pathway for combined studies, with coordinated assessment across Member States. That would be real structural change, but sponsors should not plan around it being operational before late 2027.
What to do Now
Until then, precision oncology sponsors need to build IVDR into the master trial timeline from day one. Resolve PSA/PSN classification at protocol design, not after three authorities disagree. Select Wave 1 countries based on confirmed national process, review predictability, and administrative burden. And treat the diagnostic workstream as a strategic dependency for patient access, not a parallel regulatory exercise.
Author Bio
Carlos Galamba has more than 18 years of experience in the in vitro diagnostics (IVD) sector, combining scientific expertise in transfusion medicine and infectious disease diagnostics with extensive regulatory experience gained at BSI, one of the European Union’s largest Notified Bodies. This unique background provides an integrated perspective on IVD regulatory strategy and compliance.
His expertise encompasses Class C and D IVDs, companion diagnostics, next-generation sequencing (NGS)-based assays, and software-based IVDs. In addition, he currently serves as an advisor to the European Commission on regulatory matters.
At MDx CRO, Carlos leads regulatory strategy for complex IVD development programs, supporting clients across EU IVDR, FDA, and international regulatory frameworks.
