Team-NB clarifies CDx changes under IVDR Annex IX 5.2

November 11, 2025

What the new Team-NB paper covers

Team-NB has adopted an updated position paper (Version 2, 22 Oct 2025) clarifying which changes to companion diagnostics (CDx) under IVDR Annex IX, section 5.2 must be reported to the Notified Body (NB) and when consultation with the medicinal products authority (EMA or relevant national authority) is required. Under Annex IX 5.2(f), manufacturers must inform their NB before making changes that affect performance, intended use, or suitability of the device in relation to the medicinal product. The NB then decides whether a new conformity assessment is needed or a supplement to the EU technical documentation certificate is sufficient, and whether consultation with the medicinal products authority is required.

The paper also notes that manufacturers are responsible for determining if a change requires consultation and must document and justify a decision not to consult; justifications must be available to competent authorities on request. In general, a change that requires consultation should be considered reportable to the NB.

Legacy CDx under Article 110(3)

For legacy CDx (per MDCG 2022-8), significant changes to design or intended purpose cause loss of legacy status (per MDCG 2022-6) and trigger a new IVDR conformity assessment involving a NB and a consultation with the medicinal products authority.

How Team-NB categorizes changes (with examples)

The annex introduces a practical flow that first asks: Does the anticipated change affect the CDx’s suitability for the medicinal product? Depending on the answer, changes fall into three groups.

1) No EMA/National authority consultation required

(“NO” path in the flow; changes out of scope of medicinal product authority consultation)
Examples:

Change in critical raw material or its supplier
Platform transfer (e.g., validation on a new NGS platform)
Extension of CDx shelf-life
New supplier for a reagent
New place of market in distant sales

2) Follow-up consultation (supplement) — change within the scope of the original consultation

Examples:

New limitation in use of the CDx (e.g., cross-reactivity)
Medicinal product restriction impacting the CDx claim
Large-panel NGS tumour profiling device: addition of tissue type for an existing INN
Changes to analytical parameters of the CDx
Change in reagent presentation (e.g., liquid vs lyophilized) that impacts the CDx claim

3) Initial consultation (new conformity assessment) — change outside the scope of the original consultation

Examples:

Medicinal product extension impacting the CDx claim
Addition of a new sample type that changes intended purpose
Addition of a new/expanded target patient population
Large-panel NGS tumour profiling device: additional INNs after initial certification
Addition of additional mutations with outcome data

Important: Team-NB stresses that the annex examples are illustrative, and final determinations are case-specific based on detailed evaluation.

Practical takeaways for CDx teams

Treat changes that likely affect design or intended purpose as reportable and assess them with supporting evidence.
Document your consultation decision (including rationale for no consultation) and keep it ready for competent authorities.
For legacy CDx, avoid significant changes to design/intended purpose unless you’re prepared for loss of legacy status and a new IVDR assessment with consultation.
Refer to the EMA homepage (or relevant EU/EEA medicinal product authority) for process details on consultations.

Why this matters

This Team-NB paper gives CDx manufacturers and their partners a shared interpretation baseline with Notified Bodies and medicinal product authorities, reducing ambiguity around when to notify the NB and when to seek EMA/national consultation after a change. The included flow and examples help teams pre-classify changes and plan evidence/consultation pathways efficiently.

Need a CDx-focused partner?

If you’re planning or assessing CDx changes under IVDR and want a clear pathway through NB reporting and EMA/national consultations, talk to MDx CRO—a consultancy dedicated to companion diagnostics strategy, clinical evidence, and regulatory execution.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and former BSI IVDR reviewer with deep experience in CE marking high-risk IVDs, companion diagnostics, and IVDR implementation.

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Evidence on delays and the impact on patients

The data are unambiguous: EFPIA’s survey indicates 43 percent of companies estimated six to twelve-month delays due to IVDR, with downstream consequences for trial starts and patient inclusion across major disease areas. Every month lost to mis-sequenced processes or unclear governance is a month patients wait for targeted therapies.

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Key insights from the MPP panel and fellow presenters

Compliance versus innovation is the wrong debate. The practical path forward is compliance and innovation together: a single evidence plan, shared endpoints, and a unified risk–benefit narrative that treats the diagnostic and the drug as interdependent elements of one therapy journey. That is how companion diagnostics under IVDR accelerate, rather than delay, precision medicine.

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Effective combined studies require clear governance between drug and device sponsors, modular and wave submissions across Member States, separate informed consents for the CDx component where appropriate, and proactive scientific advice with EMA or NCAs for borderline cases. With local regulatory intelligence and language capability across Europe, we coordinate roles and documentation so CTR and IVDR remain synchronised throughout the study lifecycle.

Acknowledgment to MPP and our co-presenters

Our thanks to the Medtech & Pharma Platform Association for convening this timely discussion and to the session chairs and speakers who brought regulatory, conformity assessment and patient perspectives to the same table: Fatima Bennai-Sanfourche, Andreas Emmendoerffer, Antonella Baron, Heike Möhlig-Zuttermeister and David Haerry.

Partner with MDx CRO to make CDx work under IVDR

If your programme depends on biomarker-driven enrolment or treatment decisions, partner with a team that speaks CTR and IVDR fluently. MDx CRO compresses timelines, de-risks submissions and delivers companion diagnostics that make precision medicine real for the patients who need it most

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