Why Pharma and IVD Partners Must Collaborate Earlier Than You Think

What Is a Companion Diagnostic, and Why Does It Matter?

Not all combined studies are companion diagnostic studies.

A companion diagnostic (CDx) is a medical device considered essential for the safe and effective use of a corresponding medicinal product.

Its purpose is to:

• Identify patients most likely to benefit from a targeted therapy based on the presence of a specific biomarker
• Identify patients at increased risk of adverse events
• Identify patients unlikely to respond when the relevant biomarker is absent

In the United States (US), regulations may also allow a third function in specific situations: monitoring response to treatment.

The specificity of the CDx label claim, and its direct link to drug approval, means that decisions made during early development can have long-term regulatory consequences.

The Cost of Late Engagement

A situation we encounter regularly is the following:

A pharmaceutical company completes a promising Phase II trial and approaches an IVD manufacturer with a request to develop a companion diagnostic for a Phase III study, all within a six-month timeline.

In practice, this is extremely tight.

Assay development, analytical validation, clinical validation, performance study documentation, and regulatory submissions all require time that cannot easily be compressed without increasing risk.

When earlier clinical trials use a research-use-only (RUO) assay or an in-house device, additional bridging studies are often needed before transitioning to a regulatory-grade device. An RUO kit can serve well for retrospective studies where the interest is purely research-based and no medical management decisions are made.

But as soon as the assay is used for inclusion, exclusion, or other patient management decisions in a prospective interventional trial, it may fall within the scope of applicable IVDR device regulatory requirements.

If this transition has not been planned from the start, bridging the gap between the RUO and the investigational-use device can delay your programme significantly, and these delays are entirely avoidable with earlier planning.

What Early IVD Engagement Enables

Bringing your IVD partner in early, even during Phase I or early Phase II, allows for a more strategic development path. The IVD manufacturer can advise on assay design choices that facilitate future validation. If the manufacturer operates under a quality management system aligned with IVDR requirements, the assay can be developed in a way that builds toward a CE-marked product, avoiding unnecessary duplication of work.

Early engagement also ensures that biomarker strategy, intended purpose definitions, and clinical validation planning are aligned from the start. These elements cascade through every subsequent step: performance study design, regulatory submission content, and ultimately the label claim. The intended purpose statement you define at the beginning shapes the evidence you must generate, the performance endpoints you must demonstrate, and the claims you can make at commercialisation.

Of course, there is a trade-off. In early development, the biomarker strategy may still be exploratory, and there may not yet be sufficient confidence to invest in a full CDx development programme. That is a legitimate concern. But even at this stage, an IVD partner can provide valuable insights into which development avenues to pursue and which to avoid, helping shape a more efficient path forward without requiring a full commitment.

The Pharma-IVD Language Barrier

As highlighted during a joint panel discussion at a recent industry conference involving QbD, GenDx, and representatives from a major pharmaceutical company, one of the underappreciated challenges is that pharma and IVD operate under fundamentally different regulatory languages. The CTR and the IVDR use similar terms but with different meanings and different implications.

A clinical performance study under the IVDR is regulated separately from a clinical trial under the CTR. While they differ in legal framework and terminology, they are often comparable in practice, particularly when patients are involved and clinical data are generated to support regulatory decisions. The fact that the IVDR refers to "performance studies" rather than "clinical trials" does not mean that comparable levels of scientific, ethical, and regulatory scrutiny do not apply. This distinction frequently causes confusion.

Similarly, what constitutes a "substantial modification" differs between the two frameworks. Adding a principal investigator to an already approved site might be a simple notification on the pharma side, but it can trigger a full substantial modification under the IVDR, with its own timelines and documentation requirements.

In practice, the IVD partner often plays a key role in educating pharma on these differences. Assuming the other side understands your framework leads to misalignment, delays, and avoidable RFIs from competent authorities. As noted at the conference, IVD manufacturers cannot simply expect that pharma knows how to "speak IVDR". The regulation is complex, it is relatively new in the context of combined studies, and it requires deliberate effort from both sides to achieve alignment.

Start the Conversation Early

Even when a biomarker strategy remains exploratory, early discussions with an IVD partner can provide valuable insight into:

• Regulatory implications
• Validation pathways
• Assay development considerations
• Potential future bottlenecks

You do not need a fully defined CDx programme to begin the conversation.

You simply need the willingness to plan together.

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Drug-diagnostic co-development continues to expose operational and regulatory grey zones across the pharmaceutical and IVD landscape.

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