Points to Consider for the Development of Companion Diagnostics Developed in Parallel with Anti-cancer Drugs — PMDA Early Consideration Summary

In Plain Language

A companion diagnostic is a diagnostic product used alongside a medicine to help identify patients expected to benefit, guide dosing, or support a treatment decision. This document addresses how developers of anti-cancer drugs can decide whether such a product is needed and whether it should be treated as a companion diagnostic for that drug. PMDA says the assessment should consider the role of the biomarker, the drug’s mechanism of action, and how the diagnostic product is used in pivotal clinical trials. It also emphasizes early coordination between the drug and diagnostic developers, including consultation with PMDA when the need is identified. The aim is to plan the two development programmes together so that the diagnostic product can help identify in clinical practice a patient group comparable to the group in which the drug’s efficacy was demonstrated.

What This Guidance Covers

The document concerns diagnostic products considered alongside anti-cancer drugs. It uses “diagnostic products” to refer to in vitro diagnostic products or medical devices that detect specific gene mutations or protein expression. In the context described, these products may be used when a drug is administered to identify patients expected to benefit, identify patients at high risk of a particular adverse reaction, or determine appropriate dosage and administration for individual patients.

Its scope includes deciding whether a diagnostic product is needed for use of an anti-cancer drug and assessing whether the product qualifies as a companion diagnostic (CDx). It also addresses practical development planning: the diagnostic product used in pivotal trials, the product planned for approval, consultation with PMDA, and coordination of application and approval timing. The document distinguishes this purpose from diagnostic products used to diagnose the target disease or classify disease types: those products are excluded from the stated perspective for determining whether a product is a CDx.

The considerations include cases where an already approved diagnostic product can measure the biomarker of interest, but its intended use does not describe use as a CDx for the anti-cancer drug concerned. They also include diagnostic products needed to identify patients eligible for a specific medicinal product used in combination with the anti-cancer drug, and products used to confirm patient characteristics such as genetic factors for safe use of the drug.

Why It Matters

Some anti-cancer drugs are developed for use in patients identified by a biomarker, or may need a diagnostic product to support safe or appropriate treatment. The document notes that, in principle, applications for a CDx and its corresponding therapeutic product should be submitted at approximately the same time. Aligning the development, application, and approval schedules therefore calls for developers to identify issues early, beginning with clinical-trial planning, and to establish a development strategy through consultation with PMDA.

One practical concern is that the diagnostic product used in a pivotal clinical trial may not be the same product intended for use after approval. The document says the trial product should be submitted for approval as a CDx so that clinical practice can identify a patient population comparable to the one in which efficacy was demonstrated. If a different product is expected to be used after approval, developers should consider whether analytical equivalence can be demonstrated using results from a concordance study. In other words, planning for the relationship between the trial assay and the intended clinical-use assay is part of the development strategy, not an issue to leave until the end.

The document also highlights timing beyond regulatory review. In principle, the CDx should be covered by insurance by the time the corresponding anti-cancer drug is listed on Japan’s National Health Insurance drug price list. The schedules for both products therefore need to account for the relevant application, review, and insurance-coverage timing.

Key Recommendations

1. Assess the need for a diagnostic product and whether it qualifies as a CDx. Developers should consider whether the product is essential to use of the anti-cancer drug for identifying patients expected to benefit, optimizing dosage and administration, or determining whether treatment should be discontinued. Products used to diagnose the target disease or classify disease types are excluded from this particular consideration.

   The assessment should also consider how the measured genes, proteins, or other targets relate to the drug’s mechanism of action, and their biological significance in tumors, including their contribution to cancer development and progression. Developers should consider whether the diagnostic product is needed for patient or dose selection in pivotal clinical trials, such as confirmatory trials.

2. Consider trial evidence in the relevant patient groups. If both biomarker-positive and biomarker-negative patients can be enrolled in pivotal trials, the necessity of selecting patients using a diagnostic product should be carefully determined. The document says to consider the benefit-risk balance in the overall population and in the positive and negative populations, along with the drug’s pharmacological mechanism and other relevant factors.

3. Make a comprehensive assessment and consult if qualification is uncertain. Whether a product qualifies as a CDx should be determined from a comprehensive assessment of the considerations above. If there is uncertainty about whether it qualifies, consultation with PMDA should be considered.

4. Assess the need early and coordinate between developers. Anti-cancer drug developers should assess the need for a CDx from early development and, where appropriate, share relevant information with diagnostic-product developers. The developers should collaborate and coordinate while considering the timelines for development, application, and approval of both products.

5. Evaluate the diagnostic product used in pivotal trials. Developers should consider whether its analytical performance and clinical performance have been appropriately evaluated. Analytical performance concerns how well the product measures or detects its target; clinical performance concerns how it performs in the clinical context in which it is used.

6. Plan for the relationship between the trial product and the product intended for use after approval. The diagnostic product used in pivotal clinical trials should be submitted for approval as a CDx so that clinical practice can identify a patient population comparable to the one in which efficacy was demonstrated. If a different product is expected after approval, developers should consider whether analytical equivalence between the products can be demonstrated based on concordance-study results.

7. Consider whether a CDx approval application is needed in specified situations. This includes when an approved diagnostic product can measure the biomarker targeted by the drug but its intended use does not describe use as a CDx for that drug; when a diagnostic product is needed to identify patients eligible for a specific medicinal product used in combination with the anti-cancer drug; and when confirmation of patient characteristics, including genetic factors, is needed for safe use. The document refers to an approval application or a partial change approval application, as applicable.

8. Consult PMDA early once the need for a CDx has been identified. Developers are encouraged to share the development plan and seek consultation as early as possible, and no later than consultation on the proposed design of the pivotal clinical trial. The consultation materials should cover the rationale for the CDx, the product planned for approval, and the relationship between that product and the product used in pivotal trials.

9. Coordinate application and approval timing with insurance coverage in view. In principle, a CDx should be covered by insurance by the time the corresponding anti-cancer drug is listed on the National Health Insurance drug price list. For drugs already listed, the document gives the time of regulatory approval as the reference point. The development schedule should account for the period required for CDx insurance coverage, the scheduled timing of the drug’s listing, and the standard review period based on the CDx application category. If delays are anticipated, developers should consult PMDA as early as possible.

The document also notes that a notification has been issued concerning cases where it is difficult to submit a CDx application at approximately the same time as the application for a drug developed in investigator-initiated clinical trials in patients with rare cancer.

Practical Implications

Interpretation: The document’s approach makes the CDx decision part of the anti-cancer drug’s development planning. Drug developers may need to start discussions about the biomarker and the proposed diagnostic product early enough to affect trial design, rather than waiting until the drug application is being prepared. When appropriate, relevant information should be shared with diagnostic developers so the two products’ development timelines can be coordinated.

For statisticians and clinical teams, the pivotal-trial population and the way it relates to biomarker status are central planning considerations. If positive and negative patients are both enrolled, the document specifically points to the benefit-risk balance in the overall population and in each biomarker group. That makes it important to plan how relevant efficacy and safety information in those groups will support the assessment of whether selection is needed.

For diagnostic developers, the intended product for approval should be considered alongside the assay used in pivotal trials. Teams should be prepared to describe the assay principle, how biomarker positivity is defined, the product’s analytical and clinical performance, and its regulatory approval and development status in Japan and overseas. Where products differ, developers should consider whether a concordance study can support a demonstration of analytical equivalence.

For regulatory and project teams, the consultation timing is linked to a concrete development milestone: the proposed design of the pivotal clinical trial is the latest point by which the document encourages consultation after the need for a CDx has been identified. Teams should also consider which PMDA office is appropriate for the subject matter and revisit consultation if the clinical necessity or positioning of the diagnostic product may change during development.

Finally, planning needs to connect regulatory schedules with insurance coverage. The document identifies the anticipated drug listing or approval timing, the CDx application category’s standard review period, and the time needed for insurance coverage as schedule considerations. If the combined schedule appears likely to slip, developers are advised in the document to consult PMDA as early as possible.

Technical Details

The document does not prescribe a statistical formula or numerical decision threshold. Instead, it sets out a structured assessment and describes the information and product characteristics to consider.

The information for PMDA consultation should include the rationale for considering a CDx necessary, such as the drug’s mechanism of action, the tumor biological significance of the biomarker, efficacy and safety data in biomarker-positive and biomarker-negative patients, and the proposed data package. It should also describe the planned diagnostic product and its relationship to the product used in pivotal trials. Depending on the consultation subject, the document identifies the Office of New Drug V, Office of Software as a Medical Device, or Office of In Vitro Diagnostics as the appropriate office.

Who Should Read It

This document is relevant to developers of anti-cancer drugs and diagnostic products, especially teams planning pivotal clinical trials where a biomarker may influence treatment selection, dose, or safe use. It may also be useful to clinical operations teams coordinating trial and assay development; statisticians and scientists evaluating biomarker-defined trial populations; regulatory affairs staff preparing PMDA consultation materials; and project teams responsible for application, approval, and insurance-coverage schedules.

Official PMDA Source

• Official title: Points to Consider for the Development of Companion Diagnostics Developed in Parallel with Anti-cancer Drugs(Early Consideration)
• Issuing body: Pharmaceuticals and Medical Devices Agency (PMDA); Office of New Drug V, Office of Software as a Medical Device, Office of In Vitro Diagnostics
• Date on the cover: October 5, 2026
• Official PMDA PDF: Read the PMDA document (PDF)
• PMDA list page: PMDA Early Consideration documents

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA list page. This page was created by editing and summarising the PMDA document.

Consult the official document; this summary does not replace it. PMDA provides the English version for reference purposes, and the Japanese original prevails if the two differ. PMDA describes Early Consideration documents as reference information reflecting its views at the time of publication, which may change as scientific knowledge develops.

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