Developing and Labeling Companion Diagnostics for Multiple Oncology Therapeutic Products
This guidance describes considerations for developing and labeling in vitro companion diagnostic devices to support the indicated uses of multiple oncology therapeutic products. It aims to enable broader labeling claims for companion diagnostics when appropriate, rather than limiting labels to specific individual therapeutic products.
What You Need to Know? 👇
What is a companion diagnostic device and how does it relate to oncology therapeutics?
A companion diagnostic is an in vitro diagnostic device that provides essential information for safe and effective use of corresponding therapeutic products. In oncology, these devices detect molecular biomarkers to match patients with therapeutics that will positively respond, maximizing benefits while minimizing risks.
Can companion diagnostics be labeled for multiple therapeutic products instead of just one specific drug?
Yes, when evidence is sufficient, FDA recommends companion diagnostics be labeled for a specific group of oncology therapeutic products rather than individual products. This approach provides greater flexibility for clinicians in choosing appropriate therapeutics based on patient biomarker status.
What are the key considerations for developing broader labeling claims for companion diagnostics?
Key factors include: defining the specific group of therapeutic products, understanding mechanism of action and biomarker interactions, demonstrating sufficient clinical experience with at least two therapeutics, proving analytical validity across biomarker ranges, and establishing clinical validity with therapeutic products in the disease.
How does the EGFR mutation testing example illustrate current companion diagnostic labeling challenges?
Five FDA-approved therapeutics treat NSCLC patients with EGFR exon 19 deletions or exon 21 mutations, but approved companion diagnostics only cover subsets of these drugs. This forces clinicians to potentially order different tests or obtain additional biopsies for treatment options.
What regulatory pathway should manufacturers follow to broaden existing companion diagnostic labeling?
Manufacturers should contact CDRH or CBER and submit a PMA supplement or new 510(k) as appropriate. Submissions must include justification for broader use and valid scientific evidence supporting the expanded labeling claim under 21 CFR 860.7(c)(2).
What role does analytical and clinical validity play in broader companion diagnostic labeling?
Analytical validity ensures the diagnostic performs correctly across all relevant biomarkers with proper sensitivity and specificity. Clinical validity demonstrates the diagnostic’s ability to predict treatment responses and select appropriate patients for the therapeutic products within the defined group.
What You Need to Do 👇
Recommended Actions
- Engage early with FDA (CBER, CDRH, or CDER) in coordination with OCE to discuss development plans
- Define specific group of oncology therapeutic products for companion diagnostic labeling
- Gather evidence demonstrating:
- Analytical validity across biomarker range
- Clinical validity with therapeutic products
- Understanding of mechanism of action and biomarker interactions
- Submit appropriate regulatory pathway (PMA supplement or new 510(k))
- Prepare labeling that:
- Specifies intended use with group of therapeutic products
- References FDA website for current product information
- Consider concordance studies or clinical validation if needed to demonstrate comparable performance
- Document resolution of any differences in technology or cut-offs between tests
Key Considerations
Clinical testing
- Sufficient clinical experience with at least two therapeutic products for the same biomarker-informed indications
- Clinical validity must be demonstrated with therapeutic products in the disease of interest
- Clinical validation may leverage existing data or require new studies showing concordance/comparable performance
Non-clinical testing
- Detailed understanding needed of:
- Mechanism of action of the therapeutic products
- Interaction between therapeutics and biomarkers at molecular level
- Prevalence of biomarkers in population
- Relationship between biomarker expression and therapeutic response
Labelling
- Must specify intended use
- Should name specific group of oncology therapeutic products rather than individual products when appropriate
- Should reference FDA website for current information on therapeutic products in the group
Other considerations
- Analytical validity must be demonstrated across biomarker range
- Different technologies and cut-offs between tests need to be evaluated
- Specific group of oncology therapeutic products must be clearly defined
- At least two FDA-approved therapeutic products should comprise the group
Relevant Guidances 🔗
- In Vitro Companion Diagnostic Devices: Development, Review Process, and Labeling Requirements
- In Vitro Companion Diagnostic Device and Therapeutic Product Co-Development (Draft)
Related references and norms 📂
- 21 CFR 809.10: Labeling requirements for in vitro diagnostic products
- 21 CFR 860.7: Determination of safety and effectiveness