In Vitro Companion Diagnostic Devices: Development, Review Process, and Labeling Requirements
This guidance addresses In Vitro Companion Diagnostic Devices (IVD companion diagnostic devices) that are essential for the safe and effective use of a corresponding therapeutic product. It covers the development, approval process, and labeling requirements for both the diagnostic device and its associated therapeutic product.
What You Need to Know? 👇
What is an IVD companion diagnostic device and how does it differ from regular diagnostic tests?
An IVD companion diagnostic device is an in vitro diagnostic that provides information essential for the safe and effective use of a corresponding therapeutic product. Unlike regular diagnostic tests, its use is stipulated in both the diagnostic device and therapeutic product labeling, making it mandatory for proper treatment decisions.
Do IVD companion diagnostic devices and their corresponding therapeutic products need simultaneous FDA approval?
Yes, in most circumstances FDA requires contemporaneous approval or clearance of both products. The IVD companion diagnostic device should be developed and approved alongside the therapeutic product to ensure it’s available when the therapeutic product is approved, with some exceptions for serious conditions.
What regulatory pathway applies to IVD companion diagnostic devices - 510(k) or PMA?
FDA applies a risk-based approach to determine the regulatory pathway. Most IVD companion diagnostic devices are Class III requiring PMA due to their critical role in treatment decisions, though some may qualify for 510(k) clearance depending on risk level and available controls.
Can an already approved diagnostic device be used as a companion diagnostic for a new therapeutic product?
Yes, but it requires a new premarket submission. If an existing legally marketed IVD device is intended for use as a companion diagnostic with a novel therapeutic product, the new use would require an additional PMA or 510(k) submission for the expanded indication.
What happens if a therapeutic product is approved without an approved companion diagnostic device?
FDA may approve the therapeutic product in limited scenarios, such as treating serious conditions with no alternatives. However, FDA expects subsequent approval of the companion diagnostic device and revision of therapeutic product labeling to stipulate its use, with additional safety protections considered.
How should clinical trials be conducted when studying both an IVD companion diagnostic and therapeutic product together?
Both products can be studied in the same investigational study if it meets IDE and IND regulations. Sponsors may need to submit an IND alone or both IND and IDE, depending on study details. FDA encourages early meetings with both device and therapeutic product review divisions.
What You Need to Do 👇
Recommended Actions
- Engage FDA early in development process through joint meetings with relevant device and therapeutic product review divisions
- Plan for contemporaneous development of therapeutic product and companion diagnostic
- Determine appropriate regulatory pathway (PMA vs 510(k)) based on risk assessment
- Ensure clinical trials generate adequate data to establish safety and effectiveness of both products
- Prepare coordinated submissions for both therapeutic product and diagnostic device
- Develop compliant labeling addressing requirements for both products
- Consider IDE/IND requirements for investigational studies
- Plan for post-approval updates if expanding indications or uses
- Establish quality systems and controls appropriate for risk classification
- Maintain documentation of safety and effectiveness data throughout development process
Key Considerations
Clinical testing
- Clinical performance and significance of the IVD companion diagnostic device should be established using data from clinical development program of therapeutic product
- Both therapeutic product and diagnostic device can be studied in same investigational study if meeting IDE and IND requirements
Labeling
- Therapeutic product labeling must specify use of FDA approved/cleared IVD companion diagnostic device
- IVD companion diagnostic device labeling must specify therapeutic product(s) for which it is approved/cleared
- Labeling of both products must be complete and consistent
- Updates to labeling required when new uses/indications are approved
Safety
- FDA will assess safety and effectiveness through premarket review
- Risk-based approach to determine regulatory pathway (PMA or 510(k))
- Safety measures may include REMS or postmarket requirements if needed
Other considerations
- Contemporaneous development of therapeutic product and diagnostic device is preferred
- FDA generally won’t approve therapeutic product without approved/cleared diagnostic device
- Exceptions possible for serious conditions with no alternatives if benefits outweigh risks
- Early consultation with FDA recommended
- Separate marketing applications required for therapeutic product and diagnostic device
Relevant Guidances 🔗
- In Vitro Companion Diagnostic Device and Therapeutic Product Co-Development (Draft)
- Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices
- Investigational In Vitro Diagnostic Devices Used in Therapeutic Product Clinical Trials (Draft)
Related references and norms 📂
- 21 CFR Part 812: Investigational Device Exemption regulations
- 21 CFR Part 312: Investigational New Drug regulations
- 21 CFR 809.10: Labeling requirements for in vitro diagnostic products