Bridging Strategies for Drug-Device and Biologic-Device Combination Products (DRAFT)
This guidance provides recommendations on bridging strategies for drug-device and biologic-device combination products in NDAs or BLAs. It specifically addresses bridging between combination products that employ different device constituent parts with the same drug/biologic, or different drugs/biologics with the same device constituent part.
This is a draft guidance. Not for implementation.
Recommended Actions
- Conduct gap analysis using the 5-step framework:
- Identify differences between products
- Review existing information
- Determine what can be bridged/leveraged
- Identify other available information
- Define remaining gaps requiring new data
- Meet with FDA early to discuss bridging strategy and required studies
- Document scientific rationale for bridging approach
- Generate necessary new data to address identified gaps
- Include comprehensive bridging assessment in regulatory submissions
- Ensure design control requirements are met for device modifications
- Consider conducting clinical studies with final finished combination product when possible
- Evaluate need for additional studies in new patient populations
- Assess manufacturing changes impact on product quality
- Maintain documentation of design verification and validation activities
Key Considerations
Clinical testing
- PK/bioavailability studies may be needed to assess differences between products
- Clinical studies with the final finished combination product are recommended when possible
- Local adverse event data may be needed to assess impact of device changes
Non-clinical testing
- Nonclinical data can potentially be leveraged if PK profiles are comparable between products
- Additional testing may be needed for changes affecting drug delivery or formulation
Human Factors
- HF validation studies typically needed for new user interfaces
- Bridging of HF data may be possible if user interface remains unchanged
- Additional HF studies needed for new patient populations
Biocompatibility
- Biocompatibility data can be leveraged if materials and contact remain unchanged
- New testing needed if materials or contact duration/type changes
Safety
- Safety data can potentially be leveraged if PK profiles are comparable
- Additional safety assessment needed for changes affecting drug delivery
Other considerations
- Design verification and validation required for device modifications
- CMC considerations include drug-device compatibility, stability, sterility
- Manufacturing process changes need assessment for impact on product quality
- Leachables/extractables profile needs evaluation for container closure changes
Relevant Guidances
- User Fees for Combination Products and Associated Waivers
- Classification of Products as Drugs or Devices: Interpretation and Determination Process
- Current Good Manufacturing Practice Requirements for Combination Products
- Early Development Considerations for Combination Products
- Postmarketing Safety Reporting Requirements for Combination Products
- Premarket Review Pathways for Combination Products
- Obtaining FDA Feedback for Combination Products: Best Practices and Meeting Procedures
- Postapproval Changes to Combination Products: Marketing Submission Requirements (Draft)
- Compliance Policy for Combination Product Postmarketing Safety Reporting Requirements
Related references and norms
- 21 CFR 820.30: Design Controls
- 21 CFR Part 4: Current Good Manufacturing Practice Requirements for Combination Products
Original guidance
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