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This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What is bridging in the context of drug-device combination products?
Bridging refers to the process of establishing the scientific relevance of information developed in an earlier phase or another development program to support a combination product seeking approval. Once relevance is established, applicants can leverage that information to streamline their development program.
What types of combination products does the FDA bridging guidance apply to?
The guidance applies to human prescription and nonprescription combination products subject to IND, NDA, or BLA requirements. This includes drug-device and biologic-device single entity or co-packaged combination products, but excludes those covered by over-the-counter drug monographs.
What is the five-step analytical framework for identifying information gaps in combination product development?
The framework includes: 1) Identify all differences between products and assess potential effects on safety/effectiveness, 2) Identify existing information for the proposed product, 3) Explain how existing information can be bridged and leveraged, 4) Consider other available information, and 5) Identify remaining information gaps.
When might leveraging existing data be challenging for combination products?
Leveraging may be challenging with combination products containing complex constituent parts or those likely affected by minor changes. For example, products with certain biological constituents or complex delivery systems may not allow the same degree of leveraging as well-characterized drugs or devices.
What key considerations apply when bridging from a prefilled syringe to an autoinjector presentation?
Key considerations include changes in user interface design, manufacturing process effects on drug quality, injection method impacts on local adverse reactions and pharmacokinetics, and assessment of autoinjector design features. Human factors validation and comparative pharmacokinetic studies are typically required.
What information is typically needed when modifying an autoinjector design after Phase 3 studies?
When modifying autoinjector components while maintaining performance specifications, applicants typically need design verification data demonstrating comparable device performance, side-by-side user interface comparisons, and confirmation that dose accuracy, injection time, and other critical parameters remain unchanged between prototypes.
What You Need to Do 👇
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