User Fees for Combination Products and Associated Waivers
This guidance provides information on application user fees for combination products, specifically addressing how FDA applies PDUFA (Prescription Drug User Fee Act) and MDUFA (Medical Device User Fee Amendments) fees. It covers scenarios where combination products are submitted as single applications or separate applications for constituent parts, and explains available fee waivers, reductions, exceptions, and exemptions.
What You Need to Know? 👇
What are the user fee requirements for combination products submitted as a single application?
A combination product submitted as a single application is subject to the applicable user fee for that specific application type. For example, a BLA or NDA would incur a PDUFA fee, while a PMA or 510(k) would incur a MDUFA fee.
How does FDA handle user fees when an applicant chooses to submit separate applications for a combination product?
When an applicant voluntarily submits two applications for a combination product (even though one would be appropriate), FDA assesses each application independently under the relevant user fee program, resulting in two separate application fees.
What fee reductions are available when FDA determines separate applications are warranted for combination products?
When FDA determines separate applications are necessary, PDUFA fees may be reduced through public health or barrier to innovation waivers. For innovative products, total fees may be capped at one PDUFA fee equivalent.
What factors does FDA consider when determining if a combination product qualifies for the barrier to innovation waiver?
FDA considers whether the product demonstrates new progressive methods, has no comparable alternatives, introduces unique diagnostic/treatment methods, includes new molecular entities, or receives special designations like breakthrough therapy or fast track status.
When should I submit a PDUFA fee waiver request for my combination product?
Submit PDUFA fee waiver requests 3-4 months before fees are due. Clearly identify it as a “Combination Product Waiver Request” and specify the waiver type with supporting justification addressing applicable criteria.
Which user fee programs apply to combination products and what exceptions exist?
Combination products may be subject to PDUFA (drugs/biologics) or MDUFA (devices) fees. This guidance doesn’t cover GDUFA, BsUFA, or PDUFA prescription drug program fees. Various waivers and exceptions exist for small businesses and specific circumstances.
What You Need to Do 👇
Recommended Actions
- Determine if product qualifies as a combination product under 21 CFR 3.2(e)
- Evaluate whether single or separate applications are appropriate:
- Single application is generally preferred
- Consult with FDA if considering separate applications
- For single applications:
- Identify applicable fee program (PDUFA or MDUFA)
- Determine eligibility for waivers/reductions
- For separate applications:
- Document justification if FDA determination required
- Submit waiver requests 3-4 months before fees are due
- Include “Combination Product Waiver Request” designation
- Maintain communication with:
- Office of Combination Products for general guidance
- Division of User Fee Management for PDUFA matters
- CDRH Division of Industry and Consumer Education for MDUFA matters
- Submit any fee refund requests within 180 calendar days of fee due date
Key Considerations
Other considerations
- Single application submissions are subject to the applicable user fee associated with that particular type of application (PDUFA or MDUFA)
- When two applications are submitted by applicant choice, each application fee is assessed independently
- For FDA-determined separate applications:
- Public Health Waiver may apply if product protects public health and applicant has limited resources
- Barrier to Innovation Waiver may apply if product is innovative
- Total fees are generally reduced to equivalent of one application fee
- Innovation criteria include:
- New progressive methods in treatment/diagnosis
- No comparable alternatives in US market
- Unique/superior clinical benefits
- New molecular entity or special designations (breakthrough, fast track, etc.)
Relevant Guidances đź”—
- Premarket Review Pathways for Combination Products
- Compliance Policy for Combination Product Postmarketing Safety Reporting Requirements
- Current Good Manufacturing Practice Requirements for Combination Products
- Postmarketing Safety Reporting Requirements for Combination Products
- Obtaining FDA Feedback for Combination Products: Best Practices and Meeting Procedures
- Dispute Resolution Process for Combination Product Review Timelines
- Human Factors Studies and Related Analyses for Combination Products
Related references and norms đź“‚
- 21 CFR 3.2(e): Definition of combination products
- 21 CFR 4.2: Definition of constituent parts
- 21 CFR 3.2(k): Definition of mode of action
- 21 CFR 3.2(m): Definition of primary mode of action
- 21 CFR 3.4: Assignment of combination products