The FDA has recently updated its guidance on application user fees for combination products, replacing the previous guidance issued in April 2005. This new document aligns with current user fee programs and revisions in section 503(g) of the FD&C Act, offering comprehensive directions for industry and FDA staff on managing fees for combination products. This guidance is crucial for ensuring the appropriate assessment and collection of fees, facilitating the approval process for combination products.
Definition and Assignment of Combination Products
Combination products consist of two or more types of products (drug, device, and/or biological product). The FDA classifies a product as a combination product when it includes any combination of a drug, device, or biological product. The primary mode of action (PMOA) of the product determines which FDA center—CDER (Center for Drug Evaluation and Research), CBER (Center for Biologics Evaluation and Research), or CDRH (Center for Devices and Radiological Health)—will review the product. This classification ensures that the product is evaluated by the center with the most relevant expertise.
Primary Mode of Action (PMOA)
The PMOA is the single mode of action of a combination product that provides the most significant therapeutic action. For instance, if a combination product primarily acts as a drug with a secondary device component, CDER will likely be the lead review center. Determining the PMOA is crucial as it influences the type of user fee applicable and the review process the product will undergo.
User Fees Overview
The FDA has established different user fee programs to fund the review of various product applications. The two primary user fee programs relevant to combination products are PDUFA and MDUFA.
Prescription Drug User Fee Act (PDUFA)
PDUFA applies to drug and biological product applications. Initially enacted in 1992, PDUFA is reauthorized every five years. It aims to provide the FDA with the resources needed to ensure timely review of new drug applications (NDAs) and biologics license applications (BLAs). PDUFA fees include application fees, establishment fees, and product fees, which contribute to the FDA’s ability to maintain a robust drug review process.
Medical Device User Fee Amendments (MDUFA)
MDUFA applies to medical device applications and is also reauthorized every five years. Enacted in 2002, MDUFA provides the FDA with resources to enhance the review process for medical devices, ensuring that devices are reviewed promptly and efficiently. MDUFA fees include application fees, establishment fees, and annual report fees, supporting the FDA’s efforts to keep pace with technological advancements in medical devices.
User Fee Waivers and Reductions
Understanding the available waivers and reductions under PDUFA and MDUFA is crucial for applicants looking to manage costs effectively.
PDUFA Waivers
PDUFA offers several waivers, including:
- Public Health Waivers: For applications that serve a significant public health interest.
- Barrier to Innovation Waivers: For applications that may promote innovation in drug development.
- Small Business Waivers: For small businesses submitting their first human drug application.
- Orphan Designated Products: For products intended to treat rare diseases or conditions.
- Government Entities: Waivers for applications submitted by government entities.
MDUFA Waivers
MDUFA waivers include:
- Humanitarian Device Exemptions: For devices intended to treat or diagnose conditions affecting fewer than 8,000 individuals in the United States per year.
- State or Federal Government Sponsors: For applications sponsored by state or federal government entities.
- Third-Party Premarket Notifications: For certain third-party reviewed applications.
- Pediatric Use Conditions: For devices intended solely for pediatric use.
Application Scenarios for Combination Products
Combination products can be submitted under various application scenarios, affecting how user fees are assessed.
Single Application
When a single application is submitted, the user fee is determined by the type of application—either a PDUFA or MDUFA fee, depending on the primary mode of action.
Two Applications by Choice
If an applicant submits two separate applications by choice, each application is assessed independently, incurring separate user fees. This scenario may occur when the applicant prefers to have the drug and device components reviewed separately.
Two Applications as Required by FDA
In some cases, the FDA may require two separate applications for a combination product. Under specific conditions, such as public health necessity or to promote innovation, the FDA may waive or reduce the associated fees.
Requesting Waivers or Reductions
The FDA encourages early submission of requests for waivers or reductions to ensure timely processing. Procedures for requesting waivers or reductions under PDUFA and MDUFA are detailed in the guidance, providing clear steps for applicants.
Small Business Qualifications
For MDUFA fee reductions, small businesses must qualify by meeting specific criteria, including revenue thresholds and ownership requirements. The certification process involves submitting documentation to verify the business’s eligibility for reduced fees.
The updated FDA guidance aims to streamline the application process for combination products, ensuring appropriate fee assessments while providing avenues for fee waivers and reductions. This guidance is essential for industry stakeholders navigating the complex landscape of combination product approvals. For more detailed information, industry professionals are encouraged to consult the full guidance document or contact the Office of Combination Products at the FDA.