The U.S. Food and Drug Administration (FDA) has issued its final guidance on user fees for combination products. This new guidance released in July 2024 replaces the previous version from April 2005 and is set to further streamline the regulatory process for combination products. The move is aimed at clarifying the user fee structure and improving the efficiency of the review process for these complex products.
Combination products are those that integrate multiple components, called constituent parts, such as drug-device combinations (e.g., a pre-filled syringe), biologic-device combinations (e.g., a drug-eluting stent), or even products that combine all three. These products offer advanced treatment options and are crucial in addressing various medical needs. However, their complexity necessitates a detailed and often intricate regulatory review process. Because of that, combination products are assigned to an area, or center, within the FDA to maintain the primary responsibility for the regulation of the product which is based on the primary mode of action of the combination product. The assignment to one center also provides a more streamlined approach for manufacturers to submit a single application for a premarket review of the product, avoiding unnecessary duplicative submissions, and helps provide a clear understanding of the financial requirements.
The guidance distinguishes between different types of submissions, such as new drug applications (NDAs), premarket approval (PMA) applications, and 510(k) submissions, and clarifies the associated fees for each type. This distinction ensures that manufacturers know exactly what fees apply to their specific combination product submission under the Prescription Drug User Fee Act (PDUFA) and the Medical Device User Fee Amendments (MDUFA) programs. Further, the FDA has outlined criteria for fee waivers and reductions, including provisions for small businesses and specific types of combination products, as well as exemptions under the programs.
Manufacturers may choose to submit two applications under both MDUFA and PDUFA. In such cases, the FDA will evaluate each independently for the appropriate fees to be assessed. The FDA will waive or reduce fees where a product is intended to protect the public health or where limited resources are available to the manufacturer. The guidance also lists exceptions to the application of fees in a number of cases, including but not limited to
- Orphan designated products for rare disease or condition
- Humanitarian Device Exemption (HDE) products
- Products where conditions of use are solely for a pediatric population
- Third-party premarket notification submission reviewed under the Accredited Person program
- State or Federal government submissions for products that are not distributed commercially
These efforts help to support innovation by providing financial relief to manufacturers working on novel or essential products, potentially leading to more diverse and innovative combination products entering the market.
Read the guidance here.
