FDA Issues Combination Product Application User Fee Guidance for Staff and Industry

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FDA published a guidance document on July 16, 2024 instructing staff members as well as the drug industry at large about the applicable user fees for applications for combination products, as defined under the Code of Federal Regulations (CFR), Title 21, Part 3.2(e) (1,2). Specifically, the guidance dictates that if a single application is submitted for a combination product, the user fee associated with that type of application should be assessed. It also outlines the process by which combination products are assigned for review.

A combination product, according to the CFR, is characterized by any of four criteria:

• Two or more regulated components (customarily a drug, biologic, and/or device) that are mixed or combined physically, chemically, or otherwise, and produced as one entity
• Two or more products which are separate, but packaged together as a singular unit, comprised of drug, device, and or biological products
• A drug, device, or biological product packaged separately and intended for use only with another individually specified drug, device, or biological product, required to achieve a desired effect, and for which labeling of the product would have to be changed upon approval, for example to reflect a change in intended use, strength, or dosage form
• An investigational drug, device, or biological product, packaged separately, combined for usage with another individual, investigational entity as described above (2).

Drug–drug, device–device, and products containing only multiple biologics do not meet the definition of a combination product under these terms (1).

FDA precedent states that combination products may be reviewed in a single application or in separate applications for each constituent part, both of which are scenarios reviewed in the new guidance (1). If an applicant decides to submit two applications for a cross-labeled product, each application would be assessed its own particular user fee.

FDA may determine that a single application is not appropriate for a certain combination product, and that separate applications are warranted. In that case, which FDA said in the guidance document is rare, the total amount of the application fee could be reduced if the applicant qualifies for waiver provisions under the Prescription Drug User Fee Act (PDUFA) of the Federal Food, Drug, and Cosmetic Act (1). Provisions of this guidance do not apply to PDUFA prescription drug program fees.

The guidance document contains information on how to request a fee reduction or waiver under the PDUFA provisions and also how to do the same as a small business, pursuant to medical device user fee amendment guidelines.

The guidance was jointly issued by FDA’s Office of the Commissioner, Office of Clinical Policy and Programs, and Office of Combination Products and replaces a previous final guidance for industry from April 2005.

References

1. FDA, Guidance for Industry and FDA Staff, Application User Fees for Combination Products (OCP, July 2024).
2. CFR Title 21, Part 3.2(e) (Government Printing Office, Washington, DC) 173. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-3/subpart-A/section-3.2