Guidance & Regulatory Information
The Office of Combination Products develops regulations and guidance for combination products, in collaboration with FDA’s medical product centers. The links at the left of this page provide more information about combination product regulations and guidance, and procedures that FDA follows for the intercenter review of products.
OCP is requesting applicants/sponsors to submit RFDs (requests for designation) and Pre-RFDs (pre-requests for designation) electronically. To do so, applicants/sponsors may send RFDs and Pre-RFDs to combination@fda.gov and identify the submission type (“RFD” or “Pre-RFD” as applicable) in the subject line of the email. If a sponsor makes a paper submission of an RFD pursuant to 21 CFR Part 3, or makes a paper submission of a Pre-RFD, OCP requests applicants/sponsors to also notify our mailbox at combination@fda.gov. Finally, in lieu of telephone inquiries, please send all other information requests to our mailbox at combination@fda.gov.
Spotlight
On June 28, 2024, FDA published a draft guidance that consolidates and clarifies information the agency reviews in submissions for stand-alone devices and combination products that deliver human drugs and biological products. This guidance identifies what FDA calls essential drug delivery outputs (EDDO), which are necessary to ensure the drug is delivered to the patient (i.e., delivery of the intended drug dose to the intended delivery site).
Generally, the technical data for device drug-delivery performance are the same for stand-alone devices and combination products. This guidance is intended to facilitate and streamline the development of drug delivery devices by:
- Informing applicants’ determination of the data to submit to FDA to demonstrate drug delivery performance
- Ensuring applicants evaluate the appropriate device design attributes and manufacturing processes during lifecycle changes
- Providing applicants a basis for comparing device drug-delivery performance and facilitating EDDO assessment across products
- Minimizing uncertainty by facilitating FDA’s review of drug delivery devices
To help explain the concepts, this guidance provides hypothetical examples of EDDOs for several product types.
FDA developed this draft guidance in response to requests from industry and trade groups for clarity, transparency, and consistency on information and data to demonstrate drug delivery performance for drug delivery devices.
Related links
- Federal Register Notice: Guidance: Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products
- Combination Products Guidance Documents
- Combination Product Definition Combination Product Types
- Frequently Asked Questions About Combination Products
- Feedback on Combination Products
Revised Final Guidance - Application User Fees for Combination Products
On July 16, 2024, FDA published the revised final guidance Application User Fees for Combination Products. This guidance replaces the final guidance of the same title issued in 2005, and includes revisions for consistency with the current user fee programs and revisions to reflect combination product provisions in the FD&C Act (section 503(g)).
Combination products may be reviewed in a single application or in separate applications for the constituent parts. This guidance explains that combination products for which a single application is submitted should be assessed the applicable user fee associated with that particular type of application. The document also explains how the Agency applies user fees for combination products when separate applications are submitted for the constituent parts.
This guidance should be used in conjunction with the guidance for industry Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products and the appropriate medical device user fee amendments (MDUFA) guidance document(s).
For more information see: