Combination products are product composed of any combination of two or more different product categories. Because regulatory approaches differs greatly between drugs, biologics, and medical devices, Office of Combination Products (OCP) was established in 2002 to help triage the increasingly complex product landscape. This is an emerging area as more and more combination products are introduced to the market.

The FDA is divided into multiple centers:

• Food: Center for Food Safety and Applied Nutrition (CFAN)
• Medical Devices: Center for Devices & Radiological Health (CDRH)
• Drugs: Center for Drug Evaluation & Research (CDER)
• Biologics: Center for Biologics Evaluation & Research (CBER)
• Vet Medicine: Center for Veterinary Medicine (CVN)
• Toxicology: National Center for Toxicological Research (NCTR)

The entrepreneur will need to make an assessment to determine the final form of their product and be regulated under the appropriate center. Regulatory approaches of drugs, biologics, and medical devices differ greatly, so the Office of Combination Product was established in 2002 to manage and coordinate the regulatory approaches for this class of products.

What is a Combination Product

Combination products are product composed of any combination of two or more different product categories:

Therefore the Office of Combination Product is responsible for the oversight responsibilities for the regulatory life cycle of combination products and is charged with assigning which FDA center to have the primary jurisdiction for the review process. The Office is also responsible for the review of products where the jurisdiction is unclear or in dispute. The Office of Combination Products would determine the product classification, assignment for lead center, and the regulatory pathway.

Product Determination

The Request for Designation (RFD) process, detailed in 21 CFR Part 3, provides innovator a prompt response from the Office of Combination Products on the product classification, assignment for lead center, and clarification on the regulatory pathway. If the innovator believes that there product may be a combination product, it is recommended that the innovators submit the RFD before making any regulatory submission (i.e pre-submission, marketing submission, etc.). This is because the FDA may stop the review clock while a RFD determination is being considered, extending the regulatory review timeline. The innovator may also request for a meeting with the FDA (pre-RFD meeting) to obtain informal feedback prior to their formal RFD submission. The result from the meeting is informal and non-binding, but it may provide valuable feedback for innovators to structure their RFD submission. Innovators can also submit Freedom of Information (FOIA) requests for additional information regarding the product approval process or even redacted information from other product approvals. FDA will make its jurisdictional determination no later than 60 days after filing the RFD.

Action: Submit a Request for Designation (RFD)

What Happens next inside the FDA: Lead Center

The lead center to review a combination product is usually govern by the primary mode of action (PMOA) determined by the FDA reviewer. The type of regulatory pathway usually follows the lead center. The regulatory reviews will be conducted by reviewers from the lead centers accompanying reviewer from the co-center. Office of Combination Product will act as a coordinator for the different reviewers' activities.

Incremental Strategy

For drugs and biologics, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) assesses any changes to product strength, purity, quality, or potency. Therefore, any significant change to a drug or biologic formulation requires additional product testing. In contrast for medical devices, the Center for Devices and Radiological Health (CDRH) utilizes a risk assessment process that focuses on the manufacturer maintaining design control and it is the manufacturer's responsibility for product testing. The different approaches between drug/biologics and medical devices may bring forth additional complexity as the product evolves.

Future of Combination Products

Increasingly the traditional line between pharmaceutical, medical device, biotech, and life science companies are blurred. Combination products can provide patients and health practitioners benefits that simplifying the drug delivery process. In the first few decades, drug injection systems and pulmonary inhalers made up the majority of combination products; as technology continues to evolve, more and more novel applications enters the pipeline.

What's Next:

FDA provides a great FAQ resources page that answers many of the common questions entrereneurs have:

FDA’s Combination Product Home Page

FDA’s FAQ on Combination Products

Version History

• 05.29.2017 Initial Revision.

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