MedTech Combination Products

While some combination products can rely on a single application to gain regulatory approval, the simple answer is this — it depends! There are two main factors that impact this decision:

• The intended market — U.S. and EU have key differences
• The type of combination product — There are regulatory differences for single-entity/integral products, co-packaged products, or cross-labeled products

In the U.S., combination products that are single-entity or co-packaged products are assigned to a single FDA Center that will have primary jurisdiction for its premarket review and regulation based on the most important therapeutic action. Typically, only a single marketing application is necessary for these types of combination products although inter-agency consults may be utilized during the review of the application. In an example where the most important therapeutic action is the drug, then the product will require a drug application and will be regulated by CDER. During the drug application review, a consult with CDRH may be requested for the device constituent of the product. Conversely, if the most important therapeutic action is the device, then the product will require a device submission to CDRH and may include a CDER consult during the review. Products where the drug and the device constituents would be sold separately and labeled to be used together are considered cross-labeled combination products. For these products, each constituent would typically be regulated separately, and each product would require their own marketing applications to the appropriate FDA Centers.

In the EU, Article 117 of the new EU MDR introduced new requirements for drugs with an integral medical device, which are equivalent to single-entity products in the U.S. Since 2021 the drug application will need to include a CE certificate for the device or include an opinion from a notified body on the conformity of the device if it is not CE marked. The notified body opinion could be obtained during the drug review if it is not separately CE marked. Devices with an integral medicinal product are automatically classified as Class III medical devices and may require a drug review to achieve CE marking. Co-packaged products are treated differently in the EU and would typically require separate device and drug applications. Cross-labeled products align with the U.S. in that CE marking is required separately from the drug application for these product types.