The Merging of Medical Products: Enhancing review of therapeutic and diagnostic combination products

By: Robert M. Califf, M.D. and Jill Hartzler Warner, J.D.

Combination products – medical products that do not fit into the traditional categories of drugs, devices, or biological products – are a growing and important category of therapeutic and diagnostic products under FDA’s regulatory authority.

Robert M. Califf, M.D., MACC, FDA's Commissioner of Food and Drugs

Robert M. Califf, M.D., Commissioner of the U.S. Food and Drug Administration

These products, that combine drugs, devices, and/or biological product (“constituent parts”) with one another, come in three configurations. The constituent parts may be physically or chemically combined, co-packaged, or separately distributed with specific labeling for their combined use.

Products in this category range from familiar products such as prefilled syringes and surgical kits to novel and innovative products, which target and enhance therapies. Examples of groundbreaking combination products include antibodies combined with drugs for targeted cancer therapy and products that mimic or replace organs, such as an artificial pancreas.

Combination products pose unique challenges – both because they may involve new, complex technologies – and because their review at FDA often involves the expertise of more than one Center.

While review of such products falls to a cross-center team of experts, it is led by the medical product Center responsible for the constituent part that provides the product’s primary mode of action, which, in the case of a syringe prefilled with a drug, for example, would be FDA’s Center for Drug Evaluation and Research.

Effective coordination among FDA staff, and between FDA and the company, is essential – and depends on identifying the proper experts across Centers, supporting processes for communication, and implementing systems for efficient data access and sharing.

Jill Warner

Jill Hartzler Warner, J.D., FDA’s Associate Commissioner for Special Medical Programs.

FDA’s Office of Combination Products (OCP), within the Office of Special Medical Programs, oversees and coordinates FDA’s regulation of combination products. This includes helping to resolve differences of opinion between Centers or with sponsors, developing guidance and regulations, and working with the medical product Centers to develop processes and policies..

Congress has expressed interest in FDA’s regulation of combination products as part of the 21st Century Cures legislative initiative, with one major theme being the assurance that the premarket review process runs smoothly.

While we already have policies and processes in place to address such issues, we know we can do more. To that end, we’ve recently conducted a focus group study with reviewers from the different Centers based on input from industry to assess how we’re doing. The report confirmed that differences in communication, policies, practices, systems and application types can be challenging when the Centers work together on a review of a combination product. The report also recommended actions to take, confirming the value of efforts already underway. Consistent with these findings, we’re taking a number of steps to clarify regulatory requirements and improve our internal processes and IT systems. It may sound a bit mundane, but doing this work could help us work more efficiently and avoid unnecessary surprises for sponsors. These steps include:

  • Issuing more guidance for review of combination products (e.g., our pending draft guidance document on human factors);
  • Enhancing and simplifying data access and sharing for internal staff;
  • Making it easier for staff to request and monitor inter-center consults;
  • Updating and maintaining our internal contact directory for experts to review a combination product; and
  • Improving our internal standard operating procedures for premarket reviews and compliance activities.

Some improvements are already in place and others will be coming this year and next. We continue to want to hear your ideas for enhancing how we work with you on combination products. We are listening — and excited to do our part by evaluating innovative combination products and helping to improve the well-being of patients by approving new safe and effective therapies.

Robert M. Califf, M.D., previously FDA’s Deputy Commissioner for Medical Products and Tobacco, became FDA’s Commissioner of Food and Drugs on Feb. 25, 2016.

Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs.

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