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Overview of Combination Products

Combination products are increasingly being developed to enhance the safety and effectiveness of conventional medical products. These products are defined by any of the following criteria as in 21 CFR 3.2(e):

  1. Products comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
  2. Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;
  3. A drug, device, or biological product packaged separately that, according to its investigational plan or proposed labeling, is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose;
  4. Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.

More and more combination products are incorporating cutting-edge, novel technologies that hold great promise for advancing patient care. Beyond drug-eluting stents and inhaled insulin, breakthrough new products approved after OCP was established, combination products may include drug-delivery systems, pharmacogenomic drug-device combinations, nanotechnology, gene therapy systems and products for many other diagnostic and therapeutic treatments. Some estimates forecast that the combination products market could increase from approximately $6 billion in 2004 to nearly $10 billion by 2009 (“Regulations, Guidances in the Works for Rapidly Advancing Combination Products Sector”; Food and Drug Letter, Issue No. 717, February 11, 2005). Others estimate that combination drug delivery products alone are growing at an annual rate of 14 percent, an increase expected to add up to $38 billion in yearly sales by 2008 (“Drug-Device Makers Can Expect New Guidance”; AAMI News, February 2005). Furthermore, BCC Research Inc., estimates that the total global value of the drug-device combination products market will increase from $5.4 billion in 2004 to $11.5 billion in 2010 (“Drug-Device Combinations”, BCC Research, June 2005).

The number of combination products submitted for review decreased in FY 2006; however, the number of intercenter consultation requests continued to increase. The number of combination products submitted for review in FY 2006 decreased from FY 2004 and FY 2005 levels (see graph to the right). The majority of this decrease was in the number of combination products submitted for review to CDER.

Number of combination products submitted for review in FY 2006D

          Text Box: * Numbers do not represent all of FY 2003. FDA began data collection on April 1, 2003.

More Centers were included in combination product reviews. Despite the decrease in the number of combination products submitted in FY 2006, the number of intercenter consultation requests on combination products increased by 22 percent (275 to 335, see graph below). Since combination products involve components (biologics, drugs, and devices) that would normally be regulated under
different types of regulatory authorities, and frequently by different FDA Centers, they also raise challenging regulatory, policy, and review management issues. The differences in regulatory pathways for each component can impact the regulatory processes of all aspects of the product life cycle, including preclinical testing, clinical investigation, marketing applications, manufacturing and quality control, adverse event reporting, promotion and advertising, and post-approval modifications. In addition, combination products increasingly use state-of-the-art, innovative technologies that challenge existing regulatory and scientific knowledge.
More Centers were included in combination product reviews.D

Mandated Functions of the Office of Combination Products

FDA established OCP within the Office of the Commissioner’s Office of International Activities and Strategic Initiatives (OIASI) on December 24, 2002. MDUFMA established broad responsibilities for OCP that cover the regulatory life cycle of drug-device, drug-biologic, and device-biologic combination products, and include product jurisdiction decisions and specific premarket review and postmarket processes. However, the primary responsibilities for scientific review and regulation of combination products remain in one of three product Centers – the Center for Biologics Evaluation and Research (CBER), CDER, or CDRH – to which they are assigned by OCP. Specifically, the statute (503(g)(4)(B-F)) requires OCP to:

  1. Promptly assign a Center with primary jurisdiction for a combination product.
  2. Ensure the timely and effective premarket review of combination products, by overseeing the timeliness of and coordinating reviews involving more than one Center.
  3. Ensure the consistency and appropriateness of postmarket regulation of combination products.
  4. Resolve disputes regarding the timeliness of premarket review of combination products.
  5. Review and update agreements, guidance documents or practices specific to the assignment of combination products.

OCP also serves as a focal point for addressing combination product issues raised by FDA reviewers and industry, and works with the Centers to develop guidance and/or regulations to clarify the regulation of combination products.

In addition, the Office of the Commissioner consolidated the product jurisdiction program in June 2003, giving OCP responsibility for FDA action on all RFDs submitted by industry in accordance with 21 CFR Part 3. This includes requests for classification and assignment of a particular product as a biological product, device, or drug, as well as requests for assignment of combination products. 

OCP Organizational Structure

As of September 30, 2006, OCP is staffed by seven permanent full-time positions. In addition to a Director of OCP, these positions include an Associate Director (Medical Officer), a Product Assignment Officer, a Product Classification Officer, a Senior Advisor, a Scientific Reviewer (Biologist and Emerging Leader Intern), and a Program Support Specialist. In terms of staff turnover, two staff members retired during the past year and two new staff members joined OCP. Work plans provide for an eventual projected staffing size of 11 positions when financial resources to support such needed expansion are available. The office is located at: 15800 Crabbs Branch Way, Suite 200, HFG-3, Rockville, MD 20855, (301) 427-1934, fax (301) 427-1935, email: combination@fda.gov.

Table of Contents | Report on FY 2006 OCP Activities and Impacts

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