Ex-FDA Official Publishes White Paper on Navigating Quality System Regulations for Combination Products

June 26, 2007

In a recently published white paper (registration required), Steven Richter, a former FDA official and President and Chief Scientific Officer of Microtest Labs, discusses the regulatory challenges facing combination products.  The market for combination products is growing such that it is estimated to reach approximately $9.5 billion in 2009, up from $5.9 billion in 2004, according to one analyst.  Another survey estimates that 30% of new products in development are combination products.  This increased interest is due in part to the unique therapeutic benefits of combining drugs and medical devices, which can, for example, deliver drug to specific areas of the body. 

FDA decides which center governs a combination product based on its primary mode of action (PMOA).  A product that has a pharmaceutical PMOA will be governed by the Center for Drug Evaluation and Research (CDER).  Likewise, a product with a device PMOA will be governed by the Center for Devices and Radiological Health (CDRH).  Different quality regulations, however, apply to each product:  good manufacturing practices (GMPs) (21 C.F.R. Parts 210, 211) apply to drugs, biologic product standards (21 C.F.R. Part 610) apply to biologics, and quality system regulations (QSR’s) (21 C.F.R. Part 820) apply to devices.  Richter maintains, however, that a combination product manufacturer’s “main regulatory foundation must be the drug GMP’s” and that the GMP system must “address[] some of the issues with the device QSR’s.”

Richter predicts that, as FDA continues to shift its regulatory focus from product to process, the largest challenge for combination product manufacturers will be “during the scale-up process.”  This is in part because “additional quality control (QC) measures are required to determine process scale-up parameter shift.”  Richter also expects FDA to issue guidelines specific to combination products that incorporate Process Analytical Technology (PAT) initiatives and design of experiments (DOE) requirements “regarding both small molecule and large molecule process design and scale-up.”  Moreover, Richter believes FDA will “increase[] cGMP regulatory action that affects both laboratory and manufacturing” as a result of its guidelines. 

By:  Carrie S. Martin

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