FDA Issues Proposed Rule on CGMPs for Combination Drug Products

The US Food and Drug Administration issued a proposed rule to clarify the current good manufacturing practice (CGMP) requirements applicable to combination products in the Sept. 23, 2009, Federal Register. The proposed rule is meant to set forth “a transparent and streamlined regulatory framework for firms to use when demonstrating compliance with CGMP requirements for ‘single-entity’ and ‘co-packaged’ combination products,” according to the notice.

21 CFR Part 3 defines a combination product as “any combination of a drug and a device; a device and a biological product; a biological product and a drug; or a drug, a device, and a biological product.” Approximately 300 manufacturers of combination products will be affected by the proposed rule, says the notice.

“FDA believes that the absence of clear CGMP requirements for combination products could result in inconsistent or differing application of the various CGMP requirements applicable to the constituent parts, which could affect product safety and the public health,” says the notice. According to the proposed rule, combination-product manufacturers would be able to demonstrate compliance with either 1: “the specifics of all CGMP regulations applicable to each of the constituent parts included in the combination product containing,” or 2: “the specifics of either the drug or the [quality system] regulation, rather than both, when the combination contains both a drug and a device, under certain conditions.”

There are many specific proposals included in the proposed rule depending on the type of combination product manufactured. Of note, the fact that many facilities may be involved in the manufacture of a combination product, “raises questions about whether and when the proposed streamlined approach to CGMP operating systems could be used,” says the notice. The proposed rule would “make clear that when manufacturing of a constituent part does not occur at the same facility as another type of constituent part, the operating system must be shown to comply with all of the CGMP regulations applicable to that constituent part.” In the same regard, when two or more types of constituent parts are in the same facility, a streamlined approach may be used, and when “manufacture of a constituent part occurs at a separate facility from all other types of constituent parts, the manufacture of that part must occur under the regulations applicable to that part,” says the notice.