Marie Thibault

On January 28, 2015, FDA released draft guidance on current good manufacturing practice (CGMP) requirements for combination products, two years after the agency’s final rule on the topic was published. The guidance details the requirements and gives numerous examples to better illustrate and add context to the rule.
Suzanne O’Shea, counsel at Faegre Baker Daniels, says she was impressed with the draft guidance, calling it “pretty thorough.”

At the end of the document, the guidance is applied to three specific examples: prefilled syringes, drug-coated mesh, and drug-eluting stents. These scenarios offer a level of detail that may be new for the agency.

“FDA historically hasn’t been as descriptive in their GMP guidance and expectations. GMP has always been a little ambiguous, kind of high level,” says Jim Johnson, partner at Hogan Lovells.

At its most basic, the rule allows manufacturers of combination products—that is, products that are made up of a combination of a drug, device or biological product—to use one of two approaches to meet CGMP requirements. Manufacturers can either show that they’ve met the CGMP rules for each type of product or choose a streamlined option that fulfills the rules for one type of product as well as select criteria from the other product type’s requirements.

A drug-eluting stent manufacturer, for example, could fulfill both the drug CGMPs and the device quality system (QS) regulation, or instead streamline and meet all the requirements of either the drug CGMPs or the device QS regulation and certain items from the other rule list. Combination products that include a biological product or human cell and tissue product (HCT/P) would have to meet requirements for those parts too.

Part of the draft guidance document is devoted to explaining the specific criteria from each set of regulations that must be fulfilled. This is meant to help drug manufacturers understand device QSR and, conversely, make device manufacturers more comfortable with drug CGMPs. So the guidance defines conditions that pertain to devices, like management responsibility, installation, and servicing, and those specific to drugs, like calculation of yield, expiration dating, and stability testing.

O’Shea pointed out that the draft’s discussion of “where appropriate” language is important because some manufacturers are concerned that the rule requires them to apply criteria that don’t pertain to their specific combination product. The draft guidance adds a clarifying explanation of some circumstances where specific regulations are not applicable or are already fulfilled by another regulation. Though careful consideration is required, “I think if people read that and really take that on board, that’s going to relieve a lot of concerns,” O’Shea says.

However, one remaining issue for combination product manufacturers is whether the FDA will eventually have CGMP investigators that specialize in these types of products, rather than investigators who have expertise mainly in one area. “To fully streamline the process, you really need a streamlined investigation too,” Johnson says.

The center with primary jurisdiction for premarket review and compliance with CGMP rules depends on which part of the combination product contributes to the primary mode of action (PMOA). For a drug eluting stent, the device part is viewed as contributing the PMOA, so CDRH is the lead center. Still, the drug eluting stent manufacturer does not necessarily need to choose a device QS regulation streamlined approach.

Overall, these experts view this draft guidance as a helpful resource for industry. Johnson calls the document a “step in the right direction as far as prescriptive guidance…that I hope to see more and more from the agency.”

The draft guidance is open for public comment until March 30, 2015.

Marie Thibault is a freelance contributor to MD+DI.

[image courtesy of STUART MILES/FREEDIGITALPHOTOS.NET]