FDA Clarifies GMP Requirements for Combo Products
In a 46-page draft guidance, the FDA clarified a 2013 final rule that specifies how combination product manufacturers should meet both device and drug quality regulations and implement streamlined quality systems.
Under the guidance, combination product makers have two options for GMP compliance: satisfy all drug and device GMPs, or implement a streamlined quality system that focuses primarily on one but incorporates elements of the other.
The guidance details what GMPs are applicable to a product, general methods for how to implement them, key definitions and how to make postmarket changes to a product’s quality system.
The FDA also shows how to develop a streamlined system using three detailed product scenarios: a prefilled syringe, drug-coated mesh and drug-eluting stent.
Each scenario highlights certain issues that a combination product might raise. For example, a drugmaker wants to sell a prefilled syringe, but needs to comply with certain device quality system regulations in addition to the full drug GMPs. The guidance explains how to comply with each part of the applicable device regulations, such as management responsibilities, design controls and CAPA.
The scenario also details which parts of quality system are not applicable. In the prefilled syringe case, installation and servicing need not be addressed because the syringe doesn’t need to be installed or serviced like a regular device.
FDA also notes how to deal with third party manufacturers, stressing that the sponsor of the combination product is responsible for ensuring its contractors meet GMPs. If a contractor only manufactures the device part of a combination product then it only has to meet QS regulations. In addition, the guidance notes that combination products that are simply two products that are copackaged after being made, combination product GMP requirements do not apply.
The guidance also helps clarify how combination product makers should work with the FDA; each combination product will be accepted by the agency center that will oversee its premarket review and that will be the lead center and primary point of contact for applicants.
The Office of Combination Products will offer assistance when needed for questions related to only the combination aspect of the application or to resolve disputes about which center takes the lead.
The guidance also resolves a major concern raised by biologics products makers, who were worried the 2013 rule appeared to require biologics makers to satisfy the full set of biologics GMPs. The FDA clarified that biologic combination product manufacturers can also take advantage of the same streamlined approach, with the addition of systems to meet just the biologic GMPs specific to the product type involved.
For example, if a combination product contains a spore-forming microorganism then the manufacturer must abide by that section of the biologics GMPs.
The FDA is seeking comments on the guidance, docket no. FDA-2015-D-0198, until March 30.
Because combination products blur the lines between drugs, biologics and devices, the challenge is determining which rules take precedence — drug GMP rules or device QSR rules. While these two regulations are similar, they are not the same, meaning you need to take extra steps to ensure both rules are complied with. Learn all you need to know with The Essential Guide to Combination Products cGMPs.