US FDA finalises combination drug/device product guidance
The guidance – entitled ‘Current Good Manufacturing Practice (cGMP) Requirements for Combination Products’ – was published in the Federal Register this week, two years after the US Food and Drug Administration (FDA) invited industry to comment on a draft.
The document offers drug and device makers guidelines on how to implement the FDA regulation of 2013 on combination products – defined as a product composed of two or more different types of medical products, i.e. a drug, device, and/or biological product with one another – and clarifies “that the cGMP requirements that apply to each of the constituent parts apply to the combination product they constitute.”
The Agency gives guidelines on the responsibilities of specific manufacturers and facilities, and how compliance should be coordinated across sites.
“A facility that manufacturers a constituent part of a combination product or a complete combination product must be compliant with the CGMP requirements applicable to each manufacturing process that occurs at that specific facility,” the document says.
In fitting with other FDA guidance, responsibility lies with the marketing authorization holder across all components of the manufacture, whether or not a third-party is involved.
The Agency adds: “A facility that manufactures only a finished device intended to be a constituent part of a combination must comply only with the device QS [quality system] regulation. Similarly, a facility that manufactures only a drug intended to be a constituent part of a combination product must comply only with the drug cGMPs.”
But even if a facility is manufacturing only one type of constituent part for a combination product, the Agency says the cGMP operating system should take into account considerations for the combination product as a whole, where appropriate.
“Before changes are made to the manufacturing process of a constituent part, the cGMP operating system should ensure consideration of whether such changes could affect performance and/or interaction with the other constituent part(s) and, if so, whether the safety and effectiveness of the combination product could be impacted.”
Each manufacturing facility must also have documentation specifying its respective responsibilities, the FDA says, and the manufacturer of the finished combination product should have access to this documentation.
