FDA releases compliance program for CDER, CDRH-led combination product inspections
In a newly issued compliance program, the US Food and Drug Administration (FDA) explains its approach to inspections of Center for Drug Evaluation and Research (CDER)- and Center for Devices and Radiological Health (CDRH)-led combination products.The 46-page document lays out FDA’s intended implementation of the compliance program; inspectional operations and reporting considerations; sampling and analytical testing expectations; regulatory and administrative strategy; and an explanation of center responsibilities.
FDA says the compliance program focuses mainly on single-entity and co-packaged combination products that feature drug and device or biological product and device constituent parts.
Combination product manufacturers may demonstrate compliance with current good manufacture practice (CGMP) requirements through one of two ways: compliance with all applicable CGMPs or by following a streamlined approach in which drug CGMPs or device quality system regulation and specific “called-out provisions” are followed.
“Because most combination product manufacturers use a streamlined approach, this compliance program focuses on inspections of compliance with the base CGMPs plus the called-out provisions specified in 21 CFR Part 4,” FDA writes. FDA also explains that combination products should generally follow the practices of the lead center and base compliance program in addition to “commodity-specific” compliance programs, which are referenced in the document.
The compliance program provides specific considerations for FDA investigators carrying out different types of inspections, including preapproval, postapproval, surveillance, for-cause and risk-based inspections. FDA notes that the compliance program does not apply to inspections for Center for Biologics Evaluation and Research-led combination products and should not be used for inspections of facilities that only manufacture one type of constituent part or product components (e.g., device components or active pharmaceutical ingredients).
“For cross-labeled combination products manufactured at the same facility, the agency does not intend to object to the use of a streamlined CGMP operating system for the manufacture of the combination product rather than distinct systems for the manufacture of each constituent part that is occurring at that facility,” FDA writes.
FDA also notes that certain audit and inspection programs, including third-party audits or the medical device single audit program (MDSAP) “may impact implementation of this compliance program,” and instructs staff to contact the lead center for further information.
In addition to the various types of inspections, the compliance program also provides considerations for how to approach inspections relating to convenience kits or combination products that include a device constituent part that is exempt from quality system regulations.