The current good manufacturing practice (CGMP) regulations for finished pharmaceuticals and the medical device quality system regulations require development of controls that include scientifically sound and appropriate sampling plans.
Sampling plan information is addressed in AAMI ST72, but not USP Chapter <85>. Firms should include a sampling plan as part of their application documentation. In the sampling plan, firms should consider the potential for contamination in raw materials, in-process materials, and the finished product. Specifically, firms should take into account aspects of the manufacturing design, including consistency of a manufacturing process, impact of in-process hold times, endotoxins removal steps, and finished product endotoxins specifications. The sampling plan should be considered dynamic; firms should begin with maximum coverage and adjust their sampling plans as they gain confidence in the prevention of endotoxins in their manufacturing processes. Firms should update their regulatory filings when adjusting sampling plans. For drugs and biological products, in-process changes to sampling plans are annual reportable changes. For devices, a 30-day notice may be appropriate for in-process changes to the sampling plan.
