Regulatory requirements for verification of sampling plan for solid pharmaceutical bulk product

Abstract

The most convenient sampling plan for routine testing at batch release for a solid pharmaceutical bulk product is a sampling plan with requirements for generating a composite sample. Verification is required before such a sampling plan can be used for routine testing. The verification needs to demonstrate that the composite sample is representative of the whole batch and is considering the most stressed part of the manufacturing process of the solid pharmaceutical bulk product. As part of verification, increased sampling should be performed to demonstrate that the manufacturing process yields a homogeneous product. The sampling for batch release testing of a solid pharmaceutical bulk product is performed at the end of the production process from each individual container where the batch is stored. All containers combined represent the variability of the entire batch, that is, the individual samples taken from each container. The verification process should demonstrate that individual samples taken from each container gives comparable sampling variability as a composite sample is prepared from all containers. A statistical evaluation and comparison of the results from individual samples and composite sample is most appropriate when performed by using Equivalence Test (TOST). If such equivalence is obtained between individual samples from each container and a composite sample, then it is possible to limit the routine testing to representative composite samples from predetermined containers defined in the sampling scheme. The sampling plan with a representative composite sample should be verified enough that it is suitable for all future batches. Keywords: Pharmaceutical sampling, solid pharmaceutical bulk product, representative composite sample, verification of sampling plan with composite sample, Equivalence Test (TOST)