Development of a Content Uniformity Test Suitable for Large Sample Sizes

Abstract

Applications of process analytical technology (PAT) are currently attracting wide interest. One of the potential applications of PAT is large-scale (hundreds or thousands of tablets), real-time evaluation of tablet content uniformity. An issue associated with this situation is which acceptance criteria the obtained large sample should meet. Traditionally, a sample of 10-30 tablets is assessed against criteria specified in the harmonized pharmacopeial specification for uniformity of dosage units (UDU). These criteria, however, are not directly applicable to large sample sizes as application of the acceptance criteria in the harmonized pharmacopeial specification in these situations results in an overly restrictive requirement. Industry has highlighted this issue as a potential deterrent for extended applications of PAT in this area. A one-tiered counting test for UDU with associated acceptance criteria is proposed as an alternative to the harmonized pharmacopeial specification for UDU. The proposed test is applicable to large sample sizes yet provides the same assurance of uniformity of the batch as the harmonized pharmacopeial specification.