FDA CONTENT UNIFORMITY COMPLIANCE GUIDE: TESTING SPECS ARE REQUIRED

Executive Summary

FDA CONTENT UNIFORMITY COMPLIANCE GUIDE: TESTING SPECS ARE REQUIRED for non-USP tablets and capsules that contain less than 50 mg of any active ingredient. In a recently issued "Compliance Policy Guide," FDA notes that current GMPs require "the establishment of scientifically sound and adequate specifications to assure" that products not subject to compendial requirements meet their purported standards. "Specifications for content uniformity are required, within this context," the guide states, "for tablets and capsules which contain less than 50 mg of any active ingredient." The requirements can be satisfied for such products, the guide adds, by adopting either USP test specifications, or "sound alternative specifications." The FDA guide also requires content uniformity specifications for relative standard deviation for both compendial and non-compendial products. The relative standard deviation specs are in addition to specifications for individual dosage unit assays. The guide points out that there has been "confusion" among tablet and capsule manufacturers as a result of a recent revision in the USP content uniformity requirements. Manufacturers must now include the relative standard deviation specification in order to limit large variations in test results. While "many firms have been reluctant to incorporate the relative standard deviation specification into their standard operating procedures," FDA notes, the USP monograph requirement must be met for a product to be considered in GMP compliance. FDA said that the requirement for specifications for both individual dosage unit assay and for relative standard deviation are applicable regardless of whether the product in question is subject to an NDA. The guide adds that "if an approved NDA does not currently provide for complete content uniformity testing, or provides specifications that are inconsistent with the USP monograph, the NDA holder must submit a change to provide for such testing."