During a recent inspection, FDA observed that finished product release testing sample sizes did not appear representative of the batch size.
The 483 reads:
Specifically, a review of batches of vials (expiration dates from … to …) revealed inconsistencies. The largest batch, lot …, was more than double the size of the smallest batch, lot …. However, the finished product samples submitted for batch release testing by the contract test lab were the same for both: … vials for lot … and … vials for lot …. Furthermore, the batch size and number of vials tested for sterility were not identified on the contract test lab’s finished product test report. The testing method, “Non-Component Standard Test Method Finished Goods and Stability Testing for … Vials,” specifies a fixed sterility sample size of … vials per … of randomly selected … throughout … of the batch, without considering the batch size.
Representative sampling is essential for ensuring that testing results accurately reflect the quality of the entire batch. When sample sizes do not scale with batch size, potential issues or contamination in larger batches may go undetected, leading to the release of substandard or unsafe products. This deficiency can seriously compromise product quality and patient safety, as it undermines the reliability of batch release testing.
Relevant CFR guidance is referenced in 21 CFR 211.165:
(c) Any sampling and testing plans shall be described in written procedures that shall include the method of sampling and the number of units per batch to be tested; such written procedure shall be followed.
(d) Acceptance criteria for the sampling and testing conducted by the quality control unit shall be adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release. The statistical quality control criteria shall include appropriate acceptance levels and/or appropriate rejection levels.
The general requirements for Laboratory Controls is linked here 21 CFR 211.160
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