According to the Code of Federal Regulations (21 CFR 211.192 Production Record Review), the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed. Conducting a thorough investigation is crucial to the integrity of a batch. The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy. A written record of the investigation shall be made and shall include the conclusions and follow-up.
A company recently received the following observation:
….. There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed.
Specifically, investigations of deviations are inadequate. Deviation … was opened because incoming ampule lot #… failed the internal AQL for score line defects during … inspection, and the lot was still released. The quality technical agreement (QTA) with your ampule supplier classifies score line defects as a critical defect. The inspection exceeded your AQL … but fell within the ampule supplier’s less stringent AQL … and the lot was accepted for use. The root causes are listed as “Defect level exceeding the AQL was missed during inspection and reviews” and “Defect level exceeds … AQL of … but does not exceed defect level established in the QTA with …” The investigation states that there is no product impact because lot #… meets the AQL specification in the quality agreement between you and your supplier. The corrective actions taken were retraining staff and reviewing acceptance criteria for … lots. At the time of your investigation, you did not take other corrective or preventive actions to reduce the risk of defects in ampule lot #… and to ensure the quality of finished drug product to be manufactured using the subject ampules.
According to GMP Trends® Annual Reports, over the last 5 years the observations pertaining to investigations (21 CFR 211.192) have been in the top 10 observations cited by the FDA each year.
For more observations pertaining to manufacturing controls, see our new Issue 1123 available today. It also has observations pertaining to quality systems, laboratory controls, and medical devices.
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