Have you investigated the water testing results that are OOS?

USP Purified water and USP water for injection (WFI) are components or ā€œingredient materialsā€ intended to be used in the production of drug products.  As such, according to the Code of Federal Regulations (21 CFR 211.192 Production Record Review), the failure of water testing results to meet any of its specifications shall be thoroughly investigated.  A written record of the investigation shall be made and shall include the conclusions and follow-up.

A company recently received the following observation:

ā€¦.. There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, the firm does not investigate OOS results from water testing of the … water system. Water from the … system is utilized as a component in various drug products manufactured by the firm. For example, the firm obtained OOS results from water testing for the following water use polls:

ā€¢    … , too numerous to count – >50 CFU/mL, action level specification … and

ā€¢    … too numerous to count – >50 CFU/mL, action level specification …

No investigations were initiated into the OOS results, … was not re-sampled until 3 weeks later (passing results obtained) and the firm manufactured multiple products between the first OOS result and the passing result (3-week period).

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According to GMP TrendsĀ® 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 information on conducting an Out of Specification (OOS) investigation, refer to the FDAā€™s Guidance Document, Guidance for Industry Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production Issued May 2022.

To view more observations pertaining to OOS investigations, refer to the following GMP TrendsĀ® Issues: 1117, 1115, 1113 and 1107

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