In our latest GMP Trends Report Issue #1158, a particularly concerning observation was noted regarding the failure of a sterile compounding facility to investigate sterility testing anomalies. Specifically, there were unexplained discrepancies labeled as “background too high” and over a 90-day period, this classification appeared approximately 23 times, with no formal investigations initiated.
In microbiological testing, a result flagged as “background too high” typically indicates excessive microbial growth or other interference that obscures the detection of potential contaminants. These are not benign outcomes. They can signal compromised sample integrity, equipment contamination, personnel aseptic technique failures, or environmental monitoring breakdowns.
FDA expectations are outlined in 21 CFR §211.192 that mandates “any unexplained discrepancy” must be thoroughly investigated, whether or not the batch has already been distributed. The regulation does not make exceptions based on alternate passing results or assumptions about root cause. The expectation is clear: all data anomalies must be understood and documented.
A single lapse in aseptic processing can lead to contamination that is undetectable in a standard sample size. This is precisely why anomalous results must be taken seriously. Releasing product based on “some passing results” when others are inconclusive or compromised is a dangerous precedent. Without identifying the root cause of the high background levels, the firm cannot credibly claim control over its aseptic processes.
Sterility failures often make headlines; however, the ignored signals like the “background too high” events, the missed discrepancies, or the absent investigations that quietly set the stage for regulatory action and patient risk. Firms must resist the urge to rationalize away these events and instead lean into their root causes with urgency and rigor.
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