Is the ("verification by a second individual") still the best solution for the compliance of microbiological testing?
The four eyes principle is a cornerstone of any quality system — GMP, Good Laboratory Practice (GLP) or International Organization for Standardization (ISO) 17025.
A first person performs a task, and then a second person checks it.
In U.S. GMP, there are several references to a second-person check or verification, such as QC analysis for the laboratory (§211.194).
These second-person checks are all key stages of the pharmaceutical manufacturing process. They are to ensure that mistakes can be caught and resolved early in the process.
Although this is primarily to ensure patient safety and compliance with the regulations, it is also good business sense as well, since you don’t want to commit resources to a process that will fail.
Microbiological testing is an area of pharmaceutical quality control that has seen uneven compliance with the "four-eyes requirements outlined in 21 CFR 211.1 which recommends that a result read by one operator should be verified by an independent second operator. In fact, the reading of environmental monitoring (EM) and bioburden test results is typically performed in isolation by a single operator transcribing results to a batch record without verification.
Recently, however, the FDA has become concerned about this lack of control and has included the microbiological plate counting area in their audits.
A recent update to USP <1117> seeks to bring clarity by suggesting that a second read is not required for low-criticality samples such as EM or water testing.
Only the critical samples such as a sterility test should have verification by a second analyst at the time of reading.
Cost is also an issue for pharma companies that must observe the 4 eyes principle as as part of a traditional compendial process. Significant investments in staff recruitment and training are needed to fill the verifier role. The four-eyes requirement adds one-to-two FTEs annually per 30-50.000 plate reads.
Instead of recruiting extra staff, QC microbiology labs could benefit from a suitable Rapid Microbial Method (RMM) such as an automated colony counter. Automation ensures the integrity of enumeration data while removing any doubts about incubation temperature and duration.
The use of an automated colony counter and direct transmission of the counts from plate to laboratory information management system (LIMS) databases improved security and negated any need of a second reader.
References:
- CFR21 PART 211—CGMP FOR FINISHED PHARMACEUTICALS
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Resource Person: BARBARA PIROLA
