It must be clearly established in the course of the first process step when the OOS result occurred during testing. This is done by examining the raw data (electronically or on paper) and comparing it with the defined criteria! In other words, an OOS result comes into existence the moment the respective measurement values or raw data are recorded, even if the result has not yet been documented in a final report.
When non-compliance is identified, the process is initiated. It starts immediately with the implementation of the mandatory raw data countercheck (4-eyes principle) and the mandatory communication of information (line manager, Head of QC and QA, QP, pharmaceutical company).
Figure 1 shows the layout of a cover sheet for initiating an OOS process. The illustration shows the data and information required at the start of the process.
Figure 1: OOX template: header data, relevant information
Obvious error during implementation:
If obvious errors are detected at the start of the analysis or during the ongoing analytical process (e.g. an obvious equipment failure or defect, the use of incorrect volume measuring instruments, overfilling beyond the calibration mark, incorrect instrument settings, etc.), the analysis must not be continued or must be stopped. The process error is noted on the raw data already compiled in a suitably accurate and GMP-compliant manner. In these sort of cases, an OOS process is not initiated.
In the case of tests that characterise the variability of a batch (uniformity of mass, content uniformity, hardness, degradation, dissolution, etc.), the product is evaluated in accordance with special acceptance criteria (level or stage testing). An example would be testing the release of the active ingredient (dissolution testing): Level 1: n = 6 tablets, Level 2: n = 6 tablets and Level 3: n = 12 tablets. An OOS result exists when all scheduled test phases have been carried out and the relevant requirements or extended requirements have not been met.
The GMP Series PDF Download Industry Guide to handle OOX Test Results - Managing Test Results out of Defined Criteria deals in detail with the following issues: