31 No. 2
Investigating Out-of-Specification Test Results of Chemical Composition Based on Metrological Concepts
By the current good manufacturing practice in pharmaceutical industry, out-of-specification (OOS) test results are results that fall outside the specifications or established acceptance criteria. Identifying OOS test results is described in FDA Guidance for Industry “Investigating OOS Test Results for Pharmaceutical Production” (2006). By analogy, measurement/test results obtained in other industries and such fields as environmental analysis, which do not comply with regulatory or specification limits, can be named also as OOS test results. When the compliance assessment is made on the basis of a measurement result accompanied by information on the uncertainty associated with the result, the rules developed in the EURACHEM/CITAC Guide “Use of Uncertainty Information in Compliance Assessment” (2007) are applicable.
After identification of the OOS test result it is important to determine its root causes: to ensure that another OOS test result is not possible or even inevitable. The FDA Guidance mentioned above formulates general rules for investigation an OOS test result, including production review, additional laboratory testing, reporting testing results, and determining the cause. Thus, it establishes an organizational approach to the full-scale investigation and decisions which can be accepted at the different stages of this investigation.
Another approach, outlined in the this new IUPAC project, is based on metrological concepts and includes assessment of the measurement process used for the test, from sampling to chemical analysis of a test portion. The project results will be formulated as a guide. In particular, the following should be addressed in a future development of the guide:
- assessment of validation data of the measurement process, including sampling, sample preparation, and chemical analysis
- use of the validation data for evaluation of the measurement uncertainty components
- assessment of traceability chains important for measurement parameters and environmental conditions influencing the test results
The project will be carried out in collaboration with the Cooperation on International Traceability in Analytical Chemistry. The planned IUPAC/CITAC guide will be helpful for full-scale investigations of OOS test results in pharmaceutical industry (in addition to the FDA Guidance) and in other fields of testing.
For more information and comments, contact the Task Group Chair Ilya Kuselman <[email protected]>.
last modified 3 March 2009.
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