IUPAC

To develop a guide for identification of root causes of out –of-specification (OOS) test results of chemical composition based on metrological concepts. The guide should be helpful for full-scale investigation of OOS test results, already detected according to existing requirements in pharmaceutical and other industries.

By the current good manufacturing practice in pharmaceutical industry, 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 avoid any repetition of the situation when appearance of a next OOS test result is possible or even inevitable. The FDA Guidance mentioned above formulates general rules for that including production review, additional laboratory testing, reporting testing results and concluding the investigation of the OOS test result. 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 initiated in the present proposal 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. 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, etc.

The work will be progressed in collaboration with the Cooperation on International Traceability in Analytical Chemistry (CITAC). The IUPAC/CITAC guide planned in the proposal framework will be helpful for full-scale investigating OOS test results in pharmaceutical industry (in addition to the FDA Guidance) and in other fields of testing.

> project announcement published in Chem. Int. Mar-Apr 2009

The progress in the project on different stages of its development was discussed in the following papers:

1. Kuselman, I., Pennecchi, F., Burns, C., Fajgelj, A. and de Zorzi, P. (2010) Investigating out-of-specification test results of chemical composition based on metrological concepts Accreditation and Quality Assurance 15:283-288 [doi:10.1007/s00769-009-0618-4]
   
2. Kuselman, I., Shpitzer, S., Pennecchi, F., Burns, C. (2010) Investigating out-of-specification test results of mass concentration of total suspended particulates in air based on metrological concepts - a case study Air Quality, Atmosphere & Health [doi:10.1007/s11869-010-0103-6]
   
3. Kuselman, I., Goldshlag, P., Pennecchi, F., Burns, C. (2011) Multi-component out-of-specification test results: a case study of concentration of pesticide residues in tomatoes Accreditation and Quality Assurance 16:361-367 [doi:10.1007/s00769-011-0780-3]
   
4. Kuselman, I., Schumacher, I., Pennecchi, F., Burns, C., Fajgelj, A. and de Zorzi, P. (2011) Long-term stability study of drug products and out-of-specification test results Accreditation and Quality Assurance 16:615-622 [doi:10.1007/s00769-011-0813-y]
   

Nov 2011 update: A IUPAC Technical Report is under review and have been submitted for publication in Pure Appl. Chem.

last update 20120118