Pharmaceutical test methods validation

Crowther, J. B., Validation of Pharmaceutical Test Methods, In Handbook of Modern Pharmaceutical Analysis, Vol. 3, (Ahuja, S. and Scypinski, S., Eds.), Separation Science and Technology, Academic Press, New York, pp. 415 43, 2001. 

Pharmaceutical sites will usually create a dedicated team of validation specialists to coordinate all validation activities. They should operate according to a validation master plan that has been developed using risk analysis to identify the most critical systems requiring validation/re-validation. Before validating a system or process, a written protocol should be prepared that describes the system, the critical aspects, the objectives, the test methods and the acceptance criteria that will be applied. A validation report should be prepared on completion of each protocol. 

Since the U.S. vs. Barr decision in 1993 (relevant to pharmaceuticals and related fields, rules applied by the Federal Food Drug Administration, FDA), outlier tests may no longer be applied to physicochemical tests, under the assumption that such test methods, having been optimized and validated for the particular set of circumstances, rarely produce outliers. These tests may not be applied to CU results at all. Good manufacturing practices mandate that operators work according to pre-set procedures and write down any observed irregularities as they... 

In biomedical and pharmaceutical analysis, and particularly in the pharmaceutical industry, much attention is paid to the quality of the obtained analytical results because of the strict regulations set by regulatory bodies. Proper method validation demonstrates the fit of an analytical method for a given purpose. In this context, robustness testing has become increasingly important. 

The purpose is to develop a guideline to validate the efhcacy of the sterility test method for a specihc product or material. The similarity of the validation approach with the other pharmaceutical manufacturers shall be considered coincidental due to the similarity of operations and the nature of the work. 

Laboratory equipment and procedures must be qualified and validated. Every NDA/ANDA inspection will include both an evaluation of laboratory controls and procedures and an audit of some of the raw data used to generate results. These data may be located in research and development test logs. The authenticity and accuracy of data used in the development of a test method should be established. (See the Guide to Inspection of Pharmaceutical Quality Control Laboratories, July 1993.)... 

Corbo, M.. T. W. Schultz. G. K. Wong, and G. A. Van Buskirk, Development and Validation of In Vitro Release Testing Methods for Semisolid Formulations, Pharmaceutical Technology 17(91 112-128. 1993. 

PIC (1989) Guide to Good Manufacturing Practices of Pharmaceutical Products, PIC-Doc PH 5/89 (now PH 1/97 (rev. 2) [7]) Validation of critical processes, significant amendments to manufacturing processes, significant amendments to manufacturing processes, and of all sterilization processes and test methods stipulated. 

Reproducibility encompasses the variation in analytical results between laboratories and provides a second level of method ruggedness. This is becoming an increasingly important part of method validation as the pharmaceutical industry becomes more specialized and diversified. Major manufacturers may develop and validate a method in a corporate research center for use in a foreign manufacturing site or at a contract testing laboratory. It is therefore critical that the validation demonstrates that the method is free of analyst or instrument bias. 

The efforts at harmonization of the requirements among Europe, the United States, and Japan for methods validation, stability testing, and indentification of impurities are welcomed by all pharmaceutical analysts. 

P. Sajonz, T. K. Natishan, Y. Wu, N. T. McGachy, and D. DeTora, Development and validation of a sensitive and robust wipe-test method for the detection and quantification of the antibiotic Ertapenem and its primary degradates in a pharmaceutical manufacturing environment, /. Liq. Chromatogr. Relat. Technol. 28 (2005), 713-725. 

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