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Abstract:
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According to ICH Q6A (1999) Guidance, a specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. They are usually proposed by the manufacturers, and subject to the regulatory approval for use. The conventional approach is to use data of clinical batches collected during the clinical development phases. This interval may be revised with the accumulated data collected from released batches after drug approval. Dong et al. (2015) discussed the statistical properties of the commonly used intervals and made some recommendations. However, in reviewing the proposed intervals, it is often difficult for the regulatory scientists to understand the difference between the intervals, when some intervals require only pre-specified target proportion of the distribution, and others require confidence level, in addition. Therefore, we propose to use the same confidence level of 95%, and calibrate each interval to the true coverage, under the tolerance interval setting. Based on our study results, we propose some appropriate statistical methods.
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