Regulations of Bioavailability and Bioequivalence Studies Article 16

The bioanalytical part of bioavailability and bioequivalence studies should be performed in accordance with the principles of Good Laboratory Practice, and comply with the following requirements:1.Bioanalytical method used in bioavailability and bioequivalence studies should be able to measure the parent compound or its metabolite with adequately justified lowest concentration to adapt the aim of the study. If a metabolite as a surrogate for a parent compound is the biological sample of the analysis, it should be approved in advance by the central competent health authority.2.Validation of a bioanalytical method should include determination of precision, accuracy, selectivity, martrix effect, stability and the lowest limit of quantification. They must be compatible to system suitability. Stability tests shall include freeze and thaw stability, short term temperature stability, long term stability, stock solution stability, and post preparative stability. Under special circumstances alternative approaches may be used. In such cases, the applicants must provide relevant documents to support such claim and gain approval from the central competent health authority.3.For accuracy determination, the mean concentration should be within 15% of the nominal values for each concentration level, except for the lower limit of quantification which should be within 20% of the nominal value. For precision determination, the coefficient of variation value should not exceed 15% for each concentration level, except for the lower limit of quantification which should not exceed 20%.