Incurred sample shall be selected from each subject (who has completed the study).

10% of the samples should be reanalysed in case the number of samples is less than 1000 samples and 5% of the number of samples exceeding 1000 samples. e.g 1) !otal study samples 1000 Incurred samples to be selected 1000"10% that is e#ual to 100 samples $) !otal study samples %000 Incurred samples to be selected 1000"10% that is e#ual to 100 samples &dditional samples %000 ' 1000 ($000"5% that is e#ual to 100 samples !otal incurred samples to be selected is e#ual to 100)100 ($00 samples Incurred sample reanalysis shall be performed at least for following studies : !oxico*inetic studies once per species &ll pi+otal bioe#ui+alence trials ,irst clinical trial in subjects ,irst patient trial ,irst trial in patients with impaired hepatic and-or renal function ,or selection of incurred samples preferably 50% samples shall be selected near . max/ and preferably 50% samples shall be selected near end of elimination for each subject - group of animals. In case of estimation of multiple analytes/ the incurred sample selection criteria shall be applicable to the analyte-s for which bioe#ui+alence has to be established (e.g. In case of &tor+astatin 01 study/ incurred sample selection criteria shall be applicable to &tor+astatin only and not to 2rtho and 3ara 4ydroxy &tor+astatin. !herefore incurred samples selected for &tor+astatin shall be applicable for 2rtho and 3ara 4ydroxy &tor+astatin) ,or other human studies (not co+ered by section56.1.$)/ Incurred sample reanalysis shall be performed as defined in study protocol. ,or animal studies (e.g. !oxico*inetic) incurred sample should be selected from each group of study and should represents actual study population. It can be defined in study plan based on study design. In case of animal studies (e.g. 7epeated dose toxico*inetics) if absorption phase or elimination phase is not clearly distinguishable then Instead of near . max or elimination/ other alternate samples shall be selected for incurred sample reanalysis. Incurred sample reanalysis shall be performed for first sub5chronic toxicological study (studies where test items exposure is $8 days or more) and onwards. ,or single dose study/ incurred sample analysis shall not be performed. 9amples ha+ing concentration between 1$0% of ::2; < 80% of =:2; and accepted after first analysis (with out dilution) shall be selected as incurred sample. In case of multiple analytes preferably for all analytes selected incurred samples should ha+e concentration between 1$0% of ::2; < 80% of =:2;. &+ailability of sample +olume shall be considered to repeat the sample analysis while selection of incurred sample.

Incurred sample reanalysis : Incurred sample reanalysis shall be done by the same method used for study sample analysis and recorded in study sample analysis template. Incurred sample reanalysis can be performed intermittently (after completion of repeat analysis from intended subjects-groups-batches) - after completion of study based on project re#uirement and nature of molecule. !he study with longer duration and conducted on multiple site will often ha+e intermittent sample receipt/ so incurred sample reanalysis shall be performed after completion of that particular sample batch analysis. !he same shall be followed for animal studies when sample analysis is done at different stages of the study. Acceptance Criteria : &t least >6% of the incurred samples should be within ) $0% of the original result obtained after first analysis. ?ider acceptance criteria can be defined for ligand binding assay and specific molecules (e.g. 3eptides/ 3roteins/ =nstable molecules) in respecti+e study protocol - &!3 - !emplate ,ormula of calculation % @ifference ( A(I97 +alue ' ,irst analysis +alue) - Bean of I97 and ,irst analysis +alue C D 100. 0atch acceptance criteria should be as per 923 Eo. 3F@-9-0%%/ G.hromatographic analysis of study sampleH. Evaluation of result : &t least >6% of the incurred samples should be within ) $0% of the original result obtained after first analysis. If the Incurred sample reanalysis meets the abo+e mentioned acceptance criteria after excluding the samples with assignable analytical error as per 923 Eo. 3F@-9-01I G9ample 7eanalysis and 7eporting of ,inal .oncentrationsH then those samples need not be repeated but same should be documented. If the Incurred sample reanalysis does not meet the abo+e mentioned acceptance criteria and assignable cause is found as per 923 Eo. 3F@-9-01I G9ample 7eanalysis and 7eporting of ,inal .oncentrationsH then either respecti+e samples - whole batch shall be reanalyJed after appro+al of department head. If Incurred sample reanalysis does not meet abo+e mentioned acceptance criteria/ and any assignable cause is not found then in+estigation shall be carried out to identify and e+aluate reason of I97 failure. @epending upon sample a+ailability same or new set of incurred samples shall be used for in+estigation. Note : In cases where reanalysis or in+estigation of I97 failure can not be performed with respect to 7.3.3 and 7.3. due to insufficient sample +olume/ these shall be handled on case by case basis with appro+al of department head