II. BACKGROUND 48 Remove biopharmaceutics” from line 61 as it is out of context. Proposed change: “and/or The sentence would then read: sensitive, and validated analytical methods for “Selective, the quantitative evaluation of drugs and their metabolites (analytes) and biomarkers are critical for the successful conduct of nonclinical and/or clinical studies for small-molecule 59-71 drugs and biopharmaceutics.” The guidance does not mention specificity as one of the fundamental parameters for validation of LBA assays. Proposed change: Add in case of LBA” to the list of fundamental parameters. “Specificity The guidance suggests that for exploratory methods validation may be sufficient” (line “less 78). Historically, exploratory methods (screening methods and those applied to studies) have not been within the scope of regulated bioanalysis and therefore 73-78 have not been subject to formal validation. Remove this sentence. Alternatively, further clarify how fit-for-purpose Recommendation: validation should be applied. The guidance states: modifications should be validated…”, Recommendation: Rather than using this statement, reference the partial validation section 80-86 98-116, which provides further detail on appropriate levels of validation for method changes. The details on full, partial and cross-validation should be moved from the Background section to the Validation section. 88
48 II. BACKGROUND 59-71 Proposed change: Remove “and/or biopharmaceutics” from line 61 as it is out of context. The sentence would then read: “Selective, sensitive, and validated analytical methods for the quantitative evaluation of drugs and their metabolites (analytes) and biomarkers are critical for the successful conduct of nonclinical and/or clinical studies for small-molecule drugs and biopharmaceutics.” The guidance does not mention specificity as one of the fundamental parameters for validation of LBA assays. Proposed change: Add “Specificity in case of LBA” to the list of fundamental parameters. 73-78 The guidance suggests that for exploratory methods “less validation may be sufficient” (line 78). Historically, exploratory methods (screening methods and those applied to studies) have not been within the scope of regulated bioanalysis and therefore have not been subject to formal validation. Recommendation: Remove this sentence. Alternatively, further clarify how fit-for-purpose validation should be applied. 80-86 The guidance states: modifications should be validated…”, Recommendation: Rather than using this statement, reference the partial validation section 98-116, which provides further detail on appropriate levels of validation for method changes. 88 The details on full, partial and cross-validation should be moved from the Background section to the Validation section.
IQ_Comments_on_the_FDA_Draft_Guidance_for_Industry_Bioanalytical_Method_Validation.docx