EMA and Anvisa guidances require the assessment of selectivity in hemolyzed and lipemic matrix sources when is the target matrix. Recommendation: In order to align the draft guidance with those of the other agencies we recommend that lines 196-197 be revised to state of blank samples of the “Analyses appropriate biological matrix (plasma, urine, or other matrix) should be obtained from at least six independent sources; in the case of plasma or serum, these six sources may include those that are hemolyzed and/or lipemic”. 194-199 We suggest that the agency consider aligning the need for method selectivity assessment to the inherent specificity of the detection approach that the method employs. Specifically, retention of the following text from the 2001 guidance should be considered: “for hyphenated mass methods, however, testing six independent matrices for interference may not be important.” Finally, we request that agency expectations with respect to the evidence needed to that the substance quantified is the intended analyte be stated. Is a match of the retention time of analyte peaks in standards and post-dose samples sufficient evidence for SRM LC/MS methods, or is additional information required?
194-199 EMA and Anvisa guidances require the assessment of selectivity in hemolyzed and lipemic matrix sources when is the target matrix. Recommendation: In order to align the draft guidance with those of the other agencies we recommend that lines 196-197 be revised to state “Analyses of blank samples of the appropriate biological matrix (plasma, urine, or other matrix) should be obtained from at least six independent sources; in the case of plasma or serum, these six sources may include those that are hemolyzed and/or lipemic”. We suggest that the agency consider aligning the need for method selectivity assessment to the inherent specificity of the detection approach that the method employs. Specifically, retention of the following text from the 2001 guidance should be considered: “for hyphenated mass methods, however, testing six independent matrices for interference may not be important.” Finally, we request that agency expectations with respect to the evidence needed to that the substance quantified is the intended analyte be stated. Is a match of the retention time of analyte peaks in standards and post-dose samples sufficient evidence for SRM LC/MS methods, or is additional information required?
IQ_Comments_on_the_FDA_Draft_Guidance_for_Industry_Bioanalytical_Method_Validation.docx