Q&A on Evaluating Internal Standard Response
In September, the CDER issued a level 2 guidance containing a series of questions and answers on the evaluation of internal standard responses during bioanalysis of clinical trial samples. Normally used in chromatographic tests to measure the trial drug, an internal standard (IS) is a structurally similar analog or stable isotope of the trial drug that is added in a known amount to each sample or standard to be analyzed. The response of the IS is used to normalize the response of the trial drug to correct for normal variability due to sample processing and analysis. Errors in sample preparation, instrument issues, and the sample matrix itself may create additional variation in IS response during an actual test run which may affect the results. The purpose of the guidance is to provide clear examples of IS responses that may affect the accuracy of the test data and to recommend the SOP have a pre-established procedure for evaluating IS response and re-analyzing and samples determined to be affected. As a chromatography expert, I appreciated the graphic presentation of the IS response examples, which make the characterization of aberrant IS response clear. As a level 2 guidance, this represents a clarification of an existing policy, but it’s likely addressing an issue the reviewers commonly observe when reviewing trial analytical data.
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Text Copyright © 2019 Katrina Rogers