FDA Issues Final Guidance for Industry, “Evaluation of Internal Standard Responses during Chromatographic Bioanalysis: Questions and Answers”

FDA Issues Final Guidance for Industry, “Evaluation of Internal Standard Responses during Chromatographic Bioanalysis: Questions and Answers”

Today, the Food and Drug Administration (FDA) published a final guidance for industry entitled, “Evaluation of Internal Standard Responses during Chromatographic Bioanalysis: Questions and Answers .” The guidance provides questions and answers on FDA’s current thinking on internal standard (IS) response variability in chromatographic analytical data, used to quantitate analyte concentrations in samples from nonclinical and clinical studies to support regulatory submissions.

ISs are commonly used in chromatographic analytical methods to correct for variability in sample processing and analysis. During bioanalysis, IS is added to samples including calibration standards, quality controls, and subject samples. IS response variability can include human errors made during sample preparation or processing, instrumental issues that may occur during analysis, and matrix effects.

The guidance explains when observed IS response variability may impact the accuracy of data and whether it warrants further investigation into the root causes. It also provides recommendations on addressing concerns about IS response variability.