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GUIDANCE DOCUMENT

Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers September 2019

Final Level 2 Guidance
Issued by:
Guidance Issuing Office
Center for Drug Evaluation and Research

This guidance provides recommendations to sponsors, applicants, and contract research organizations regarding internal standard (IS) response variability in chromatographic analytical data submitted in investigational new drug applications, new drug applications, abbreviated new drug applications, biologics license applications, and supplements. Chromatographic analytical methods are commonly used to quantitate analyte concentrations in samples from nonclinical and clinical studies to support regulatory submissions. Depending upon its source, IS response variability may impact the accuracy of analyte concentration measurements. This question and answer (Q&A) document provides the Agency’s current thinking on IS response variability and its potential impact on the accuracy of analyte concentration measurements. This Q&A also suggests approaches to determine whether observed IS response variability is likely to impact the accuracy of the data such that further investigation into the root cause(s) is warranted.


Submit Comments

Submit comments on this guidance document electronically via docket ID: FDA-2013-S-0610 - Specific Electronic Submissions Intended For FDA's Dockets Management Staff (i.e., Citizen Petitions, Draft Proposed Guidance Documents, Variances, and other administrative record submissions)

If unable to submit comments online, please mail written comments to:

Dockets Management
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852

All comments should be identified with the title of the guidance.