For all Sponsors submitting INDs, NDAs, ANDAs, BLAs, and supplements, and the bioanalytical laboratories analyzing and reporting the data to support these submissions, the FDA just issued its Guidance for Industry, “Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers.” The Q&A guidance contains five questions, along with the Agency’s current thinking on each topic. Included with the answers are plots of Internal Standard (IS) responses to provide visual examples for: similar IS responses, IS responses with gradual drift or repeating pattern, and an IS response that is substantially different. The fifth and final question within the guidance provides insight on how the sponsor may address variability observed in the IS response.
The guidance document does not define “substantially different” nor “similar” IS responses. These definitions will fall squarely on the shoulders of the bioanalytical laboratory analyzing the data.
The take-home point for all sponsors is to ensure that the bioanalytical laboratories supporting their regulatory submissions have adequate procedures in place to address variable IS responses.
If you or your organization have any questions or are in need of support for any aspect of your bioanalytical studies, please contact David O’Connor at firstname.lastname@example.org.
The full guidance can be found here.