September 13, 2019
Authored and Edited by Nicholas J. Doyle; M. Andrew Holtman, Ph.D.
On September 4, 2019, FDA issued final guidance on the Evaluation of Internal Standard Responses during Chromatographic Bioanalysis. The guidance gives recommendations to sponsors, applicants, and contract research organizations regarding internal standard (IS) response variability in chromatographic analytical data submitted in INDs, NDAs, ANDAs, BLAs, and supplements.
The guidance begins by noting that, depending on the source, IS response variability may impact the accuracy of analyte concentration measurements. The guidance also identifies several common sources of IS response variability, such as human error in preparing the standards, instrumental issues that may occur during analysis of the standards, and matrix effects within the standards.
In a question and answer format, the guidance provides examples of when IS response variability is likely and not likely to impact the accuracy of the reported data. For example, if the range of IS response for subject samples is similar to the range of IS responses for calibration standards and quality control samples, the IS response variability is not likely to impact the accuracy of the data. If, on the other hand, the IS responses are substantially different than responses for the other samples, and the calibration standards and quality control samples do not demonstrate similar variability, the IS response variability can impact the accuracy of the data. The guidance suggests three general categories of problematic IS response variability: (1) IS responses significantly different than the responses for calibration standards and quality control samples, (2) IS responses that gradually drift, and (3) IS responses that are consistently lower or higher than the IS responses for calibration standards and quality control samples.
For each observed variance in IS responses, the guidance suggests approaches that sponsors can adopt to mitigate the variability. For category 1 variances, pre-established criteria for repeat analysis should be followed on such IS responses that significantly differed. For drifting variance, category 2, subject samples displaying the aberrant IS responses should be reanalyzed. The guidance then offers further steps that sponsors should take based on the results of the reanalysis. Finally, for category 3 where constantly lower and higher IS responses are observed, a subset of subject samples should be reanalyzed. Again, the guidance offers further steps to be taken based on the results of this reanalysis.
Readers are encouraged to read the final guidance, also available on FDA’s website.
Copyright © 2019 Finnegan, Henderson, Farabow, Garrett & Dunner, LLP.
DISCLAIMER: Although we wish to hear from you, information exchanged in this blog cannot and does not create an attorney-client relationship. Please do not post any information that you consider to be personal or confidential. If you wish for Finnegan, Henderson, Farabow, Garrett & Dunner, LLP to consider representing you, in order to establish an attorney-client relationship you must first enter a written representation agreement with Finnegan. Contact us for additional information. One of our lawyers will be happy to discuss the possibility of representation with you. Additional disclaimer information.
Conference
4th Annual Passport to Proficiency on the Essentials of Hatch-Waxman and BPCIA
October 8-24, 2024
Virtual
Conference
2024 Corporate Counsel Women of Color: Career Strategies Conference
October 2-5, 2024
Las Vegas
Seminar
Intellectual Property in the Age of AI: What Do You Own and How Do You Balance Risks?
September 25, 2024
Boston
Virtual Seminar
U.S. Patent Application & Litigation Practice Development and Response
September 6, 2024
Virtual
Due to international data regulations, we’ve updated our privacy policy. Click here to read our privacy policy in full.
We use cookies on this website to provide you with the best user experience. By accepting cookies, you agree to our use of cookies. Please note that if you opt not to accept or if you disable cookies, the “Your Finnegan” feature on this website will be disabled as well. For more information on how we use cookies, please see our Privacy Policy.
Finnegan is thrilled to announce the launch of our new blog, Ad Law Buzz, devoted solely to breaking news, developments, trends, and analysis in advertising law.