Abstract
In September 2013, the FDA released a draft revision of the Bioanalytical Method Validation (BMV) Guidance, which included a number of changes to the expectations for bioanalysis, most notably the inclusion of biomarker assays and data. To provide a forum for an open, inclusive discussion of the revised draft BMV Guidance, the AAPS and FDA once again collaborated to convene a two-and-a-half day workshop during early December 2013 in Baltimore, MD, USA. The resulting format embodied extensive open discussion and each thematic session included only brief, concise descriptions by Agency and industry representatives prior to opening the floor discussion. The Workshop was built around four thematic sessions (Common Topics, Chromatographic, Ligand-Binding Assays, and Biomarkers) and a final session with international regulators, concluding with a review of the outcomes and recommendations from the thematic sessions. This Workshop report summarizes the outcomes and includes topics of agreement, those where the FDA will consider the Industry’s perspective, and those where the workshop provided a first open dialogue. This article will be available to the bioanalytical community at http://www.aaps.org/BMV13.
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Abbreviations
- A&P:
-
Accuracy and Precision
- ADC:
-
Antibody-Drug Conjugate
- BQL:
-
Below Quantitation Limit, <LLOQ is also used
- Conjugated Antibody:
-
Antibody with DAR equal or greater than 1
- DAR:
-
Drug Antibody Ratio
- Dx:
-
Diagnostic
- HQC:
-
High Quality Control
- LLOQ:
-
Lower Limit of Quantitation
- LQC:
-
Low Quality Control
- MQC:
-
Mid Quality Control
- ULOQ:
-
Upper Limit of Quantitation
- Unconjugated Drug:
-
drug spontaneously released in vivo from an ADC
- Antibody-Conjugated Drug:
-
drug conjugated to the antibody moiety
- Total Antibody:
-
Antibody with DAR equal or greater than 0. Includes conjugated and fully unconjugated antibody.
- Mock Clinical Sample:
-
Samples prepared by pooling samples or spiking over endogenous levels. Used in the context of demonstrating biomarker stability on storage and measured periodically with a Dx.
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Acknowledgments
We would like to acknowledge all of the panelists, moderators, and note takers for their contributions to the success of the workshop. Stanley Au, U.S. Food and Drug Administration, Silver Spring, MD USA; Surendra K. Bansal, Roche TCRC Inc., New York, NY, USA; Chris Beaver, inVentiv Health Clinical, Montréal, QC, Canada; Ronald R. Bowsher, B2S Consulting, Indianapolis, IN USA; Margarete Brudny-Kloeppel, Bayer Pharma AG, Berlin, Germany; Christopher Evans, GlaxoSmithKline, King of Prussia, PA USA; Douglas M. Fast, Covance Laboratories, Madison, WI, USA; Chad A. Ray, Pfizer Inc., San Diego, CA; Scott Fountain, Pfizer Inc., San Diego, CA USA; Fabio Garofolo, Algorithme Pharma, Laval, QC Canada; Russell P Grant, Laboratory Corporation of America, Burlington, NC, USA; Michael Hayes, Novartis, East Hanover, NJ USA; Roger N. Hayes, MPI Research, Mattawan, MI USA; Olutosin Remi Idowu, U.S. Food and Drug Administration, Silver Spring, MD USA; Rand Jenkins, PPD, Richmond, VA USA; Marian Kelley, MKelley Consulting LLC, West Chester, Pa, USA; Lindsay E. King,, Pfizer Inc., Groton, CT USA; Johanna Mora, Bristol-Myers Squibb Co, Princeton, NJ USA; William Nowatzke, Radix BioSolutions, Georgetown, TX, USA; Mark Rose, CHDI Management, Inc., Los Angeles, CA USA; Nilufer Tampal, U.S. Food and Drug Administration, Silver Spring, MD USA; Theingi Thway, Amgen Inc, Thousand Oaks, CA USA; Peter van Amsterdam, Abbott, Weesp The Netherlands; Faye Vazvaei, Roche TCRC Inc., New York, NY, USA; Leah Williamson U.S. Food and Drug Administration, Silver Spring, MD USA; Chongwoo Yu, U.S. Food and Drug Administration, Silver Spring, MD USA; Paul Wielowieyski, Health Canada, Canada; Olivier Leblaye, l’Agence Française de Sécurité Sanitaire des Produits de Santé AFSSAPS, France; Noriko Katori, National Institutes of Health Sciences, Japan; Joao Tavares Neto, ANVISA, Brazil.
The views expressed in this article are those of the authors and do not reflect official policy of their individual organizations. No official endorsement is intended or should be inferred.
A special thank you to Elizabeth Scuderi and the AAPS staff who handled all of the background activities to enable a smoothly functioning workshop.
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Booth, B., Arnold, M.E., DeSilva, B. et al. Workshop Report: Crystal City V—Quantitative Bioanalytical Method Validation and Implementation: The 2013 Revised FDA Guidance. AAPS J 17, 277–288 (2015). https://doi.org/10.1208/s12248-014-9696-2
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DOI: https://doi.org/10.1208/s12248-014-9696-2