Neutralizing Antibody Sample Testing and Report Harmonization

Darshana Jani¹, Michele Gunsior^#², Robin Marsden^#³, Kyra J Cowan⁴, Susan C Irvin⁵, Laura Schild Hay⁶, Bethany Ward⁶, Luke Armstrong⁷, Mitra Azadeh⁸, Liching Cao⁹, Rebecca Carmean⁶, Jason DelCarpini¹⁰, Sanjay L Dholakiya¹¹, Amanda Hays¹², Sarah Hosback¹³, Zheng Hu¹⁴, Nadia Kulagina¹⁵, Seema Kumar¹⁶, Ching Ha Lai⁵, Marit Lichtfuss¹³, Hsing-Yin Liu¹⁷, Susana Liu¹⁸, Reza Mozaffari¹⁹, Luying Pan²⁰, Jason Pennucci¹⁰, Marie-Eve Poupart²¹, Gurleen Saini²², Veerle Snoeck²³, Kristine Storey²⁴, Amy Turner¹⁵, Inna Vainshtein²⁵, Daniela Verthelyi²⁶, Iwona Wala²⁷, Lili Yang²⁸, Lin Yang²⁹

Affiliations

¹ Bioanalytical and Molecular Assays, Moderna, 325 Binney Street, Cambridge, Massachusetts, USA. darshana.jani@modernatx.com.
² Translational Sciences, Astria Therapeutics, Boston, Massachusetts, USA.
³ Revelation Biosciences, San Diego, California, USA.
⁴ Drug Metabolism & Pharmacokinetics, New Biological Entities, Merck KGaA, Darmstadt, Germany.
⁵ Bioanalytical Sciences, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
⁶ Bioanalytical Lab, PPD Clinical Research Business, Thermo Fisher Scientific, Richmond, Virginia, USA.
⁷ Bioanalytical Operations, BioAgilytix Labs, Durham, North Carolina, USA.
⁸ Bioanalytical and Biomarker Development, Ultragenyx Pharmaceutical, Inc, Novato, California, USA.
⁹ Biomarker and BioAnalytical Sciences, Sangamo Therapeutics, Brisbane, California, USA.
¹⁰ Bioanalytical Sciences, Moderna, Cambridge, Massachusetts, USA.
¹¹ Non-Clinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹² Scientific Office, BioAgilytix Labs, Durham, North Carolina, USA.
¹³ Research and Clinical Bioanalytics, CSL, Melbourne, Australia.
¹⁴ Translational Safety & Bioanalytical Science, Amgen Inc, Thousand Oaks, California, USA.
¹⁵ Pharmaceutical Development Services, Smithers, Gaithersburg, Maryland, USA.
¹⁶ DMPK and Bioanalysis, Pioneering Medicines at Flagship Pioneering, Cambridge, Massachusetts, USA.
¹⁷ Janssen Research & Development LLC, Spring House, Montgomery County, Pennsylvania, USA.
¹⁸ Clinical Pharmacology, Biologics & Immunogenicity Clinical Assay Group, Pfizer Inc, Kirkland, Quebec, Canada.
¹⁹ Bioanalysis, Immunogenicity & Biomarkers (BIB), IVIVT, Research, GSK, Collegeville, Pennsylvania, USA.
²⁰ Takeda Development Center Americas Inc, Cambridge, Massachusetts, USA.
²¹ Immunology, Charles River Laboratories, Senneville, Quebec, Canada.
²² Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA.
²³ Translational Biomarkers and Bioanalysis, UCB Biopharma SRL, 1420, Braine-L'Alleud, Belgium.
²⁴ Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc, Rahway, New Jersey, USA.
²⁵ Discovery and Translational Research, Exelixis, Alameda, California, USA.
²⁶ Office of Pharmaceutical Quality Research, Division IV, Center for Drugs Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
²⁷ Translational Safety and Bioanalytical Sciences, Amgen, Thousand Oaks, California, USA.
²⁸ Takeda Development Center Americas, Inc, Cambridge, Massachusetts, USA.
²⁹ Bioanalytical Sciences, REGENXBIO Inc, Rockville, Maryland, USA.

^# Contributed equally.

PMID: 38992280
DOI: 10.1208/s12248-024-00955-1

Neutralizing Antibody Sample Testing and Report Harmonization

Darshana Jani et al. AAPS J. 2024.

. 2024 Jul 12;26(4):80.

doi: 10.1208/s12248-024-00955-1.

Authors

Affiliations

¹ Bioanalytical and Molecular Assays, Moderna, 325 Binney Street, Cambridge, Massachusetts, USA. darshana.jani@modernatx.com.
² Translational Sciences, Astria Therapeutics, Boston, Massachusetts, USA.
³ Revelation Biosciences, San Diego, California, USA.
⁴ Drug Metabolism & Pharmacokinetics, New Biological Entities, Merck KGaA, Darmstadt, Germany.
⁵ Bioanalytical Sciences, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
⁶ Bioanalytical Lab, PPD Clinical Research Business, Thermo Fisher Scientific, Richmond, Virginia, USA.
⁷ Bioanalytical Operations, BioAgilytix Labs, Durham, North Carolina, USA.
⁸ Bioanalytical and Biomarker Development, Ultragenyx Pharmaceutical, Inc, Novato, California, USA.
⁹ Biomarker and BioAnalytical Sciences, Sangamo Therapeutics, Brisbane, California, USA.
¹⁰ Bioanalytical Sciences, Moderna, Cambridge, Massachusetts, USA.
¹¹ Non-Clinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹² Scientific Office, BioAgilytix Labs, Durham, North Carolina, USA.
¹³ Research and Clinical Bioanalytics, CSL, Melbourne, Australia.
¹⁴ Translational Safety & Bioanalytical Science, Amgen Inc, Thousand Oaks, California, USA.
¹⁵ Pharmaceutical Development Services, Smithers, Gaithersburg, Maryland, USA.
¹⁶ DMPK and Bioanalysis, Pioneering Medicines at Flagship Pioneering, Cambridge, Massachusetts, USA.
¹⁷ Janssen Research & Development LLC, Spring House, Montgomery County, Pennsylvania, USA.
¹⁸ Clinical Pharmacology, Biologics & Immunogenicity Clinical Assay Group, Pfizer Inc, Kirkland, Quebec, Canada.
¹⁹ Bioanalysis, Immunogenicity & Biomarkers (BIB), IVIVT, Research, GSK, Collegeville, Pennsylvania, USA.
²⁰ Takeda Development Center Americas Inc, Cambridge, Massachusetts, USA.
²¹ Immunology, Charles River Laboratories, Senneville, Quebec, Canada.
²² Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA.
²³ Translational Biomarkers and Bioanalysis, UCB Biopharma SRL, 1420, Braine-L'Alleud, Belgium.
²⁴ Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc, Rahway, New Jersey, USA.
²⁵ Discovery and Translational Research, Exelixis, Alameda, California, USA.
²⁶ Office of Pharmaceutical Quality Research, Division IV, Center for Drugs Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
²⁷ Translational Safety and Bioanalytical Sciences, Amgen, Thousand Oaks, California, USA.
²⁸ Takeda Development Center Americas, Inc, Cambridge, Massachusetts, USA.
²⁹ Bioanalytical Sciences, REGENXBIO Inc, Rockville, Maryland, USA.

^# Contributed equally.

PMID: 38992280
DOI: 10.1208/s12248-024-00955-1

Erratum in

Correction to: Neutralizing Antibody Sample Testing and Report Harmonization.
Jani D, Gunsior M, Marsden R, Cowan KJ, Irvin SC, Hay LS, Ward B, Armstrong L, Azadeh M, Cao L, Carmean R, DelCarpini J, Dholakiya SL, Hays A, Hosback S, Hu Z, Kulagina N, Kumar S, Lai CH, Lichtfuss M, Liu HY, Liu S, Mozaffari R, Pan L, Pennucci J, Poupart ME, Saini G, Snoeck V, Storey K, Turner A, Vainshtein I, Verthelyi D, Wala I, Yang L, Yang L. Jani D, et al. AAPS J. 2024 Sep 4;26(5):98. doi: 10.1208/s12248-024-00965-z. AAPS J. 2024. PMID: 39231893 No abstract available.

Abstract

Immunogenicity testing and characterization is an important part of understanding the immune response to administration of a protein therapeutic. Neutralizing antibody (NAb) assays are used to characterize a positive anti-drug antibody (ADA) response. Harmonization of reporting of NAb assay performance and results enables efficient communication and expedient review by industry and health authorities. Herein, a cross-industry group of NAb assay experts have harmonized NAb assay reporting recommendations and provided a bioanalytical report (BAR) submission editable template developed to facilitate agency filings. This document addresses key bioanalytical reporting gaps and provides a report structure for documenting clinical NAb assay performance and results. This publication focuses on the content and presentation of the NAb sample analysis report including essential elements such as the method, critical reagents and equipment, data analysis, study samples, and results. The interpretation of immunogenicity data, including the evaluation of the impact of NAb on safety, exposure, and efficacy, is out of scope of this publication.

Keywords: bioanalytical report; immunogenicity; multi-functional therapeutics; neutralizing antibody; template.

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References

1. Jani D, Marsden R, Gunsior M, Hay LS, Ward B, Cowan K, et al. Anti-drug Antibody Sample Testing and Reporting Harmonization. AAPS J. 2022;24(6):113. https://doi.org/10.1208/s12248-022-00762-6 . - DOI - PubMed
1. Gupta S, Devanarayan V, Finco D, Gunn GR 3rd, Kirshner S, Richards S, et al. Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics. J Pharm Biomed Anal. 2011;55(5):878–88. https://doi.org/10.1016/j.jpba.2011.03.038 . - DOI - PubMed
1. Myler H, Pedras-Vasconcelos J, Lester T, Civoli F, Xu W, Wu B, et al. Neutralizing Antibody Validation Testing and Reporting Harmonization. AAPS J. 2023;25(4):69. https://doi.org/10.1208/s12248-023-00830-5 . - DOI - PubMed
1. Immunogenicity Testing of Therapeutic Protein Products - Developing and Validating Assay for Anti-Drug Antibody Detection: Guidance for Industry. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER); 2019.
1. Guideline on immunogenicity assessment of therapeutic proteins. European Medicines Agency, EMEA/CHMP/BMWP/14327/2006 Rev 1; 2017.

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Neutralizing Antibody Sample Testing and Report Harmonization

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Neutralizing Antibody Sample Testing and Report Harmonization

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