REGEN-COV ® antibody cocktail bioanalytical strategy: comparison of LC-MRM-MS and immunoassay methods for drug quantification

• Published in: Bioanalysis Vol. 13; no. 24; pp. 1827 - 1836
• Main Authors: Irvin, Susan C, Ganguly, Samit, Weiss, Rachel, Elango, Chinnasamy, Zhong, Xuefei, Mao, Yuan, Yan, Hong, Li, Ning, Sumner, Giane, Turner, Kenneth C, Davis, John D, DiCioccio, A Thomas, Andisik, Matthew D, Partridge, Michael A, Torri, Albert
• Format: Journal Article
• Language: English
• Published: England Newlands Press Ltd 01-12-2021
• Subjects: Antibodies, Monoclonal - analysis; Antibodies, Monoclonal - therapeutic use; Bioanalytical Challenge; Chromatography, Liquid - methods; COVID-19 - therapy; COVID-19 - virology; Electrochemical Techniques; Humans; Luminescence; Mass Spectrometry - methods; SARS-CoV-2 - immunology; SARS-CoV-2; bioanalytical; monoclonal antibody therapeutic; Bland-Altman; drug concentration assay
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/bio-2021-0190

In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV
(RONAPREVE
outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use.
Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters.
This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.