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ABSTRACT
Co-formulation of multiple drug products is an efficient and convenient approach to simultaneously deliver multiple biotherapeutics with the potentially added benefit of a synergistic therapeutic effect. However, co-formulation also increases the risk of heteromeric interactions, giving rise to unique impurities with unknown efficacy and immunogenicity. Therefore, it is critical to develop methods to evaluate the risk of heteromers as an impurity that could affect potency, efficacy, and/or immunogenicity. The most direct strategy to evaluate antibody heteromers is via specific enrichment. However, the fact that antibody heterodimers generated from the co-formulated cocktail share highly similar molar mass and size properties as homodimers natively present in each individual antibody drug product poses a unique purification challenge. Here, we report the path to successful enrichment of heterodimers from co-formulated REGEN-COVⓇ and discuss its potential impacts on drug quality.
Abbreviations
| ADCC | = | Antibody-dependent cellular cytotoxicity |
| CEX | = | Cation exchange chromatography |
| Covid-19 | = | Coronavirus disease 2019 |
| DPBS | = | Dulbecco’s phosphate-buffered saline |
| HIC | = | Hydrophobic interaction chromatography |
| HIC-UV-MS | = | Hydrophobic interaction chromatography coupled to mass spectrometry |
| HIC-HPLC | = | Hydrophobic interaction high-performance liquid chromatography |
| HMW | = | High molecular weight |
| mAb | = | Monoclonal antibody |
| MMC | = | Mixed-mode chromatography, multi-modal chromatography |
| MMC-UPLC | = | Mixed-mode chromatography or multi-modal ultra-performance chromatography |
| MS | = | Mass spectrometry |
| SARS-CoV-2 | = | Severe acute respiratory syndrome coronavirus 2 |
| SCX-UV-MS | = | Strong cation exchange chromatography coupled to mass spectrometry |
| SEC | = | Size-exclusion chromatography |
| SE-UPLC | = | Size-exclusion ultra-performance liquid chromatography |
| VSV | = | Vesicular stomatitis virus |
Acknowledgments
The authors gratefully acknowledge Polat Abdubek and Glynn O’Grady for providing enriched homodimer from casirivimab and imdevimab. We also thank Yuan Cao for consulting on formulations development for this program and Lauren Salvador for editorial support and a critical reading of the manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2024.2338301