Harnessing Amino Acid Derivatives for Enhanced Viscosity Reduction and Stability of Monoclonal Antibodies
Most monoclonal antibodies (mAbs) are developed with low protein concentrations, and typically delivered to the patient in liquid form via injection or intravenous infusion (IV). However, there are a growing number of indications that prefer intramuscular or subcutaneous injections - mainly so that a patient can self-administer the drug at home and reduce hospital stays and/or treatment costs, increasing patient compliance.
While drugs delivered subcutaneously have significant patient benefits, they add additional manufacturing challenges - mainly due to pain and pressure at the injection site when volumes exceed 1 - 2 ml. This limited volume means that mAbs must be formulated in higher concentrations to administer an efficacious dose to the patient. Higher concentrations create high viscosity, and can also create undesirable protein-protein attractive interactions that leads to protein aggregation.
This article summarizes our research to identify novel excipients that not only reduce viscosity of high-concentration formulation but also improve stability across a wide concentration range.
Authors
Arvind Srivastava, Ph.D.
Technical Fellow, Research - Bioprocessing
Dr. Arvind Srivastava is a Vice President at Avantor, leading contract development and manufacturing organization (CDMO). Before joining Avantor, Dr. Srivastava was Research Advisor at Eli Lilly and Company, where he managed drug product development from early development stage through commercial registration. Dr. Srivastava did his postdoctoral training from the University of North Carolina at Chapel Hill, NC, USA. He got his Ph.D. degree in biochemistry from the prestigious Tata Institute of Fundamental Research (TIFR) and M.S. in chemistry from the Banaras Hindu University (BHU). Dr. Srivastava has published numerous papers in international journals and has been frequently invited to present his research at the national and international conferences.
Suman McLinden
Senior Scientist at Avantor
Suman McLinden is a Sr. Research Scientist in Avantor’s Technology and Innovation group in Bridgewater, NJ for the past 3 years. She is currently working on analytical method and product development, also providing bio-analytical support to ongoing projects focused to improve bioprocess workflow. Prior to working at Avantor, Suman spent 15+ years on biophysical characterization and various aspects of analytical techniques of monoclonal antibody.
Courtney O’Dell
Senior Scientist at Avantor
Courtney O’Dell is a senior scientist with Avantor’s Technology and Innovation group in Bridgewater, NJ for the past 3 years. She is working on cell lysis projects for viral vector release and novel protein additives to reduce viscosity of high concentration protein formulations. Prior, Courtney spent 11 years working in solution formulation development of mAbs at ImClone Systems and then Eli Lilly & Co., focusing on stability, structural characterization, and use-time compatibility studies for parenteral drug delivery.
Lori Fortin
Senior Manager, R&D
Evon Bolessa
Manager, R&D
Dr. Nandu Deorkar
Senior Vice President, Research & Development – Biopharma Production, Avantor
Nandu Deorkar is Senior Vice President, Biopharma Production Research & Development for Avantor. He is responsible for innovation strategy and planning, and execution of new products and technology development. During his more than 25-year career in research & development, Dr. Deorkar has been leading teams working on various aspects of upstream and downstream bioprocessing, single use systems, chemical/polymer R&D, drug development, formulation, drug delivery technologies, process development, and technology transfer. He has published more than 30 articles and holds more than 20 patents. Dr. Deorkar received Ph.D. from Indian Institute of Technology, Mumbai, India and MBA in Marketing from Fairleigh Dickinson University, Madison, NJ, USA.