Utility of High Throughput Screening Techniques to Predict Stability of Monoclonal Antibody Formulations During Early Stage Development

Selecting optimal formulation conditions for monoclonal antibodies for first time in human clinical trials is challenging due to short timelines and reliance on predictive assays to ensure product quality and adequate long-term stability. Accelerated stability studies are considered to be the gold s...

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Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 106; no. 8; p. 1971
Main Authors:	Goldberg, Deborah S, Lewus, Rachael A, Esfandiary, Reza, Farkas, David C, Mody, Neil, Day, Katrina J, Mallik, Priyanka, Tracka, Malgorzata B, Sealey, Smita K, Samra, Hardeep S
Format:	Journal Article
Language:	English
Published:	United States 01-08-2017
Subjects:	Antibodies, Monoclonal - chemistry Drug Compounding Drug Stability Excipients - chemistry High-Throughput Screening Assays - methods Humans Immunoglobulin G - chemistry Light Protein Aggregates Protein Stability Scattering, Radiation formulation high throughput technologies excipients protein aggregation stability
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Summary:	Selecting optimal formulation conditions for monoclonal antibodies for first time in human clinical trials is challenging due to short timelines and reliance on predictive assays to ensure product quality and adequate long-term stability. Accelerated stability studies are considered to be the gold standard for excipient screening, but they are relatively low throughput and time consuming. High throughput screening (HTS) techniques allow for large amounts of data to be collected quickly and easily, and can be used to screen solution conditions for early formulation development. The utility of using accelerated stability compared to HTS techniques (differential scanning light scattering and differential scanning fluorescence) for early formulation screening was evaluated along with the impact of excipients of various types on aggregation of monoclonal antibodies from multiple IgG subtypes. The excipient rank order using quantitative HTS measures was found to correlate with accelerated stability aggregation rate ranking for only 33% (by differential scanning fluorescence) to 42% (by differential scanning light scattering) of the antibodies tested, due to the high intrinsic stability and minimal impact of excipients on aggregation rates and HTS data. Also explored was a case study of employing a platform formulation instead of broader formulation screening for early formulation development.
ISSN:	1520-6017
DOI:	10.1016/j.xphs.2017.04.039