Application of Formulation Principles to Stability Issues Encountered During Processing, Manufacturing, and Storage of Drug Substance and Drug Product Protein Therapeutics

Samadhi Vitharana; Joshua M Stillahn; Derrick S Katayama; Charles S Henry; Mark Cornell Manning

doi:10.1016/j.xphs.2023.08.003

Application of Formulation Principles to Stability Issues Encountered During Processing, Manufacturing, and Storage of Drug Substance and Drug Product Protein Therapeutics

J Pharm Sci. 2023 Nov;112(11):2724-2751. doi: 10.1016/j.xphs.2023.08.003. Epub 2023 Aug 10.

Authors

Samadhi Vitharana¹, Joshua M Stillahn², Derrick S Katayama³, Charles S Henry⁴, Mark Cornell Manning⁵

Affiliations

¹ Technical Consultant, Biologics CMC, San Diego, CA, USA.
² Legacy BioDesign LLC, Johnstown, CO 80534, USA; Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
³ Samsung Biologics, 201-2, Songdo-dong, Yeonsu-gu, Incheon, Korea.
⁴ Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
⁵ Legacy BioDesign LLC, Johnstown, CO 80534, USA; Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: Manning@LegacyBioDesign.com.

PMID: 37572779
DOI: 10.1016/j.xphs.2023.08.003

Abstract

The field of formulation and stabilization of protein therapeutics has become rather extensive. However, most of the focus has been on stabilization of the final drug product. Yet, proteins experience stress and degradation through the manufacturing process, starting with fermentaition. This review describes how formulation principles can be applied to stabilize biopharmaceutical proteins during bioprocessing and manufacturing, considering each unit operation involved in prepration of the drug substance. In addition, the impact of the container on stabilty is discussed as well.

Keywords: Aggregation; Bioprocessing; Bulk freezing; Chemical instability; Fermentation; Manufacturing; Protein stability; Protein therapeutics; Purification.

Publication types

Review