Controlled Polysorbate 20 Hydrolysis - A new Approach to Assess the Impact of Polysorbate 20 Degradation on Biopharmaceutical Product Quality in Shortened Time.

Controlled Polysorbate 20 Hydrolysis - A new Approach to Assess the Impact of Polysorbate 20 Degradation on Biopharmaceutical Product Quality in Shortened Time. Eur J Pharm Biopharm. 2020 May 20;: Authors: Graf T, Abstiens K, Wedekind F, Elger C, Markus H, Wurth C, Leiss M Abstract Hydrolysis of polysorbate in biopharmaceutical liquid formulations upon long-term storage represents a risk factor, since reduction of the intact surfactant concentration may compromise protein stability. Moreover, accumulation of polysorbate degradation products is associated with the formation of particulates potentially affecting drug product stability and quality. These effects are conventionally assessed by real-time end-of-shelf life studies constituting an integral yet lengthy process of formulation development. To accelerate this procedure, we describe here a powerful tool to conduct shake stress studies based on the controlled hydrolysis of polysorbate 20 by beads-immobilized lipases. For this purpose, the production of stable, partially degraded material characterized by a representative presence of non-emulsifying degradants such as ethoxylated sorbitan and free fatty acids was monitored by state-of-the-art chromatographic methods ensuring realistic pharmaceutical conditions. Freeze-thaw, shaking and shipping stress studies of a mAb formulation did not only demonstrate that this approach is useful to determine the critical degradation level impa...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research