Analytical techniques for the evaluation of liquid protein therapeutics

Abstract

A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. Analytical techniques are required to study the propensity of solutions to form aggregates and particles and to allow the investigation of the effect of conditions encountered during manufacture and storage. A key challenge is to utilize appropriate specific and sensitive techniques to allow the early detection of initial aggregation events, thereby avoiding the need to resort to extended stability trials. The present review evaluates a range of techniques for the detection of changes in protein conformation and the formation of aggregates and particles. It is hoped that the availability of this information will encourage and facilitate studies to resolve stability issues associated with protein therapeutics.

Differential scanning calorimetry: An invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions

“…This has been directly applied to investigate the propensity of liquid protein therapeutics, to aggregate during storage. [46] DSC allows for a quick scanning procedure to detect the presence of aggregates without the need for extended stability trials.…”

Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging

“…However, which aggregate types are immunogenic is not well understood, and the causes of antidrug antibody formation remain controversial. , It has been well recognized that the chemical composition of subvisible particles may reveal the mechanism of particle formation in drug products. Unfortunately, current analytical methods used to detect subvisible particles only provide limited morphological information and often conflicting results. − …”