Stabilization of Therapeutic Proteins by Chemical and Physical Methods

Abstract

Proteins are complex molecules composed of numerous reactive chemical groups and delicate three-dimensional structures. The chemical (oxidation, deamidation, hydrolysis) and physical (unfolding, aggregation) changes of proteins during the formulation process and storage not only reduce biological activity, but they can cause adverse reactions, such as immune responses, even when the total protein population is at a low level (Table 1) (1–5). Developing new formulations that maintain the integrity of the purified protein during the manufacturing process, delivery, and 1–2 yr of storage is a minimum requisite for bringing protein pharmaceuticals to the market. Aqueous solutions that are ready for injection are often the most convenient and preferable dosage forms for therapeutic proteins, whereas many purified proteins are not stable enough in the solutions to meet the shelf-life requirements, even when they are stored at low temperatures.

Table 1 Suggested Prewashing and Discharged Volume