Oxidation biopharmaceutical proteins

Many potential degradation products are not observed in protein pharmaceuticals, primarily because much care is taken in the choice of formulations, lyophilization, and storage conditions in order to maintain protein stability. Thus, degradation is minimized and usable shelf lives are on the order of years. In order to study the degradation pathways of a biopharmaceutical protein, and to evaluate the stability-indicating ability of the analytical methods, it is sometimes necessary to perform forced degradation studies, where the biopharmaceutical protein is subjected to a variety of stress conditions, such as varying pH, elevated temperature, or the addition of oxidants. 

High-performance ion-exchange chromatography (HPIEC) is used to determine and quantify oxidized, deamidated, clipped or truncated forms of protein biopharmaceuticals based upon changes in product charge. 

A protein biopharmaceutical may encounter various environments during and after the manufacturing process that lead to its degradation. Proteins degrade by chemical and physical pathways. Chemical pathways can include deamidation and related reactions, oxidation, and peptide bond hydrolysis (chemical and enzymatic). Physical pathways can include aggregation, precipitation, denaturation, and adsorption to surfaces. 

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