Proteins in such drug products can develop aggregation as high concentrations promote associations among them, ultimately decreasing drug stability and compromising shelf life. Sometimes, highly concentrated liquid formulations are required to achieve a desired therapeutic dose. #Capto q resin freeChemical aggregation pathways include disulfide-bond formation or exchange due to oxidation, deamidation, and formation of free thiol groups. Protein aggregation can be initiated by a number of physical factors, including temperature (e.g., freezing and thawing), ionic strength, and interacting microenvironment exposure in a bioprocess (e.g., mixing during a change in pH or temperature). Depending on the physicochemical characteristics of a protein, oligomers can compromise product quality - specifically in safety, efficacy, delivery, dosing, and/or marketability. Protein aggregation can be reversible or irreversible because the oligomers formed may be soluble or insoluble, covalent or noncovalent, and native or nonnative. Thus, techniques are needed that can reduce oligomers to well below acceptance limits and ensure optimal safety levels. Much research is ongoing in this area, with limited successes in purifying proteins from oligomers. A downstream process should be robust and reproducible at scale-up with minimum impact on recovery. To minimize the yield loss during extensive reduction of oligomers, we considered the use of novel techniques with process optimization. With those pI similarities, removal of oligomers to a considerable extent by ion exchangers can compromise protein recovery, thus causing unacceptable product loss during processing. Proteins such as hormones have pI ranges similar to their oligomers and thus can be difficult to separate out using a conventional polishing chromatographic step such as ion exchange. Sometimes it is difficult to purify monomeric proteins from oligomers because of similarities in their isoelectric points (pIs). Aggregation is a common cause of protein instability, which renders a biologic product unfit for therapeutic use.
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