Protein aggregation can occur at all steps in the manufacturing process (cell culture, purification and formulation), storage, distribution and handling of products. It results from various kinds of stress such as agitation and exposure to extremes of pH, temperature, ionic strength, or various interfaces (e.g. air–liquid interface). High protein concentrations (as in the case of some monoclonal antibody formulations) can further increase the likelihood of aggregation.
A wide variety of aggregates are encountered in biopharmaceutical samples ranging in size and characteristics (e.g. soluble or insoluble, covalent or non-covalent, reversible or irreversible). Protein aggregates span a broad size range, from small oligomers (nanometers) to insoluble micron-sized aggregates that can contain millions of monomer units.
Aggregation needs to be carefully characterized and controlled during development, manufacture and subsequent storage of a formulated product. Similarly, by monitoring the state of aggregation, modification or optimization of the production process can be achieved.
- For more information about Protein Aggregation, visit the Application Note
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