Product-related impurities formed during cell culture fermentation are known to potentially cause a variety of issues related to stability and efficacy of the affected drug product. Incomplete cleavage of signal peptides in Pichia pastoris cultures yields product variants with very similar protein properties to the drug target, and in the case of Interferon alpha-2b, induces aggregation of properly cleaved material. Linear gradient data from a one-time, labor intensive chromatographic characterization of Pichia impurities was paired with a rapid screen of product variants and aggregates to identify retention behavior of host cell proteins, variants, and drug product. These data were analyzed by custom software to identify orthogonal, isocratic step purification processes capable of recovering product and removing host- and product-related impurities. Constraints are taken by the software and imposed upon the purification processes generated, including the requirement for integrated process steps. Identification and verification of a process that sufficiently recovered and purified the target biologic was completed for Interferon alpha-2b in a one month time frame and extended to additional biologics.

Rapid, integrated purification process development for non-mAb biologics with variant challenges

253rd National Meeting (2017)

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