The endogenous proteins derived from host cells, e.g., Chinese Hamster Ovary (CHO) Cells, are major process-related impurities in recombinant therapeutic protein production. Even at low levels they can potentially compromise the safety of biopharmaceuticals. Therefore, host cell proteins (HCPs) need to be adequately removed via the downstream purification process. Recent literature shows that some depth filters are able to separate the product protein from CHO HCPs through charge interaction, hydrophobic interaction or size differences. In our studies, we compared Millistak+ HC Pro X0SP filter, a novel and synthetic depth filter, and Millistak+ CR40 filter, an activated carbon filter, for HCP reduction at various downstream process steps in an enzyme purification process. Due to the low pI of the enzyme product, which is similar to the CHO HCPs, reducing HCP to the generally accepted level was demonstrated to be very challenging. The HCP reduction effectiveness and scalability from nanoPOD (5cm2) to laboratory scale POD filter (270cm2) was demonstrated. The lot-to-lot variation, impact of flux and leachable removal were also explored. Our studies suggest that depth filtration can be used in downstream purification process as an alternative tool for HCP reduction.

Improving HCP reduction by depth filtration in an enzyme purification process

2019 Spring National Meeting

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