Effect of Sterilizing Filters on Process Economics in Bio-pharmaceuticals

Bio-pharmaceutical manufacturing is a complex, multistep process involving a very wide variety of process streams under different process conditions at different steps. These process streams include cell culture media, media additives, growth regulators in the upstream and post centrifuge cell harvest supernatants, post viral inactivation process intermediates, buffers, and high value product concentrates in the downstream. Filtration and purification of such a wide spectrum of process streams, to achieve different process objectives at each process step, is quite a challenge for the process owner. Also the increasingly competitive market conditions, due to the introduction of biosimilars, further escalates the demand for higher standards of filter performance, with respect to economy, safety, and impact on final product quality.

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Clarification of Cell Harvests from Micro Bioreactors

Lab scale clarification of cell harvests is increasingly becoming more challenging as the standard clarification techniques such as centrifugation, tangential flow filtration (TFF) and depth filtration are not easily adaptable to micro bioreactors which require multiple processing of small volumes of cell harvests, typically 50 mL. Centrifugation may damage the shear sensitive mammalian cells and not only release undesirable intra cellular proteins and DNA into the broth but also submicron particles which are difficult to remove. TFF systems require long setup time and are prohibitively expensive for lab scale volumes. Depth filters on the other hand necessitate monitoring of differential pressures and sometimes allow passage of cell debris and other fine particulate which tend to choke the downstream 0.2µm sterilizing grade filters. Also, these require large pre-use flush volumes to remove inherent extractables owing to their cellulosic matrix with inorganic filter aids such as diatomaceous earth or perlite. Continue reading “Clarification of Cell Harvests from Micro Bioreactors”