Advanced Bioprocess Engineering: Fed‐Batch and Perfusion Processes

Mehra, Sarika; Chandrawanshi, Vikas; Prashad, Kamal

doi:10.1002/9783527800599.ch14

Cited by 1 publication

(1 citation statement)

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“…Therapeutic proteins, including monoclonal antibodies (mAb), bispecifics, cytokines, and enzymes are commonly manufactured using fed‐batch or perfusion mammalian cell culture processes where the target protein is expressed and secreted by the cell 1–4 . The target protein is recovered from the harvest cell culture fluid (HCCF) using either centrifugation and/or depth filtration as the primary recovery step to remove cells and cellular debris, and to reduce process‐related impurities such as host cell proteins, nucleic acids, and lipids 5–16 …”

Section: Introductionmentioning

confidence: 99%

Single‐stage chromatographic clarification of Chinese Hamster Ovary cell harvest reduces cost of protein production

O’Mara

Singh

Menendez

et al. 2023

Biotechnology Progress

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A single‐stage clarification was developed using a single‐use chromatographic clarification device (CCD) to recover a recombinant protein from Chinese Hamster Ovary (CHO) harvest cell culture fluid (HCCF). Clarification of a CHO HCCF is a complex and costly process, involving multiple stages of centrifugation and/or depth filtration to remove cells and debris and to reduce process‐related impurities such as host cell protein (HCP), nucleic acids, and lipids. When using depth filtration, the filter train consists of multiple filters of varying ratios, layers, pore sizes, and adsorptive properties. The depth filters, in combination with a 0.2‐micron membrane filter, clarify the HCCF based on size‐exclusion, adsorptive, and charge‐based mechanisms, and provide robust bioburden control. Each stage of the clarification process requires time, labor, and utilities, with product loss at each step. Here, use of the 3M™ Harvest RC Chromatographic Clarifier, a single‐stage CCD, is identified as an alternative strategy to a three‐stage filtration train. The CCD results in less overall filter area, less volume for flushing, and higher yield. Using bioprocess cost modeling, the single‐stage clarification process was compared to a three‐stage filtration process. By compressing the CHO HCCF clarification to a single chromatographic stage, the overall cost of the clarification process was reduced by 17%–30%, depending on bioreactor scale. The main drivers for the cost reduction were reduced total filtration area, labor, time, and utilities. The benefits of the single‐stage harvest process extended throughout the downstream process, resulting in a 25% relative increase in cumulative yield with comparable impurity clearance.

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Section: Introductionmentioning

confidence: 99%