Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures

Abstract

Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost‐effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale‐down (USD) mimics requiring 25–110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost‐effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario.

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

“…To extend this work, Liu, S. and Papageorgiou, L. [89] considered uncertainty in the biopharmaceutical manufacturing such as upstream titer, chromatography downstream yield and level of impurity reduction and addressed multi-objective optimization problem to determine chromatography sequencing and column strategy. Popva, D. et al [90] applied multi-attribute decision making method (MADM) and economic analysis to select among alternative primary recovery options (3 types of centrifugation, depth filtrations and two tangential flow filtrations). MADM analysis evaluated the selected criteria such as yield and purity and economic analysis helped to select cost-effective operations.…”

Computer-Aided Strategies for Determining the Amino Acid Composition of Medium for Chinese Hamster Ovary Cell-Based Biomanufacturing Platforms

“…Huge efforts have been made to bridge the evident gap between model-based approaches and empirical methods that are predominantly data-intensive in addressing different challenges faced in biomanufacturing platforms, let it be metabolic challenges [66,67,68] or the thermodynamic and kinetic limitations of the host system [69,70,71], or challenges associated with the biomanufacturing process itself [72,73,74,75,76]. Models can provide a mechanistic understanding of the processes, and suggest guidelines for narrowing down the search space for experimental analysis.…”

Progression of continuous downstream processing of monoclonal antibodies: Current trends and challenges

“…Continuous centrifugation, operating at 10,000 to 12,000 g with a short residence time, is not highly efficient at removing particles <1 µm (Yavorsky, Blanck, Lambalot, & Brunkow, ). Moreover, at high cell densities a centrifugation process requires frequent desludging, leading to a decrease in product recovery (Popova, Stonier, Pain, Titchener‐Hooker, & Farid, ). This limits the use of continuous centrifugation as a standalone unit operation for clarification and hence requires a secondary clarification technique like depth filtration (Berthold & Kempken, ).…”