Abstract
This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete‐event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision‐making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E‐factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium‐sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed‐batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision‐making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854–866, 2017
Highlights
This paper has presented a feasibility evaluation of continuous biopharmaceutical manufacturing strategies utilising perfusion cell culture and semicontinuous chromatography throughout the product life cycle from Pre-Clinical to Commercial manufacture
The framework enabled a rigorous analysis of the feasibility of monoclonal antibody (mAb) manufacturing facilities based on the standard batch platform compared to alternative integrated and hybrid continuous manufacturing strategies across a range of manufacturing and company scales so as to represent scenarios of relevance to industry
The analysis determined the key cost contributors in each strategy, as well as the robustness via an operational risk score and environmental indices that act as useful E-factor benchmarks for continuous processes
Summary
A major challenge facing the biopharmaceutical industry centers on how best to improve research and development (R&D) productivity while reducing R&D and manufacturing costs.[1,2,3,4] Identification of strategies to reduce nonclinical. Current address of Jon Coffman: Boehringer Ingelheim Fremont, Inc, CA, USA. R&D costs can yield significant improvements in R&D productivity given that they typically represent 20–30% of R&D costs.[5,6] Clinical manufacturing costs and process validation batches account for a significant proportion of the nonclinical R&D costs. Complex, and highly regulated nature of the development pathway for biopharmaceutical drugs, the industry has been debating which biopharmaceutical production technologies will facilitate industrialization of the sector.[7,8,9,10]
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