Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture

TLDR

The study evaluates integrated continuous bioprocessing for monoclonal antibody manufacture across the product lifecycle. The authors employed a prototype UCL decisional tool that integrates process economics, discrete‑event simulation, environmental impact, operational risk, and multiattribute decision‑making to compare batch, continuous, and hybrid bioprocesses for cell culture, capture, and polishing across different clinical phases and company sizes. The tool predicts that early‑phase, small/medium companies should adopt an integrated continuous strategy, while commercial production and large‑portfolio firms favor a hybrid strategy, and that prioritizing operational feasibility over economics would make the hybrid approach preferable at all scales. Process development costs for adopting continuous processing were noted as outside the study’s scope, and the article is © 2017 The Authors, Biotechnology Progress, 33:854‑866.

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.