Novel platform technology for scale down and process optimisation for regenerative medicine

Abstract

Clinical and commercial success of allogeneic cellular therapies will depend on robust, well defined and cost effective manufacturing processes. The bioprocessing industry employs Quality by Design (QbD) to understand the manufacturing process, how a process affects product critical quality attributes (CQAs) and relationships between CQAs and a product's clinical properties. In Regenerative Medicine such studies are extremely labour intensive and costly, and conventional cell culture vessels often lack suitable analytical technology for effective monitoring and control. We describe an advanced automated system, ambrTM, based on a novel, scaled-down 10-15ml culture vessel. The vessel mimics features of a full scale bioreactor; 24 or 48 bioreactors can be processed in parallel, sensors provide continuous monitoring and control of culture pH, dissolved oxygen, temperature and stirring rate, there is sampling for off-line analysis (e.g. metabolites) and integrated cell count and viability measurement. This innovative platform supports investigation and analysis of multiple conditions in a single run; media, growth factors, cell density and O2 can be systematically varied and optimised, greatly improving efficiency. Increasingly suspension cell culture (on microcarriers) is being explored for large scale production. We show ambr provides controlled conditions for mammalian cells growing in suspension, as cell aggregates (e.g. embryoid bodies) or on a range of microcarriers. The availability of consistent, reliable tools that increase the numbers of parallel experiments at a micro scale will significantly reduce cost per experiment, and precise control will allow QbD approaches to be adopted at an early stage. Reducing the time and labour required to develop, optimise and characterise the complex processes involved in making novel Regenerative Medicine therapies has the potential to reduce development timescales, and helps address a major biomanufacturing bottleneck.