Application of response surface methodology to maximize the productivity of scalable automated human embryonic stem cell manufacture

Ratcliffe, Elizabeth and Hourd, Paul and Guijarro-Leach, Juan and Rayment, Erin and Williams, David J. and Thomas, Robert J. (2013) Application of response surface methodology to maximize the productivity of scalable automated human embryonic stem cell manufacture. Regenerative Medicine, 8 (1). pp. 39-48. ISSN 1746-0751

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Abstract

Aim: Commercial regenerative medicine will require large quantities of clinical-specification human cells. The cost and quality of manufacture is notoriously difficult to control due to highly complex processes with poorly defined tolerances. As a step to overcome this, we aimed to demonstrate the use of 'quality-by-design' tools to define the operating space for economic passage of a scalable human embryonic stem cell production method with minimal cell loss.
Materials & methods: Design of experiments response surface methodology was applied to generate empirical models to predict optimal operating conditions for a unit of manufacture of a previously developed automatable and scalable human embryonic stem cell production method. Results & conclusion: Two models were defined to predict cell yield and cell recovery rate postpassage, in terms of the predictor variables of media volume, cell seeding density, media exchange and length of passage. Predicted operating conditions for maximized productivity were successfully validated. Such 'quality-by-design type approaches to process design and optimization will be essential to reduce the risk of product failure and patient harm, and to build regulatory confidence in cell therapy manufacturing processes.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2013 Future Medicine Ltd. This publication is copyright. It may be reproduced in whole or in part for the purposes of study, research, or review, but is subject to the inclusion of an acknowledgment of the source.
Faculty / Department / School: Current - USQ Other
Date Deposited: 05 Nov 2014 06:25
Last Modified: 08 Mar 2017 02:07
Uncontrolled Keywords: automation; cost of goods; human embryonic stem cell; manufacture; process control; response surface methodology; scalabilit
Fields of Research : 15 Commerce, Management, Tourism and Services > 1503 Business and Management > 150313 Quality Management
10 Technology > 1004 Medical Biotechnology > 100404 Regenerative Medicine (incl. Stem Cells and Tissue Engineering)
15 Commerce, Management, Tourism and Services > 1503 Business and Management > 150307 Innovation and Technology Management
09 Engineering > 0903 Biomedical Engineering > 090301 Biomaterials
Socio-Economic Objective: B Economic Development > 86 Manufacturing > 8608 Human Pharmaceutical Products > 860899 Human Pharmaceutical Products not elsewhere classified
Identification Number or DOI: 10.2217/rme.12.109
URI: http://eprints.usq.edu.au/id/eprint/26322

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