2134/13171
Elizabeth Ratcliffe
Elizabeth
Ratcliffe
Paul Hourd
Paul
Hourd
Juan-Jose Guijarro-Leach
Juan-Jose
Guijarro-Leach
Erin Rayment
Erin
Rayment
David Williams
David
Williams
Rob Thomas
Rob
Thomas
Application of response surface methodology to maximize the productivity of scalable automated human embryonic stem cell manufacture
Loughborough University
2013
Automation
Cost of goods
Human embryonic stem cell
Manufacture
Process control
Response surface methodology
Scalability
Mechanical Engineering not elsewhere classified
2013-09-18 14:15:15
Journal contribution
https://repository.lboro.ac.uk/articles/journal_contribution/Application_of_response_surface_methodology_to_maximize_the_productivity_of_scalable_automated_human_embryonic_stem_cell_manufacture/9559988
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.