Stem Cell Biomanufacturing under Uncertainty: A Case Study in Optimizing Red Blood Cell Production

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Title: Stem Cell Biomanufacturing under Uncertainty: A Case Study in Optimizing Red Blood Cell Production
Author(s): Misener, R
Allenby
Fuentes-Gari, M
Gupta, K
Wiggins, T
Panoskaltsis
Pistikopoulos
Mantalaris
Item Type: Journal Article
Abstract: As breakthrough cellular therapy discoveries are translated into reliable, commercializable applications, effective stem cell biomanufacturing requires systematically developing and optimizing bioprocess design and operation. This manuscript proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling; single- and multivariate sensitivity analysis; global topological superstructure optimization; robust optimization. We quantitatively demonstrate the advantages of the proposed bioprocess optimization framework using, as a case study, a dual hollow fiber bioreactor producing red blood cells from progenitor cells. The optimization phase reduces the cost by a factor of 4 and the price of insuring process performance against uncertainty is approximately 15% over the nominal optimal solution. Mathematical modeling and optimization can guide decision making; we quantitatively evaluate the possible commercial impact of this cellular therapy using the disruptive technology paradigm.
Publication Date: 28-Nov-2017
Date of Acceptance: 13-Nov-2017
URI: http://hdl.handle.net/10044/1/53945
DOI: https://dx.doi.org/10.1002/aic.16042
ISSN: 0001-1541
Publisher: Wiley
Journal / Book Title: AIChE Journal
Copyright Statement: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/aic.16042
Sponsor/Funder: Royal Academy Of Engineering
Commission of the European Communities
Engineering & Physical Science Research Council (E
Funder's Grant Number: 10216/118
340719
EP/M028240/1
Keywords: 0904 Chemical Engineering
0914 Resources Engineering And Extractive Metallurgy
Chemical Engineering
Publication Status: Published online
Appears in Collections:Faculty of Engineering
Computing
Chemical Engineering
Department of Medicine
Faculty of Medicine



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