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Title: Quantification of biological variation in blood-based therapy – a summary of a meta-analysis to inform manufacturing in the clinic
Authors: Thurman-Newell, Jamie A.
Petzing, Jon N.
Williams, David J.
Keywords: Biological variation
Quality control
Process design
Issue Date: 2015
Publisher: Wiley on behalf of the International Society of Blood Transfusion
Citation: THURMAN-NEWELL, J.A., PETZING, J.A. and WILLIAMS, D.J., 2015. Quantification of biological variation in blood-based therapy – a summary of a meta-analysis to inform manufacturing in the clinic. Vox Sanguinis, 109 (4), pp. 394–402.
Abstract: Background and Objectives Biological raw materials, the basis for cellular therapies such as stem cells, have a significantly greater degree of complexity than their traditional pharmaceutical counterparts. This can be attributed to the inherent variation of its source – human beings. Currently, cell therapies are made in small, ad hoc batches, but larger scale production is a prerequisite to meeting future demand and will require a quality-by-design approach to manufacturing that will be designed around, or be robust to this variation. Quantification of variation will require understanding of the current baseline and stratification of its sources. Materials and Methods Haematopoietic stem cell therapy was chosen as a case study to explore this variation, and a PRISMA-guided (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) systematic meta-analysis was carried out for a number of predetermined cell measurements. Results From this data set, it appears that the extent of variation in therapeutic dose (in terms of transplanted total nucleated cells and CD34+ cells per kilogram) for HSCT is between one and four orders of magnitude of the median. Conclusions This is tolerated under the practice of medicine but would be unmanageable from a biomanufacturing perspective and raises concerns about comparable levels of efficacy and treatment. A number of sources that will contribute towards this variation are also reported, as is the direction of travel for 4 greater clarity of the scale of this challenge.
Description: This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/
Sponsor: EPSRC grant (EP/FS00491/1) as part of the Doctoral Training Centre for Regenerative Medicine
Version: Published
DOI: 10.1111/vox.12288
URI: https://dspace.lboro.ac.uk/2134/18302
Publisher Link: http://dx.doi.org/10.1111/vox.12288
ISSN: 1423-0410
Appears in Collections:Published Articles (Mechanical, Electrical and Manufacturing Engineering)

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