2134/21083
Jamie Thurman-Newell
Jamie
Thurman-Newell
Jon Petzing
Jon
Petzing
David Williams
David
Williams
A meta-analysis of biological variation in blood-based therapy as a precursor to bio-manufacturing
Loughborough University
2016
Biological variation
Blood
HSCT
Process design
Quality control
Mechanical Engineering not elsewhere classified
2016-04-27 10:01:19
Journal contribution
https://repository.lboro.ac.uk/articles/journal_contribution/A_meta-analysis_of_biological_variation_in_blood-based_therapy_as_a_precursor_to_bio-manufacturing/9570245
Currently cellular therapies, such as hematopoietic stem cell transplantation (HSCT), are produced at a small scale on a case-by-case basis, usually in a clinical or near-clinical setting. Meeting the demand for future cellular therapies will require a robust and scalable manufacturing process that is either designed around or controls the variation associated with biological starting materials. Understanding variation requires both a measure of the allowable variation (that does not negatively affect patient outcome) and the achievable variation (with current technology). The prevalence of HSCT makes it an ideal case study to prepare for more complex biological manufacturing with more challenging regulatory classifications. A systematic meta-analysis of the medical literature surrounding HSCT has been completed of which the key outcomes are the following: (i) the range of transplanted CD34+ cells/kg can be up to six orders of magnitude around the median for allogeneic procedures and four orders of magnitude for autologous procedures, (ii) there is no improvement in variation encountered over a period of 30 years and (iii) as study size increases, the amount of variation encountered also increases. A more detailed, stratified source from a controlled single-site clinical center is required to further define a control strategy for the manufacture of biologics.