title: Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor.
abstract: Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor.
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom;
authors.forename: Liani
authors.initials: L
authors.lastname: Devito
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom;
authors.forename: Anastasia
authors.initials: A
authors.lastname: Petrova
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom;
authors.forename: Cristian
authors.initials: C
authors.lastname: Miere
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom; St8Biologics, QA Consultancy, London, United Kingdom;
authors.forename: Stefano
authors.initials: S
authors.lastname: Codognotto
authors.affiliation: SGS Vitrology Ltd., Glasgow, United Kingdom;
authors.forename: Nicola
authors.initials: N
authors.lastname: Blakely
authors.affiliation: SGS Vitrology Ltd., Glasgow, United Kingdom;
authors.forename: Archie
authors.initials: A
authors.lastname: Lovatt
authors.affiliation: Guy's & St. Thomas' Centre for Preimplantation Genetic Diagnosis and Genetics Centre and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ogilvie
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom; Assisted Conception Unit, Guy's & St. Thomas' National Health Services Foundation Trust, London, United Kingdom.
authors.forename: Yacoub
authors.initials: Y
authors.lastname: Khalaf
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom; dusko.ilic@kcl.ac.uk.
authors.forename: Dusko
authors.initials: D
authors.lastname: Ilic
mesh_terms: D002460:Cell Line; D006801:Humans; D039904:Pluripotent Stem Cells; D060888:Real-Time Polymerase Chain Reaction; D014015:Tissue Banks / Q000592:standards*
keywords: Clinical-grade human embryonic stem cell lines; Clinical-grade iPS cell lines; Current good manufacturing practice; Human viral pathogens; Master cell bank; Validation