Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee

Marinna Madrid; Uma Lakshmipathy; Xiaokui Zhang; Kapil Bharti; Dominic M Wall; Yoji Sato; George Muschler; Anthony Ting; Nathan Smith; Shuhei Deguchi; Shin Kawamata; Jennifer C Moore; Bar Makovoz; Stephen Sullivan; Veronica Falco; Arwa Z Al-Riyami

doi:10.1016/j.jcyt.2024.05.022

Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee

Cytotherapy. 2024 Nov;26(11):1382-1399. doi: 10.1016/j.jcyt.2024.05.022. Epub 2024 Jun 12.

Authors

Marinna Madrid¹, Uma Lakshmipathy², Xiaokui Zhang³, Kapil Bharti⁴, Dominic M Wall⁵, Yoji Sato⁶, George Muschler⁷, Anthony Ting⁸, Nathan Smith⁹, Shuhei Deguchi¹⁰, Shin Kawamata¹¹, Jennifer C Moore¹², Bar Makovoz¹, Stephen Sullivan¹³, Veronica Falco¹⁴, Arwa Z Al-Riyami¹⁵

Affiliations

¹ Cellino Biotech, Cambridge, USA.
² Pharma Services, Thermo Fisher Scientific, Carlsbad, USA.
³ Aspen Neuroscience Inc., San Diego, USA.
⁴ National Eye Institute of the National Institutes of Health, Bethesda, USA.
⁵ Peter MacCallum Cancer Centre, Melbourne Australia; Cell Therapies Pty Ltd, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
⁶ National Institute of Health Sciences, Kawasaki, Japan.
⁷ Cleveland Clinic, Cleveland, USA.
⁸ BRL C&GT consulting, LLC., Cleveland, USA.
⁹ Cell Therapies Pty Ltd, Melbourne, Australia.
¹⁰ CIRA Foundation, Facility for iPS Cell Therapy (FiT), Kyoto, Japan.
¹¹ Cyto-Facto Inc., Kobe, Japan; Kobe University, Kobe, Japan. Electronic address: [email protected].
¹² Sampled, New York City, USA.
¹³ iPSirius, Paris, France; Lindville Bio, London, UK.
¹⁴ Lindville Bio, London, UK.
¹⁵ Department of Hematology, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman.

PMID: 38958627
PMCID: PMC11471376 (available on 2025-11-01)
DOI: 10.1016/j.jcyt.2024.05.022

Abstract

Since their first production in 2007, human induced pluripotent stem cells (iPSCs) have provided a novel platform for the development of various cell therapies targeting a spectrum of diseases, ranging from rare genetic eye disorders to cancer treatment. However, several challenges must be tackled for iPSC-based cell therapy to enter the market and achieve broader global adoption. This white paper, authored by the Japanese Society for Regenerative Medicine (JSRM) - International Society for Cell Therapy (ISCT) iPSC Committee delves into the hurdles encountered in the pursuit of safe and economically viable iPSC-based therapies, particularly from the standpoint of the cell therapy industry. It discusses differences in global guidelines and regulatory frameworks, outlines a series of quality control tests required to ensure the safety of the cell therapy, and provides details and important considerations around cost of goods (COGs), including the impact of automated advanced manufacturing.

Keywords: critical quality attributes (CQAs); good manufacturing practice (cGMP); iPSC-derived cell therapies; quality by design (QbD); quality control (QC); regenerative medicine; the cost of goods (COGs).

Publication types

Review

MeSH terms

Cell- and Tissue-Based Therapy* / methods
Humans
Induced Pluripotent Stem Cells* / cytology
Quality Control
Regenerative Medicine* / methods

Grants and funding

ZIA EY000542/ImNIH/Intramural NIH HHS/United States