Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective
This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical.
After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined. This includes understanding biodistribution, persistence and toxicity, including potential for malignant transformation. These elements need to be considered in the context of the intended clinical development.
This article describes regulatory mechanisms available to developers to support product development that aim to resolve scientific issues prior to marketing authorization application, to enable patients to have faster access to the product than would otherwise be the case.
Developers are encouraged to be aware of both the scientific issues and regulatory mechanisms to ensure patients can be supplied with these products.
Keywordsbiodistribution cell therapy regulatory science toxicity tumorigenicity
Committee for Advanced Therapies
cell based medicinal product
Committee for Human Medicinal Products
Cell Products Working Party
European Medicines Agency
Food and Drug Administration
Good Laboratory Practice
human pluripotent stem cells
hematopoietic stem cells
International Conference on Harmonisation
mesenchymal stromal cells
Scientific Advice Working Party
Safety Working Party
Acknowledgments and Disclosures
The authors did not receive any funding from any agency in the public, commercial or not-for-profit sectors to write this article. JW McBlane is an alternate member of the Committee for Advanced Therapies (CAT) and of the Scientific Advice Working Party (SAWP) of the Committee for Human Medicinal products (CHMP), both operated by the European Medicines Agency. However, views expressed in this article represent only those of the authors and not those of these committees and working party.
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