Guidelines for Preclinical Development

Abstract

Preclinical development encompasses the set of activities required to initiate testing for safety and effi cacy in humans. These requirements are defi ned by national and international regulations, and are generally focused on defi nition of drug composition and safety as well as scientifi c rationale and establishing a proposed dose regimen. The preclinical regulatory requirements for cell therapies broadly parallel those for small molecules and proteins, but the complexity of cells can bring additional challenges to the defi nition of potency, composition, immunogenicity, and toxicity. As a consequence of their pluripotent origins, stem cell therapies require additional preclinical considerations related to potential tumorigenicity and genetic/epigenetic stability. The fi rst FDA approved stem cell therapy study initiated clinical trial in 2010. Thus, the fi eld is young and there are few completed studies to provide precedents for planned preclinical development of novel stem cell approaches. Rather, the fi eld must draw practical lessons from other somatic cell therapies. The evolution and harmonization of regulatory guidances for stem cells must also contend with a growing number of unregulated sites around the world that offer unproven stem cell treatments. It takes time for any new technology to identify safety and effi cacy barriers to clinical application, and to develop strategies to overcome them. As current research and clinical experience guide the next generation of stem cell therapies in preclinical development, the establishment of validated assays based on cells differentiated from human stem cells may revolutionize the preclinical safety testing for all classes of drugs.

A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis

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