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7428215 
Journal Article 
Guidelines for Preclinical Development 
Spack, E; , 
2016 
Springer International Publishing 
Cham 
Regenerative Medicine - from Protocol to Patient 
51-82 
Preclinical development encompasses the set of activities required to initiate testing for safety and efficacy in humans. These requirements are defined by national and international regulations, and are generally focused on definition of drug composition and safety as well as scientific 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 definition 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 first FDA approved stem cell therapy study initiated clinical trial in 2010. Thus, the field is young and there are few completed studies to provide precedents for planned preclinical development of novel stem cell approaches. Rather, the field 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 efficacy 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.