Comparison of international guidelines for early-phase clinical trials of cellular and gene therapy products.

Cellular and gene therapies (CGT) are promising fields that are bringing significant clinical benefits to patients by directly targeting the underlying cause of disease. In line with this trend, regulatory agencies in every country have been making efforts to accelerate CGT product development. For acceleration, it is necessary to increase the efficiency of clinical trials, thus the early-phase clinical trials for CGT products should be elaborate and productive. The guidelines of international regulatory agencies were compared and analyzed to examine the considerations for the design of early-phase CGT products. The guidelines described a safety evaluation, preliminary evidence of effectiveness gathering, dose exploration, and a feasibility assessment as common objectives of early-phase clinical trials for CGT products. In addition, the considerations for the design of early-phase CGT products included pretreatment effects and problems in the manufacturing and administration process. The guidelines also covered selection of a study population, control group/blinding, and dose/regimen planning. There were differences in the degree of detail, description, and the scope of the content covered by each guideline. The guideline published by FDA was the most specific. However, when compared with the previous guidelines for designing early-phase clinical trials for small molecules and biologics, the current guidelines need to be revised to suggest more detailed and practical principles and rules.