Route of Administration

Most gene transfer studies, both in humans and in animals, are expected to involve either single administrations or a small number of repeat administrations over a short duration of time. CBER recommends that both the route of administration and the dosing schedule in animal studies mimic those intended for the clinical trial as closely as possible. However, there are issues specific to the gene transfer that need to be incorporated into the study design, for example, the persistence of gene expression following transduction of the target organ, which will impact upon the duration of the toxicity study. Another example would be the physical characteristics of the agent being studied (i.e., vector aggregation at high concentrations). The dose and the route of administration for the preclinical safety studies of cellular and gene therapies should mimic those intended for the clinical trial as closely as possible. It is understood, however, that some dosing techniques and/or regimens intended for the clinical trial may be difficult to achieve in a small animal species, such as a rodent. In these cases, a method of administration similar to that planned for use in the clinic is advised. For example, intrapulmonary instillation of adenoviral vectors by intranasal administration in Cotton rats or mice is an acceptable approach in lieu of direct intrapulmonary administration through a bronchoscope.

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