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Overview of Guidance for Non Clinical Biodistribution Studies For AAV Gene Therapy

The ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) provides guidance on the conduct of nonclinical biodistribution studies for AAV gene therapy products. The guidance is designed to ensure that biodistribution studies are conducted in a manner that is consistent with regulatory requirements and that provides relevant information on the distribution and persistence of the AAV vector in different tissues and organs.

According to the ICH guidance, nonclinical biodistribution studies for AAV gene therapy products should include the following:
  • Dose selection: The highest dose tested in the study should be the intended clinical dose, or a dose that is expected to produce a similar level of transgene expression.
  • Study design: The study should include a minimum of three animal species, with at least two non-rodent species.
  • Sample collection: Samples should be collected at multiple time points after administration of the AAV vector, with a focus on tissues that are likely to be affected by the gene therapy.
  • Analytical methods: Analytical methods should be validated and sensitive enough to detect low levels of the AAV vector in tissues and organs.
  • Data analysis: Data should be analyzed to determine the tissue distribution, persistence, and clearance of the AAV vector.
  • Reporting: Results of the biodistribution study should be reported in a comprehensive manner, including details of the study design, sample collection, analytical methods, and data analysis.

Compliance with the ICH guidance on nonclinical biodistribution studies is important for demonstrating the safety and efficacy of AAV gene therapy products, and for obtaining regulatory approval for their use in clinical trials and commercialization.

Reference: ICH SGT 5: Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals.

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