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Writer's pictureSharan Murugan

ICH/ USFDA Guidance: S12 Nonclinical Biodistribution Considerations for Gene Therapy Products

On 27th April, 2023 the United States Food & Drug Administration Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research announced the availability of final guidance on "S12 Nonclinical Biodistribution Considerations for Gene Therapy Products".


The aim of this guidance is to provide harmonized nonclinical biodistribution (BD) recommendations for the development of gene therapy products (GT).

Gene Therapy products are drugs that contain genetic material intended to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic purposes. Some examples of GT products can include purified nucleic acid (e.g., plasmids and RNA), microorganisms (e.g., viruses, bacteria, fungi) genetically modified to express transgenes (including products that edit the host genome), and ex vivo genetically modified human cells.


BD is the in vivo distribution, persistence, and clearance of a GT product at the site of administration and in target and nontarget tissues, including biofluids (e.g., blood, cerebrospinal fluid, vitreous fluid). Nonclinical biodistribution (BD) studies are preclinical studies conducted in animal models to assess the distribution and elimination of a test substance in various organs and tissues of the body typically conducted as part of the overall nonclinical safety assessment.


The purpose of this guidance is to provide details on how nonclinical biodistribution (BD) assessments should be conducted. It also includes recommendations on how BD data should be interpreted and applied to support nonclinical development and clinical trial design.


The scope of this guidance encompasses GT products whose effect is mediated by the translation or transcription of genetic materials. This guidance can help facilitate the development of gene therapy products by reducing, refining, and replacing animal use as much as possible.


To know more about the Timing & Design of nonclinical biodistribution (BD) studies, click this LINK.






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