Bioanalytical Techniques By Wilson And Walker Pdf Download [VERIFIED]
Understanding the biodistribution of a gene therapy product in nonclinical species is critical for establishing its safety and efficacy prior to clinical development. The quantitative biodistribution pattern of an rAAV-based modality is influenced by its serotype, route of administration (ROA), the animal species (including characteristics like age, sex, and strains), the manufacturing process, and bioanalytical techniques used in the study. The biodistribution characterization approach of rAAV may vary at different stages of the gene therapy program. During lead generation, the DMPK function may conduct a platform biodistribution study that is suitable for early discovery stages of an rAAV-based therapy before finalizing the vector design. If the sponsor decides to engineer the capsid to improve tissue tropism, or to modify the cassette sequence, a new biodistribution study with the final gene therapy product intended for clinical trials will need to be conducted. However, since regulatory agencies recognize that a high number of animals are necessary for a proper biodistribution assessment, in some instances, they have suggested alternatives such as conducting in vitro studies and/or in silico modeling (4, 11). In addition, when the same capsid serotype is used as a platform capsid to treat multiple indications by the same ROA and vector process development, the biodistribution data generated in an appropriate transducible nonclinical species (non-disease model, e.g., non-human primates) can inform and support multiple programs. Leveraging the established platform data may allow for a limited or abbreviated biodistribution assessment to be sufficient for the pivotal investigational new drug application (IND)-enabling Good Laboratory Practice (GLP)-compliant toxicology studies, which would be more cost effective. An abbreviated biodistribution assessment reduces animal usage, optimizes and streamlines manufacturing processes (as the capsid remains the same), saves resources, and reduces the time dedicated to manufacturing. According to FDA guidelines, such approaches or strategies that reduce animal usage can be considered, but should be communicated to the FDA well in advance of the IND filing, perhaps in an INTERACT meeting, for the sponsor to gain alignment with the agency (4, 11).
Bioanalytical Techniques By Wilson And Walker Pdf Download