Regulatory Expectations
Where feasible, preparation and administration of gene therapy in IND-enabling animal studies should reflect the procedures planned for the clinical trial, including utilization of the delivery device intended for administration in human subjects. Animal studies should include assessments evaluating whether the device has any impact on key quality attributes of the gene therapy such as vector potency, particle count, and aggregation levels before administration and after the entire dose is advanced through the device. These assessments allow for an evaluation of the device’s compatibility with the gene therapy and regulatory guidance emphasizes the importance of demonstrating minimal impact to product quantity or product activity in such studies [8] [9].
The following delivery device information should be provided in the IND:
Device description, including manufacturer and model number.
Device 510k or PMA summary.
Any reprocessing procedures, including sterilization (if reprocessed by the clinical site or hospital).
Industry Practices
As stated previously, delivery device compatibility studies may be included as part of animal studies or may be performed as separate standalone in vitro simulation studies. Test article samples should be sourced from GMP or clinically representative batches. Importantly, the device and components (e.g., infusion lines, needles, catheters, filters) should be tested for use under worst-case conditions, such as maximum thawing times, high / low doses, and temperature conditions. Key measures include potency or infectivity assays, physical titer (vector genomes or particles), aggregation or sub-visible particulate counts, and sterility tests before and after the gene therapy is administered through the device [8]. Leveraging safety information from previously FDA-approved devices for similar use is possible, but product-specific compatibility data remains necessary [9].
Best Practice Recommendations
Methods, data, and results of the delivery device compatibility testing may be included either as part of the animal study documents or if performed as a standalone study, a separate protocol and report should be completed. Instructions on how to prepare the gene therapy for administration as well as instructions on using the tested devices in the clinical trial should be documented in the Pharmacy Manual.