Kashiv BioSciences, LLC – FDA CRL

The FDA has issued a Complete Response Letter (CRL) to Kashiv BioSciences, LLC for their Biologics License Application (BLA) 761084 for TPI-120, submitted under section 351(k) of the Public Health Service Act. The application cannot be approved in its present form due to significant deficiencies across microbiology, product quality, and device design, identified following the BLA submission on August 11, 2020, and subsequent information requests.

In microbiology, issues include inadequate media fill studies requiring updated results and detailed descriptions, and an insufficient bacterial retention study performed with drug substance instead of the final drug product solution. For product quality, deficiencies encompass insufficient data to support consistent protein concentration and accurate fill volume during filling operations, a deficient control strategy for sequence variants (requiring robust RP-HPLC and CEX-HPLC characterization), inadequate stability protocols for Primary and Working Reference Standards, and unresolved qualification issues for a Working Reference Standard lot. Furthermore, changes to potency assays and the CEX-HPLC method lacked adequate supporting validation data.

From the Center for Devices and Radiological Health, inadequate data was provided for needle safety performance, particularly concerning the activation force testing methods and acceptance criteria for the prefilled syringe's automatic safety device. To address these concerns, Kashiv BioSciences, LLC must submit comprehensive data, updated protocols, validation reports, and characterization studies to demonstrate appropriate control, consistency, and safety of their product and device.