FDA CRL - Cyclomedica Australia Pty Ltd

The FDA issued a Complete Response Letter (CRL) to Cyclomedica Australia Pty Ltd. regarding its New Drug Application (NDA 0222335) for Technegas Technetium Tc-99m carbon aerosol. The application, initially submitted on March 26, 2020, was deemed unapprovable due to significant deficiencies primarily in product quality and manufacturing processes.

Key issues highlighted by the FDA include inadequate characterization and control of the aerosol drug product, lacking proper assessment of its composition, stability, purity, and delivered dose, which contravenes 21 CFR 314.50(d)(ii)((a)). The agency also noted the absence of validated analytical methods for critical attributes like particle size distribution and radioactivity, crucial given the product's short expiry. Furthermore, the manufacturing processes for the critical crucible component exhibited deficiencies, including insufficient specifications, a lack of stability data, and inadequate environmental controls within the manufacturing suite, failing to meet requirements under 21 CFR Part 211.46. Issues extended to an unacceptable reliability assessment report, reliance solely on customer complaints, and a failure to address adverse observations in shipping studies for packaging.

To address these concerns, Cyclomedica must develop a comprehensive quality program for the aerosol and its crucible. This includes validating analytical methods, establishing specifications, providing extensive batch and stability data, and enhancing environmental controls and manufacturing process validation. The company is required to re-evaluate and provide updated shipping studies with proposed corrective actions for packaging and submit a proper verification protocol for the system's reliability assessment.