FDA CRL - Leo Pharma A/S

The U.S. FDA issued a Complete Response Letter (CRL) for LEO Pharma A/S's Biologics License Application (BLA 761180) for tralokinumab injection, 150 mg/ML, submitted on April 27, 2020. The application was deemed unapprovable in its current form due to significant product quality and labeling deficiencies, alongside administrative requirements for resubmission. A primary issue under product quality relates to the needle safety performance of the final finished combination product. The FDA found LEO Pharma's provided data insufficient, as it focused on a 510(k)-cleared component rather than the complete product and lacked critical preconditioning testing, including aging to shelf-life, drop testing, and simulated shipping per ASTM 4169-16, evaluated at a 95% confidence/99% reliability limit. The FDA emphasized that inadequate needle safety poses serious risks, such as accidental contaminated needle sticks, and directed the company to relevant guidance for sharps injury prevention devices. Additionally, the proposed Prescribing Information did not conform to the content and format regulations specified in 21 CFR 201.56(a), (d), and 201.57, requiring revision to align with Physician Labeling Rule and Pregnancy and Lactation Labeling Rule requirements. While previously acceptable, the proposed proprietary name must be resubmitted with the corrected application. Upon resubmission, LEO Pharma must also provide a comprehensive safety update as outlined in 21 CFR 314.50(d)(5)(vi)(b), detailing any significant changes in the safety profile and presenting new and combined safety data from clinical trials. The company has one year to address all deficiencies and resubmit the application as a complete response.