FDA CRL - Astellas Pharma US Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Astellas Pharma US, Inc. regarding their Biologics License Application (BLA) 761365 for IMAB362. The application, filed under section 351(a) of the Public Health Service Act, cannot be approved in its current form due to several outstanding issues. A primary concern stems from unresolved deficiencies identified during a pre-license inspection of a manufacturing facility. Astellas must provide satisfactory responses to these inspection deficiencies to the FDA's inspection team before resubmitting their complete response, including the date of the FDA Form 483 response. Additional technical issues include the sterility test method, which currently specifies testing 10 vials per medium, but needs to be updated to 20 vials in accordance with USP <71>. The Container Closure Integrity Test (CCIT) method for drug product stability testing, a non-compendial method, requires further validation for precision and robustness, as outlined in FDA guidance. The FDA also requested additional data to support the manufacturing process's capability for reproducible commercial production of IMAB362. Astellas is required to provide a comprehensive safety update, incorporating new clinical and nonclinical data, re-tabulated adverse event frequencies, and worldwide safety experience, as per 21 CFR 314.50(d)(5)(vi)(b). The proposed proprietary name, VYLOY, remains conditionally acceptable pending resolution of these deficiencies. Astellas must address all issues within one year and resubmit a complete response, as the product cannot be marketed until approved.