Braeburn, Inc. – FDA CRL

Braeburn Inc. received a Complete Response Letter (CRL) from the FDA for its New Drug Application (NDA) 210136 for BRIXADI (buprenorphine) extended-release injection. The FDA determined the application could not be approved due to several critical deficiencies, primarily citing Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act.

During recent inspections, the Pharmaceutics International manufacturing and testing facilities in Cockeysville, MD, and its warehouse and testing facility in Hunt Valley, MD, were found to have unresolved deficiencies. Satisfactory resolution of these issues is mandatory for approval.

Additionally, the proposed Prescribing Information (labeling) was non-compliant, requiring revision to address FDA's electronic communications, correct formatting, and conform to regulatory content and format requirements (21 CFR 201.56 and 201.57), including submission in Structured Product Labeling (SPL) format. Braeburn must also resubmit the proposed proprietary name, BRIXADI.

A comprehensive safety update is required per 21 CFR 314.50(d)(5)(vi)(b), necessitating detailed descriptions of safety profile changes, retabulation of adverse events, case reports for serious events, updated exposure data, worldwide safety experience, and translated foreign labeling.

Finally, under Section 505(o)(3) of the FDCA, the FDA stipulated postmarketing requirements. These include a clinical trial to explore safe initiation of BRIXADI at higher doses (24-32 mg weekly) without titration, assessing the risks of precipitated withdrawal or inadequate dosing. Another key requirement is to evaluate the unexpected risk of serious systemic histopathological changes, reproductive/developmental effects, or cancer due to elemental impurities or leachables from the container closure.