DuPont Nutrition USA Inc. – FDA Warning Letter, Dec 15, 2021

The FDA issued a Warning Letter to DuPont Nutrition USA Inc. following a November-December 2021 inspection of their Newark, Delaware facility, citing significant CGMP deviations in the manufacture of the excipient Avicel. Avicel, a major component in drug products, was deemed adulterated under sections 501(a)(2)(B) and 501(b) of the FD&C Act due to non-conformance to CGMP and compendial standards (USP) for conductivity.

Key violations include: 1. **Inadequate Complaint Investigations:** Approximately 50 complaints regarding Avicel's failure to meet conductivity specifications were not adequately investigated. A malfunctioning conductivity meter probe, discovered seven months later, was linked to OOS results, but customers were not timely notified (over three months delay). 2. **Insufficient OOS Investigations:** Failing conductivity results were inadequately investigated, lacking thorough root cause analysis, expansion to affected lots, and timely CAPA implementation. Elevated ammonium chloride levels were identified as a root cause, raising concerns about nitrosamine formation. 3. **Unsuitable Test Methods:** Compendial and non-compendial conductivity test methods lacked adequate verification and validation. Discrepancies were found in method verification, and a non-compendial method, despite poor correlation, was used for release testing, potentially leading to the release of OOS Avicel. Inappropriate composite sampling further exacerbated this. 4.