FDA WARNING_LETTER - Novartis Vaccines and Diagnostics - September 27, 2007

The FDA issued a Warning Letter to Novartis Vaccines and Diagnostics following a September 2007 inspection of their Marburg, Germany facility, citing significant deviations from current Good Manufacturing Practices (CGMP) in the manufacture of Rabies Vaccine (RabAvert) and Diphtheria and Tetanus Toxoids Adsorbed concentrate. These violations contravene section 501(a)(2)(B) of the FD&C Act, section 351(a) of the PHS Act, and 21 CFR Part 601.

Key deficiencies include: 1. **Production and Process Controls:** Unassured sterility of media lot# [redacted] used in RabAvert production, leading to contamination events with *Candida guilliermondii* in multiple lots. Inadequate "Master Plan Stability of Media, MPS-001" lacking defined media groups, worst-case rationale, and representative storage containers. Inadequate stability study Q312-001 for Diphtheria and Tetanus Toxoids Adsorbed concentrate, using non-representative containers. Inadequate validation study for [redacted] connectors due to unaddressed deviations and inaccurate reporting. Failure to follow written procedures for rabies virus inactivation, with insufficient incubation times for several RabAvert batches. 2. **Investigation of Failures:** Incomplete sterility failure investigations, including discarding contaminated media without testing, not testing retain samples, and delayed implementation of corrective