Midland Pharmaceutical LLC – FDA Warning Letter, Sep 5, 2007

The FDA issued a Warning Letter to Midland Pharmaceutical LLC following a July-September 2007 inspection, citing numerous deviations from Current Good Manufacturing Practice (CGMP) regulations (21 CFR Parts 210 and 211) for finished pharmaceuticals. These violations render their drug products, specifically Sulfamethoxazole/Trimethoprim (SMZ/TMP) USP tablets, adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act).

Key violations include: 1. **Inadequate Production and Process Controls (21 CFR § 211.100(a)):** Deficient process validation for SMZ/TMP tablets, lacking defined ranges for critical steps, scientifically sound retrospective validation, inclusion of lower-strength products, consistent settings, and stability evaluation for changed parameters. The firm also failed to implement a change control program for significant process parameter alterations. 2. **Failure to Follow Written Procedures (21 CFR § 211.100(b)):** Manufacturing processes were not conducted within established critical parameters, and deviations were not recorded or justified. 3. **Inadequate Investigations (21 CFR § 211.192):** Out-of-specification (OOS) results for Content Uniformity, drug residue, and appearance were not thoroughly investigated. Corrective actions, such as test method changes