FDA WARNING_LETTER - Biotest Pharmaceuticals Corp. - August 15, 2014

The FDA conducted an inspection of Biotest Pharmaceuticals Corporation in Boca Raton, Florida, from August 5 to August 15, 2014, revealing significant deviations from current good manufacturing practice (CGMP) requirements in the manufacture of Bivigam, (b)(4)-HB, and Rabies Immune Globulin intermediates. These deviations violate Section 501(a)(2)(B) of the FD&C Act, requirements of the biologics license application, and 21 CFR Part 601. Key violations include the failure to document manufacturing investigations for out-of-specification (OOS) test results, and the failure to validate minimum and maximum process times and mixing times for the Bivigam and (b)(4) HB manufacturing processes. Additionally, the firm failed to validate Method QC 2100 Revision 16 for total protein determination in Rabies Immune Globulin intermediates. A significant deficiency was the failure to inform the FDA about changes in product, production process, quality controls, equipment, facilities, personnel, or labeling, as mandated by 21 CFR 601.12. These issues indicate a failure of the quality control unit to ensure product identity, strength, quality, and purity. FDA requires a comprehensive, global assessment of all manufacturing operations to achieve CGMP compliance. Biotest's initial response was deemed insufficient, lacking details on quality unit oversight. The company must provide a detailed written response within 15 working days outlining specific corrective actions and preventative measures. Failure to promptly correct these deviations may result in severe regulatory actions, including license suspension, revocation, seizure, or injunction.