Bristol Myers Squibb Holdings Pharma., Ltd. – FDA Warning Letter, Mar 31, 2010

The FDA issued a Warning Letter to Bristol-Myers Squibb Company following a March 17-31, 2010 inspection of their Manati, Puerto Rico facility, identifying significant Current Good Manufacturing Practice (CGMP) violations, rendering drug products adulterated. The firm's April 14, 2010 response was deemed insufficient.

Violations include: 1. **Failure to prevent microbiological contamination (21 C.F.R. § 211.113(b)):** Operators repeatedly failed to comply with aseptic operation procedures, and SOPs were inadequate. The firm's aseptic process simulation (media fill) was not adequately designed to reflect routine production, a repeat observation from 2005 and 2009 inspections. 2. **Inadequate investigation of batch failures/environmental excursions (21 C.F.R. § 211.192):** The firm failed to thoroughly investigate numerous environmental excursions in Class 100 areas from January-February 2010, and did not verify the effectiveness of prior corrective actions for similar excursions. The investigation into gown quality was also insufficient. 3. **Lack of scientifically sound specifications (21 C.F.R. § 211.160(b)):** Acceptance criteria for major defects in visual inspection of lyophilized products lacked scientific justification; critical defects like glass