Teva Parenteral Medicines, Inc. – FDA EIR, May 14, 2010

The FDA conducted a comprehensive Current Good Manufacturing Practices (cGMP) inspection of Teva Parenteral Medicines Inc. in Irvine, CA, from March 29 to May 14, 2010. This inspection served as a follow-up to a July 2009 inspection that resulted in a Warning Letter and Official Action Indicated classification due to severe cGMP deficiencies, particularly concerning Propofol manufacturing and contamination.

Despite some corrections, the current inspection identified numerous, significant, and recurring cGMP violations. Key issues included a persistent failure in the Quality System to thoroughly investigate unexplained discrepancies, such as out-of-specification bioburden and bacterial endotoxins in Propofol, and inadequate follow-up on contamination. Field alert reports were also not submitted promptly.

The Laboratory Control System exhibited repeated failures in method validation, lack of stability-indicating methods for seven drug products, and deficient raw material impurity testing. Facilities and Equipment issues encompassed poor maintenance of Propofol compounding equipment, inadequate revalidation, and deficiencies in water purification systems (WFI/RO). Material System violations involved insufficient testing of raw materials and inadequate evaluation of ready-to-sterilize stoppers. Production System observations cited inadequate bulk product holding studies for Propofol.

In response to the issued FDA-483 forms, Teva's management ceased all manufacturing and distribution, including Propofol processing. The company also initiated recalls for several drug products (including Haloperidol Decanoate, L-Cysteine Hydrochloride, Tobramycin Sulfate, Pancuronium Bromide) and market withdrawals for Dexamethasone Sodium Phosphate and Dexamethasone. The Senior Vice President committed to providing a formal written response within fifteen working days.