FDA 483 - Teva Parenteral Medicines, Inc. - July 24, 2009

The FDA Form 483 details numerous deficiencies at a drug manufacturing facility. The quality control unit lacks responsibility for approving/rejecting procedures impacting drug product identity, strength, quality, and purity. The company failed to submit post-approval or change-being-effected changes for a BI challenge in steam sterilization.

Several issues relate to product testing and release: - Out-of-trend bacterial endotoxin results were observed in finished product lots (e.g., MIR 09-003, MIR 09-015). - Drug product release does not include appropriate laboratory determination of conformance to final specifications. - There is no assurance that Propofol Injectable Emulsion 1% is free of bacterial endotoxin. - In-process materials are not tested for quality/purity or approved/rejected by QC. - Bioburden levels are sampled from non-sterile bulk solution and end-of-run samples (aseptically filled vials prior to sterilization). - Acceptance criteria for QC sampling/testing are inadequate to assure batches meet statistical quality control criteria.

Investigation failures include: - Unexplained discrepancies are not thoroughly reviewed, even for distributed batches. - Investigations do not extend to other batches or drug products potentially affected. - No consideration was given to other Propofol products manufactured on the same filling line.

Quality system and documentation issues: - QC unit responsibilities and procedures are not in writing.