FDA 483 - No company name found in the provided text due to extraction error. - February 23, 2001

This FDA Form 483 details numerous cGMP violations at a facility manufacturing Olanzapine (Zyprexa®) and other aseptically filled products including Vancomycin, Humulin R, and Gemzar.

**Quality Unit and Media Fill Deficiencies:** The Quality Unit failed to comprehensively review operations and raw data for Olanzapine manufacturing. Media fill operations, crucial for aseptic process validation, exhibited significant issues. The NDA specifies a 0.1% contamination acceptance criterion, but the firm does not incubate all media-filled bottles or for the required duration. Specifically, redacted liquid growth medium samples, samples for microbial growth promotion testing, and discarded media-filled vials (e.g., capper discards, end-of-operation discards, thermocouple vials) are not incubated or included in total counts. Incubation temperatures (14 days at 20-25°C) are not optimal for bacterial growth (30-35°C), despite the facility's normal flora including bacteria. Procedures for aseptic process validation and related testing were not followed, preventing substantiation of the contamination rate.

**Environmental Control and Facility Issues:** Partially stoppered vials are not kept in a Class 100 environment during transfer to lyophilizers. Video recordings of aseptic media fill operations are discarded after review, and there's no written procedure for this common practice. Aseptic solution preparation and filtration processes lack similar video review. Fill room operators exhibited