1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed. (21 CFR 211.192)
...b. Sterility Test Positive Investigations
You also did not thoroughly investigate sterility test positives. For example, your investigation of a sterility test failure for [redacted] injection (batch [redacted]) did not adequately assess the hazards in the aseptic manufacturing operation that led to the sterility failure. You also did not determine whether other batches made on the same production line were affected.
In addition, you invalidated multiple sterility test positive results obtained during batch release testing. However, we note that your firm uses a sterility test [redacted] as well as a sterility testing kit that minimizes potential for adventitious contamination that could cause false positives....
2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes. (21 CFR 211.113(b))
a. Poor Aseptic Behavior
During the inspection, our investigators observed poor aseptic processing techniques that had been previously videotaped at your facility. For example, video from September 8 and 9, 2015, showed the following during the set-up and filling of the sterile injectable drug [redacted]:
- an operator passing a pen directly over the stopper bowl to another operator.
- an operator sitting on the clean room floor during set-up of the filling line and not changing the gown after standing up.
- operators leaning against the cleanroom walls.
- an operator leaving the RABS [redacted] open for extended periods of time during filling line set-up, even when he was not working in the immediate area.