In case of serious violations of GMP requirements, the American FDA issues a Warning Letter to the company in question. The company must react to this within 15 working days and submit a corrective action plan to the FDA.
The FDA inspected the Hungarian company Teva Pharmaceutical Works Private Limited from 21 to 29 January 2016 and the inspector witnessed serious violations of GMP regulations. The company's reply on 22. February 2016 was not sufficient and led to a Warning Letter issued on 13. October 2016. The violations were considered to be so serious by the FDA that the company was put on import alert already on 27. May 2016.
The violations observed are referred to the respective GMP regulations in 21 CFR Part 211 by the authority. In this case, the deficits were divided into 7 different chapters.
In this second part, we cover the violations of 21 CFR 211.113 (b) "Your firm failed to establish and follow appropriate 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" and of 21 CFR 211.42 (c)(10) "Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas".
Two aspects were criticized with regard to 21 CFR 211.113: "inadequate aseptic techniques" and "mechanical faults during media fill". The inspector supported the "inadequate aseptic techniques" with a video recording of a line set-up followed by the filling. It showed the following incorrect behaviour:
The company's response to these observations was inadequate. In the response to their Warning Letter, the FDA expects the following:
The following was observed during a media fill. The company rejected numerous filled vials during a media fill due to mechanical problems (issues with the conveyor belt motor). About 3,700 filled vials were not incubated and the media fill was invalidated without adequate justification. The company indicated that it would have released the filled vials of this production batch as a sub-lot. However, a procedure for such a case was not available.
Here as well, the company's response to these observations was inadequate. In the response to their Warning Letter, the FDA expects the following: