On 9 June 2020, the FDA issued a Warning Letter to the Japanese company Takeda Pharmaceutical Company Limited following an inspection conducted in November 2019. Among other things, issues with the Media Fill, inadequate "aseptic behaviour" and inadequate controls of materials used in the aseptic area were reported. Part 1 of the News will deal with the latter two deviations while part 2 will address media fill problems. FDA Warning Letters always refer to the corresponding chapters of 21 CFR Part 211.
Your firm failed to 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)).
What deficiencies were identified by the inspector in aseptic performance, what was the company's response and why was this response inadequate from the FDA's perspective?
The company's response that it had trained its employees to behave adequately in an aseptic environment was not sufficient for the FDA. Rather, the company should extend this training to supervisory staff and generally demonstrate the effectiveness of the training.
What deficiencies were identified by the inspector in the review of materials used in the aseptic area, what was the company's response and why was this response insufficient from the FDA's perspective?
The wipes used for disinfection in the aseptic area could not be traced. The irradiation certificate of the wipes shown to the inspector did not match the material identification number. The inspector criticised the lack of adequate records in the quality unit on material reception and use.
The company replied that a risk assessment had concluded that the placing of the wipes in the clean room did not pose a risk to product quality. This risk assessment related to the use of disinfectants, environmental monitoring and a qualitative sterilisation indicator. However, the FDA expected adequate controls of material acceptance and an evaluation before entering the clean room. The company confirmed the lack of traceability of the material identification number.