IN-HOUSE STERILITY TESTING METHOD NOT EQUIVALENT TO USP<71>
During the time frame of June 4 – 14, 2012, the Hameln facility was audited by the FDA. Following the audit, the firm responded on July 4, August 2 and 31, and September 8, 2012. Even with all of these responses, the FDA found that the firm lacked sufficient corrective actions.
For example:
The firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a)).
1. For example, an employee examining (b)(4) plates was unable to read and accurately record microbial counts. Additionally, our investigator observed employees functioning in roles supporting your sterile filling operations that were not following the procedures that govern their activities, such as glove change frequency, the handling of dropped objects, personnel monitoring, and sample acquisition. Â Your responses indicate that the employees observed during the inspection had been trained in their respective job functions and that they have now been re-trained on these procedures, several of which were made more specific. Your response did not provide an explanation for why your system was unable to recognize, identify and mitigate these performance lapses.
2. Your firm has not established or followed appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile. Such procedures shall include validation of all aseptic and sterilization processes. (21 CFR 211.113(b))
We observed that your smoke study videos were not sufficient to evaluate the quality of your Class A airflow. In your response, you included a written evaluation of the smoke studies. However, the videos you provided as raw data did not provide sufficient evidence to support the conclusions you drew. These studies should show that unidirectional flow is maintained and that particles will be swept away from the critical area. In your response to this letter, provide additional evidence to support your conclusion that sufficient smoke studies were done to evaluate the quality of your Class A airflow or, alternatively, you can repeat the smoke studies.
3. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
There was no justification for the failure to place nonviable probes in locations related to the risk to exposed containers and product. Your placement of non-viable probes in the Class B areas, situated (b)(4) from the (b)(4), were also in locations providing information of little value in describing the quality of this adjacent environment that may impact the product.
COMMENT:
The Observations observed above represent basic requirements that should be in place in pharmaceutical operations and in aseptic processing operations, in particular. 21 CFR 211.113(b) represents a very common Observation for firms that are attempting to manufacture aseptic products. One should view the FDA Aseptic Processing Guidance (Sept 2004) for additional information on this important topic.
21 CFR 211.42(c)(10)(iv) represents one of ten subsections under 21 CFR 211.42 Design and Construction Features. Under “c.10”, please review all six sections to learn of all of items one should consider.
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