FDA 警告信指出美国一家无菌非处方药生产企业的监测、RABS 与培养基灌装缺陷

In March 2026, the FDA inspected a US manufacturer of sterile OTC medicines. The agency criticises, among other things, deficiencies in monitoring, in the design of a RABS line, in the aseptic working practices of staff, in airflow management and in the media fills. As the company's response did not adequately address the deficiencies from the FDA's point of view, a Warning Letter has now been issued.Environmental and personnel monitoringThe FDA considers the environmental and personnel monitoring in the classified areas to be inadequate. Important sources of contamination, such as telephones in the aseptic area, are not adequately monitored, according to the agency. Some of the culture media used were partly unsuitable or damaged.Between 2023 and 2025, microorganisms outside the specified limits were regularly detected in the ISO 5 areas, including the Gram-negative rods Serratia marcescens and Stenotrophomonas maltophilia. These organisms are typical for a moisture problem. However, the company continued production without implementing adequate CAPA measures to address the ongoing contamination. In addition, the FDA criticises deficiencies in the design of a RABS line, including ergonomic problems, inadequate barrier protection and insufficiently demonstrated effectiveness of the unidirectional airflow. The data provided by the company on environmental monitoring, sterility tests, complaint rates and additional disinfection measures are not sufficient in the FDA's view. In particular, the agency lacks a concrete commitment to implement essential design improvements and to evaluate monitoring and complaint data appropriately in future.The FDA points out that a sterility test alone cannot justify the release of a batch. After all, microbiological deviations and adverse trends in the WFI system and in the environmental and personnel monitoring were not adequately investigated. The repeatedly detected microorganisms were not adequately identified. Of particular concern is that Pseudomonas aeruginosa and Aspergillus brasiliensis were detected in the operating environment and also in several samples from consumer complaintsDeficiencies in the aseptic working practices and cleanroom behaviourThe FDA also describes repeatedly observed deficiencies in the aseptic working practices and cleanroom behaviour of staff during aseptic filling. The objections relate in particular to manual interventions, inadequate disinfection, contact with sterile areas and actions that may compromise product protection provided by the unidirectional airflow.During filling, staff repeatedly reached over openly exposed, already sterilised containers in order to remove jammed units. In addition, they failed to disinfect certain components used in the aseptic process, including before handling sterile materials and between the use of different tools. The FDA also describes situations in which the unidirectional airflow was blocked to open, sterilised containers. The FDA further reports that staff came into contact with the sterile parts of aseptic forceps used to remove stuck bottles. The affected containers were subsequently returned to the process. Bags used to transfer sterile components, in this case bottles, were exposed to an ISO 7 environment before further handling and touched internal areas of the equipment housing. In addition, staff used an unsuitable tool to push waste into a container located below the process line, instead of using the designated equipment.Inadequate Media Fills or Aseptic Process Simulations (APS)In addition, the FDA considers the media fills, or Aseptic Process Simulations (APS), to be inadequate. The data show, according to the agency, that the number of units in the media fills is significantly lower than the commercial, aseptically manufactured batch sizes. The FDA particularly highlights a failed media fill in July 2025: two units showed contamination - one with the fungus Neovaginatispora magiferae and one with the spore-forming Gram-positive bacterium Geodermatophilus obscurus.You can find the full Warning Letter on the FDA website.