Following the agency’s inspection at the company’s North Ryde, Australia, facility in late October, 2010, inspectors found the company “failed to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product.”
The failure to provide humidity control in some of the blister rooms where capsules could have an impact on the effectiveness of the unnamed products. Process design studies on this product found that the capsules are sensitive to humidity and that after a certain point, approximately 50% of the capsules exhibited brittleness, which can lead to “performance problems” for the distributed products.
The company previously said that it installed a humidification unit for one of the blister packaging lines but the FDA deemed that action “inadequate because you did not adequately investigate and address the impact on the drug product already distributed to the U.S. market. Your response also does not indicate whether your contract packaging facility plans to use the blister line that still lacks adequate humidity controls to repack products for the U.S. market.”
“Furthermore, you did not provide a scientific rationale for the current placement of the humidity probe during routine in-process humidity monitoring during packaging,” the FDA said.
CPSA also “failed to identify the root cause of the humidity excursion and provide the appropriate corrective and preventive actions.”
In its response to the warning letter, the FDA sought a mapping study report of the temperature and humidity mapping study of the warehouse by the end of Q1 2013, as well as the company’s plan to monitor and control the relative humidity in the company’s warehouse, as well as a copy of the bulk standard specification for some of the capsules.
In addition, the FDA called for more detailed description of the changes and improvements that will be made to the company’s investigation system, including improved procedures, provisions for root cause determination and better staff training and qualifications.
CPSA failed to respond to a request for comment before press time.