Gerber Christoph, Toelle Heinz-Gerhard
F. Hoffmann-La Roche Ltd., Grenzacher Strasse, 4070 Basel, Switzerland.
Toxicol Lett. 2009 Nov 12;190(3):248-53. doi: 10.1016/j.toxlet.2009.02.020. Epub 2009 Mar 9.
A technical review of the events leading to the global recall of Viracept film coated tablets 250 mg in June 2007 is given from the drug substance manufacturing perspective. Root cause analysis performed and corrective actions implemented are presented. Using the decay rate of ethyl methane sulfonate in Viracept film coated tablets 250 mg at 25 degrees C derived from stability studies, establishing of the worst case scenario for patient exposure to ethyl methane sulfonate, is outlined. Whereas the first evaluation based on ethyl methane sulfonate levels found in the drug substance suggested a worst case patient exposure of 2300 ppm, the decay rate of ethyl methane sulfonate in the drug product and the time gap between drug product manufacture and earliest possible use by patients led to the conclusion that 920 ppm (+/-10%) over a period of approx. 90 days is a reasonably cautious assumption for the worst case patient exposure scenario.
从原料药生产的角度，对导致2007年6月全球召回250毫克维乐命薄膜包衣片事件进行了技术审评。介绍了所开展的根本原因分析及实施的纠正措施。利用稳定性研究得出的25℃下250毫克维乐命薄膜包衣片中甲磺酸乙酯的降解速率，概述了确定患者接触甲磺酸乙酯的最坏情况。虽然基于原料药中发现的甲磺酸乙酯水平进行的首次评估表明患者最坏情况的接触量为2300 ppm，但药品中甲磺酸乙酯的降解速率以及药品生产与患者最早可能使用时间之间的间隔导致得出结论：在约90天的时间内，920 ppm（±10%）是对患者最坏情况接触场景的合理谨慎假设。
