What happened: the chemistry side of the incident with EMS contamination in Viracept tablets.
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.
Gerber
Christoph
C
F. Hoffmann-La Roche Ltd., Grenzacher Strasse, 4070 Basel, Switzerland. christoph.gerber@roche.com
Toelle
Heinz-Gerhard
HG
D004305:Dose-Response Relationship, Drug; D004340:Drug Contamination; D004781:Environmental Exposure; D005020:Ethyl Methanesulfonate / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D009153:Mutagens / Q000032:analysis*; D019888:Nelfinavir / Q000138:chemical synthesis / Q000737:chemistry*; D011358:Product Surveillance, Postmarketing; D013607:Tablets
D017320:HIV Protease Inhibitors; D009153:Mutagens; D013607:Tablets; D005020:Ethyl Methanesulfonate; D019888:Nelfinavir