Savage M, Torres J, Franks L, Masecar B, Hotta J
Bayer Corporation, Pharmaceutical Division, 8368 US Highway 70, Clayton, NC 27520, USA.
Biologicals. 1998 Jun;26(2):119-24. doi: 10.1006/biol.1998.0140.
A requirement for a minimal threshold level of moisture in order for efficient virus inactivation to occur during dry heat treatment of freeze-dried coagulation factor concentrates is described. Techniques used to determine moisture content during heating were Loss on Drying and Karl Fischer. The Loss on Drying was suspected to have occasional errors as a result of sample preparation being influenced by interference from atmospheric moisture. Therefore, a non-invasive, non-destructive method for determination of residual moisture content using near infrared spectrometry (NIR) was developed for freeze-dried antihaemophilic factor (AHF). Calibration equations were determined against Loss on Drying and Karl Fischer assay methods and these equations evaluated for the predictive efficiency. Both Loss on Drying and NIR were used to evaluate the effect of moisture content on the efficiency of virus inactivation by dry heat at 80 degrees C. A minimum level of moisture of greater than 0.7%, as determined by Loss on Drying, was necessary for a virus reduction in the magnitude of 4 log10 for hepatitis A virus, porcine parvovirus and pseudorabies virus.
本文描述了在冻干凝血因子浓缩物的干热处理过程中，为实现有效的病毒灭活所需的最低水分阈值水平。加热过程中用于测定水分含量的技术是干燥失重法和卡尔费休法。由于样品制备受到大气水分干扰的影响，干燥失重法被怀疑偶尔会出现误差。因此，开发了一种使用近红外光谱法（NIR）测定冻干抗血友病因子（AHF）残留水分含量的非侵入性、非破坏性方法。根据干燥失重法和卡尔费休测定法确定了校准方程，并对这些方程的预测效率进行了评估。干燥失重法和近红外光谱法都用于评估水分含量对80℃干热病毒灭活效率的影响。通过干燥失重法测定，水分含量最低水平大于0.7%是甲型肝炎病毒、猪细小病毒和伪狂犬病病毒实现4 log10量级病毒减少所必需的。
