Dichtelmüller H, Rudnick D, Breuer B, Kotitschke R, Kloft M, Darling A, Watson E, Flehmig B, Lawson S, Frösner G
Biotest Pharma GmbH, Dreieich, Germany.
Biologicals. 1996 Jun;24(2):125-30. doi: 10.1006/biol.1996.0016.
In order to increase the virus safety of a solvent/detergent-treated Factor VIII concentrate in regard to non-lipid coated viruses and to respond to the continuous discussion about reports on hepatitis A transmission by Factor VIII preparations, we have investigated the effect of a terminal dry heat treatment (30 min 100 degrees C) on HAV and various other viruses. By this treatment Hepatitis A virus was inactivated below detectable level after a few minutes (> 5.3 log10). Other RNA viruses such as the Human Immunodeficiency Virus (> 6.6 log10), bovine viral diarrhoea virus (> 6.6 log10) and vesicular stomatitis virus (> 5.8 log10) were also inactivated below detectable level. Pseudo rabies virus and reovirus Type 3 are inactivated by 5.7 and > 6.0 log10, respectively. SV40 and bovine parvo virus showed significant resistance to dry heat treatment. We conclude that the involvement of two strong virus inactivation steps, acting by different mechanisms, improves the virus safety of Factor VIII concentrates without destroying the Factor VIII activity. Moreover, the terminal 100 degrees C heat treatment for 30 min represents an effective measure to inactivate non-lipid enveloped viruses, in particular hepatitis A, which is resistant to solvent/detergent treatment.
为了提高经溶剂/去污剂处理的凝血因子VIII浓缩物对非脂质包膜病毒的病毒安全性，并回应关于凝血因子VIII制剂传播甲型肝炎报告的持续讨论，我们研究了终端干热处理（100℃，30分钟）对甲型肝炎病毒及其他多种病毒的影响。通过这种处理，甲型肝炎病毒在几分钟内（>5.3 log10）就被灭活至检测不到的水平。其他RNA病毒，如人类免疫缺陷病毒（>6.6 log10）、牛病毒性腹泻病毒（>6.6 log10）和水疱性口炎病毒（>5.8 log10）也被灭活至检测不到的水平。伪狂犬病病毒和呼肠孤病毒3型分别被灭活5.7 log10和>6.0 log10。SV40和牛细小病毒对干热处理表现出显著抗性。我们得出结论，两个通过不同机制起作用的强效病毒灭活步骤的结合，在不破坏凝血因子VIII活性的情况下提高了凝血因子VIII浓缩物的病毒安全性。此外，100℃终端热处理30分钟是灭活非脂质包膜病毒，特别是对溶剂/去污剂处理有抗性的甲型肝炎病毒的有效措施。
