Burnouf T
Service de Fractionnement du Plasma, Centre Régional de Transfusion Sanguine, Lille.
Ann Pharm Fr. 1994;52(3):124-36.
In the last few years, plasma fractionation has been subjected to major technological changes which have contributed to improve the viral safety and overall purity of plasma derivatives. New viral inactivation treatments, primarily solvent-detergent and pasteurization, have been introduced in the manufacturing processes of plasma derivatives to ensure the inactivation of major plasma-borne viruses, including HIV and hepatitis B and C viruses. Concurrently, new highly purified products obtained by chromatographic methods (mainly ion exchange and/or immunopurification) have been developed in the last five years and have replaced former preparations, providing a significantly higher safety level in terms of purity and viral risks. For an example, the new generation of Factor VIII and Factor IX concentrates (to treat hemophilia A and hemophilia B, respectively), which have been introduced in the last five years, are purified over 10,000- to 20,000-fold from plasma, as compared to only 50- to 100-fold for the former products. Similarly, new, standardized, clotting factor or protease inhibitor concentrates have been made available, thus permitting to carry out selective hemotherapy of specific diseases. Examples include the development of von Willebrand factor, factor XI, protein C, or alpha 1-antitrypsin concentrates for the substitutive therapy of congenital or acquired deficiencies. In addition, the concept of good manufacturing practices has been implemented, whereas carefully controlled, validated processes are contributing to the consistency in the quality of those products. Current major problems in plasma fractionation relate to the potential occurrence of new pathogenic agents that could resist present viral inactivation treatments and to the potential effect of given purification technologies on the development of immunogenic properties of proteins. Current trends indicate that significant progress in viral safety of plasma derivatives (for example through the introduction of new concept such as viral filtration) are to be expected very soon. Further research in this very important field is mandatory as plasma should remain the starting material of important therapeutic products in the coming years.
在过去几年中，血浆分馏技术经历了重大变革，这些变革有助于提高血浆衍生物的病毒安全性和整体纯度。新的病毒灭活处理方法，主要是溶剂-去污剂法和巴氏消毒法，已被引入血浆衍生物的制造过程中，以确保灭活主要的血源病毒，包括艾滋病毒、乙型肝炎病毒和丙型肝炎病毒。与此同时，在过去五年中开发了通过色谱法（主要是离子交换和/或免疫纯化）获得的新型高纯度产品，这些产品已取代了以前的制剂，在纯度和病毒风险方面提供了显著更高的安全水平。例如，在过去五年中推出的新一代凝血因子VIII和凝血因子IX浓缩物（分别用于治疗甲型血友病和乙型血友病），与以前的产品相比，从血浆中纯化的倍数超过10000至20000倍，而以前的产品仅为50至100倍。同样，新的、标准化的凝血因子或蛋白酶抑制剂浓缩物也已面市，从而能够对特定疾病进行选择性血液治疗。实例包括开发用于先天性或后天性缺陷替代治疗的血管性血友病因子、凝血因子XI、蛋白C或α1-抗胰蛋白酶浓缩物。此外，良好生产规范的概念已经实施，而经过严格控制和验证的工艺有助于保证这些产品质量的一致性。血浆分馏当前的主要问题涉及可能出现对现有病毒灭活处理有抗性的新病原体，以及特定纯化技术对蛋白质免疫原性特性发展的潜在影响。当前趋势表明，血浆衍生物的病毒安全性将很快取得重大进展（例如通过引入病毒过滤等新概念）。在这个非常重要的领域进行进一步研究是必不可少的，因为在未来几年血浆仍应作为重要治疗产品的起始原料。
