Aranha-Creado H, Brandwein H
Scientific and Laboratory Services Department, Pall Corporation, Port Washington, New York, USA.
PDA J Pharm Sci Technol. 1999 Mar-Apr;53(2):75-82.
Infectivity-based assays are the assays of choice for the detection of pathogenic mammalian viruses. While it is intuitively appropriate to conduct testing and validation studies with the known viral burden or a closely related mammalian species, logistic considerations often dictate otherwise. Consequently, bacteriophages have served as suitable surrogates for mammalian viruses in both medical and environmental virology applications. The wide range of bacteriophages available offers a powerful analytical tool amenable to several different applications: filter validation studies (where removal is based on size exclusion), investigations into virus contamination control issues, evaluation of barrier materials, etc. There is a considerable body of evidence to suggest and support the use of bacteriophages as surrogates for mammalian viruses. Use of appropriately sized bacteriophages provides an innocuous, efficacious and expeditious method for economical testing and validation of viral clearance capabilities of virus removal filters, thus facilitating performance of filter validation studies in biopharmaceuticals under product- and process-specific conditions in an overall effort towards ensuring the virological safety of biologicals. This paper discusses the limitations associated with mammalian virus assays and provides a rationale for the use of bacteriophages as surrogates for mammalian viruses. Data from published literature documenting applicability of bacteriophages in filter validation studies, especially when removal is based on size exclusion, is reviewed along with examples of studies from the fields of medical and environmental virology.
基于感染性的检测方法是检测致病性哺乳动物病毒的首选检测方法。虽然直观上用已知病毒载量或密切相关的哺乳动物物种进行测试和验证研究是合适的，但后勤方面的考虑往往另有要求。因此，在医学和环境病毒学应用中，噬菌体已成为哺乳动物病毒的合适替代物。现有的多种噬菌体提供了一种强大的分析工具，适用于多种不同的应用：过滤器验证研究（其中去除基于尺寸排阻）、病毒污染控制问题调查、屏障材料评估等。有大量证据表明并支持使用噬菌体作为哺乳动物病毒的替代物。使用尺寸合适的噬菌体为经济地测试和验证病毒去除过滤器的病毒清除能力提供了一种无害、有效且迅速的方法，从而有助于在特定产品和工艺条件下对生物制药中的过滤器进行验证研究，以全面确保生物制品的病毒学安全性。本文讨论了与哺乳动物病毒检测相关的局限性，并为使用噬菌体作为哺乳动物病毒的替代物提供了理论依据。回顾了已发表文献中记录噬菌体在过滤器验证研究中的适用性的数据，特别是当去除基于尺寸排阻时的数据，以及医学和环境病毒学领域的研究实例。
