ABSTRACT

Introduction

Before release, vaccine batches are assessed for quality to evaluate whether they meet the product specifications. Vaccine batch tests, in particular of inactivated and toxoid vaccines, still largely rely on in vivo methods. Improved vaccine production processes, ethical concerns, and suboptimal performance of some in vivo tests have led to the development of in vitro alternatives.

Areas covered

This review describes the scientific constraints that need to be overcome for replacement of in vivo batch tests, as well as potential solutions. Topics include the critical quality attributes of vaccines that require testing, the use of cell-based assays to mimic aspects of in vivo vaccine-induced immune responses, how difficulties with testing adjuvanted vaccines in vitro can be overcome, the use of altered batches to validate new in vitro test methods, and how cooperation between different stakeholders is key to moving the transition forward.

Expert opinion

For safety testing, many in vitro alternatives are already available or at an advanced level of development. For potency testing, in vitro alternatives largely comprise immunochemical methods that assess several, but not all critical vaccine properties. One-to-one replacement by in vitro alternatives is not always possible and a combination of methods may be required.

中文翻译：

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克服人类和兽用疫苗从体内到非动物批次测试过渡的科学障碍

摘要

介绍

在发布之前，对疫苗批次进行质量评估，以评估它们是否符合产品规格。疫苗批次测试，特别是灭活疫苗和类毒素疫苗，仍然很大程度上依赖于体内方法。改进的疫苗生产过程、伦理问题和一些体内测试的次优性能导致了体外替代品的开发。

涵盖的领域

这篇综述描述了替代体内批次测试需要克服的科学限制，以及潜在的解决方案。主题包括需要测试的疫苗的关键质量属性、使用基于细胞的分析来模拟体内疫苗诱导的免疫反应的各个方面、如何克服体外测试佐剂疫苗的困难、使用改变批次进行验证新的体外测试方法，以及不同利益相关者之间的合作如何成为推动过渡的关键。

专家意见

对于安全性测试，许多体外替代品已经可用或处于高级开发阶段。对于效力测试，体外替代方法主要包括评估几种但不是所有关键疫苗特性的免疫化学方法。体外替代品的一对一替代并不总是可行的，可能需要多种方法的组合。