Thorpe R, Wadhwa M, Page C, Mire-Sluis A
Division of Immunobiology, The National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK.
Dev Biol Stand. 1999;97:61-71.
The primary value of bioassays is that they alone directly assess the biological activity of bioactive substances and products like cytokines. Appropriately designed bioassays reflect the fundamental aspects of the biological activity of a cytokine molecule, including ligand-receptor binding, signal transduction processes (often poorly understood) and the final observed biological effects. Biological assays therefore complement physicochemical and biochemical procedures which normally only assess precise molecular structural features of cytokines. Bioassays provide valuable information concerning the potency of cytokine products. This is essential for evaluating batch-to-batch consistency, appropriate formulations and stability. Bioassay data are crucial at all stages in the development of cytokine products, from early research to final quality control of finished product. However, the type and design of bioassays may differ according to the information required and its intended use. The assays may or may not directly relate to the clinical use of the product. Bioassays can be difficult to perform and time consuming, although this often reflects bad assay choice and/or design. Correct analysis of the assay results is essential if valid data are to be obtained. Standardisation, using correctly calibrated primary and secondary standards, is essential. In vivo bioassays are normally more unreliable than in vitro procedures, but in some cases in vitro systems are either not available or do not address important biological characteristics of a product. Bioassays must be validated for their intended purpose and for the types of samples to be measured. Appropriate statistical analysis should be used to derive the significance and specifications of results. This needs to address both variability in samples and assay performance. Specifications (limits) for product acceptability need to be derived from real data using several batches of cytokine product.
生物测定的主要价值在于，只有它们能直接评估生物活性物质和细胞因子等产品的生物活性。设计合理的生物测定反映了细胞因子分子生物活性的基本方面，包括配体-受体结合、信号转导过程（通常了解甚少）以及最终观察到的生物学效应。因此，生物测定补充了物理化学和生化程序，这些程序通常仅评估细胞因子精确的分子结构特征。生物测定提供了有关细胞因子产品效力的有价值信息。这对于评估批次间一致性、合适的配方和稳定性至关重要。生物测定数据在细胞因子产品开发的各个阶段都至关重要，从早期研究到成品的最终质量控制。然而，生物测定的类型和设计可能因所需信息及其预期用途而异。这些测定可能与产品的临床用途直接相关，也可能不相关。生物测定可能难以进行且耗时，不过这往往反映出测定选择和/或设计不当。如果要获得有效的数据，对测定结果进行正确分析至关重要。使用正确校准的一级和二级标准进行标准化是必不可少的。体内生物测定通常比体外方法更不可靠，但在某些情况下，体外系统要么不可用，要么无法体现产品的重要生物学特性。生物测定必须针对其预期目的和要测量的样品类型进行验证。应使用适当的统计分析来得出结果的显著性和规格。这需要考虑样品的变异性和测定性能。产品可接受性的规格（限度）需要从使用几批细胞因子产品的实际数据中得出。
