Liu D T
Center for Biological Evaluation and Research, FDA, Bethesda, MD 20892.
Dev Biol Stand. 1988;69:193-7.
Cytokines are natural endogenous substances whose biological effects in humans are little known when given in therapeutic rather than physiologic doses. Yet, there is intense interest in seeking their possible clinical use. While E. coli are effective in making "simple proteins" with few disulfide bonds, mammalian cells are becoming more generally used for the production of "complex proteins" with multiple disulfide bonds and glycoproteins. There appears to be much less concern about the safety of possibly oncogenic residual DNA from transformed cell lines, but viral contamination of products continues to be an active concern. Both physicochemical and biological methods are necessary to establish the identity, purity and potency of biological drugs. For proteins to manifest their proper biological and therapeutic effects in humans, their correct conformation must be maintained throughout production, purification and formulation. Regulating novel biological drugs such as the cytokines might raise new scientific issues that are not currently apparent, but the basic principles involved will be consistent with those used to evaluate other biologics, e.g., sound scientific principles, flexibility, case-by-case approach, good common sense and risk vs benefit assessment.
细胞因子是天然内源性物质，当以治疗剂量而非生理剂量给药时，其在人体内的生物学效应鲜为人知。然而，人们对探寻它们可能的临床用途兴趣浓厚。虽然大肠杆菌在制造二硫键较少的“简单蛋白质”方面很有效，但哺乳动物细胞正越来越普遍地用于生产具有多个二硫键的“复杂蛋白质”和糖蛋白。对于来自转化细胞系的可能致癌的残留DNA的安全性，似乎关注较少，但产品的病毒污染仍然是一个备受关注的问题。物理化学方法和生物学方法对于确定生物药物的身份、纯度和效力都是必要的。为了使蛋白质在人体内发挥其适当的生物学和治疗作用，在整个生产、纯化和制剂过程中都必须保持其正确的构象。监管诸如细胞因子之类的新型生物药物可能会引发一些目前尚不明显的新科学问题，但所涉及的基本原则将与用于评估其他生物制品的原则一致，例如合理的科学原则、灵活性、逐案处理方法、良好的常识以及风险与效益评估。
