Jones A J, O'Connor J V
Dev Biol Stand. 1985;59:175-80.
Traditional methods of product release for human pharmaceutical use are designed and selected to ensure control of purity, potency, safety and identity. The selection of these tests depends upon the nature of the product. In addition to the control achieved by these methods, control of the efficiency of the manufacturing process in removing substances that cannot be tested for in the final product is achieved by "process validation". Process validation allows the use of sophisticated experimental techniques that do not lend themselves to final product testing or the use of others which, when applied to the final product, are insufficiently sensitive to be used for product release. The removal of such components as DNA and process materials can be demonstrated by these studies. Demonstrations that the manufacturing process reproducibly removes these components, eliminate the need for these tests on every batch. The essential elements of a process validation study are development of a sensitive assay technique for the component of interest and quantitation of the efficiency of individual process steps in removing that component. Even when that component is undetectable in normal process samples, the efficiency of any process step can still be determined by the addition of that component during the validation studies. The values of process validation in demonstrating the removal of DNA and in the determination of E. coli protein contamination levels during the manufacture of methionyl human growth hormone is illustrated.
用于人类药品放行的传统方法经过设计和选择，以确保对纯度、效价、安全性和特性进行控制。这些测试的选择取决于产品的性质。除了通过这些方法实现的控制外，通过“工艺验证”可实现对制造过程去除最终产品中无法检测物质的效率的控制。工艺验证允许使用复杂的实验技术，这些技术不适用于最终产品测试，或者使用其他应用于最终产品时不够灵敏而无法用于产品放行的技术。这些研究可以证明DNA和工艺材料等成分的去除情况。证明制造过程可重复性地去除这些成分，就无需对每一批产品进行这些测试。工艺验证研究的基本要素是开发针对目标成分的灵敏检测技术，并对各个工艺步骤去除该成分的效率进行定量。即使在正常工艺样品中检测不到该成分，在验证研究期间通过添加该成分仍可确定任何工艺步骤的效率。文中举例说明了工艺验证在证明甲硫氨酰人生长激素生产过程中DNA的去除以及大肠杆菌蛋白质污染水平测定方面的价值。
