|
3.13 Stage 1 Manufacturing and Technology Considerations 阶段1 生产和技术上的注意事项 The capability of the production equipment and procedures has a significant influence on the ability to maintain process parameters within pre-set limits. The measurement and control capability of the process equipment is one of the subjects of Stage 2, Process Qualification, and can be found in Section 4.1 Equipment qualification exercises should confirm the suitability of equipment for its intended use. 生产设备的能力和程序对于将工艺参数保持在预先设定的限度范围内的能力有关键影响。工艺设备的测量和控制能力是第二阶段，工艺确认的主题。4.1部分有介绍设备确认活动应该确认设备对预期用途的适用性。 Compatibility of the process streams with the equipment and materials that they contact (e.g., polymeric membranes, elastomers, disposable bags, and other plastic parts) is necessary to ensures product safety and efficacy. Product contact materials as well as extractables and leachables need to be evaluated for compatibility. This work should begin in Stage 1, may include studies that require long lead times, and should be completed in conjunction with Stage 2. 工艺流与设备和它们接触的材质（例如聚合膜、橡胶、免洗袋和其它塑料部分）的相容性要能保证产品的安全和有效。产品接触材质和溶出物、萃取物需要评价他们的相容性。这个工作在第一阶段开始，可能包括一些需要长的前置时间的研究，并且应该结合阶段二来完成。 Compatibility of the process streams with equipment surfaces is a measure of their reactivity, absorption, and stability when in contact during manufacturing. Compatibility tests should demonstrate that the material properties of the equipment surfaces are not altered by contact with the solutions or other product-related materials. In addition, the contact materials should not alter the process solutions or materials (either by adsorption of product components or excessive leaching that could adulterate the product). 工艺流与设备表面的相容性是对在生产接触时他们的反应、吸收和稳定性的衡量。相容性测试是为了证明设备表面的材料性质不会因接触溶液或其它产品相关物料而改变。另外，接触材料也不应该改变工艺溶液或物料（通过吸附产品组分或者过量吸出而掺混产品） Extractables are components of a material (e.g., a product contact surface that is used in drug manufacture or storage) that are recovered by use of an exaggerated force (solvent, time, temperature). Leachables are contact material components from process equipment or storage containers that migrate into the product under normal conditions of use. 萃取物是一种材料的成分（例如用于药品生产或储存的产品接触表面），通过使用一种夸大的外力（溶剂、时间、温度）而得到。浸出物是来自工艺设备或存储容器的接触材料的成分，它们在正常使用状态下转移到产品中。 The identity and quantity of leachables from polymeric wetted components (plastic storage containers, filters, primary packaging materials, gaskets and O-rings) used in drug manufacture, storage, and packaging must be documented to assure that the product is not adulterated. A combination of literature reviews, risk assessments, and laboratory studies can be used to address leachables. Various approaches to determine the extent of testing and identification of leachable species, and the setting of acceptable levels, have been published. 来自于用于药品生产、储存、包装得聚合膜盒的组件（塑料存储器、滤器、内包装材料、垫片、O形圈）的浸出物的种类和数量必须通过文件列明以此保证产品不会被掺入杂质。要结合文献查阅、风险评估和实验室研究来说明浸出物。各种确定测试的程度和浸出物种类的鉴别。还有可接受水平的设定的方法都已经出版。 · “Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products” (30) · “Evaluation of Extractables from Product-Contact Surfaces” (31) · “Application of Quality by Design (QbD) Principles to Extractables/Leachables Assessment: Establishing a Design Space for Terminally Sterilized Aqueous Drug Products Stored in a Plastic Packaging System” (32) · “Leachables Evaluation for Bulk Drug Substances” (33) “口服吸入和鼻喷药物的萃取物和浸出物的安全阈值和良好实践”（30） “产品接触表面的萃取物的评价”（31） “使用QbD对萃取物/浸出物评估的原则：为储存在塑料包装系统的最终灭菌的液体药物确立设计空间”（32） “原料药的浸出物的评价”（33） |
|
|
