《合成原料药DMF起草大纲》.docVIP

《合成原料药DMF起草大纲》 一、公司和生产场地的基本描述 1、第一类的DMF文件建议由位于美国之外的人提供，以帮助FDA对他们的生产设施进行现场检查。DMF文件应描述生产场地、设备能力、生产流程图等。A Type I DMF is recommended for a person outside of the United States to assist FDA in conducting on site inspections of their manufacturing facilities. The DMF should describe the manufacturing site, equipment capabilities, and operational layout. 2、第一类的DMF文件对美国国内设施通常不需要，除非该设施没有登记并定期接受检查。A Type I DMF is normally not needed to describe domestic facilities, except in special cases, such as when a person is not registered and not routinely inspected. 3、场地的描述应包括面积、实际地址以及表明该场地与最近的城市的距离的地图。提供该场地的鸟瞰图和平面图。The description of the site should include acreage, actual site address, and a map showing its location with respect to the nearest city. An aerial photograph and a diagram of the site may be helpful. 4、主要生产和加工区域的平面图对于理解整个生产布局会有帮助。应当描述主要设备的生产能力、用途和位置。 通常不用描述设备的制造商和型号，除非特别新或独特的设备。A diagram of major production and processing areas is helpful for understanding the operational layout. Major equipment should be described in terms of capabilities, application, and location. Make and model would not normally be needed unless the equipment is new or unique. 5、公司主要的组成部门结构图， 包括总公司和生产场地的关键生产、质量控制、质量保证岗位，A diagram of major corporate organizational elements, with key manufacturing, quality control, and quality assurance positions highlighted, at both the manufacturing site and corporate headquarters, is also helpful.二、原料药的物理和化学特征 1、特性 Properties 相关法规要求对原料药的物理和化学特征做出详细描述。该要求可以通过提供下述信息来满足： 名称（通用名、化学名、编码等）、化学摘要服务(CAS)编码、性状描述（如：外观、颜色、物理状态）、分子式和分子重量、结构式（包括离子状态）、立体化学（找出手性中心、顺式反式异性等）、对映结构体比率（如：外消旋物、规定的异构体、对映异构物和固态形式的混合物）、溶解度概况（水溶性的或非水溶性的）、分配系数、溶液pH值、解离常数、熔点或沸点、折射率、比重。对于蛋白质原料药，参见：“CRC生物化学和分子生物学手册” “酶学方法”和有关描述蛋白质特性的专论。The regulations require a full description of the physical and chemical characteristics of the drug substance. This requirement may be satisfied by the submission of information such as the following: name (generic name, chemical name, code number); Chemical Abstract