Material Controls
物料控制
Starting materials
起始物料
Definition of starting material
起始物料的定义
What constitutes the "starting material" may not always be obvious. For example, if a manufacturer carries out a simple final procedure, e.g., the esterification of a carboxylic acid, to yield the drug substance, he may consider the acid as the starting material. However, the full synthesis of this acid may well be, and frequently is, quite lengthy and/or difficult; the acid is thus not the actual starting material. Without reporting the full synthesis of this acid from the actual starting material(s), the manufacturer has not adequately described the synthetic process for evaluation by FDA. The complete synthesis from the actual starting material(s) should be submitted.
什么构成了“起始物料”并不总是很明显。如，制造商对最后的简单工序进行操作，如羧酸的酯化制得原料药。制造商可能会认为此羧酸为起始物。然而，此酸的合成可能是，通常是，相当长和/或困难，此酸因此不是实际的起始物料。没有上报从实际的起始物开始的完整合成，制造商就没有充分叙述用于FDA评估的合成工艺。从实际起始物料的完整的合成应递交。
While a definition of starting material applicable to all situations cannot be given, the following criteria for defining a starting material may be helpful:
然而确定适用于所有情况的起始物料并不能给出。如下的标准对确定起始物料很有用：
(a) It is incorporated into the new drug substance as an important
structural element.
以重要的结构元素并入新原料药中
(b) It is commercially available.
市场上可购得
(c) It is a compound whose name, chemical structure, chemical and physical characteristics and properties, and impurity profile are well defined in the chemical literature (see Glossary).
名称，化学结构，化学和物理特征和性质，和杂质情况在化学文献中得到很好的确定（见术语）
(d) It is obtained by commonly known procedures (this applies principally to starting materials extracted from plants and animals, and to semisynthetic antibiotics).
由常见的方法获得（这主要适用于由植物和动物提取的起始物质，和半合成抗体）
Frequently, the starting material will meet several of these criteria. If it does not meet any, it is probably not the starting material. When an applicant wishes to use a starting material that is not commercially available, the material should meet criterion (c). In
addition, for material that is not commercially available, it may be necessary to carry out more testing for impurities than would be needed for a commercially available product.
通常地，起始物料应满足这些标准中的几项。如果一项都不满足，它就不是起始物料。当申请者想要使用市场上不可购得的起始物料时，物料应满足标准（C），此外，市场上不可以购得的物料，需要比市场上可得的起始物料做更多的杂质检测。
The starting material may be the subject of a DMF (e.g., some starting materials for semisynthetic antibiotics). When the starting material is itself a drug substance, the synthesis of this material should be provided either in full or by authorized reference to an NDA or DMF. Generally the decision about what is the starting material has been reached by agreement between the applicant and the FDA chemist before submission of the NDA (e.g., during an IND End-of Phase 2 meeting, or pre-NDA meeting).
起始物料可能是DMF的主题（如，用于半合成抗体的某些起始物料）。当起始物料本身是原料药时，此物料的合成应完成的或以授权参考部分提供给NDA或DMF申请。一般说来，什么是起始物料的决定应在申请人和FDA化学家达成一致确定（如，在2期IND结束会议或NDA前会议）
Control procedures for starting materials
起始物料的控制方法
Starting materials should be listed. Acceptance specifications and tests defining identity, quality, and purity should be provided. The analytical test methods should be briefly described. The source of the starting material need not be identified, but may be requested.
应列出起始物料。应提供认可规格标准和确定鉴别，质量和纯度的检测。分析检测方法应简明地叙述。起始物料的来源不需要鉴定，但也可以要求鉴定
A specific identity test should be performed, as well as an assay, with limits for impurities. In those cases where impurities (e.g., positional isomers of aromatic compounds) could be carried through to the drug substance, a purity profile should be provided (e.g., chromatography with quantitation/identification of impurities). Assurances or statements of quality from the supplier are acceptable for the profile, provided that the manufacturer establishes the reliability of the supplier's analyses through validation, initially and at appropriate intervals. These statements from suppliers should include specifications and results and should indicate the type of method used for analyses.
需做具体的鉴别试验以及含量测定（需带有杂质限度）。在杂质（如，芳香族化合物的位置异构体）可能会被携带至原料药中，应提供纯度概况（如，杂质的定量/鉴定色谱图），假如，制造商在起初及合理的时间间隔内通过验证，对供应商的分析建立了信任机制，供应商对质量的确认或声明可用于纯度概况。供应商的声明应包括规格标准以及应指定用于分析的方法类型。
Reagents, solvents, and auxiliary materials controls
试剂，溶剂和辅料控制
These chemicals should also be listed. The specifications and test methods for each such material should be stated, and/or a statement of quality provided. The applicant should describe the specific identity test performed (unless omitting such a test has been otherwise justified, e.g., because of hazard). The extent of additional testing performed – whether by the supplier or by the applicant -- should be based on the role of the chemical in the synthesis. For example: a base (e.g., sodium hydroxide) used to neutralize excess acid in a synthetic reaction mixture would not normally require extensive purity testing; in contrast, an optically active organic acid used in a resolution step (e.g., one enantiomer of dibenzoyltartaric acid) would require such additional testing.
应列出这些化学物质，每一个这些物料的规格标准和检测方法应说明，和/或提供质量说明。申请人应叙述所做的具体的鉴别实验（除非由于危害，经论证，省略这个检测）。其它所做检测的范围—不管是由供应商还是申请人所做，应根据合成中化学物质的作用。如，用于中和化学合成反应中过多酸的碱（如，氢氧化钠）通常不需要过多的纯度检测；相反地，用于分离步骤的旋光活性的有机酸（如，二苯甲酰酒石酸）需要这些其它的检测。
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