467_残留溶剂_usp

Testing of drug substances, excipients, and drug products for residual solvents should be performed when production or purification processes are known to result in the presence of such residual solvents. It is only necessary to test for residual solvents that are used or produced in the manufacture or purification of drug substances, excipients, or products. 应该在生产或纯化工艺已知会导致此类残留溶剂时，进行对原料药、辅助剂、成药的残留 溶剂测试。仅仅需要对在原料药、辅助剂、成药的生产或纯化中所使用或生成的残留溶剂 进行检测。
INTRODUCTION 介绍
This general chapter applies to existing drug substances, excipients, and products. All substances and products are subject to relevant control of solvents likely to be present in a substance or product. 本通则适用于现有原料药、辅助剂、成药。所有原料药和成药均需对可能存在其中的溶剂 进行控制。
<467> RESIDUAL SOLVENTS 残留溶剂
(Chapter under this new title—to become official July 1, 2008) （这个新名称下的通则----2008 年 7 月 1 日起生效）
(Current chapter title is <467> Organic Volatile Impurities) （当前通则名称是<467>有机挥发性杂质）
Although manufacturers may choose to test the drug product, a cumulative procedure may be used to calculate the residual solvent levels in the drug product from the levels in the ingredients used to produce the drug product. If the calculation results in a level equal to or below that provided in this general chapter, no testing of the drug product for residual solvents need be considered. If, however, the calculated level is above the recommended level, the drug product should be tested to ascertain whether the formulation process has reduced the relevant solvent level to within the acceptable amount. A drug product should also be tested if a residual solvent is used during its manufacture. 虽然生产商们可能选择检测成药，但是也可以使用累加法，从用于生产成药的原料药的残
Where the limits to be applied comply with those given below, tests for residual solvents are not generally mentioned in specific monographs because the solvents employed may vary from one manufacturer to another. 在所适用的限度与下面所述相符的情况下，残留溶剂检测一般不在具体各论中提及，因为 每个生产商所使用的溶剂可能都不相同。
other quality-based requirements. Drug products should contain no higher levels of residual solvents than can be supported by safety data. Solvents that are known to cause unacceptable toxicities (Class 1, Table 1) should be avoided in the production of drug substances, excipients, or drug products unless their use can be strongly justified in a risk-benefit assessment. Solvents associated with less severe toxicity (Class 2, Table 2) should be limited in order to protect patients from potential adverse effects. Ideally, less toxic solvents (Class 3, Table 3) should be used where practical. The complete list of solvents included in this general chapter is given in Appendix 1. These tables and the list are not exhaustive. For the purposes of this Pharmacopeia, when a manufacturer has received approval from a competent regulatory authority for the use of a new solvent not currently listed in this general chapter, it is the responsibility of that manufacturer to notify the USP regarding the identity of this solvent, the approved residual solvent limit in the article, and the appropriate test procedure for this residual solvent in the article. The USP will then address this topic in the individual monograph. When a new solvent has been approved through the ICH process, this new solvent will be added to the appropriate list in this general chapter. At that time consideration will be given for removal of the specific solvent test requirement in the individual monograph. 由于残留溶剂不提供治疗作用，它们应当被尽可能地去掉，以达到原料药和成药质量标准、 药品优良生产规范、和其他质量控制要求。成药含有的残留溶剂应该不超过有安全数据所 支持水平。已知会产生不可接受的毒性（一类，表 1）的溶剂应该避免用于原料药、辅助 剂、成药的生产中，除非它们的使用得到了风险-收益评估的强力支持。毒性严重程度稍低 （二类，表 2）的溶剂应当被限制使用，以使病人远离潜在的不良反映。较理想的是，在 可行的地方使用毒性较低（三类，表 3）的溶剂。在本通则中包含的完整溶剂清单在附件 1 中给出。这些表格和溶剂清单并非全部。对于本药典而言，当某个生产商从具备能力的监 管当局收到了对使用目前本通则未列入的溶剂的许可时，该生产商有义务通知 USP 该溶剂 的鉴别、在物品中准许的残留溶剂限度、对于物品中残留溶剂的适当检测规程。然后，USP 将会在具体的各论中涉及此主题。当新溶剂通过 ICH 程序被批准，此新溶剂将会被加入到 本通则里的适当清单中。到那时，将会考虑去掉在具体各论中对具体残留溶剂的要求。
For pharmacopeial purposes, residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. The residual solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of a drug substance or an excipient may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Therefore, the solvent may sometimes be a critical element in the synthetic process. This general chapter does not address solvents deliberately used as excipients nor does it address solvates. However, the content of solvents in such products should be evaluated and justified. 在药典中，药物中的残留溶剂被定义为有机挥发性化学品，其用于或产生于原料药或辅助 剂的生产过程中，或成药的制备过程中。残留溶剂并未通过实际生产技术完全去除。适当 选择用于合成原料药或辅助剂的溶剂可以增加得率，或确定特性，例如结晶状态、纯度、 溶解性。因此，溶剂有时可以成为合成工艺中的重要部分。本通则并未涉及故意用于辅助 剂的溶剂，也未涉及溶剂化物。但是，在此类产品中的溶剂含量也应进行评估或论证。
The objective of this general chapter is to provide acceptable amounts of residual solvents in pharmaceuticals for the safety of the patient. The general chapter recommends the use of less toxic solvents and describes levels considered to be toxicologically acceptable for some residual solvents. 本通则的目的是为了保障病人的安全，提供在药物中残留溶剂的可接受数量。本通则建议 使用毒性较低的溶剂，并描述了对于某些残留溶剂而言其毒性可接受的数量水平。
Because residual soit, they should be removed, to the extent possible, to meet ingredient and product specifications, good manufacturing practices, or