USP残留溶剂常见问题Q&A

本文来源于USP官方网站，特此声明。
Q1.What are USP’s expectations relating to General Chapter<467> between now and July 1, 2008 and after July 1, 2008 for all pharmaceutical companies?
提问:在 2008年7月1日前后，USP预期通则<467>对制药企业会有怎样的影响？
A:The USP General Notices require all products to meet the requirements in General Chapter<467> by July 1, 2008. The purpose of the chapter is to limit the amount of solvent that patients receive.
回答:USP凡例要求所有的制剂产品在2008年7月1日后需符合通则<467>规定。本通则的目的是限制病人服药时摄入的有机溶剂量。
Q2.Are dermatological products and topical products required to comply with <467>?
提问:治疗皮肤病产品和外用产品要符合<467>吗？
A:USP defers to FDA on enforcement questions, but the chapter does include language indicating that in some cases the ICH limit may not be appropriate.This language is not specific to dermatological and topical products.
回答:在执行问题上USP遵照FDA的要求，但本通则的确包含文字说明某些情况下ICH限度可能是不适宜的。该文字不特别针对治疗皮肤病产品和外用产品。
Q3.Protein manufacturers do not use solvents in their manufacturing processes. What are the expectations with regards to <467> in proteins?
提问:蛋白生产商在其生产工艺中不使用有机溶剂，通则<467>对蛋白质产品有什么规定吗？
A:The chapter states that no testing is required if you know that solvents are not present.However, it is always prudent to evaluate your starting materials and finished product.
回答:本章节已声明，若(生产商)确定产品不存在有机溶剂，则不需任何残留溶剂测试，然而，谨慎的做法是评估起始物料和最终产品。
Q4.Is it possible that USP will consider setting standards for residual solvents in packaging components?
提问:USP可能会在未来考虑建立包装组件残留溶剂的标准吗？
A:Residual solvents in packaging are not addressed by this chapter. We are aware of extractables and leachables, and we may consider this aspect in the future.
回答:本通则不包括包装材料的残留溶剂。目前我们意识到了溶出物和析出物议题，并考虑未来在此方面建立标准。(目前，USP已在药典论坛发布有关提取物和可浸出物的提议通则)
Q5.ICH Q3C does not apply to existing commercial drug product. Please confirm that the USP requirement applies to all existing commercial drug products.
提问:ICH Q3C不适用于现有市售药品。请确认USP的规定适用于所有现有市售药品。
A:That is correct. USP sees no reason to exclude product from the <467>requirements, as the goal is to limit residual solvents in all products.
回答:以上阐述是正确的，USP认为没有理由把制剂产品从<467>规定中剔除，因为此项检查的目的是限制所有产品中的残留溶剂。
Q6.Is it accurate to state that <467> applies only to products that are labeled "USP" or "NF", and that if the substance or product is not labeled "USP" or "NF", then<467> is only guidance?
提问:以下表述是否正确：<467>只适用于标明“USP”或“NF”的产品，若产品未标明“USP”或“NF”，则<467>仅作为指导原则。
A:No. If the product or substance is covered by a USP or NF monograph, the monograph standards and the General Notices apply, whether or not it is labeled "USP" or"NF", The General Notices requirement that the substance or product comply with <467> applies to all substances and products covered by USP and NF monographs.
回答:以上表述是错误的。如果某制剂产品或药用原料收载于USP各论和NF各论中，则无论是否标明“USP”或“NF”，均应符合各论标准和凡例，凡例要求药用原料或制剂产品符合<467>的规定适用于收载于USP各论和NF各论中的所有药用原料和制剂产品。
Q7.<467> applies to the drug product. Are manufacturers of finished products required to test the active ingredient and the excipients?
提问:<467>适用于制剂产品。最终产品生产商需测试活性成分和辅料吗？
A:<467> gives you the option of testing either all of the individual components or the final finished product.
回答:<467>要求用户自己决定测试所有单个成分还是最终产品。
Q8.If we use Water for Injection for dilution of drug substances to make drug products, do we need to test Water for Injection for residual solvents?
提问:如果在原料药制成制剂产品时使用注射用水作为稀释剂，我们还需要测试注射用水的残留溶剂吗？
A:If you don't use any of the solvents listed in the manufacture of Water for Injection,<467> does not require you to test the water for solvents.
回答:如果注射用水生产过程中未使用到<467>列表中的任何有机溶剂，则<467>不要求进行此项测试。
Q9.How do the <467> requirements apply to animal health items, if at all? Will the chapter apply to veterinary products in the future?If so, when?
提问:如果可能的情况下，<467>的规定怎样适用于动物保健产品？该通则在未来会适用于动物用药吗？如果会，具体时间是？
A:The <467>requirements apply to items for veterinary use. However, the current limits are based on human use and limits for different species of animals probably would need to be different.
回答:<467>规定适用于动物用产品。然而，目前通则中的限度是基于人类使用而设定的，不同种类动物的限度会有所不同。
Q10.What about material that is not an API or Excipient, but is a material used in the API, or a salt or hydrochloric acid? Q3C does not address the issue of raw materials used in an API.
提问:对于非活性药用成分或辅料但用于活性药用成分的物质，盐或盐酸，通则有怎样的规定?ICH Q3C不涉及活性药用成分中的原始物料。
A:The bottom line is to assure the material that is going out to patients does not harm them. If you do option 1, this test takes care of the solvent issues for these materials. It's up to the manufacturer to make sure the product complies withthe limits for solvents.
回答:控制残留溶剂的最基本要求是确保病人服用的物质不会对其健康造成危害。如果您选择“选项1”（通则中关于“二类残留溶剂描述限度的选项之一），该测试关注这些物质的有机溶剂问题。应当由生产商保证其产品符合残留溶剂限度要求。
Q11.Do we need to confirm that no solvent contamination occurs during packaging or repackaging?
提问:我们是否需要确认在包装和分装过程中不存在有机溶剂污染问题？
A:The chapter covers only those solvents used in the manufacturing process. Accidental contamination during packaging, handling, or shipping should be managed through good handling and shipping practices.
回答:本通知只涵盖了在生产过程中使用的有机溶剂。应通过良好处理规范和良好运输规范管理在包装，处置，运输过程中的意外污染。
Vendor Materials（供应商物料）
Qo we need to perform a complete residual solvent analysis to verify the information provided by our vendor?
提问:是否需要进行完整的残留溶剂分析来确认物料供应商提供的信息？
A:It is up to the manufacturer to determine whether or not to test. The decision may depend on the confidence and the relationship between the manufacturer and supplier. The manufacturer may choose to audit the vendor.
回答:应由生产商决定是否进行测试。做该决定取决于生产商和供应商之间的信任度和关系。生产商可选择对供应商做审计。
USP Methods（USP方法）
Q1:What is the history/source of the USP method? Could the USP make changes to the method in the future?
提问:USP方法的建立背景和来源是什么？未来USP可能会改变方法吗？
A:USP's primary source for these methods is the European Pharmacopeia (EP) method. The USP is under continuous revision, and we make changes to the methods to improve existing procedures or to allow the user to obtain better results. USP may revise this chapter in response to additional comments received.
回答:USP方法的主要来源是《欧洲药典》方法。USP对方法进行持续修订，并对方法持续变更以优化现有测试方法或让用户得到更合理的结果。USP基于其他收到的评议对本通则进行修订。
Q2:Chromatographic question: How does USP propose to deal with peak co—elutions in the current proposed chapter?
提问:色谱问题：USP如何处理在当前提议通则中出现色谱峰同时洗脱的问题？
A:There are two procedures, A&B. These procedures provide orthogonal separation. For quantitative analysis, A is preferred, but B should be used if A does not work (for instance, due to co—eluting peaks).
回答:有两种测试方法，方法A和方法B，该方法可实现正交分离。对于定量分析，推荐方法A，但若方法A无效时（例如色谱峰同时洗脱），应采用方法B。
Q3: What happens to peaks in sample that are non—target solvent peaks?
提问:样品中的色谱峰是非目标溶剂峰怎么办？
A:If you come up with an unexpected peak while looking for a specific solvent, use good science to identify the peak and work with a toxicologist for the acceptable level in that material.
回答:若在检查某种有机溶剂时发现了未知峰(非目标峰)，应基于良好的科学技术和理念鉴别该峰，并与毒理学家协作确定样品中该未知成分的可接受限度水平。
Q4uring method development, did USP experiment with"salting" agent for the headspace analysis? If so, what did you find as far as efficacy for increasing responses — or "inefficacy"?
提问:在方法开发阶段，USP会在顶空进样分析时使用“成盐类”试剂吗？若使用，在提高响应有效性上有何发现？或使用后结果证明“无效”？
A:USP did not experiment with salting agents because we found that method as written providesacceptable sensitivity.
回答:USP在该测试方法中未使用成盐试剂，因为USP科学家发现通则中收录的方法具有符合要求的灵敏度。
Q5:How do you suggest testing a product that only has class 3 solvents present that cumulatively are greater than 0.5%? Example:
Ethanol 0.3%
Ethyl Ether 0.2%
1—propanol 0.3%
提问:USP对测试一个只含有三类溶剂，且其累计含量超过0.5% 的产品有什么建议？该产品残留溶剂含量分别为：乙醇 0.3%；乙酸乙酯 0.2%；正丙醇 0.3%
A:It is not appropriate to use Loss on Drying (LOD) if the amount of class 3 solvent exceeds 0.5%. In those cases, gas chromatography should be used. If you have process validation information indicating that you can reduce the amount of class 3 solvent to 0.5% or lower in the final product, you can discuss with FDA the possibility of using LOD.
回答:若三类溶剂总量大于0.5%，使用干燥失重方法是不适宜的。在这种情况下，应使用气相色谱方法。若用户有工艺验证信息表明在最终产品中可将三类溶剂总量降至0.5%或更低，用户可与FDA讨论使用LOD方法的可能性。
Q6:If a material has class 3 and Class 1 or 2 solvents in it,what is the USP method, since procedures A, B, and C are only for class 2 solvents and Loss on Drying (LOD) is only for class 3?
提问:若一种物料含三类溶剂以及一类或二类溶剂中的一种，应采用哪种USP测试方法。因为方法A，B和C只适用于二类溶剂，干燥失重法只适用于三类溶剂？
A:If you have a Class 3 solvent and either a Class 1 or 2 solvent, use LOD to demonstrate acceptance in class 3 as long as LOD result is not more than 0.5%. If it is more than 0.5%, use gas chromatography to demonstrate compliance
回答:若您的产品中含三类溶剂以及一类溶剂或二类溶剂中的一种，只要干燥失重法的测试结果不超过0.5%，则应采用干燥失重法证明三类溶剂符合限度规定。若测试结果超过0.5%，应采用气相色谱法确认产品是否符合药典规定。
Harmonization(药典协调)
Q1:If USP is working to harmonize USP General Chapters, why doesn't USP completely harmonize <467> with the EP before implementing the chapter?
提问:若USP正在致力于《美国药典》通则的协调工作，为什么USP在执行前不完全将本通则与《欧洲药典》做完全地协调呢？
A:There are only minor differences between the USP and EP methods. The reference standard mixtures are different in the USP. Also, the calculation is different. In the USP, methods A and B are limit tests, method C is a quantitative test. Other than those minor changes, the chapter is harmonized.
回答:《美国药典》与《欧洲药典》方法仅存在较小的差异。《美国药典》中标准品混合物与之不同。同时，计算方法亦不相同。在《美国药典》中，方法A和方法B是限度测试，方法C是定量测试。除了以上小的变动外，本通则与《欧洲药典》对应章节是协调一致的。
Q2:Industry has just finished implementing ICH Q3C to meet European regulatory expectations. Can the USP clarify what is additionally expected to achieve compliance with <467>?
提问:业界刚刚完成执行ICH Q3C以符合欧洲监管机构的规定，USP能否阐明符合通则<467>会达到何种目的？
A:ICH appliesonly to new products. <467> applies the same requirements to all existing products covered by USP monographs.
回答:ICH只适用于新产品。<467>适用于收载于USP各论中的所有产品。
Changes to Methods(改变方法)
Q1:The USP method shows less recovery for some of the solvents. Will USP propose                   recovery correction factor for calculations?
提问:USP方法在测定某些有机溶剂时回收率较低。USP是否将提出计算用回收率校正因子？
A:When using procedure C, a spiked solution will compensate for the differences in recovery.
回答:在使用方法C时，加标溶液可弥补回收率差异。
Q2:Would USP consider separating methods in <467> to a separate chapter?
提问:USP会考虑将<467>中的方法抽离出来单独建立一篇通则吗？
A:This has not been discussed internally yet.
回答:目前USP还没有讨论过此议题。
Alternative Methods(替代方法)
Q1:Can USP add a statement to <467> that will provide companies the flexibility to use the USP method or their own validated procedure?
提问:USP能否增加一项针对<467>的声明，给予企业使用USP方法或企业自己已验证方法的灵活性？
A:The General Notices also allow for the use of other validated methods.
回答:凡例规定允许采用其他经过验证的方法。

感谢楼主分享，这种中英文对照的文献都很不错的。