转：USP:元素杂质修订常见问题解答

USP:元素杂质修订常见问题解答  

2014-06-03 11:01:51|  分类： USP|举报|字号 [url=]订阅[/url]

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Frequently Asked Questions: USP's Proposed Standards for Elemental Impurities

常见问题解答：USP提议的元素杂质标准

Q. Why is USP revising its standards for elemental impurities? 为什么USP要修订元素杂质标准？

A. USP is revising its standards for elemental impurities in the interest of better protecting public health. The revisions focus on two areas of work:

USP正在修订其元素杂质标准，以更好保护公众健康。修订集中在以下两方面：

• Updating the methodology used to test for elemental impurities in drugs and dietary supplements to include procedures that rely on modern analytical technology; and
• 更新用于药品和膳食补充剂中元素杂质的检测方法，以包括依靠现代化分析技术的检测方法；以及
• Establishing limits for acceptable levels of elemental impurities (including, but not limited to, lead, mercury, arsenic, and cadmium) in drugs and dietary supplements.
• 建立药品和膳食补充剂中各元素杂质的可接受标准限度（包括，但不限于，铅、汞、砷和镉）。
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Q. Why is any level of elemental impurities considered "acceptable?" Shouldn't the level always be zero? 为什么所有元素杂质都被认为是“可以接受”的？难道可接受水平不都应该是零吗？

A.The human body requires trace elements of many substances to function properly. For example, iron is an element that would be harmful or toxic beyond certain levels, but is frequently taken as a dietary supplement to help ensure healthy blood. The human body is also well suited to eliminate a small amount of most toxins. For most toxic elemental impurities, toxicologists have indicated that daily ingestion of low part-per-million levels constitutes a very low risk even in chronic applications.

人类身体需求一些物质痕量元素 以维持适当的功能。例如，铁是人体基本元素，但超出特定水平会有害或有毒，但作为膳食补充剂常规摄入会帮助保持身体血液健康。人体也有能力排除少量毒素，对于大多数有毒的元素杂质，毒理学家指出，日常摄入低PPM水平，即使是长期摄入其风险也是非常低的。

Additionally, the definition of "zero" or "absence" is very easy in a general sense (i.e. there are zero apples in a basket) but much more difficult from a measurement perspective. Requiring that "zero" molecules of an impurity may be present bases the standard on the technical ability to make the measurement rather than making it health based. Basing the standard on the best available detection technology may be prohibitively difficult for users to implement and not best serve public health.

另外，“零”或“未检出”的定义很容易给人一种感觉（即完全没有<篮子里一个苹果都没有>），但从方法学的角度来说这是很困难的。要求产品中的杂质分子数为“零”与其说是为了保证产品对健康无害，不如说更多是对技术能力的要求。将标准制订建立在现行最好的检测技术上可能会让使用者实施起来困难的令人望而却步，反而无法以最好的方式服务于公众健康。

Q. What is wrong or deficient about the current test methodology? 目前的检验方法有什么错误或缺陷吗？

A. The test methodology currently described in the USP–NF, was first introduced more than 100 years ago. The test can be difficult to conduct, and can fail to detect some important elementals such as mercury at toxicologically-relevant levels.

USP-NF目前的方法是100多年前引入的。该方法难以实施，可能无法检出在毒性相关水平的重要元素，例如汞。

Q. Why has USP waited until now to revise standards for elemental impurities? Was there a specific event that prompted the revision? 为什么USP等到现在才修订元素杂质的标准？是有什么特殊的事件推动此次修订吗？

A. USP undergoes regular re–evaluation and revision of all its standards to update their scientific and public health relevance. There was no specific event that triggered the revision of elemental impurities standards, but our scientific experts felt that the elemental impurity standards should be updated to incorporate modern methods and health information. As we have gained a better understanding of the limitations of the current methods, it has become clear that a revision is called for.

USP正在对所有标准进行常规的再评估和修订，将它们更新达到最新的科学和公众健康要求。并没有发生什么特殊的事件，引发对元素杂质标准进行修订，但是我们的科学专家觉得元素杂质标准应进行更新以迎合现代的检测方法和健康资料。由于我们对现行方法已经有了更好的了解，因此很明显需要对该通论进行修订。

Q. How is USP approaching the revision? USP是怎么修订该通论的？

A. USP is taking a risk–based approach that focuses on the likelihood of a given impurity being found in a drug or dietary supplement and on a consensus-based evaluation of the health implications of the impurity at levels that may be found. We have included toxicologists as well as chemists in the group of experts revising the standards to obtain the best available input on both health and methodology issues.

USP采用的是基于风险的方法，主要集中于在药品或膳食补充剂中发现的，可能存在的已知杂质；以及以共识为基础，评估可以发现的杂质水平对健康的影响。我们邀请了毒理学家和化学家加入专家团，对标准进行修订以达到健康和方法学方面最佳程度。

Q. What is the timing of the new standard? 新标准的实施时间表是什么？

A. USP's standards–revision process involves international collaboration among USP experts, industry, regulators, and the general public. When there is no specific medical emergency, as is the case with elemental impurities, it is beneficial to allow careful deliberation and scientific dialog to reach conclusions that are supported by a maximum number of interested stakeholders. In addition, where the new standards represent a significant change from existing standards, as is also the case with elemental impurities, it is important to provide sufficient time for manufacturers to incorporate the changes in their processes necessary to implement the new standards. The new elemental impurities standards, which are intended to replace the existing methods in General Chapter <231> Heavy Metals, are expected to be finalized sometime in 2010 and become official at a later date which has not yet been determined.

USP的标准---修订过程包括USP专家、制药企业、法规人员和民众的国际合作，如果没有特殊的与元素杂质有关的医疗事件，我们会慎重科学地进行讨论，并使结论获得最多涉险利益人的支持。另外，如果新的标准与现有标准差异太大，如元素杂质面临的情形，则需要让生产商有充分的时间来来实施必要的变更。新的元素杂质标准将要取代现有通论<231>“重金属”，预期会在2010年定稿，并在稍后时间正式实施，但实施时间尚未确定。

Q. Some in the pharmaceutical industry believe that USP is creating unrealistic, unworkable requirements for testing, which could lead to non–compliance and shortages of key medicines. For example, the article published in USP's Pharmacopeial Forum (PF) (2008, 34(5), page 1345) includes a list of 31 substances to be tested. And the proposed limits for each individual element may be unworkable across the many quality assurance labs that would be affected. 有些制药企业认为USP创建的检测要求不实际，无法实行，会导致不符合以及关键药品的短缺。例如，在USP药典论坛（2008, 34(5), page 1345）中包括了要检测的31种物质清单；而所建议的每个单个元素的限度可能对许多受到影响的化验室来说无法执行。

A. USP does not intend to burden industry with unwieldy and unnecessary testing requirements. The list in the PF article was intended as a proposal for discussion. As the revision moved forward, that list has been shortened. USP will not mandate the methodology that each lab must use. Manufacturers will have the flexibility to choose a test that best fits their processes.

USP并不准备采用不方便和不必要的测试要求来增加企业的负担。在药典论坛上列出的清单是讨论用的，随着修订深入，清单会缩短。USP不会强制要求各化验室实施某一方法。生产商可以自由选择最适合其工艺的方法。

Q. The proposed leeway for manufacturers to choose their own test methods is attractive because of the added flexibility. But doesn't that expose manufacturers to added risk of FDA rejection? 提议给生商有选择自己的方法的余地，似乎很有吸引力，因为它增加了一些执行的弹性。但是，这是否使得生产商被FDA拒绝的风险增加了呢？

A. Potentially, but USP is going to great lengths to work with both FDA and industry to ensure widespread agreement on interpretation of the revised standard. And the revision will include two referee methods, which manufacturers can choose from if they want to ensure a means of demonstrating unquestioned compliance to the standard.

可能的，但是USP将不遗余力地与FDA和制药行业一起努力来保证对修订后的标准的解释获得广泛的同意。修订会包括两个参考方法，如果生产商想要保证其方法完全符合标准，可以在两者中选择其一。

Q. Have imports posed an increased problem with elemental impurities? How is USP dealing with this? 进口产品是否在元素杂质方面的问题有增长趋势？USP如何处理这个问题呢？

A. To date, there have been no known incidents involving elemental impurities in pharmaceuticals. However, there are continuing concerns above the quality of imports. Ultimately, manufacturers are responsible for assuring conformance to FDA requirements and USP standards, no matter what the source. As more ingredients are sourced abroad, the presence of modern, scientifically sound quality standards will help protect both manufacturers and patients in the United States.

到目前为止，在进口药品方面并没有发生与元素杂质有关的事件。但是，对进口产品的质量我们会持续关注。从根本上来说，不论产品产地是哪里，生产商均要保证符合FDA要求和USP标准。由于越来越多的药品成分从国外进口，制订更现代化、科学合理的质量标准有助于保护美国生产商和患者的利益。

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