【分享】USP药典通则<231>重金属修订情况

2. Provides limits of metal catalysts that can be added in the production of a drug substance or excipient.

提供生产原辅料时加入的金属催化剂限度

–PDE: 100-2500 ugfor oral dose, parental dose 10 times less

–每日最大摄入量100-2500 微克，注射剂限量小10倍

–Conducted only when these elements are added during the manufacture of the article.

–只关注生产过程中加入的元素


<232> Elemental Impurities –Limits

<232> 元素杂质–限度

Describes three separate options for determination of compliance to the limits、

提供了三种符合限度规定的方案

􀂋Drug Product Analysis Option

药品制剂分析方案

􀂋Individual Component Option

单个组分方案

􀂋Summation Option

总和方案


<233> Elemental Impurities-Procedures

<233>元素杂质–测试步骤

1.Details two procedures 具体描述了两种测试步骤

–ICP-OES with closed-vessel microwave digestion

–ICP-发射光谱及微波消解

–ICP-MS with closed-vessel microwave digestion

–ICP-MS及微波消解

2.Provides criteria for the approval of alte-rnative procedures for the measurement of elemental impurities.

提供了测量元素杂质替代性方法接受标准


<2232> Elemental Contaminants in Dietary Supplements

<2232> 膳食补充剂中的污染元素

1. Focus on the four most toxic and well-understood metals (As (inorganic), Pb, CdHg(total) and Methylmercury).

重点关注已知的4种最具毒性元素（As （无机），Pb, Cd，Hg （总和）和甲基汞）

–Oral limits similar to those presented in General Chapter 232. PDE range from 5-15ug/day.

–口服限度与通则232类似，每日最大摄入量5-15 微克

–PDE of Methylmercuryis 2ug/day

–甲基汞每日最大摄入量2微克

2. Describes three separate options for determination of compliance to the limits-Dietary Supplement Analysis Option, Individual Component Option, Summation Option

提供了膳食补充剂三种符合限度规定的方案, 分析方案，单组份方案，及总和

3. Speciation of specific elements of particular concern for dietary supplements.

对某些特定元素需关注形态

–For As, non speciation procedure may be used. If limit is exceeded, then a speciation procedure shall be performed to demonstrate compliance测As时可使用无形态的步骤，如果超出限度，则需要用测形态的步骤

–For Hg, methylmercuryspeciation procedure is not necessary if content of total Hg is less than methylmercurylimit (2ug/day）

–测Hg时如总汞不超过甲基汞（2微克/天)的限度，那么不需要用测形态的步骤进行测量



Impact of <231> Revision

<231>修订的影响

1.Scope 范围

􀂋<232> applies to drug substances and products including natural-source and rDNAbiologics, ophthalmics, parenteralnutrients, and excipients.

􀂋<232>适用于原料药及制剂并包括天然产物，DNA重组，眼科，注射营养及辅料

􀂋<2232> covers dietary supplements and ingredients.

􀂋<2332>涵盖膳食补充剂及其原料

2.Implementation 实施

􀂋Recommend an official date that coincides with the official date of the EMEA Metal Catalyst guideline (Sept. 2013).

推荐在2013年9月实施，与EMEA金属催化剂指南实施日期相同



Up-date on Harmonization of <231> Revision

国际统一协调近况

•USP is discussing these chapters with EP and JP as part of the PDG harmonization effort. The development of two chapters to replace <231> was exe-cuted on the advice of EP to allow an easier route to accomplish a harmonized standard.

USP正在与EP，JP讨论这些通则。USP正是在EP的建议下用两个通则替代原来的<231>通则以使将来标准协调更容易

•General Chapter <232> incorporates the limits described in the EMEA guidance as Class 2 impurities.

通则<232>将EMEA指南中所列限度收录为二类杂质

•EMEA/EDQM/JP have fully participated in either the Advisory Panel or USP workshop on this topic.

•EMEA/EDQM/JP积极参与了该议题的顾问组或研讨会

太好啦！谢谢！