2024年2月28日发(作者：壬歆)
EP 51000 药用物质的杂质控制（中英文）
(2014-06-06 16:50:06)
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分类： 食品药品
51000E 药用物质的杂质控制
04/2012:51000
5.10. CONTROL OF IMPURITIES IN SUBSTANCES FOR PHARMACEUTICAL
USE 药用物质的杂质控制
Preamble 前言
The monographs of the European Pharmacopoeia on substances for pharmaceutical
use are designed to ensure acceptable quality for users. The role of the
pharmacopoeia in public health protection requires that adequate control of impurities
be provided by monographs. The quality required is based on scientific, technical and
regulatory considerations.
欧洲药典对药用物质的各论是设计以保证其达到用户可接受品质的。药典在公众健康保护中的作用是要求对各论中所列的杂质进行充分控制。这些所要求的品质是基于科学、技术和法规的考虑的。
Requirements concerning impurities are given in specific monographs and in the
general monograph Substances for pharmaceutical use (2034). Specific monographs
and the general monograph are complementary: specific monographs prescribe
acceptance criteria for impurities whereas the general monograph deals with the need
for qualification, identification and reporting of any organic impurities that occur in
active substances.
在各论中和通论2034（药用物质）中给出的杂质要求是互补的：各论描述各杂质的可接受标准，而通论指出所有在活性物质中出现的有机杂质的界定、鉴别和报告阈值。
The thresholds for reporting, identification and qualification contained in the general
monograph Substances for pharmaceutical use (2034) apply to all related substances.
However, if a monograph does not contain a related substances test based on a
quantitative method, any new impurities occurring above a threshold may be
overlooked since the test is not capable to detect those impurities.
在通论2034（药用物质）中的报告阈、鉴别阈和界定阈适用于所有有关物质。但是，如果各论中没有有关物质的定量检测方法，则需要关注所有在阈值以上的新杂质，因为该方法无法检测到这些杂质。
The provisions of the Related substances section of the general monograph
Substances for pharmaceutical use (2034), notably those concerning thresholds, do
not apply to excipients; also excluded from the provisions of this section are:
biological and biotechnological products; oligonucleotides; radiopharmaceuticals;
fermentation products and semisynthetic products derived therefrom; herbal products
and crude products of animal and plant origin. Although the thresholds stated in the
general monograph do not apply, the general concepts of reporting, identification
(wherever possible) and qualification of impurities are equally valid for these classes.
通论2034（药用物质）中“有关物质”条款，特别是那些关于阈值的内容，不适用于辅料，也不适用于以下品种：生物和生物技术产品、寡聚核苷酸、放射药品、发酵产品和半合成产品及其衍生物、草药制品和动植物来源粗品。尽管在通论中的阈值并不适用，关于杂质报告阈、鉴别阈（可能时）和界定阈对这些品种仍然有效。
Basis for the elaboration of monographs of the European Pharmacopoeia 欧洲药典各论起草的基础
European Pharmacopoeia monographs are elaborated on substances that are
present in medicinal products that have been authorized by the competent authorities
of Parties to the European Pharmacopoeia Convention. Consequently, these
monographs do not necessarily cover all sources of substances for pharmaceutical
use on the world market.
欧洲药典各论是针对用于由欧洲药典委员会相关方药监局批准的药用产品的物质而起草的。因此，这些各论不一定包括在世界范围内使用的所有来源药用物质。
Organic and inorganic impurities present in those substances that have been
evaluated by the competent authorities are qualified with respect to safety at the
maximum authorized content (at the maximum daily dose) unless new safety data that
become available following evaluation justify lower limits.
这些物质里的有机和无机杂质已由适当的药监机构进行评估，认为其符合安全要求的最大许可含量（基于最大日服用量），除非有新的安全数据证明其可以采用更低的限度。
European Pharmacopoeia monographs on substances for pharmaceutical use are
elaborated by groups of experts and working parties collaborating with national
pharmacopoeia authorities, the competent authorities for marketing authorization,
national control laboratories and the European Pharmacopoeia laboratory; they are
also assisted by the producers of the substances and/or the pharmaceutical
manufacturers that use these substances.
欧洲药典中药用物质的各论由专家工作组和与国家药典机构合作的工作团队、适当的上市批准药监机构、国家控制实验室和欧洲药典实验室起草；同时还有物质的生产商和/或使用该物质的药品生产商进行协助。
Control of impurities in substances for pharmaceutical use 药用物质的杂质控制
The quality with respect to impurities is controlled by a set of tests within a monograph.
These tests are intended to cover organic and inorganic impurities that are relevant in
view of the sources of active substances in authorized medicinal products.
杂质的质量由各论中一系列的检测来控制。这些检查的需要包括用于批准的药用产品的活性物质中所有与来源有关的有机和无机的杂质，
Control of residual solvents is provided by the general monograph Substances for
pharmaceutical use (2034) and general chapter 5.4. Residual solvents. The certificate
of suitability of a monograph of the European Pharmacopoeia for a given source of a
substance indicates the residual solvents that are controlled together with the
specified acceptance criteria and the validated control method where this differs from
those described in general chapter 2.4.24. Identification and control of residual
solvents.
残留溶剂的控制在通论2034（药用物质）和通则5.4残留溶剂中给出。CEP会对特定来源的物质指明其中残留溶剂，及其可接受标准，如果检测方法与通则2.4.24残留溶剂的鉴别和控制不同，则会在CEP中列出。
Monographs on organic chemicals usually have a test entitled “Related substance”
that covers relevant organic impurities. This test may be supplemented by specific
test there the general test does not control a given impurity or where there are
particular reasons (for example, safety reasons) for requiring special control.
有机化学物的各论通常有一个检测项目称为“有关物质”，其中包括了有关的有机杂质。如果通用检测无法控制一个给定的杂质，或者有一些特殊原因，该测试可能需要其它特定的检测项目加以补充。
Where a monograph has no Related substances (or equivalent) test but only specific
tests, the user of a substance must nevertheless ensure that there is suitable control
of organic impurities; those occurring above the identification threshold are to be
identified (wherever possible) and, unless justified, those occurring above the
qualification threshold are to be qualified (see also under Recommendations to users
of monographs of active substances).
如果各论中没有“有关物质”项（或相当的项目），而只有特定检测项目，物质使用者必须保证有必要的方法来控制有机杂质。凡高于鉴别阈的杂质需要进行鉴别（只要可能），除非经过论证，凡高于界定阈的杂质需要进行界定（参见本通论“对活性物质各论使用者的建议”部分）
Where the monograph covers substances with different impurities profiles, it may
have a single related substances test to cover all impurities mentioned in the
Impurities section or several tests may be necessary to give control of all known
profiles. Compliance may be established by carrying out only the tests relevant to the
known impurity profile for the source of the substance.
如果各论包括了不同杂质概况的物质，可能有一个单独的有关物质检测包括在杂质部分提及的所有杂质，或可能需要几个不同的检测方法对所有已知杂质概况进行控制。如要证明物质符合要求，可能只需要根据所采用工艺分析物质的杂质概况，采用针对该杂质概况的检测方法即可。
Instructions for control of impurities may be included in the Production section of a
monograph, for example where the only analytical method appropriate for the control
of a given impurities is to be performed by the manufacturer since the method is too
technically complex for general use or cannot be applied to the final drug substance
and/or where validation of the production process (including the purification step) will
give sufficient control.
对杂质控制要求可能包括在各论的生产部分，例如，如果仅有一个分析方法适用于某给定的杂质，生产商需要采用该方法检测，但该方法技术太复杂，无法普遍使用，或无法应用于原料药成品和/或生产工艺验证（包括精制步骤）可能会给出足够的控制。
Impurities section in monographs on active substances 活性物质各论的杂质部分
The Impurities section in a monograph includes impurities (chemical structure and
name wherever possible), which are usually organic, that are known to be detected by
the tests prescribed in the monograph. It is based on information available at the time
of elaboration or revision of the monograph and is not necessarily exhaustive. The
section includes specified impurities and, where so indicated, other detectable
impurities.
各论中的杂质部分包括杂质（可能时会列出化学结构和名称）通常为无机物，可以由各论的方法检测出。这是基于在各论起草或修订时已有的信息，不一定包括了所有杂质。这部分包括了已识别杂质和，如果有指出，其它可检出杂质。
Specified impurities have an acceptance criterion not greater than that authorized by
the competent authorities.
已识别杂质可接受标准应不大于相关药监机构指定的限度。
Other detectable impurities are potential impurities with a defined structure but not
known to be normally present above the identification threshold in substances used in
medicinal products that have been authorized by the competent authorities of Parties
to the Convention. They are given in the Impurities section for information.
在被相关药监机构批准的药品中使用的物质中，其它可检出杂质是一些具有已知结构的潜在杂质，但并通常不在鉴别阈以上。这些杂质信息在杂质部分给出供参考。
Where an impurity other than a specified impurity is found in an active substance it is
the responsibility of the user of the substance to check whether it has to be
identified/qualified, depending on its content, nature, maximum daily dose and
relevant identification/qualification threshold, in accordance with the general
monograph on Substances for pharmaceutical use (2034), Related substances
section.
如果在活性物质中发现有特定杂质以外的杂质，活性物质的使用者应根据通论2034（药用物质）有关物质部分的要求，检查是否需要对该杂质地鉴别/界定，判定的依据是其成份、特性、最大日服用量或相应的识别/界定阈。
It should be noted that specific thresholds are applied to substances exclusively for
veterinary use.
需要注意的是识别阈不适用于兽用物质。
Interpretation of the test for related substances in the monographs on active
substances
活性物质各论中有关物质检测的解释
A specific monograph on a substance for pharmaceutical use is to be read and
interpreted in conjunction with the general monograph on Substances for
pharmaceutical use (2034).
药用物质的各论应与通论2034（药用物质）结合解读。
Where a general acceptance criterion for impurities (“any other impurity”, “other
impurities”, “any impurity”) equivalent to a nominal content greater than the applicable
identification threshold (see the general monograph on Substances for
pharmaceutical use (2034)) is prescribed, this is valid only for specified impurities
mentioned in the Impurities section. The need for identification (wherever possible),
reporting, specification and qualification of other impurities that occur must be
considered according to the requirements of the general monograph. It is the
responsibility of the user of the substance to determine the validity of the acceptance
criteria for impurities not mentioned in the Impurities section and for those indicated
as other detectable impurities.
如果杂质的通用可接受标准（“其它单杂”、“其它杂质”、“任何杂质”）等同的名义浓度大于所适用的鉴别阈（见通论2034药用物质）中所述水平，则该标准仅对杂质部分提到的特定杂质有效。对于存在的其它杂质，其鉴别阈（可能时）、报告阈、质量标准和界定阈应根据通论要求进行考虑。物质使用者有责任决定在杂质部分未提及的杂质和其中指出的其它可检出杂质的可接受标准是否有效。
Acceptance criteria for the related substances test are presented in different ways in
existing monographs; the decision tree (Figure 5.10-1) may be used as an aid in the
interpretation of general acceptance criteria and their relation with the Impurities
section of monograph.
有关物质检测方法的可接受标准在已有各论中以不同方式表现。在解读通用可接受标准和其与各论中杂质部分的关系时可以利用图5.10-1的决策树。
General acceptance criteria for “other” impurities are expressed in various ways in the
monographs: “any other impurity”, “other impurities”, “any impurity”, “any spot”, “any
band”, etc. The general acceptance criteria may apply to certain specified impurities
only or to unspecified impurities and certain specified impurities, depending on the
nature of the active substance and the applicable identification threshold. Pending
editorial adaption of already published monographs using unequivocal terminology,
the decision tree (Figure 5.10-1) may be used to determine the acceptance criterion to
be applied.
“其它”杂质的通用可接受标准在各论中以不同方式表达：“其它单杂”、“其它杂质”、“任何杂质”、“任何斑点”、“任何波长”等。通用可接受标准可能只用于某些特定杂质，或用于非特定杂质，以及某此特定杂质。这种情况下取决于活性物质特性和所采用的鉴别阈。已出版的各论中待定编辑性内容如果采用了明确的术语，可以应用5.10-1的决策树来决定可接受标准。
Recommendations to users of monographs of active substances 给活性物质各论使用者的建议
Monographs give a specification for suitable quality of substance with impurity profiles
corresponding to those taken into account during elaboration and/or revision of the
monograph. It is the responsibility of the user of the substance to check that the
monograph provide adequate control of impurities for a substance for pharmaceutical
use from a given source, notably by using the procedure for certification of suitability
of the monographs of the European Pharmacopoeia.
如果各论中给出了适当品质的物质的质量标准，其中包括了在各论起草和/或修订时考虑的杂质概况。物质使用者有责任检查各论对其所用的给定来源的药用物质中的杂质控制是否充分，特别是采用CEP程序时。
A monograph with a related substances test based on a quantitative method (such as
liquid chromatography, gas chromatography and capillary electrophoresis) provides
adequate control of impurities for a substance from a given source if impurities
present in amounts above the applicable identification threshold are specified
impurities mentioned in the Impurities section.
如果各论中有关物质检测是采用定量方法（例如液相色谱、气相色谱和毛细管电泳），可以对已知生产工艺的物质中的杂质进行充分的控制，如果所检出的高于适用的鉴别阈的杂质是在杂质部分已提及的特定杂质。
If the substance contains impurities other than those mentioned in the Impurities
section, it has to be verified that these impurities are detectable by the method
described in the monograph, otherwise a new method must be developed and
revision of the monograph must be requested. Depending on the content found and
the limits proposed, the identification and/or the qualification of these impurities must
be considered.
如果物质中含有杂质未提及的杂质，则需要确认这些杂质是否可以被各论中的方法所检出，如果不能，则必须开发新的检测方法，申请修订各论。根据所发现的杂质含量和提议的限度，需要考虑这些杂质是否要进行鉴别和/界定。
Where a single related substances test covers different impurity profiles, only
impurities for the known profile from a single source need to be reported in the
certificate of analysis unless the marketing authorization holder uses active
substances with different impurity profiles.
如果单个有关物质检测方法包括了不同的杂质概况，除非上市许可持有人所用的活性物质具有不同的杂质概况，则在检验报告中只需要报告已知杂质概况中的杂质。
Identification of impurities (peak assignment) 杂质的鉴别（峰识别）
Where a monograph has an individual limit for an impurity, it is often necessary to
define means of identification, for example using a reference substance, a
representative chromatogram or relative retention. The user of the substance may
find it necessary to identify impurities other than those for which the monograph
provides a means of identification, for example to check the suitability of the
specification for a given impurity profile by comparison with the Impurities section. The
European Pharmacopoeia does not provide reference substances, representative
chromatograms or information on relative retentions for this purpose, unless
prescribed in the monograph. Users will therefore have to apply the available scientific
techniques for identification.
如果各论中有某杂质的限度，通常需要定义该杂质的鉴别方法。例如，采用对照品，代表性图谱或相对保留时间。药用物质的使用者可能会发现有必要对各论中未提供鉴别方法的杂质进行鉴别，例如通过与各论杂质部分进行比较来检查质量标准是否适用某个特定的杂质谱。除非在各论中的描述，否则欧洲药典不会为了该目的而提供对照物质、代表性图谱或相对保留时间信息，因此使用者需要采用可获得的科学技术对杂质进行鉴别。
* The requirements of this section apply to active substances, with the exception of:
biological and biotechnological products; oligonucleotides; radiopharmaceuticals;
products of fermentation and semi-synthetic products derived therefrom; crude
products of animal or plant origin; herbal products.
本部分的要求适用于活性物质，以下品种除外：生物和生物技术产品、寡聚核苷酸、放射药品、发酵产品和半合成产品及其衍生物、草药制品和动植物来源粗品。
**To apply the Related substances section of the monograph Substances for
pharmaceutical use (2034): 在应用药用物质各论中有关物质部分时
—
an individual acceptance criterion must be defined for any impurity that may be
present above the identification threshold;
—
对可能会高于鉴别阈的单个任意杂质必须设定可接受标准
—
any impurity with an acceptance criterion above the identification threshold must
wherever possible be identified;
—
任何可接受标准高于鉴别阈的杂质，只要可能均应进行鉴别
—
any impurity with an acceptance criterion above the qualification threshold must
be qualified.
—
任何可接受标准高于界定阈的杂质需要进行界定
Figure 5.10-1—Decision tree for interpretation of general acceptance criteria for „other‟
impurities in monographs
图5.10-1---各论中“其它”杂质可接受标准解读决策树
New impurities/Specified impurities above the specified limit 高于指定限度的新杂质/特定杂质
Where a new manufacturing process or change in an established process leads to the
occurrence of a new impurity, it is necessary to apply the provisions of the general
monograph on Substances for pharmaceutical use (2034) regarding identification and
qualification and to verify the suitability of the monograph for control of the impurity. A
certificate of suitability is a means for confirming for a substance from a given source
that the new impurity is adequately controlled or the certificate contains a method for
control with a defined acceptance criterion. in the latter case revision of the
monograph will be initiated.
如果新的生产工艺或对已有工艺变更导致出现新杂质，则需要应用通论2034（药用物质）中鉴别阈和界定阈，确认各论是否适于控制其中杂质。CEP是一种手段来证明某种工艺生产出的物质中的新杂质均已被充分控制，或者可以在证书中包括一个控制方法及可接受标准。在后一种情况下，需要启动对各论的修订。
Where a new manufacturing process or change in an established process leads to the
occurrence of a specified impurity above the specified limit, it is necessary to apply
the provisions of the general monograph on Substances for pharmaceutical use (2034)
regarding qualification.
如果新的生产工艺或对已有工艺的变更导致特定杂质高于识别限，则需要应用通论2034（药用物质）进行中界定的概念。
Expression of acceptance criteria 可接受标准的表达方式
The acceptance criteria for related substances are expressed in monographs either in
terms of comparison of peak areas (comparative tests) or as numerical values.
各论中有关物质的表达方式可以是与峰面积的比较（面积对照试验），也可以是数值。
Chromatographic methods 色谱方法
General chapter 2.2.46. Chromatographic separation techniques deals with various
aspects of impurities control.
通则2.2.46色谱分离技术介绍了杂质控制的各方面信息。
Information is available via the EDQM website on commercial names for columns and
other reagents and equipment found suitable during monograph development, where
this is considered useful.
在EDQM网站上可以查到在各论研究期间发现适用的各色谱柱的商品名，其它的试剂和仪器等有用的信息。
GLOSSARY 术语
Disregard limit: 忽略限
In chromatographic tests, the nominal content at or below which peaks/signals are not
taken into account for calculating a sum of impurities. The numerical values for the
disregard limit and the reporting threshold are usually the same.
在色谱检测中，等于或低于该峰值/信号值即不计算总杂质的名义含量。忽略限的数值一般与报告阈值相同。
Identification threshold: 鉴别阈
A limit above which an impurity is to be identified.
达到即需要进行鉴别的杂质水平。
Identified impurity 已鉴别的杂质
An impurity for which structural characterization has been achieved.
已进行了结构确证的杂质。
Impurity 杂质
Any component of a substance for pharmaceutical use that is not the chemical entity
defined as the substance.
任何存在于药用物质中但并不是该物质的化学主体的成份，
Nominal concentration 名义浓度
Concentration calculated on the basis of the concentration of the prescribed reference
and taking account of the prescribed correction factor.
在已知的对照品浓度基础上计算出的浓度，考虑到已知的校正因子。
Other detectable impurities 其它可检出杂质
Potential impurities with a defined structure that are known to be detected by the tests
in a monograph but not known to be normally present above the identification
threshold in substance used in medicinal products that have been authorized by the
competent authorities of Parties to the Convention. They are unspecified impurities
and are thus limited by a general acceptance criterion.
可能存在于已由药监机构批准用于药品生产的物质中，按药典方法检测可以被检出，但通常不会超出鉴别阈的已知结构杂质。这类杂质为非特定杂质，因此由通用可接受标准进行限度规定。
Potential impurity 潜在杂质
An impurity that theoretically can arise during manufacture or storage. it may or may
not actually appear in the substance. Where a potential impurity is known to be
detected by the tests in a monograph but not known to be normally present in
substances used in medicinal products that have been authorized by the competent
authorities of Parties to the Convention, it will be included in the Impurities section
under Other detectable impurities for information.
在生产工艺或存储过程中，从理论上分析可能会产生的杂质，实际可能出现，也可能不出现。
Qualification 界定
The process of acquiring and evaluating data that establishes the biological safety of
an individual impurity or a given impurity profile at the level(s) specified.
为建立指定限度的某单个杂质或给定杂质谱的生物安全性数据而进行的数据获取和评估过程。
Qualification threshold 界定阈
A limit above which an impurity is to be qualified.
杂质的限度，如果杂质水平高于该限度则该杂质需要进行界定。
Related substances 有关物质
Title used in monographs for general tests for organic impurities.
在各论中使用的一个项目名称，内容为对有机杂质进行检查通用检测。
Reporting threshold 报告阈
a limit above which an impurity is to be reported. Synonym: reporting level.
杂质的限度，如果杂质水平高于该限度则该杂质需要进行报告。同义词：报告水平。
Specified impurity 特定杂质
An impurity that is individually listed and limited with a specific acceptance criterion in
a monograph. A specified impurity can be either identified or unidentified.
在各论中单独列出，并给定特定可接受标准的杂质。特定杂质可以是鉴别出的也可以未鉴别出的。
Unidentified impurity 未鉴别杂质
An impurity for which a structural characterization has not been achieved and that is
defined solely by qualitative analytical properties (for example, relative retention)
未知结构，仅对其分析属性进行定性的杂质（例如，相对保留时间）
Unspecified impurity 非特定杂质
An impurity that is limited by a general acceptance criterion and not individually listed
with its own specific acceptance criterion.
以通用可接受标准来规定其限度，不单独列出特定的可接受标准的杂质。
2024年2月28日发(作者：壬歆)
EP 51000 药用物质的杂质控制（中英文）
(2014-06-06 16:50:06)
转载▼
分类： 食品药品
51000E 药用物质的杂质控制
04/2012:51000
5.10. CONTROL OF IMPURITIES IN SUBSTANCES FOR PHARMACEUTICAL
USE 药用物质的杂质控制
Preamble 前言
The monographs of the European Pharmacopoeia on substances for pharmaceutical
use are designed to ensure acceptable quality for users. The role of the
pharmacopoeia in public health protection requires that adequate control of impurities
be provided by monographs. The quality required is based on scientific, technical and
regulatory considerations.
欧洲药典对药用物质的各论是设计以保证其达到用户可接受品质的。药典在公众健康保护中的作用是要求对各论中所列的杂质进行充分控制。这些所要求的品质是基于科学、技术和法规的考虑的。
Requirements concerning impurities are given in specific monographs and in the
general monograph Substances for pharmaceutical use (2034). Specific monographs
and the general monograph are complementary: specific monographs prescribe
acceptance criteria for impurities whereas the general monograph deals with the need
for qualification, identification and reporting of any organic impurities that occur in
active substances.
在各论中和通论2034（药用物质）中给出的杂质要求是互补的：各论描述各杂质的可接受标准，而通论指出所有在活性物质中出现的有机杂质的界定、鉴别和报告阈值。
The thresholds for reporting, identification and qualification contained in the general
monograph Substances for pharmaceutical use (2034) apply to all related substances.
However, if a monograph does not contain a related substances test based on a
quantitative method, any new impurities occurring above a threshold may be
overlooked since the test is not capable to detect those impurities.
在通论2034（药用物质）中的报告阈、鉴别阈和界定阈适用于所有有关物质。但是，如果各论中没有有关物质的定量检测方法，则需要关注所有在阈值以上的新杂质，因为该方法无法检测到这些杂质。
The provisions of the Related substances section of the general monograph
Substances for pharmaceutical use (2034), notably those concerning thresholds, do
not apply to excipients; also excluded from the provisions of this section are:
biological and biotechnological products; oligonucleotides; radiopharmaceuticals;
fermentation products and semisynthetic products derived therefrom; herbal products
and crude products of animal and plant origin. Although the thresholds stated in the
general monograph do not apply, the general concepts of reporting, identification
(wherever possible) and qualification of impurities are equally valid for these classes.
通论2034（药用物质）中“有关物质”条款，特别是那些关于阈值的内容，不适用于辅料，也不适用于以下品种：生物和生物技术产品、寡聚核苷酸、放射药品、发酵产品和半合成产品及其衍生物、草药制品和动植物来源粗品。尽管在通论中的阈值并不适用，关于杂质报告阈、鉴别阈（可能时）和界定阈对这些品种仍然有效。
Basis for the elaboration of monographs of the European Pharmacopoeia 欧洲药典各论起草的基础
European Pharmacopoeia monographs are elaborated on substances that are
present in medicinal products that have been authorized by the competent authorities
of Parties to the European Pharmacopoeia Convention. Consequently, these
monographs do not necessarily cover all sources of substances for pharmaceutical
use on the world market.
欧洲药典各论是针对用于由欧洲药典委员会相关方药监局批准的药用产品的物质而起草的。因此，这些各论不一定包括在世界范围内使用的所有来源药用物质。
Organic and inorganic impurities present in those substances that have been
evaluated by the competent authorities are qualified with respect to safety at the
maximum authorized content (at the maximum daily dose) unless new safety data that
become available following evaluation justify lower limits.
这些物质里的有机和无机杂质已由适当的药监机构进行评估，认为其符合安全要求的最大许可含量（基于最大日服用量），除非有新的安全数据证明其可以采用更低的限度。
European Pharmacopoeia monographs on substances for pharmaceutical use are
elaborated by groups of experts and working parties collaborating with national
pharmacopoeia authorities, the competent authorities for marketing authorization,
national control laboratories and the European Pharmacopoeia laboratory; they are
also assisted by the producers of the substances and/or the pharmaceutical
manufacturers that use these substances.
欧洲药典中药用物质的各论由专家工作组和与国家药典机构合作的工作团队、适当的上市批准药监机构、国家控制实验室和欧洲药典实验室起草；同时还有物质的生产商和/或使用该物质的药品生产商进行协助。
Control of impurities in substances for pharmaceutical use 药用物质的杂质控制
The quality with respect to impurities is controlled by a set of tests within a monograph.
These tests are intended to cover organic and inorganic impurities that are relevant in
view of the sources of active substances in authorized medicinal products.
杂质的质量由各论中一系列的检测来控制。这些检查的需要包括用于批准的药用产品的活性物质中所有与来源有关的有机和无机的杂质，
Control of residual solvents is provided by the general monograph Substances for
pharmaceutical use (2034) and general chapter 5.4. Residual solvents. The certificate
of suitability of a monograph of the European Pharmacopoeia for a given source of a
substance indicates the residual solvents that are controlled together with the
specified acceptance criteria and the validated control method where this differs from
those described in general chapter 2.4.24. Identification and control of residual
solvents.
残留溶剂的控制在通论2034（药用物质）和通则5.4残留溶剂中给出。CEP会对特定来源的物质指明其中残留溶剂，及其可接受标准，如果检测方法与通则2.4.24残留溶剂的鉴别和控制不同，则会在CEP中列出。
Monographs on organic chemicals usually have a test entitled “Related substance”
that covers relevant organic impurities. This test may be supplemented by specific
test there the general test does not control a given impurity or where there are
particular reasons (for example, safety reasons) for requiring special control.
有机化学物的各论通常有一个检测项目称为“有关物质”，其中包括了有关的有机杂质。如果通用检测无法控制一个给定的杂质，或者有一些特殊原因，该测试可能需要其它特定的检测项目加以补充。
Where a monograph has no Related substances (or equivalent) test but only specific
tests, the user of a substance must nevertheless ensure that there is suitable control
of organic impurities; those occurring above the identification threshold are to be
identified (wherever possible) and, unless justified, those occurring above the
qualification threshold are to be qualified (see also under Recommendations to users
of monographs of active substances).
如果各论中没有“有关物质”项（或相当的项目），而只有特定检测项目，物质使用者必须保证有必要的方法来控制有机杂质。凡高于鉴别阈的杂质需要进行鉴别（只要可能），除非经过论证，凡高于界定阈的杂质需要进行界定（参见本通论“对活性物质各论使用者的建议”部分）
Where the monograph covers substances with different impurities profiles, it may
have a single related substances test to cover all impurities mentioned in the
Impurities section or several tests may be necessary to give control of all known
profiles. Compliance may be established by carrying out only the tests relevant to the
known impurity profile for the source of the substance.
如果各论包括了不同杂质概况的物质，可能有一个单独的有关物质检测包括在杂质部分提及的所有杂质，或可能需要几个不同的检测方法对所有已知杂质概况进行控制。如要证明物质符合要求，可能只需要根据所采用工艺分析物质的杂质概况，采用针对该杂质概况的检测方法即可。
Instructions for control of impurities may be included in the Production section of a
monograph, for example where the only analytical method appropriate for the control
of a given impurities is to be performed by the manufacturer since the method is too
technically complex for general use or cannot be applied to the final drug substance
and/or where validation of the production process (including the purification step) will
give sufficient control.
对杂质控制要求可能包括在各论的生产部分，例如，如果仅有一个分析方法适用于某给定的杂质，生产商需要采用该方法检测，但该方法技术太复杂，无法普遍使用，或无法应用于原料药成品和/或生产工艺验证（包括精制步骤）可能会给出足够的控制。
Impurities section in monographs on active substances 活性物质各论的杂质部分
The Impurities section in a monograph includes impurities (chemical structure and
name wherever possible), which are usually organic, that are known to be detected by
the tests prescribed in the monograph. It is based on information available at the time
of elaboration or revision of the monograph and is not necessarily exhaustive. The
section includes specified impurities and, where so indicated, other detectable
impurities.
各论中的杂质部分包括杂质（可能时会列出化学结构和名称）通常为无机物，可以由各论的方法检测出。这是基于在各论起草或修订时已有的信息，不一定包括了所有杂质。这部分包括了已识别杂质和，如果有指出，其它可检出杂质。
Specified impurities have an acceptance criterion not greater than that authorized by
the competent authorities.
已识别杂质可接受标准应不大于相关药监机构指定的限度。
Other detectable impurities are potential impurities with a defined structure but not
known to be normally present above the identification threshold in substances used in
medicinal products that have been authorized by the competent authorities of Parties
to the Convention. They are given in the Impurities section for information.
在被相关药监机构批准的药品中使用的物质中，其它可检出杂质是一些具有已知结构的潜在杂质，但并通常不在鉴别阈以上。这些杂质信息在杂质部分给出供参考。
Where an impurity other than a specified impurity is found in an active substance it is
the responsibility of the user of the substance to check whether it has to be
identified/qualified, depending on its content, nature, maximum daily dose and
relevant identification/qualification threshold, in accordance with the general
monograph on Substances for pharmaceutical use (2034), Related substances
section.
如果在活性物质中发现有特定杂质以外的杂质，活性物质的使用者应根据通论2034（药用物质）有关物质部分的要求，检查是否需要对该杂质地鉴别/界定，判定的依据是其成份、特性、最大日服用量或相应的识别/界定阈。
It should be noted that specific thresholds are applied to substances exclusively for
veterinary use.
需要注意的是识别阈不适用于兽用物质。
Interpretation of the test for related substances in the monographs on active
substances
活性物质各论中有关物质检测的解释
A specific monograph on a substance for pharmaceutical use is to be read and
interpreted in conjunction with the general monograph on Substances for
pharmaceutical use (2034).
药用物质的各论应与通论2034（药用物质）结合解读。
Where a general acceptance criterion for impurities (“any other impurity”, “other
impurities”, “any impurity”) equivalent to a nominal content greater than the applicable
identification threshold (see the general monograph on Substances for
pharmaceutical use (2034)) is prescribed, this is valid only for specified impurities
mentioned in the Impurities section. The need for identification (wherever possible),
reporting, specification and qualification of other impurities that occur must be
considered according to the requirements of the general monograph. It is the
responsibility of the user of the substance to determine the validity of the acceptance
criteria for impurities not mentioned in the Impurities section and for those indicated
as other detectable impurities.
如果杂质的通用可接受标准（“其它单杂”、“其它杂质”、“任何杂质”）等同的名义浓度大于所适用的鉴别阈（见通论2034药用物质）中所述水平，则该标准仅对杂质部分提到的特定杂质有效。对于存在的其它杂质，其鉴别阈（可能时）、报告阈、质量标准和界定阈应根据通论要求进行考虑。物质使用者有责任决定在杂质部分未提及的杂质和其中指出的其它可检出杂质的可接受标准是否有效。
Acceptance criteria for the related substances test are presented in different ways in
existing monographs; the decision tree (Figure 5.10-1) may be used as an aid in the
interpretation of general acceptance criteria and their relation with the Impurities
section of monograph.
有关物质检测方法的可接受标准在已有各论中以不同方式表现。在解读通用可接受标准和其与各论中杂质部分的关系时可以利用图5.10-1的决策树。
General acceptance criteria for “other” impurities are expressed in various ways in the
monographs: “any other impurity”, “other impurities”, “any impurity”, “any spot”, “any
band”, etc. The general acceptance criteria may apply to certain specified impurities
only or to unspecified impurities and certain specified impurities, depending on the
nature of the active substance and the applicable identification threshold. Pending
editorial adaption of already published monographs using unequivocal terminology,
the decision tree (Figure 5.10-1) may be used to determine the acceptance criterion to
be applied.
“其它”杂质的通用可接受标准在各论中以不同方式表达：“其它单杂”、“其它杂质”、“任何杂质”、“任何斑点”、“任何波长”等。通用可接受标准可能只用于某些特定杂质，或用于非特定杂质，以及某此特定杂质。这种情况下取决于活性物质特性和所采用的鉴别阈。已出版的各论中待定编辑性内容如果采用了明确的术语，可以应用5.10-1的决策树来决定可接受标准。
Recommendations to users of monographs of active substances 给活性物质各论使用者的建议
Monographs give a specification for suitable quality of substance with impurity profiles
corresponding to those taken into account during elaboration and/or revision of the
monograph. It is the responsibility of the user of the substance to check that the
monograph provide adequate control of impurities for a substance for pharmaceutical
use from a given source, notably by using the procedure for certification of suitability
of the monographs of the European Pharmacopoeia.
如果各论中给出了适当品质的物质的质量标准，其中包括了在各论起草和/或修订时考虑的杂质概况。物质使用者有责任检查各论对其所用的给定来源的药用物质中的杂质控制是否充分，特别是采用CEP程序时。
A monograph with a related substances test based on a quantitative method (such as
liquid chromatography, gas chromatography and capillary electrophoresis) provides
adequate control of impurities for a substance from a given source if impurities
present in amounts above the applicable identification threshold are specified
impurities mentioned in the Impurities section.
如果各论中有关物质检测是采用定量方法（例如液相色谱、气相色谱和毛细管电泳），可以对已知生产工艺的物质中的杂质进行充分的控制，如果所检出的高于适用的鉴别阈的杂质是在杂质部分已提及的特定杂质。
If the substance contains impurities other than those mentioned in the Impurities
section, it has to be verified that these impurities are detectable by the method
described in the monograph, otherwise a new method must be developed and
revision of the monograph must be requested. Depending on the content found and
the limits proposed, the identification and/or the qualification of these impurities must
be considered.
如果物质中含有杂质未提及的杂质，则需要确认这些杂质是否可以被各论中的方法所检出，如果不能，则必须开发新的检测方法，申请修订各论。根据所发现的杂质含量和提议的限度，需要考虑这些杂质是否要进行鉴别和/界定。
Where a single related substances test covers different impurity profiles, only
impurities for the known profile from a single source need to be reported in the
certificate of analysis unless the marketing authorization holder uses active
substances with different impurity profiles.
如果单个有关物质检测方法包括了不同的杂质概况，除非上市许可持有人所用的活性物质具有不同的杂质概况，则在检验报告中只需要报告已知杂质概况中的杂质。
Identification of impurities (peak assignment) 杂质的鉴别（峰识别）
Where a monograph has an individual limit for an impurity, it is often necessary to
define means of identification, for example using a reference substance, a
representative chromatogram or relative retention. The user of the substance may
find it necessary to identify impurities other than those for which the monograph
provides a means of identification, for example to check the suitability of the
specification for a given impurity profile by comparison with the Impurities section. The
European Pharmacopoeia does not provide reference substances, representative
chromatograms or information on relative retentions for this purpose, unless
prescribed in the monograph. Users will therefore have to apply the available scientific
techniques for identification.
如果各论中有某杂质的限度，通常需要定义该杂质的鉴别方法。例如，采用对照品，代表性图谱或相对保留时间。药用物质的使用者可能会发现有必要对各论中未提供鉴别方法的杂质进行鉴别，例如通过与各论杂质部分进行比较来检查质量标准是否适用某个特定的杂质谱。除非在各论中的描述，否则欧洲药典不会为了该目的而提供对照物质、代表性图谱或相对保留时间信息，因此使用者需要采用可获得的科学技术对杂质进行鉴别。
* The requirements of this section apply to active substances, with the exception of:
biological and biotechnological products; oligonucleotides; radiopharmaceuticals;
products of fermentation and semi-synthetic products derived therefrom; crude
products of animal or plant origin; herbal products.
本部分的要求适用于活性物质，以下品种除外：生物和生物技术产品、寡聚核苷酸、放射药品、发酵产品和半合成产品及其衍生物、草药制品和动植物来源粗品。
**To apply the Related substances section of the monograph Substances for
pharmaceutical use (2034): 在应用药用物质各论中有关物质部分时
—
an individual acceptance criterion must be defined for any impurity that may be
present above the identification threshold;
—
对可能会高于鉴别阈的单个任意杂质必须设定可接受标准
—
any impurity with an acceptance criterion above the identification threshold must
wherever possible be identified;
—
任何可接受标准高于鉴别阈的杂质，只要可能均应进行鉴别
—
any impurity with an acceptance criterion above the qualification threshold must
be qualified.
—
任何可接受标准高于界定阈的杂质需要进行界定
Figure 5.10-1—Decision tree for interpretation of general acceptance criteria for „other‟
impurities in monographs
图5.10-1---各论中“其它”杂质可接受标准解读决策树
New impurities/Specified impurities above the specified limit 高于指定限度的新杂质/特定杂质
Where a new manufacturing process or change in an established process leads to the
occurrence of a new impurity, it is necessary to apply the provisions of the general
monograph on Substances for pharmaceutical use (2034) regarding identification and
qualification and to verify the suitability of the monograph for control of the impurity. A
certificate of suitability is a means for confirming for a substance from a given source
that the new impurity is adequately controlled or the certificate contains a method for
control with a defined acceptance criterion. in the latter case revision of the
monograph will be initiated.
如果新的生产工艺或对已有工艺变更导致出现新杂质，则需要应用通论2034（药用物质）中鉴别阈和界定阈，确认各论是否适于控制其中杂质。CEP是一种手段来证明某种工艺生产出的物质中的新杂质均已被充分控制，或者可以在证书中包括一个控制方法及可接受标准。在后一种情况下，需要启动对各论的修订。
Where a new manufacturing process or change in an established process leads to the
occurrence of a specified impurity above the specified limit, it is necessary to apply
the provisions of the general monograph on Substances for pharmaceutical use (2034)
regarding qualification.
如果新的生产工艺或对已有工艺的变更导致特定杂质高于识别限，则需要应用通论2034（药用物质）进行中界定的概念。
Expression of acceptance criteria 可接受标准的表达方式
The acceptance criteria for related substances are expressed in monographs either in
terms of comparison of peak areas (comparative tests) or as numerical values.
各论中有关物质的表达方式可以是与峰面积的比较（面积对照试验），也可以是数值。
Chromatographic methods 色谱方法
General chapter 2.2.46. Chromatographic separation techniques deals with various
aspects of impurities control.
通则2.2.46色谱分离技术介绍了杂质控制的各方面信息。
Information is available via the EDQM website on commercial names for columns and
other reagents and equipment found suitable during monograph development, where
this is considered useful.
在EDQM网站上可以查到在各论研究期间发现适用的各色谱柱的商品名，其它的试剂和仪器等有用的信息。
GLOSSARY 术语
Disregard limit: 忽略限
In chromatographic tests, the nominal content at or below which peaks/signals are not
taken into account for calculating a sum of impurities. The numerical values for the
disregard limit and the reporting threshold are usually the same.
在色谱检测中，等于或低于该峰值/信号值即不计算总杂质的名义含量。忽略限的数值一般与报告阈值相同。
Identification threshold: 鉴别阈
A limit above which an impurity is to be identified.
达到即需要进行鉴别的杂质水平。
Identified impurity 已鉴别的杂质
An impurity for which structural characterization has been achieved.
已进行了结构确证的杂质。
Impurity 杂质
Any component of a substance for pharmaceutical use that is not the chemical entity
defined as the substance.
任何存在于药用物质中但并不是该物质的化学主体的成份，
Nominal concentration 名义浓度
Concentration calculated on the basis of the concentration of the prescribed reference
and taking account of the prescribed correction factor.
在已知的对照品浓度基础上计算出的浓度，考虑到已知的校正因子。
Other detectable impurities 其它可检出杂质
Potential impurities with a defined structure that are known to be detected by the tests
in a monograph but not known to be normally present above the identification
threshold in substance used in medicinal products that have been authorized by the
competent authorities of Parties to the Convention. They are unspecified impurities
and are thus limited by a general acceptance criterion.
可能存在于已由药监机构批准用于药品生产的物质中，按药典方法检测可以被检出，但通常不会超出鉴别阈的已知结构杂质。这类杂质为非特定杂质，因此由通用可接受标准进行限度规定。
Potential impurity 潜在杂质
An impurity that theoretically can arise during manufacture or storage. it may or may
not actually appear in the substance. Where a potential impurity is known to be
detected by the tests in a monograph but not known to be normally present in
substances used in medicinal products that have been authorized by the competent
authorities of Parties to the Convention, it will be included in the Impurities section
under Other detectable impurities for information.
在生产工艺或存储过程中，从理论上分析可能会产生的杂质，实际可能出现，也可能不出现。
Qualification 界定
The process of acquiring and evaluating data that establishes the biological safety of
an individual impurity or a given impurity profile at the level(s) specified.
为建立指定限度的某单个杂质或给定杂质谱的生物安全性数据而进行的数据获取和评估过程。
Qualification threshold 界定阈
A limit above which an impurity is to be qualified.
杂质的限度，如果杂质水平高于该限度则该杂质需要进行界定。
Related substances 有关物质
Title used in monographs for general tests for organic impurities.
在各论中使用的一个项目名称，内容为对有机杂质进行检查通用检测。
Reporting threshold 报告阈
a limit above which an impurity is to be reported. Synonym: reporting level.
杂质的限度，如果杂质水平高于该限度则该杂质需要进行报告。同义词：报告水平。
Specified impurity 特定杂质
An impurity that is individually listed and limited with a specific acceptance criterion in
a monograph. A specified impurity can be either identified or unidentified.
在各论中单独列出，并给定特定可接受标准的杂质。特定杂质可以是鉴别出的也可以未鉴别出的。
Unidentified impurity 未鉴别杂质
An impurity for which a structural characterization has not been achieved and that is
defined solely by qualitative analytical properties (for example, relative retention)
未知结构，仅对其分析属性进行定性的杂质（例如，相对保留时间）
Unspecified impurity 非特定杂质
An impurity that is limited by a general acceptance criterion and not individually listed
with its own specific acceptance criterion.
以通用可接受标准来规定其限度，不单独列出特定的可接受标准的杂质。