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2034E 药用物质

04/2013:2034

EP 7.5

SUBSTANCES FOR PHARMACEUTICAL USE

药用物质

DEFINITION 定义

Substances for pharmaceutical use are any organic or inorganic substances that are

used as active substances or excipients for the production of medicinal products for

human or veterinary use. They may be obtained from natural sources or produced by

extraction from raw materials, fermentation or synthesis.

药用物质是指人用或兽用医疗产品生产中所使用的活性物质或辅料，其可能是有机的或无

机的物质。这些物质可能是从自然途径获取，或从原料中萃取、发酵或合成得到。

This general monograph does not apply to herbal drugs, herbal drugs for homoeopathic

preparations, herbal drug preparations, extracts, or mother tinctures for homoeopathic

preparations, which are the subject of separate general monographs (Herbal drugs

(1433), Herbal drugs for homoegopathic preparations (2045), Herbal drug preparations

(1434), Extracts (0765), Mother tinctures for homoeopathic preparations (2029)). It does

not apply to raw materials for homoeopathic preparations, except where there is an

individual monograph for the substance in the non-homoeopathic part of the

Pharmacopoeia.

本通论不适用于草药制品、顺势疗法制剂用草药、草药制剂、提取物、或顺势闻法制剂的

药酒母体，这些品种应参照各自的各论（草药制品（1433）、顺势疗法制剂用草药

（2045）、草药制剂（1434）、提取物（0765）、或顺势闻法制剂的药酒母体（2029））

。也不适用于顺势疗法制剂用的原料，除非在药典的非顺势疗法部分另有各论。

Where a substance for pharmaceutical use not described in an individual monograph of

the Pharmacopoeia is used in a medicinal product prepared for the special needs of

individual patients, the need for compliance with the present general monograph is

decided in the light of a risk assessment that takes account of the available quality of the

substance and its intended use.

如果某种药用物质在药典里没有各论，这种物质用于满足个别病人的特殊需求的医疗产品

制备，则应该考虑可以获得的该物质的质量及其用途，基于风险评估来决定该药用物质需

符合的相关总论要求，且该物质应满足这些要求。

Where medicinal products are manufactured using substances for pharmaceutical use of

human or animal origin, the requirements of chapter 5.1.7. Viral safety apply.

如果药品生产中使用的药用物质是人类或动物来源，则需要满足5.1.7病毒安全性的要求

Substances for pharmaceutical use may be used as such or as starting materials for

subsequent formulation to prepare medicinal products. Depending on the formulation,

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2034E 药用物质

certain substances may be used either as active substances or as excipients. Solid

substances may be compacted, coated, granulated, powdered to a certain fineness, or

process in other ways. A monograph is applicable to a substance processed with an

excipient only where such processing is mentioned in the definition section of the

monograph.

药用物质可能会直接使用，或用作药用产品生产的原料。根据剂型不同，特定的物质可能

会用作活性物质，或用作辅料。固体物质可能会被压制、涂层、整粒、磨粉至特定细度，

或经过其它形式的加工。只有当某加工在各论定义部分被提及时，该各论方适用于与辅料

一起加工的物质。

Substance for pharmaceutical use of special grade. Unless otherwise indicated or

restricted in the individual monographs, a substance for pharmaceutical use is intended

for human and veterinary use, and is of appropriate quality for the manufacture of all

dosage forms in which it can be used.

特殊规格药用物质。除另有说明，或在各论中有限制外，药用物质适用于人兽通用，具备

的品质可以用于使用该药用物质的所有制剂形式。

Polymorphism. Individual monographs do not usually specify crystalline or amorphous

forms, unless bioavailability is affected. All forms of a substance for pharmaceutical use

comply with the requirements of the monograph, unless otherwise indicated.

多晶型。除非对生物利用度会造成影响，各论中通常不说明晶形或非晶型形态。除非另有

说明，物质的所有形态均符合各论的要求。

PRODUCTION 生产

Substances for pharmaceutical use are manufactured by procedures that are designed to

ensure a consistent quality and comply with the requirements of the individual

monograph or approved specification.

药用物质应根据程序进行生产，

The manufacture of active substances must take place under conditions of good

manufacturing practice.

活性物质的生产应在GMP条件下进行。

The provisions of general chapter 5.10 apply to the control of impurities in substances for

pharmaceutical use.

总论5.10适用于药用物质中的杂质控制。

Whether or not it is specifically stated in the individual monograph that the substance for

pharmaceutical use:

无论在各论中是否申明为药用，该药用物质

— Is a recombinant protein or another substance obtained as a direct gene product

based on genetic modification, where applicable, the substance also complies with

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2034E 药用物质

the requirements of general monograph Products of recombinant DNA technology

(0784);

— 如果是重组蛋白质或另一物质为基于基因修饰的直接基因产品，适当时，该物质应

符合通论0784重组DNA技术产品要求

— Is obtained from animals susceptible to transmissible spongiform encephalopathies

other than by experimental challenge, where applicable, the substance also

complies with the requirements of the general monograph Products with risk of

transmitting agents of animal spongiform encephalopathies (1483);

— 如果是动物来源物质，可能会有TSE风险，适用时，该物质还应符合通论1483具

有TSE风险的产品要求

— Is a substance derived from a fermentation process, whether or not the micro-

orgnisms involved are modified by traditional procedures or recombinant DNA

(rDNA) technology, where applicable, the substance also complies with the

requirements of the general monograph Products of fermentation (1468).

— 如果是经发酵工艺生产获得，无论是传统发酵还是采用DNA重组微生物发酵技术，

适用时，该物质应符合通论1468发酵产品的要求。

If solvents are used during production, they are of suitable quality. In addition, their

toxicity and their residual level are taken into consideration (5.4). If water is used during

production, it is of suitable quality.

如果在生产中有使用溶剂，则溶剂应具有适当的品质。另外，其毒性和残留水平应加以考

虑（5.4）。如果生产中使用水，则水应具有适当的品质。

If substances are produced or processed to yield a certain form or grade, that specific

form or grade of the substance complies with the requirements of the monograph.

Certain functionality-related tests may be described to control properties that may

influence the suitability of the substance and subsequently the properties of dosage

forms prepared from it.

如果该物质生产工艺会生成特定形状或级别，该特定形状或级别应符合各论要求。应说明

特定的检测，用于控制那此可能会对物质稳定性造成影响的特性，这些特性可能会对采用

该物质生产的制剂产生影响。

Powdered substances may be processed to obtain a certain

粉状物质可能需要进一步处理以获得一定的细度（2.9.35）

Compacted substances are processed to increase the particle size or to obtain particles

of a specific form and/or to obtain a substance with a higher bulk density.

重粉是指经过压制，增加其粒径，或获得指定形态的颗粒和/或获得较大堆密度的产品。

Coated active substances consist of particles of the active substance coated with one or

more suitable excipients.

带涂层的物质包含了活性物质和一种或多种合适的辅料。

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Granulated active substances are particles of a specified size and/or form produced from

the active substance by granulation directly or with one or more suitable excipients.

整粒过的活性物质具有一定的粒径和/或形态，这种特性是将物质经过直接整粒或添加一种

或多种辅料获得。

If substances are processed with exeipients, these excipients comply with the

requirements of the relevant monograph or, where no such monograph exists, the

approved specification.

如果物质与辅料一起加工，这些辅料应符合相应的各论要求，或者如果没有适合的各论，

则应符合批准过的质量标准。

Where active substance have been processed with excipients to produced, for example,

coated or granulated substances, the processing is carried out under conditions of good

manufacturing practice and the processed substances are regarded as intermediates in

the manufacture of a medicinal product.

如果活性物质与辅料一起加工而得到，例如，带涂层或整粒过的物质，该加工过程应在

GMP条件下进行，所获得的产品作为药用产品生产过程的中间体。

CHARACTERS 性状

The statements under the heading Characters (e.g. statements about the solubility or a

decomposition point) are not to be interpreted in a strict sense and are not requirements.

They are given for information.

在性状项下给出的说明（例如，溶解度或降解温度）不应进行严格意义的解释，不是质量

标准的要求，而是给出的参考信息。

Where a substance may show polymorphism, this may be stated under Characters in

order to draw this to the attention of the user who may have to take this characteristic into

consideration during formulation of a preparation.

如果物质可能表现出多晶型，则可能会在性状项下给出，以引起使用者的注意，因为使用

者可能在生产制剂时会需要考虑该特性。

IDENTIFICATION 鉴别

Where under Identification an individual monograph contains subdivisions entitled “First

identification” and “Second identification”, the test or tests that constitute the “First

identification” may be used in all circumstances. The test or tests that constitute the

“Second identification” may be used in pharmacies provided it can be demonstrated that

the substance or preparation is fully traceable to a batch certified to comply with all the

other requirements of the monograph.

如果各论中在鉴别项下包括了子项“第一鉴别”和“第二鉴别”，在“第一鉴别”中的测试项目可

以在任何情况下使用。在“第二鉴别”中的测试项目如果能确认该物质或制剂完全可追踪到

某个符合各论所有其它要求的批次，则可以在药房使用。

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2034E 药用物质

Certain monographs give two or more sets of test for the purpose of the first

identification, which are equivalent and may be used independently. One or more of

these sets usually contain a cross-reference to a test prescribed in the Tests section of

the monograph. It may be used to simplify the work of the analyst carrying out the

identification and the prescribed tests. For example, one identification set cross-refers to

a test for enantiomeric purity while the other set gives a test for specific optical rotation:

the intended purpose of the two is the same, that is, verification that the correct

enantiomer is present.

某些各论在第一鉴别中给出了两个或更多的测试，这些测试是等效的，可能可以单独采用。

一般来说，一个或多个鉴别测试会引用各论中检查部分项下某一测试，这时可以减少化验

室做鉴别的工作。例如，一个鉴别引用了光学纯度的测试，而另一套鉴别给出了比旋度的

检测：这两个鉴别的目的都是一样的，即确认光学结构正确。

TESTS 检查

Polymorphism (5.9). If the nature of a crystalline or amorphous form imposes

restrictions on its use in preparations, the nature of the specific crystalline or amorphous

form is identified, its morphology is adequately controlled and its identity is stated on the

label.

多晶型（5.9）如果晶型或非晶型会对其用途产生影响，则应对指定的晶型或非晶型形态进

行鉴别，充分控制其晶型，并在标签上注明。

Related substances. Unless otherwise prescribed or justified and authorized, organic

impurities in active substances are to be reported, identified wherever possible, and

qualified as indicated in Table 2034-1 or in table 2034-2 for peptides obtained by

chemical synthesis.

有关物质。除非另有说明，或论证并获得批准，活性物质中的有机杂质必须报告、可能时

需要鉴别，由化学合成中所得的多肽必须按表2034-1和2034-2中要求制定限度。

Table 2034-1-Reporting, identification and qualification of organic impurities in active

substances

表

2034-1

活性物质中有机杂质的报告、鉴别和界定阈值

Use 用途

Maximum daily Reporting

dose 最大日摄

threshold

入量

报告阈值

>0.05 per cent

Identification

threshold

鉴别阈值

>0.10 per cent

or a daily intake

of >1.0 mg

(whichever is

the lower 从低

Qualification

threshold

界定阈值

>0.15 per cent

or a daily intake

of >1.0 mg

(whichever is

the lower 从低

Human use or ≤2g/day

human and

veterinary use

人用或人兽通用

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2034E 药用物质

者)

Human use or >2g/day

human and

veterinary use

人用或人兽通用

Veterinary use Not applicable

only

不适用

仅兽用

>0.10 per cent>0.20 per cent

>0.03 per cent>0.05 per cent

者)

>0.05 per cent

>0.50 per cent

Reporting threshold

报告阈值

>0.1 per cent

Identification threshold

鉴别阈值

>0.5 per cent

表2034-2 化学合成获得多肽中有机杂质的报告、鉴别和界定阈值

Qualification threshold

界定阈值

>1.0 per cent

Specific thresholds may be applied for impurities known to be unusually potent or to

produce toxic or unexpected pharmacological effects.

对于已知异常烈性，或产生毒性或意外药学效果的毒性，可能需要采用特殊的阈值。

If the individual monograph does not provide suitable control for a new impurity, a

suitable test for control must be developed and included in the specification for the

substance.

如果在各论中未对新杂质提供适当的控制，则必须建立新方法进行控制，并将新杂质的限

度包括在该物质的质量标准中。

The requirements above do not apply to biological and biotechnological products,

oligonucleotides, radiopharmaceuticals, products of fermentation and semi-synthetic

products derived therefrom, to crude products of animal or plant origin or herbal products.

上述要求不适用于生物和生物技术产品、代寡核苷酸、放射药品、发酵产品、及由此衍生

的半合成产品、动物或植物来源粗品、草药产品。

For active substances in a new application for a medicinal product for human use, the

requirements of the guideline on the limits of genotoxic impurities and the corresponding

questions and answers documents published on the website of the European Medicines

Agency (or similar evaluation principles for non-European Union member states) must be

followed.

对人用药物产品新申请中使用的活性物质，应满足在EMA（或类似的非欧盟成员国评价原

则）官网上发布的基因毒性杂质限度指南和相应的问答文件中的要求。

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Table 2034-2---Reporting, identification and qualification of organic impurities in peptides

obtained by chemical synthesis

2034E 药用物质

Residual solvents are limited according to the principles defined in chapter 5.4, using

general method 2.4.24 or another suitable method. where a quantitative determination of

a residual solvent is carried out and a test for loss on drying is not carried out, the content

of residual solvent is taken into account for calculation of the assay content of the

substance, the specific optical rotation and the specific absorbance.

残留溶剂。应根据通则5.4的要求制订限度，采用通则2.4.24中的方法或其它适当的方法

进行检测。如果对某一残留溶剂进行定量检测，同时没有干燥失重项目，则残留溶剂的检

测结果应在计算含量、比旋和比吸收度时考虑。

微生物质量：如果微生物质量控制是必须的，应在各论中给出微生物质量的可接受标准。

在通则（5.1.4非无菌制剂和药用物质的微生物质量的表5.1.4-2 非无菌药用物质的微生物

质量可接受标准）中给出了可能会被微生物污染的非无菌药用物质的微生物质量要求。根

据物质的特性、用途不同，可能需要对不同物质制订并论证不同的可接受标准。

Sterility (2.6.1). If intended for use in the manufacture of sterile dosage forms without a

further appropriate sterilization procedure, or if offered as sterile grade, the substance for

pharmaceutical use complies with the test for sterility.

无菌（2.6.1）如果药用物质在不进行进一步适当灭菌处理即用于无菌制剂的生产，或所提

供的是无菌规格时，该物质应满足无菌要求。

Bacterial endotoxins (2.6.14). If offered as bacterial endotoxin-free grade, the

substance for pharmaceutical use complies with the test for bacterial endotoxins. The

limit and test method (if not gelation method A) are stated in the individual monograph.

The limit is calculated in accordance with Test for bacterial endotoxins: guidelines in

chapter 2.6.14. Bacterial endotoxins, unless a lower limit is justified from results from

production batches or is required by the competent authority. Where a test for bacterial

endotoxins is prescribed, a test for pyrogens is not required.

细菌内毒素（2.6.14）如果所提供的是无细菌内毒素的规格，则该药用物质应符合细菌内

毒素的检测要求。检测方法（如果不是凝胶法A）和限度在各论中应指出。如果生产批准

结果未表明需要制订更低的限度，或者相关药监当局要求制订更低限度，则应根据总则

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Microbiological quality. Individual monographs give acceptance criteria for

microbiological quality wherever such control is necessary. Table 5.1.4-2---Acceptance

criteria for microbiological quality of non-sterile substances for pharmaceutical use in

chapter 5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and

substances for pharmaceutical use gives recommendations on microbiological quality

that are of general relevance for substances subject to microbial contamination.

Depending on the nature of the substance and its intended use, different acceptance

criteria may be justified.

2034E 药用物质

2.6.14：细菌内毒素中细菌内毒素检测要求计算限度。如果在各论描述了细菌内毒素的检

测要求，则不需要检测热原。

Pyrogens (2.6.8). If the test for pyrogens is justified rather than the test for bacterial

endotoxins and if a pyrogen-free grade is offered, the substance for pharmaceutical use

complies with the test for pyrogens. The limit and test method are stated in the individual

monograph or approved by the competent authority. Based on appropriate test validation

for bacterial endotoxins and pyrogens, the test for bacterial endotoxins may replace the

test for pyrogens.

热原（2.6.8）如果需要进行热原测试，而不是细菌内毒素测试，并且提供的就是无热原规

格，则该药用物质应满足热原测试要求。该测试限度和方法均应在单独各论中列出，或由

相应药监当局批准。如果细菌内毒素和热原方法经过适当验证，细菌内毒素检测可以取代

热原检测。

Additional properties. Control of additional prperties (e.g. physical characteristic,

functionality-related chracteristics) may be necessary for individual manufacturing

processes or formulations. Grades (such as sterile, endotoxin-free, pyrogen-free) may be

produced with a view to manufacture of preparations for parenteral administration or

other dosage forms and appropriate requirements may be specified in an individual

monograph.

附加特性。对于各生产工艺或制剂来说，对附加特性的控制（例如，物理特性、功能相关

特性）可能是必须的。在各论中可能需要指出不同剂型，如注射剂或其它剂型，以及适当

针对规格（如无菌、无内毒素、无热原）的要求。

ASSAY 含量

Unless justified and authorized, contents of substances for pharmaceutical use are

determined. Suitable methods are used.

除非另有论述并被批准，药用物质的成分应采用适当的方法进行检测。

In general, labeling is subject to supranational and national regulation and to international

agreements. The statements under the heading Labelling therefore are not

comprehensive and, moreover, for the purposes of the Pharmacopoeia only those

statements that are necessary to demonstrate compliance or non-compliance with the

monograph are mandatory. Any other labeling statements are included as

recommendations. When the term “label” is used in the Pharmacopoeia, the labeling

statements may appear on the container, the package, a leaflet accompanying the

package or a certificate of analysis accompanying the article, as decided by the

competent authority.

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LABELLING 标签

2034E 药用物质

— 无菌

— 重粉

— Sterile

— Coated

— 水合度

— 有涂层

— 不含热原

— 经过整粒

— Granulated

— Compacted

— 含有光滑剂

— 有特定用途

— 具有特定的晶型

— 不含量细菌内毒素

— Free from pyrogens

— 具有特定程度的细度

适当时，标签应说明该物质

— The degree of hydration

— Containing gliding agents

— Intended for a specific use

— Of a distinct crystalline form

— Free from bacterial endotoxins

— Of a specific degree of fineness

— The name and concentration of any excipient

Where applicable, the label states 适当时，标签应说明

Where appropriate, the label states that the substance is:

一般来说，标签需要符合超国家和国内、国际协议的要求。在标签项下的内容并不是综合

信息，进一步说，对于药典要求而言，只有是否符合各论的信息是必要的，标签中任何其

它信息均只是推荐。当术语“标签”在药典中使用时，标签内容可能会出现在容器上、包裹

上、与包装一起的文件页上、或随货的分析报告上，具体由适当的药监当局来决定。

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2034E 药用物质

— 所有辅料名称和浓度

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