观察蚯蚓-感受节日

欧洲药品管理局《GUIDELINE ON QUALITY OF COMBINATION
HERBAL（复方草药质量指南）》内容解析
COMMITTEE ON HERBAL MEDICINAL PRODUCTS
(HMPC)
草药产品委员会
This guideline applies to herbal medicinal products containing
combinations of herbal substances
本指导适用于含有草药和草药提取物的草药制品
本指南引用的其它指南附件
(1), “Guideline on specifications: test procedures and acceptance
criteria for herbal substances, herbal preparations and herbal
medicinal productstraditional herbal medicinal products”
“草药材、草药制剂和草药产品传统草药产品的分析程序和验收标准
的指导原则”

(2), Annex 7 “Manufacture of herbal medicinal products” of Good
Manufacturing Practices (GMP) for medicinal products, Volume 4,
Rules governing medicinal products in the European Union
附件7：草药产品良好生产规范(GMP),第4卷,欧盟医药产品管理规定

MAIN GUIDELINE TEXT
Herbal medicinal products contain herbal substancespreparations
each consisting of a large number of chemical constituents of which
only a few may be characterized.
草药产品中含有的草 药材草药提取物包含大量的化学组成，但是其
中只有少数可明确其成分及结构。
Furthermore, herbal substances are natural in origin and
consequently their chemical composition varies. In addition, in most
cases the constituents responsible for the therapeutic activity are
unknown or only partly explained and often markers are used to
characterize these products.
另外，由于草药材来源于自然，其化学成分多变，在多数情况下，这
些起到治疗作用的活性成分往往是未知的或者仅仅部分可知，其标记
物经常被用来指示产品质量 。
In herbal medicinal products containing combinations of herbal
substances andor herbal preparations, quality control may be more
problematic because, in addition to the above- mentioned difficulties,
other herbal substances andor preparations may interfere with the
analysis, e.g. extraction or detection of a marker may be affected by
other herbal substances present (co-elution) in the finished product.
在含有混合草药材和或草药提取物的草药产品中，质量控制可能会

变得很复杂，因为除了上述提及的检测困难外，其他草药材和或提
取物也可能会干扰分析结果， 举例来说，在产品中某一个标记物的提
取或分析可能会受到产品中其他草药材的影响。
The quality of a combination herbal medicinal product should in
general be guaranteed and demonstrated in accordance with the
existing guidance. All relevant parameters should be tested in the
finished product， and identification and assay of each herbal
substanceherbal preparation included in the product are required.
复方草药产品的质量标准一般来说应保证和与现有指南相一致。在进
行所有的终产品检测项时， 产品中每一味药材提取物的鉴定和含量
分析也是必需的。
The stability of the finished product must be guaranteed. For
some combination herbal medicinal products, identification and
quantification of individual herbal substancesherbal preparations in
the product are difficult to perform and sometimes impossible.
Clarification on how the requirements on identification and assay
should be interpreted is provided below. It should be stressed that
notwithstanding the guidance given, all usual analytical methods for
identification and assay should be investigated first, e.g. the methods
described in the Ph. Eur. General Chapter 2 “Methods of analysis”.
Furthermore, each approach taken should be justified by the

applicant, and should take into account the combination herbal
medicinal product that is subject of the application.
草药产品的稳定性必须得到保证。对于某些复方草药产品来说，< br>终产品中每一味药材提取物的鉴别和含量分析很难进行，有时甚至
不可能做到。复方草药分析和鉴 别的具体要求将在以下章节详细说
明，需要强调的是，虽然已经给出了相关的指南文件，但所有通用的< br>鉴定和分析方法，如欧洲药典通则二中所描述的“分析方法”，在正
式采用前都应先作调查。此外 ，每一个方法的合理性均需申请者自行
判断，并考虑是否符合复方草药申请标准。
If individual active substance testing for identity, assay or to
demonstrate stability cannot be performed in the finished product,
alternative strategies may be considered. The simple omission of (a)
test(s) is not acceptable as the quality of combination herbal
medicinal products should be fully comparable to the quality of other
(herbal) medicinal products.
如果针 对产品中单一物质的鉴别、含量分析或申明其稳定性的分
析检测不可能完成，可以考虑替代策略。由于复 方草药的质量标准参
照其它医药品的质量，因此，忽略其中一个（或多个）检测项是不能
接受的 。

In this regard, reducing the number of active substances in the

herbal medicinal product could increase the possibilities to perform
all tests (e.g. identification, assay etc.) in the finished product.
就这一点而言，减少 复方草药产品的药味数，助于完成产品中所
有的相关检测项目（如鉴别和含量分析等）。
As required for all medicinal products, GMP, process validation
and batch records documenting each step in the manufacturing
process of the finished product and including results of IPC testing
should ensure that, in combination with suitable testing criteria, a
product of good and consisting quality is obtained. The
manufacturing process should, as required for all medicinal products,
be designed in such a way that the manufacture and composition of
the finished product is well-controlled and conforms with the
declared composition.
对 所有药品的要求而言，产品GMP、过程验证、记载生产过程
每一步骤的批记录以及包括中间品检测都应 该得到保证（与适当的测
试标准一起），以达到产品质量的良好一致性。生产过程应该进行良
好 设计，以保证使产品组成均有良好控制并与已声明的质量组成一
致。
The manufacturing process design should be supported by strict
and well-documented process validation.
制造过程设计应由严格且良好记录的过程验证结果来支持。

An appropriate IPC testing programme (e.g. testing at various
points during the stepwise addition of the herbal
substancespreparations) and an identification test of the herbal
substanceherbal preparation immediately before the introduction in
the manufacturing process of the finished product are measures to
ensure the consistent quality and declared composition of the finished
product.
应进行适当的IPC分析（如在草药材提取物生产步骤中进行的多
点取样检测）和制剂生产工序 前引入的药材提取物鉴定分析，以保
证产品与所声明质量和组成的一致性。
Each step of the manufacturing process should be regarded as
critical and appropriate procedures to ensure correct addition of
ingredients should be in place as routine control. Documentation on
GMP should be available to the Competent Authorities upon
inspection, and manufacturing and process validation data should be
submitted in the marketing authorisationregistration dossier.
生 产过程中的每一步都应被认定为关键和适当步骤，以保证正确
的常规控制方法得到使用。同时，GMP文 件应该留用以备药政当局
现场审查，生产和过程验证的数据应该在申请产品许可时递交。
Where a joint assay is performed, the active substance
specification should include a (additional, if different from the

pharmacopoeial marker) limit for the common marker.
当进行综合分析时，药材质量标准应该包括通用标记物的限量分
析。
Where applicable, the same principles apply to control tests
carried out at an intermediate stage of the manufacturing process of
the finished product.
如适用，同样的原则适用于产品生产过程的中间品控制。
The following requirements apply for identification and
quantitative determination of each active substance in the
combination herbal medicinal product:
以下要求适用于复方草药中每一味药材的鉴别和定量分析：

IDENTIFICATION TEST OF EACH ACTIVE SUBSTANCE
每一味药材的鉴别
(read in conjunction with Decision tree # 1: Identification test of
each active substance in combination herbal medicinal products)
（阅读决策树#1：复方草药中每一味药材的鉴别分析）
 Where constituents with known therapeutic activity or active
markers of the herbal substancepreparation are known, the

identification of the active constituents should be performed in the
finished product in accordance with the Guideline on
specifications (2).

针对 在药材

提取物中起治疗作用的成分或活性标记物已知的情
况，产品中活性成分都应按照 质量标准指南的要求（
2
）进行鉴别。


 Where constituents with known therapeutic activity or active
markers of the herbal substancepreparation are not known:
针对在药材

提取物中治疗作用成分或活性标记物未知的情况：

- Each herbal substancepreparation that can be identified
should be identified in the finished product in accordance
with the Guideline on specifications (2).
- 每一个能鉴别的药材提取物，都应该根据质量标准指南（2）
的要求进行鉴别。
- Where the herbal substancepreparation cannot be identified
in the finished product, appropriate justification and
documentation that all usual analytical methods, e.g. the
methods described in the Ph. Eur. General Chapter 2
“Methods of analysis”, have been investigated should be
provided. Furthermore:

- 对于产品中未知部分的草药材提取物应有适当的证明表示
所有常用的分析方 法，例如欧洲药典第2章中所述的“分析方
法”，均使用过，此外：
 The identification test of the herbal
substancepreparation should be performed as an in
process control at the latest point in the manufacturing
process of the finished product where analysis is still
possible. The approach taken should be fully justified by
the applicant. The identification test should be supported
by documented evidence on the manufacture of the
finished product batch and process validation.
 草药材提取物的鉴别分析应作为工序控制的一部分，如
有可能，应在制剂生产的最后检测点进行。所采用方法的
合理性应由申请者自行判断。鉴别分析 方法的有效性应由
良好记录的制剂生产和过程验证数据来支持。
In addition, the release specifications of the finished product
should include suitable identification methods for the combination,
e.g. characteristic fingerprints, in line with the Guideline on
specifications (2). The sum of the identification methods should allow
appropriate characterisation of the combination.
此外，产品放行标准应该包括复方制剂适当的鉴别方法。如结构

图谱，以与质量标准指南原则（2）是的要求一致，多种鉴别方法应
该允许复方草药得到 适当的结构确证。
If IPC testing of the herbal substancepreparation is not
possible, it is required that the herbal substancepreparation is
identified according to the active substance specifications
immediately before the introduction of the active substance in the
manufacture of the finished product. The approach taken should be
fully justified by the applicant. The identification test should be
supported by documented evidence on the manufacture of the
finished product batch and process validation.
如果药材草药提取物的IPC分析不可行，则复方产品中 药材提
取物的鉴别应在引入制剂生产以前，根据药材的质量标准来进行。所
采用方法的合理性应 被申请人自行判断，鉴别分析方法的有效性应由
良好记录的制剂生产和过程验证数据来支持。
In addition, the release specifications of the finished product
should also include suitable identification methods, e.g. characteristic
fingerprints in line with the Guideline on specifications (2). The sum
of the identification methods should allow appropriate
characterisation of the combination
此外，终产 品的放行标准应包括适当的鉴别方法，如特征指纹图
谱信息，以与质量标准指南保持一致。多种鉴别方法 应该允许复方草

药得到适当的结构确证。

ASSAY OF EACH ACTIVE SUBSTANCE
每一味药材的含量分析
(read in conjunction with Decision tree # 2: Assay of each active
substance in combination herbal medicinal products)
（阅读决策树#2：复方草药产品中每一味药材的含量分析）

 Where constituents with known therapeutic activity or active
markers of the herbal substancepreparation are known

针对药材

提取物中治疗作用的有效成分已知的情况

- an individual assay of the active substance should be
performed in the finished product in accordance with the
Guideline on specifications (2).
-
应根据质量标准指南的要求，可进行制剂中药材单一组分的
含量分析

- If an individual assay of the herbal substancepreparation is
not possible, the quantitative determination can be carried
out jointly for two or more herbal substancespreparations

(e.g. joint determination of group of
anthraquinone- derivatives) in accordance with the Guideline
on specifications (2).
- 如果针对药材提取物单一成分的含量 分析不可行，可针对两
种或多种药材提取物进行综合定量分析（如蒽醌衍生物成分
群的综合定量 分析），其方法可参照质量标准指导原则进行。

 where constituents with known therapeutic activity or active
markers of the herbal substancepreparation are not known:

针对药材

提取物中治疗作用的有效成分未知的情况

 Each herbal substancepreparation that can be assayed, should be
quantified in the herbal medicinal product in accordance with
the Guideline on specifications (2).
 每一种可以进行含量分析的药材提取物，应该根据质量标准指南
的要求，在终产品中进行含量分析。
 If an individual assay of the herbal substancepreparation is not
possible, the quantitative determination can be carried out
jointly for two or more herbal substancespreparations in
accordance with the Guideline on specifications (2).
 如果针对药材提取物进 行的单一成分含量分析不可行，其定量分

析可以针对两种或多种药材提取物进行，分析方 法可参照质量
标准指导原则进行。
An assay of a common marker gives limited information on the
relative composition of the concerned herbal substancespreparations
in the herbal medicinal product. As such, markers for joint analysis
should be carefully selected and justified. If a joint analysis is
considered acceptable, the specifications of the concerned herbal
substancespreparations should include a (additional, if different
from the pharmacopoeial marker) limit for the common marker. The
approach taken should be fully justified by the applicant. Each
approach should be supported by careful process validation and
documentary evidence should be available.
如果对某一通用标记物的含量测定结果得出制剂中相关药材提
取物相关组成很有限的信息，在这 一种情况下，应谨慎选择和判断是
否对标记物成分进行综合分析。如果综合分析的结果可被接受，制剂< br>中相关草药材提取物的质量标准应包括（另外，如果不同于药典标
记物）通用标记物的限量。所采 用的方法应该由严谨的过程验证结果
以及有记录的数据来支持。
 Where the herbal substancepreparation cannot be quantified
in the finished product, appropriate justification and
documentation that all usual analytical methods, e.g. the

methods described in the Ph. Eur. General Chapter 2 “Methods
of analysis”, have been investigated should be provided.
如果产品中的药材提取物不能被定量，应提供针对所有通 用分
析方法的适当判断和文献信息，如欧盟药典中所述分析方法的确认。
Furthermore, an appropriate manufacturing process design,
supported by strict and well- documented process validation, should
ensure that the manufacture and quality of the finished product is
well-controlled and that the composition of the finished product
conforms with the declared composition.
此外，由严格和良好记录的过程 验证数据支持的适当生产工艺设
计应确保产品生产工艺和质量标准已经得到了良好控制，而且产品的组成与声明的质量相一致。
The manufacturing process development studies (e.g. analytical
profiles during the stepwise addition of the herbal
substancespreparations, degradation studies during the manufacture
of the finished product) and other studies [e.g. stability studies of the
active substance(s)] are pivotal in this regard and should underpin
the proposed approach to ensure the quality and composition of the
finished product e.g. assay of the active substance as IPC.
工艺过程开发研究（药材提取物生产过程中的全面分析，终产
品生产过程中的降解研究）以及其他研究【如药材的稳定性研究】作

为关键过程 ，应该强化这一途径以保证产品质量和组成（如IPC过程
中药材的含量分析）。
The approach taken should be fully justified by the applicant.
Tests should be supported by documented evidence on the
manufacture of the finished product batch.
方法合理性由申请人自行判断，检测分析应有终产品生产批次记
录的数据来支持。
In addition, the release and shelf life specification of the
combination should include suitable assay methods for the
combination in line with the Guideline on specifications (2), including
e.g. semi- quantitative fingerprints, allowing a characteristic
quantitative determination of the combination.
另外，复方草药的放行及货架期标准应该包括合适的含量分析方
法，这一方法基于质量标准指南（2）进行，包括诸如半定量指纹图
谱分析，允许复方草药中特 征性的定量测定。
The requirements above apply to the identification and
quantification of each herbal substancepreparation in a combination
herbal medicinal product. The overall release and shelf life
specifications of a combination herbal product will therefore in
general be a mixture of tests that individually identify and quantify
the herbal substance(s)preparation(s) in the finished product andor

tests that jointly quantify herbal substancespreparations in the
finished product, and all other suitable identification tests and assays
that allow an appropriate characterisation and a characteristic
quantitative determination of the combination.
上文所述要求适用于复方草药产品中的每一味草药材提取物的
鉴别定量分析。复方草药的整体的 放行及货架期标准因此是混合型分
析检测，第一种混合的情况是针对复方草药种的每一味药材提取物的鉴别和定量分析的混合，第二种混合的情况是复方草药制剂中所有
药材提取物的联合分析，第三种 情况是所有其他适当的鉴别和定量分
析的混合，这种方式允许复方草药中采用一种适当的结构确认和特征
性定量测定。
Stability of the finished product
终产品的稳定性
The stability of the combination herbal medicinal product
should be determined in accordance with existing guidance on
stability and the specific herbal guidelines (1, 2).
复方草药品的稳定性根据现有的草药稳定性指南（1,2）来确定。
For a finished product containing herbal
substancespreparations where constituents with known therapeutic
activity or active markers are known, the appropriate stability of
these active constituents must be demonstrated (see also Decision

Tree #2).
对于治疗成分或活性标记物已知的 复方草药产品，必须证实这些
活性组成的适当的稳定性。（决策树#2）
In accordance with the Guideline on the quality of the herbal
medicinal product, if a herbal medicinal product contains
combinations of several herbal substances andor herbal
preparations, and if it is not possible to determine the stability of
each active substance, the stability of the combination has to be
demonstrated by appropriate fingerprint chromatograms,
appropriate overall methods of assay and physical or other
appropriate tests. The appropriateness of the tests shall be justified
by the applicant (1).
根据草药产品质量指 导原则，如果一种草药产品含有多味草药材
和或提取物的组合，以及如果无法确定每一味药材的稳定性， 则复
方草药产品的稳定性必须通过适当的指纹图谱信息，适当的整体分析
方法，以及物理或其他 适当的检测来证实。检测的实用性由申请者自
行判断。

是
治疗成分或活性标记物
已知的药材
决策树#1
复方草药中每一味药材的鉴别

根据质量标准指南（2）进行
鉴别检测。

否
草药产品中活性
物质可识别
是
根据质量标准指南(2)进行鉴
别检测
否
活性物质可在过程
控制中识别
是
否
过程控制中有记录的活性物质
鉴别实验
在生产过程中投入药材以前，
由草药产品的生产商完成的有
记录的鉴别实验。
以及
以及
草药产品的质量标准也包括适
用于确证复方草药的鉴别实验
草药产品的质量标准也包括适
用于确证复方草药的鉴别实验

决策树#2
复方草药产品中每一味药材的含量分析
是
活性成分或活性标
记物已知的药材
否
对于草药产品中的每
一味药材，每一个单独
的含量分析都可行
草药产品中的药材
可以进行含量分析
是
否
是
根据质量标准指南
（2）进行单独的含
量分析
根据质量标准指南（2）
对药材进行联合含量
分析
根据质量标准指南（2）
进行单独的含量分析
否
根据质量标准指南（2），进
行活性物质的联合含量分析
是
根据质量标准指南
（2）可以进行活性
物质联合含量分析
否
以及
草药产品的质量标准包括允许一种特征性的含量分析
适当的生产过程设计和验
证以保 证申明的产品组成
如过程控制中对活性物质
进行的有记录的含量分析