ISO 19609-1:2021
(Main)Traditional Chinese medicine — Quality and safety of raw materials and finished products made with raw materials — Part 1: General requirements
Traditional Chinese medicine — Quality and safety of raw materials and finished products made with raw materials — Part 1: General requirements
This document specifies general requirements within a quality control framework for raw materials and finished products used in and as traditional Chinese medicine (TCM) and derivative forms, and the comparison between the starting materials and the finished products, if necessary.
Médecine traditionnelle chinoise — Qualité et sécurité des matières premières et des produits finis fabriqués à partir de matières premières — Partie 1: Exigences générales
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INTERNATIONAL ISO
STANDARD 19609-1
First edition
2021-01
Traditional Chinese medicine —
Quality and safety of raw materials
and finished products made with raw
materials —
Part 1:
General requirements
Médecine traditionnelle chinoise — Qualité et sécurité des matières
premières et des produits finis fabriqués à partir de matières
premières —
Partie 1: Exigences générales
Reference number
ISO 19609-1:2021(E)
©
ISO 2021
---------------------- Page: 1 ----------------------
ISO 19609-1:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
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ISO 19609-1:2021(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Overview of herbal medicinal products . 3
4.1 Raw materials . 3
4.2 Products of raw materials . 3
4.2.1 General. 3
4.2.2 Decoction pieces, medicinal decoctions prepared from decoction pieces
and wine preparations or powders . 4
4.2.3 Finished products for modernized traditional therapy . 4
4.2.4 Non-traditionally produced finished products for phytotherapy. 5
5 Quality testing . 5
5.1 General . 5
5.2 Testing procedure . 6
6 Testing of physical parameters . 6
6.1 General . 6
6.2 Sampling . 7
6.2.1 General. 7
6.2.2 Bulk sampling method . 7
6.2.3 Test sampling method . 7
6.3 Estimation of the water content of herbals and resulting products . 8
6.3.1 General. 8
6.3.2 Testing methods . 8
6.4 Requirements and testing methods for finished products for modernized
traditional therapy and non-traditionally produced finished products for phytotherapy .11
6.4.1 General.11
6.4.2 Estimation of the uniformity of dosage units .11
6.4.3 Disintegration test for solid dosage forms like tablets and capsules .12
6.4.4 Estimation of particle size for powders and other small dosage forms .14
6.4.5 Estimation of the pH-value of liquids, solutions or suspensions by
potentiometric determination .15
6.4.6 Dissolution test for solid dosage forms .15
6.5 Estimation of the content of residual solvents .17
6.5.1 General.17
6.5.2 Types of typically used solvents .17
6.5.3 Reagents .19
6.5.4 Sample preparation .19
6.5.5 Apparatus .19
6.5.6 Procedure .19
6.5.7 System suitability .21
6.5.8 Calculation .21
6.6 Stability of TCM products .21
6.6.1 General.21
6.6.2 Estimation of the stability of TCM products .21
Bibliography .22
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ISO 19609-1:2021(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to
the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www .iso .org/ iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 249, Traditional Chinese medicine.
A list of all parts in the ISO 19609 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
iv © ISO 2021 – All rights reserved
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ISO 19609-1:2021(E)
Introduction
The ISO 19609 series consists of four parts with different content as shown in Figure 1.
Figure 1 — Overview of the ISO 19609 series
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INTERNATIONAL STANDARD ISO 19609-1:2021(E)
Traditional Chinese medicine — Quality and safety of
raw materials and finished products made with raw
materials —
Part 1:
General requirements
1 Scope
This document specifies general requirements within a quality control framework for raw materials
and finished products used in and as traditional Chinese medicine (TCM) and derivative forms, and the
comparison between the starting materials and the finished products, if necessary.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 760, Determination of water — Karl Fischer method (General method)
ISO 3310-1, Test sieves — Technical requirements and testing — Part 1: Test sieves of metal wire cloth
ISO 10523, Water quality — Determination of pH
ISO 12937, Petroleum products — Determination of water — Coulometric Karl Fischer titration method
ISO 19609-2, Traditional Chinese medicine — Quality and safety of raw materials and finished products
made with raw materials — Part 2: Identity testing of constituents of herbal origin
ISO 22217, Traditional Chinese medicine — Storage requirements for Chinese materia medica and
decoction pieces
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
active substance
substance of physiological or pharmacological action
3.2
finished product for modernized traditional therapy
concentrated product from hot aqueous decoctions of decoction pieces (3.3) or other starting materials
(3.11) as well as powder made from starting materials described in pharmacopoeias, applied in the
dosage forms of capsules, granules or tablets
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ISO 19609-1:2021(E)
3.3
decoction piece
prescription medicinal processed from Chinese Materia Medica under the direction of TCM and
processing methods for Chinese medicines and derivative forms, which can be directly used in clinical
practice or the production of prepared medicines
[SOURCE: ISO 18668-1:2016, 3.3, modified — Note 1 to entry amalgamated with definition.]
3.4
disintegration
physical breakdown of a material into very small fragments in a pharmaceutical context except
insoluble coating materials or broken capsule shell
[SOURCE: ISO 17088:2012, 3.6, definition modified.]
3.5
dissolution
process of obtaining a solution containing the analyte of interest in a pharmaceutical context
[SOURCE: ISO/TR 19057:2017, 3.6, definition modified.]
3.6
finished product
commercial product intended for sale and use, including decoction pieces (3.3)
3.7
foreign matter
material consisting of any or all foreign tissues (matter coming from the source plant but not defined
as the right herbal material) and foreign elements (other matter of vegetable, animal or mineral origin)
3.8
non-traditionally produced finished product for phytotherapy
product made from TCM raw materials (3.9) which are not decoction pieces (3.3) or finished products for
modernized traditional therapy (3.2)
EXAMPLE Organic extracts and products made from these extracts.
3.9
raw material
substance going into or involved in the manufacturing of a bulk product
[SOURCE: ISO 22716:2007, 2.28]
3.10
residual solvent
organic volatile chemical used or produced in the manufacturing of extracts or excipients or in the
preparation of medicinal products, and not completely removed by practical manufacturing techniques
3.11
starting material
material received by a manufacturer to be commercially processed, manufactured or packaged
Note 1 to entry: This includes raw materials (3.9) and other materials, for example solvents, excipients and
capsule shells.
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ISO 19609-1:2021(E)
4 Overview of herbal medicinal products
4.1 Raw materials
Raw materials of TCM are:
a) herbal material (e.g. flowers, herbs, seeds, fruits, roots and other parts of medicinal plants, fresh
juices, gums, natural essential oils, resins);
b) parts of animals (e.g. mussels, bombyx);
c) minerals.
NOTE Herbal and animal material can be subject to CITES rules.
4.2 Products of raw materials
4.2.1 General
Products of raw materials are divided into three groups depending on the form of therapy:
a) decoction pieces, medicinal decoction prepared from decoction pieces and wine preparations or
powders for traditional therapy;
b) finished products for modernized traditional therapy (e.g. capsules, coated and uncoated tablets,
powders and granules);
c) non-traditionally produced finished products for phytotherapy (e.g. regulated formulas as
remedies, made from extracts with other solvents instead of water).
Figure 2 shows the different types of products applied in the field of TCM. The categorization is
necessary based on the different requirements of pharmaceutical products.
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ISO 19609-1:2021(E)
Figure 2 — Classification of products of raw materials
4.2.2 Decoction pieces, medicinal decoctions prepared from decoction pieces and wine
preparations or powders
The typical raw materials used in and as TCM are decoction pieces in the form of cut raw materials.
These are intended to produce a preparation using hot or boiling water.
NOTE 1 In the classical TCM therapy, herbal and animal material as well as minerals were cut into smaller
pieces and used during or after a processing step (e.g. steaming, cooking, calcinating) as a source for the
individual mixture after a practitioner's or doctor's prescription.
NOTE 2 A special cutting is used for KAMPO herbals in Japan.
[10] [11]
NOTE 3 In some cases, wine can be used as a solvent instead of water according to the Chinese , Japanese
[9]
and Korean pharmacopoeias.
4.2.3 Finished products for modernized traditional therapy
Finished products for modernized traditional therapy are:
a) concentrates from hot aqueous preparations;
NOTE 1 Only hot water decoctions can be seen as typically traditional, without toxicity risks.
NOTE 2 Traditionally produced wine preparation can also be used.
[10] [11] [9]
b) powders made from raw materials which are described in the Chinese , Japanese and Korean
pharmacopoeias;
NOTE 3 In the case of powdered materials, there are risks for the patients because of the potential toxicity
of the raw materials.
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ISO 19609-1:2021(E)
c) capsules, coated and uncoated tablets, powders and granules as dosage forms based on a) or b).
NOTE 4 The toxic risks cannot be extrapolated from traditional use of the decoctions. A lot of lipophilic
compounds can be seen as toxic (e.g. aristolochic acid, which was not a problem in decoctions in TCM). The
toxic risks of lipophilic compounds do not appear in water decoctions, but in powders, alcoholic extracts and
lipophilic concentrates.
4.2.4 Non-traditionally produced finished products for phytotherapy
Non-traditionally produced finished products for phytotherapy are raw materials and products not
listed in 4.2.2 and 4.2.3.
The pharmacology and toxicology of these products shall be tested by the producer before marketing.
NOTE 1 TCM products can be seen in parallel to the “European Phytomedicine”.
NOTE 2 KAMPO products extracted with up to 30 % ethanol do not need to be declared in Japan.
NOTE 3 For the markets in Europe and associated countries a registration is required for each product
independent of specific dosage forms.
NOTE 4 Products made with supercritical carbon dioxide are not allowed in countries which apply the
[14]
European Pharmacopoeia .
5 Quality testing
5.1 General
The quality of therapeutics is internationally defined with three general criteria: potency, safety and
accuracy. These criteria are also relevant for TCM therapeutics (see Figure 3).
Figure 3 — General criteria for TCM therapeutics
Quality criteria of raw materials and products of raw materials are defined in the ISO 19609 series as
follows:
— correct physical parameters;
— correct identity of herbal ingredients;
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ISO 19609-1:2021(E)
— absence of contaminants;
— absence of preservatives and unwanted compounds.
5.2 Testing procedure
Products of raw materials shall be tested for physical parameters, if applicable, in accordance with
Clause 6.
Products of raw materials shall be tested for the identity of the herbal ingredients in accordance with
ISO 19609-2.
Products of raw materials shall be tested for the absence of contaminants.
Products of raw materials shall be tested for the absence of preservatives and unwanted compounds
for individual materials.
6 Testing of physical parameters
6.1 General
The physical tests detailed in Figure 4 should be used, if applicable.
Figure 4 — Physical parameters for TCM products (if applicable)
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ISO 19609-1:2021(E)
The requirements and methods are typically unique for a specific dosage form and listed also in the
different pharmacopoeias.
6.2 Sampling
6.2.1 General
In order to reduce the effect of inhomogeneity of the sample in qualitative and quantitative analysis, the
composition of the sample used shall be representative of the batch of material being examined.
6.2.2 Bulk sampling method
The bulk sample shall be collected by combining and thoroughly mixing the part samples taken from
containers, bales and bags.
One part sample from each container shall be sampled. Samples shall be taken from the upper, middle
and lower section of the container and shall be combined so that the samples are representative of
different parts of the containers.
In the case of large bales or bags, samples shall be taken from a depth of at least 10 cm.
6.2.3 Test sampling method
6.2.3.1 General
The reduction of the size of the bulk sample shall be done by the method of quartering.
Other appropriate methods that produce a homogeneous sample may be used, making sure that each
retained portion remains representative of the whole.
The minimum retained quantity of the test samples shall conform to the conditions in Table 1.
Table 1 — Minimum weight of test samples
Type of herbal material Minimum weight of test sample
Roots, rhizomes, bark, herbs 250 g or mass of whole sample if bulk sample is less
than 250 g
Leaves, flowers, seeds, fruits 125 g or mass of whole sample if bulk sample is less
than 125 g
Broken or fragmented crude materials (where the 75 g
average mass of the pieces is less than 0,5 g)
After reduction of sample size a test for foreign matter shall be done.
For the preparation of the test samples for chemical and chromatographic analysis, as well as for
determination of microscopic characteristics, a milling and sieving process is necessary.
6.2.3.2 Apparatus
Use the usual laboratory equipment and, in particular, the following.
6.2.3.2.1 Analytical balance, weighing to an accuracy of 1 mg.
6.2.3.2.2 Milling apparatus.
6.2.3.2.3 Sieves, with 1 mm and 0,355 mm screen in accordance with ISO 3310-1.
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ISO 19609-1:2021(E)
6.2.3.3 Procedure for producing specific test samples
6.2.3.3.1 Quartering
The bulk sample shall be placed after thoroughly mixing as a level and square-shaped heap. The
material shall be divided diagonally into four equal parts. Two opposite quarters shall be retained and
carefully remixed. The process shall be repeated as necessary until the required minimum mass (see
Table 1) is obtained for the test sample.
6.2.3.3.2 Test for foreign matter
Herbal materials should be free of mould, insects and other animal contaminants. Accepted levels of
foreign matter are documented in the relevant monographs.
Materials identified visually as foreign matter shall be separated manually and weighed with an
analytical balance.
The content of foreign matter shall be calculated as a percentage of the whole test sample. The result
shall be documented.
6.2.3.3.3 Preparing test samples for chemical and chromatographic analysis
The test sample shall be milled and sieved through a 1 mm screen or the screen size specified in a
specific monograph. The use of a milling machine is recommended.
The residue retained on the sieve shall not be more than 10 % of the total mass of the milled sample.
In those cases where this requirement cannot be met because of physical specifities of the raw material,
the test sample for analysis shall be composed of the two parts measured separately. Therefore, the
quantity required for each analysis shall be derived by weighing proportional quantities of the powder
and the residue.
6.2.3.3.4 Preparing test samples for determination of microscopic characters
A portion of the milled test sample (see 6.2.3.3.3) shall be re-milled and sieved through a 0,355 mm
screen or a finer screen.
NOTE The details of microscopic characterization are also described in ISO 19609-2 and ISO/TS 21310.
6.3 Estimation of the water content of herbals and resulting products
6.3.1 General
The water content should be not higher than 10 %, because this reduces the stability of dried raw
materials and resulting products made from herbal materials. Different water contents are specified in
the individual monographs.
NOTE On one hand chemical reactions need, in a high number of reaction types, water as solvent or as
reagent. On the other hand, higher amounts of residual water in raw materials as well as in ready products are,
together with organic substances and temperature, the best growing conditions for microorganisms and their
degradation of substrate.
6.3.2 Testing methods
6.3.2.1 General
For the estimation of the water content one of the following methods shall be used:
— loss on drying (see 6.3.2.2);
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ISO 19609-1:2021(E)
— quantitative analysis of water content (see 6.3.2.3).
6.3.2.2 Loss on drying
6.3.2.2.1 General
The estimation of the loss on drying is a method to estimate the total content of water and other volatile
constituents, for example essential oils. In accordance with the expected content of these volatile
constituents, one the following methods shall be used:
— method for raw materials and products with no or low content of essential oils;
— method for raw materials and products with higher content of essential oils;
— method for raw materials and products with unstable constituents.
6.3.2.2.2 Sample preparation
In a flat-bottomed weighing bottle about 50 mm in diameter and 30 mm in height quickly weigh about
0,50 g of the material or product to be examined in powdered form.
6.3.2.2.3 Reagents
6.3.2.2.3.1 Diphosphorus pentoxide.
6.3.2.2.3.2 Anhydrous silica gel.
6.3.2.2.4 Apparatus
Use the usual laboratory equipment and, in particular, the following.
6.3.2.2.4.1 Analytical balance, weighing to an accuracy of 0,1 mg.
6.3.2.2.4.2 Desiccator.
6.3.2.2.4.3 Laboratory oven (100 °C to 105 °C), if applicable.
6.3.2.2.4.4 Vacuum unit (1,5 kPa to 2,5 kPa), if applicable.
6.3.2.2.5 Method for raw materials and products with no or low content of essential oils
Drying shall be done in an oven at 100 °C to 105 °C for 3 h. After cooling in a desiccator over diphosphorus
pentoxide or anhydrous silica gel, the material shall be weighed. The calculation of the result shall be
expressed as a mass percentage.
6.3.2.2.6 Method for raw materials and products with higher content of essential oils
Drying of the material shall be done to constant mass in a desiccator. The drying shall be carried out
over diphosphorus pentoxide at atmospheric pressure and at room temperature. After weighing, the
result shall be calculated and expressed as a mass percentage.
6.3.2.2.7 Method for raw materials and products with unstable constituents
Drying of the material shall be done to constant mass in vacuo in a desiccator. The drying is carried out
over diphosphorus pentoxide at a pressure of 1,5 kPa to 2,5 kPa at room temperature. After weighing,
the result shall be calculated as a mass percentage.
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ISO 19609-1:2021(E)
6.3.2.3 Quantitative analysis of water content
6.3.2.3.1 General
The estimation of the quantitative analysis of water content is a method to estimate the total content of
water. One of the following methods shall be used:
— titration according to Karl Fischer in accordance with ISO 760;
— coulometric determination of water in accordance with ISO 12937;
— determination of water with distillation;
— determination of water with gas chromatography with thermal conductivity detector (TCD)
(see 6.3.2.3.2).
6.3.2.3.2 Determination of water with gas chromatography with thermal conductivity
detector (TCD)
6.3.2.3.2.1 Sample preparation
50 mg of powdered test sample shall be correctly weighed. The resulting powder shall be dissolved in
200 µl of dried dimethyl sulfoxide (DMSO) in a disposable special dried vial.
6.3.2.3.2.2 Reagents
Dried DMSO.
6.3.2.3.2.3 Apparatus
Use the usual
...
FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 19609-1
ISO/TC 249
Traditional Chinese medicine —
Secretariat: SAC
Quality and safety of raw materials
Voting begins on:
2020-10-01 and manufacturing products made
with raw materials —
Voting terminates on:
2020-11-26
Part 1:
General requirements
Partie 1: Généralités
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/FDIS 19609-1:2020(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
©
NATIONAL REGULATIONS. ISO 2020
---------------------- Page: 1 ----------------------
ISO/FDIS 19609-1:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/FDIS 19609-1:2020(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Overview of herbal medicinal products . 3
4.1 Raw materials . 3
4.2 Products of raw materials . 3
4.2.1 General. 3
4.2.2 Decoction pieces, medicinal decoctions prepared from decoction pieces
and wine preparations or powders . 4
4.2.3 Finished products for modernized traditional therapy . 4
4.2.4 Non-traditionally produced finished products for phytotherapy. 5
5 Quality testing . 5
5.1 General . 5
5.2 Testing procedure . 6
6 Testing of physical parameters . 6
6.1 General . 6
6.2 Sampling . 7
6.2.1 General. 7
6.2.2 Bulk sampling method . 7
6.2.3 Test sampling method . 7
6.3 Estimation of the water content of herbals and resulting products . 8
6.3.1 General. 8
6.3.2 Testing methods . 8
6.4 Requirements and testing methods for finished products for modernized
traditional therapy and non-traditionally produced finished products for phytotherapy .11
6.4.1 General.11
6.4.2 Estimation of the uniformity of dosage units .11
6.4.3 Disintegration test for solid dosage forms like tablets and capsules .12
6.4.4 Estimation of particle size for powders and other small dosage forms .14
6.4.5 Estimation of the pH-value of liquids, solutions or suspensions by
potentiometric determination .15
6.4.6 Dissolution test for solid dosage forms .15
6.5 Additional requirements for non-traditionally produced finished products for
phytotherapy .17
6.5.1 Estimation of the content of residual solvents .17
6.6 Stability of TCM products .22
6.6.1 General.22
6.6.2 Estimation of the stability of TCM products .22
Bibliography .23
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ISO/FDIS 19609-1:2020(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to
the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www .iso .org/ iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 249, Traditional Chinese medicine.
A list of all parts in the ISO 19609 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
iv © ISO 2020 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/FDIS 19609-1:2020(E)
Introduction
The ISO 19609 series consists of four parts with different content as shown in Figure 1.
Figure 1 — Overview of the ISO 19609 series
© ISO 2020 – All rights reserved v
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FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 19609-1:2020(E)
Traditional Chinese medicine — Quality and safety of raw
materials and manufacturing products made with raw
materials —
Part 1:
General requirements
1 Scope
This document specifies general requirements within a quality control framework for raw materials
and finished products used in and as traditional Chinese medicine (TCM) and derivative forms, and the
comparison between the starting materials and the finished products, if necessary.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 760, Determination of water — Karl Fischer method (General method)
ISO 3310-1, Test sieves — Technical requirements and testing — Part 1: Test sieves of metal wire cloth
ISO 10523, Water quality — Determination of pH
ISO 12937, Petroleum products — Determination of water — Coulometric Karl Fischer titration method
ISO 19609-2, Traditional Chinese medicine — Quality and safety of raw materials and manufacturing
products made with raw materials — Part 2: Identity testing of constituents of herbal origin
ISO 22217, Traditional Chinese medicine — Storage requirements for Chinese materia medica and
decoction pieces
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
active substance
substance of physiological or pharmacological action
3.2
finished product for modernized traditional therapy
concentrated product from hot aqueous decoctions of decoction pieces (3.3) or other starting materials
(3.11) as well as powder made from starting materials described in pharmacopoeias, applied in the
dosage forms of capsules, granules or tablets
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3.3
decoction piece
prescription medicinal processed from Chinese Materia Medica under the direction of TCM and
processing methods for Chinese medicines and derivative forms, which can be directly used in clinical
practice or the production of prepared medicines
[SOURCE: ISO 18668-1:2016, 3.3, modified — Note 1 to entry amalgamated with definition.]
3.4
disintegration
physical breakdown of a material into very small fragments in a pharmaceutical context except
insoluble coating materials or broken capsule shell
[SOURCE: ISO 17088:2012, 3.6, definition modified.]
3.5
dissolution
process of obtaining a solution containing the analyte of interest in a pharmaceutical context
[SOURCE: ISO/TR 19057:2017, 3.6, definition modified.]
3.6
finished product
commercial product intended for sale and use, including decoction pieces (3.3)
3.7
foreign matter
material consisting of any or all foreign organs (matter coming from the source plant but not defined
as the right herbal material) and foreign elements (other matter of vegetable, animal or mineral origin)
3.8
non-traditionally produced finished product for phytotherapy
product made from TCM raw materials (3.9) which are not decoction pieces (3.3) or finished products for
modernized traditional therapy (3.2)
EXAMPLE Organic extracts and products made from these extracts.
3.9
raw material
substance going into or involved in the manufacturing of a bulk product
[SOURCE: ISO 22716:2007, 2.28]
3.10
residual solvent
organic volatile chemical used or produced in the manufacturing of extracts or excipients or in the
preparation of medicinal products, and not completely removed by practical manufacturing techniques
3.11
starting material
material received by a manufacturer to be commercially processed, manufactured or packaged
Note 1 to entry: This includes raw materials (3.9) and other materials, for example solvents, excipients and
capsule shells.
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4 Overview of herbal medicinal products
4.1 Raw materials
Raw materials of TCM are:
a) herbal material (e.g. flowers, herbs, seeds, fruits, roots and other parts of medicinal plants, fresh
juices, gums, natural essential oils, resins);
b) parts of animals (e.g. mussels, bombyx);
c) minerals.
NOTE Herbal and animal material can be subject to CITES rules.
4.2 Products of raw materials
4.2.1 General
Products of raw materials are divided into three groups depending on the form of therapy:
a) decoction pieces, medical decoction prepared from decoction pieces and wine preparations or
powders for traditional therapy;
b) finished products for modernized traditional therapy (e.g. capsules, coated and uncoated tablets,
powders and granules);
c) non-traditionally produced finished products for phytotherapy (e.g. regulated formulas as
remedies, made from extracts with other solvents instead of water).
Figure 2 shows the different types of products applied in the field of TCM. The categorization is
necessary based on the different requirements of pharmaceutical products.
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Figure 2 — Classification of products of raw materials
4.2.2 Decoction pieces, medicinal decoctions prepared from decoction pieces and wine
preparations or powders
The typical raw materials used in and as TCM are decoction pieces in the form of cut raw materials.
These are intended to produce a preparation using hot or boiling water.
NOTE 1 In the classical TCM therapy, herbal and animal material as well as minerals were cut into smaller
pieces and used during or after a processing step (e.g. steaming, cooking, calcinating, paozhi) as a source for the
individual mixture after a practitioner's and doctor's prescription.
NOTE 2 A special cutting is used for KAMPO herbals in Japan.
[10] [11]
NOTE 3 In some cases, wine can be used as a solvent instead of water according to the Chinese , Japanese
[9]
and Korean pharmacopoeias.
4.2.3 Finished products for modernized traditional therapy
Finished products for modernized traditional therapy are:
a) concentrates from hot aqueous preparations;
NOTE 1 Only hot water decoctions can be seen as typically traditional, without toxicity risks.
NOTE 2 Traditionally produced wine preparation can also be used.
[10] [11] [9]
b) powders made from raw materials which are described in the Chinese , Japanese and Korean
pharmacopoeias;
NOTE 3 In the case of powdered materials, there are risks for the patients because of the potential toxicity
of the raw materials.
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c) capsules, coated and uncoated tablets, powders and granules as dosage forms based on a) or b).
NOTE 4 The toxic risks cannot be extrapolated from traditional use of the decoctions. A lot of lipophilic
compounds can be seen as toxic (e.g. aristolochic acid, which was not a problem in decoctions in TCM). The
toxical risks of lipophilic compounds do not appear in water decoctions, but in powders, alcoholic extracts
and lipophilic concentrates.
4.2.4 Non-traditionally produced finished products for phytotherapy
Non-traditionally produced finished products for phytotherapy are raw materials and products not
listed in 4.2.2 and 4.2.3.
The pharmacology and toxicology of these products shall be tested by the producer before marketing.
NOTE 1 TCM products can be seen in parallel to the “European Phytomedicine”.
NOTE 2 KAMPO products extracted with up to 30 % ethanol do not need to be declared in Japan.
NOTE 3 For the markets in Europe and associated countries a registration is required for each product
independent of specific dosage forms.
NOTE 4 Products made with supercritical carbon dioxide are not allowed in countries which apply the
[14]
European Pharmacopoeia .
5 Quality testing
5.1 General
The quality of therapeutics is internationally defined with three general criteria: potency, safety and
accuracy. These criteria are also relevant for TCM therapeutics (see Figure 3).
Figure 3 — General criteria for TCM therapeutics
Quality criteria of raw materials and products of raw materials are defined in the ISO 19609 series as
follows:
— correct physical parameters;
— correct identity of herbal ingredients;
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— absence of contaminants;
— absence of preservatives and unwanted compounds.
5.2 Testing procedure
Products of raw materials shall be tested for physical parameters, if applicable, in accordance with
Clause 6.
Products of raw materials shall be tested on the identity of the herbal ingredients in accordance with
ISO 19609-2.
Products of raw materials shall be tested on the absence of contaminants.
Products of raw materials shall be tested on the absence of preservatives and unwanted compounds for
individual materials.
6 Testing of physical parameters
6.1 General
The physical tests detailed in Figure 4 should be used, if applicable.
Figure 4 — Physical parameters for TCM products (if applicable)
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The requirements and methods are typically unique for a specific dosage form and listed also in the
different pharmacopoeias.
6.2 Sampling
6.2.1 General
In order to reduce the effect of inhomogeneity of the sample in qualitative and quantitative analysis, the
composition of the sample used shall be representative of the batch of material being examined.
6.2.2 Bulk sampling method
The bulk sample shall be collected by combining and thoroughly mixing the part samples taken from
containers, bales and bags.
One part sample from each container shall be sampled. Samples shall be taken from the upper, middle or
lower section of the container and shall be combined so that the samples are representative of different
parts of the containers.
In the case of large bales or bags, samples shall be taken from a depth of at least 10 cm.
6.2.3 Test sampling method
6.2.3.1 General
The reduction of the size of the bulk sample shall be done by the method of quartering.
Other appropriate methods that produce a homogeneous sample may be used, making sure that each
retained portion remains representative of the whole.
The minimum retained quantity of the test samples shall conform with the conditions in Table 1.
Table 1 — Minimum weight of test samples
Type of herbal material Minimum weight of test sample
Roots, rhizomes, bark, herbs 250 g or mass of whole sample if bulk sample is less
than 250 g
Leaves, flowers, seeds, fruits 125 g or mass of whole sample if bulk sample is less
than 125 g
Broken or fragmented crude materials (where the 75 g
average mass of the pieces is less than 0,5 g)
After reduction of sample size a test for foreign matter shall be done.
For the preparation of the test samples for chemical and chromatographic analysis, as well as for
determination of microscopic characters, a milling and sieving process is necessary.
6.2.3.2 Apparatus
Use the usual laboratory equipment and, in particular, the following.
6.2.3.2.1 Analytical balance, weighing to an accuracy of 1 mg.
6.2.3.2.2 Milling apparatus.
6.2.3.2.3 Sieves, with 1 mm and 0,355 mm screen in accordance with ISO 3310-1.
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6.2.3.3 Procedure for producing specific test samples
6.2.3.3.1 Quartering
The bulk sample shall be placed after thoroughly mixing as a level and square-shaped heap. The
material shall be divided diagonally into four equal parts. Two opposite quarters shall be retained and
carefully remixed. The process shall be repeated as necessary until the required minimum mass (see
Table 1) is obtained for the test sample.
6.2.3.3.2 Test for foreign matter
Herbal materials should be free from moulds, insects and other animal contaminants. Accepted levels
of foreign matter are documented in the relevant monographs.
Materials identified visually as foreign matter shall be separated manually and weighed with an
analytical balance.
The content of foreign matter shall be calculated as a percentage of the whole test sample. The result
shall be documented.
6.2.3.3.3 Preparing test samples for chemical and chromatographic analysis
The test sample shall be milled and sieved through a 1 mm screen or the screen size specified in a
specific monograph. The use of a milling machine is recommended.
The residue retained on the sieve shall not be more than 10 % of the total mass of the milled sample.
In those cases where this requirement cannot be met because of physical specifities of the raw material,
the test sample for analysis shall be composed of the two parts measured separately. Therefore, the
quantity required for each analysis shall be derived by weighing proportional quantities of the powder
and the residue.
6.2.3.3.4 Preparing test samples for determination of microscopic characters
A portion of the milled test sample (see 6.2.3.3.3) shall be re-milled and sieved through a 0,355 mm
screen or a finer screen.
NOTE The details of microscopic characterization are also described in ISO 19609-2 and ISO/TS 21310.
6.3 Estimation of the water content of herbals and resulting products
6.3.1 General
The water content should be not higher than 10 %, because this reduces the stability of dried raw
materials and resulting products made from herbal materials. Different water contents are specified in
the individual monographs.
NOTE On one hand chemical reactions need, in a high number of reaction types, water as solvent or as
reagent. On the other hand, higher amounts of residual water in raw materials as well as in ready products are,
together with organic substances and temperature, the best growing conditions for microorganisms and their
degradation of substrate.
6.3.2 Testing methods
6.3.2.1 General
For the estimation of the water content one of the following methods shall be used:
— loss on drying (see 6.3.2.2);
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— quantitative analysis of water content (see 6.3.2.3).
6.3.2.2 Loss on drying
6.3.2.2.1 General
The estimation of the loss on drying is a method to estimate the total content of water and other volatile
constituents, for example essential oils. In accordance with the expected content of these volatile
constituents, one the following methods shall be used:
— method for raw materials and products with no or low content of essential oils;
— method for raw materials and products with higher content of essential oils;
— method for raw materials and products with unstable constituents.
6.3.2.2.2 Sample preparation
In a flat-bottomed weighing bottle about 50 mm in diameter and about 30 mm in height the material or
product to be examined shall be weighed rapidly at about 0,50 g in powdered form.
6.3.2.2.3 Reagents
6.3.2.2.3.1 Diphosphorus pentoxide.
6.3.2.2.3.2 Anhydrous silica gel.
6.3.2.2.4 Apparatus
Use the usual laboratory equipment and, in particular, the following.
6.3.2.2.4.1 Analytical balance, weighing to an accuracy of 0,1 mg.
6.3.2.2.4.2 Desiccator.
6.3.2.2.4.3 Laboratory oven (100 °C to 105 °C), if applicable.
6.3.2.2.4.4 Vacuum unit (1,5 kPa to 2,5 kPa), if applicable.
6.3.2.2.5 Method for raw materials and products with no or low content of essential oils
Drying shall be done in an oven at 100 °C to 105 °C for 3 h. After cooling in a desiccator over diphosphorus
pentoxide or anhydrous silica gel, the material shall be weighted. The calculation of the result shall be
expressed as a mass percentage.
6.3.2.2.6 Method for raw materials and products with higher content of essential oils
Drying of the material shall be done to constant mass in a desiccator. The drying shall be carried out
over diphosphorus pentoxide at atmospheric pressure and at room temperature. After weighing, the
result shall be calculated and expressed as a mass percentage.
6.3.2.2.7 Method for raw materials and products with unstable constituents
Drying of the material shall be done to constant mass in vacuo in a desiccator. The drying is carried out
over diphosphorus pentoxide at a pressure of 1,5 kPa to 2,5 kPa at room temperature. After weighing,
the result shall be calculated as a mass percentage.
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6.3.2.3 Quantitative analysis of water content
6.3.2.3.1 General
The estimation of the quantitative analysis of water content is a method to estimate the total content of
water. One of the following methods shall be used:
— titration according to Karl Fischer in accordance with ISO 760;
— coulometric determination of water in accordance with ISO 12937;
— determination of water with distillation;
— determination of water with gas chromatography with thermal conductivity detector (TCD)
(see 6.3.2.3.2).
6.3.2.3.2 Determination of water with gas chromatography with thermal conductivity
detector (TCD)
6.3.2.3.2.1 Sample preparation
50 mg of powdered test sample shall be correctly weighted. The resulting powder shall be dissolved
within 200 µl of dried dimethyl sulfoxide (DMSO) in a disposable special dried vial.
6.3.2.3.2.2 Reagents
Dried DMSO.
6.3.2.3.2.3 Apparatus
Use the usual laboratory equipment and, in particular, the following:
Gas chromatograph, with TCD.
6.3.2.3.2.4 Procedure and analytical conditions
The gas chromatography with TCD shall be done following the conditions in Table 2.
Table 2 — Conditions for gas chromatography analysis
Solvent DMSO
Column Gas chromatography (GC) column packed with 6 % cyanopropylphenyl/94 % di-
methylpolysiloxan or another appropriate stationary phase material
Gradient Time Temperature Slope
0 min 40 °C
2 min 40 °C
18 min 200 °C 10 °C/min
Detection TCD
Conditions Carrier Helium 45 kPa
Injector temperature 250 °C
Detector temperature TCD 260 °C
Sensitivity 0 - 1 000 mV
Record interval 18 mi
...
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