ISO 19609-4:2022

INTERNATIONAL ISO
STANDARD 19609-4
First edition
2022-12
Traditional Chinese medicine —
Quality and safety of raw materials
and finished products made with raw
materials —
Part 4:
Testing for preservatives and
unwanted compounds
Médecine traditionnelle chinoise — Qualité et sécurité des matières
premières et des produits finis fabriqués à partir de matières
premières —
Partie 4: Essais des conservateurs et composés indésirables
Reference number
© ISO 2022
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
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Testing for the absence of unwanted compounds and radiation . 2
4.1 General . 2
4.2 Overview . 2
4.3 Determination of preservatives . 2
4.3.1 General . 2
4.3.2 Determination of preservatives . 2
4.3.3 Declaration . 3
4.3.4 Analysis of sulfur and sulfur derivatives . 3
4.3.5 Analysis of ethylene oxide . 5
4.4 Determination of irradiated material . 6
4.4.1 General . 6
4.4.2 Analysis of irradiated traditional Chinese medicine using photostimulated
luminescence . 6
4.5 Determination of toxic compounds . 7
4.5.1 General . 7
4.5.2 Natural toxins . 7
4.5.3 Toxins resulting from degradation reactions .13
Annex A (informative) Materia medica .14
Annex B (informative) Examples of typical chromatograms of Ephedra herba, Strychni
semen, Sophorae tonkinensis radix et rhizoma and their toxic compounds .15
Bibliography .22
iii
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
Introduction
The ISO 19609 series consists of four different parts with different content as shown in Figure 1.
Figure 1 — Overview of the ISO 19609 series
v
INTERNATIONAL STANDARD ISO 19609-4:2022(E)
Traditional Chinese medicine — Quality and safety of
raw materials and finished products made with raw
materials —
Part 4:
Testing for preservatives and unwanted compounds
1 Scope
This document specifies the testing of preservatives and unwanted compounds within a quality control
framework for starting materials and finished products used in and as traditional Chinese medicine.
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 22256, Traditional Chinese medicine — Detection of irradiated natural products by photostimulated
luminescence
ISO 22590, Traditional Chinese medicine — Determination of sulfur dioxide in natural products by titration
ISO 23190, Traditional Chinese medicine — Determination of aristolochic acids in natural products by high-
performance liquid chromatography (HPLC)
ISO 23956, Traditional Chinese medicine — Determination of benzopyrene in processed natural products
ISO 23962, Traditional Chinese medicine — Processed Aconitum carmichaelii lateral root
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
unwanted compound
Constituent of a product which is unsuitable or unsafe for the intended use of that product.
Note 1 to entry: Such compounds can be those added for preservation or which result from a degradation process.
Toxic natural compounds can also be considered unwanted compounds.
3.2
preservative
component intended to prevent the growth of microorganisms in or on a product
[SOURCE: ISO 18369-1:2017, 3.1.11.7]
3.3
excipient
material that is present in a therapeutic product administered to a patient, other than the active
substance(s)
[SOURCE: ISO/TS 20399-1:2018, 3.7, modified — Definition revised, example and note to entry
removed.]
4 Testing for the absence of unwanted compounds and radiation
4.1 General
For the risk assessment of traditional Chinese medicine products, the presence and/or the amount of
unwanted compounds shall be estimated.
4.2 Overview
These unwanted compounds and radiation can be categorized in three main groups:
a) preservatives;
b) radiation;
c) toxic compounds:
— natural toxins;
— toxins resulting from degradation reactions;
d) other additives.
4.3 Determination of preservatives
4.3.1 General
Preservatives are pharmaceutical excipients added to therapeutic products to extend their shelf life
and prevent contamination with microorganisms such as bacteria and fungi. Their possible adverse
effects include allergic reactions and irritation.
4.3.2 Determination of preservatives
4.3.2.1 General
The determination and quantification should be done by specific and valid analytical procedures.
Preservatives in traditional Chinese medicine products are listed on the product ingredient list.
4.3.2.2 Sulfur and sulfur derivatives
Sulfur and sulfur derivatives include elemental sulfur and sulfites such as potassium sulfide and sodium
sulfite, as well as sulfur dioxide and other sulfur-containing additives.
NOTE Sulfur dioxide or sulfite formed in aqueous solution has a preserving effect by irretrievably inhibiting
metabolism and damage to the cell membranes from microorganisms as well as destroying the secondary and
tertiary structure of microbial enzymes.
4.3.2.3 Ethylene oxide
Ethylene oxide gas kills bacteria, viruses and fungi, so it can be used for fumigation of heat-sensitive
substances. Sterilization with ethylene oxide is a widespread process in the industrial manufacture of
medical products, especially disposable products such as dressings, sutures or syringes and catheters.
NOTE The use of ethylene oxidein pharmaceuticals has been banned in the territory of the European
pharmacopoeia since 1981 because it can produce toxic 2-chloroethanol.
4.3.3 Declaration
Preservatives shall be declared in all traditional Chinese medicine products and starting materials on
the product label or in related documents such as a Certificate of Analysis (CoA).
4.3.4 Analysis of sulfur and sulfur derivatives
4.3.4.1 General
Based on the chemical inhomogeneity of the variety of preservatives, a few specific valid analytical
methods shall be implemented.
NOTE Sulfur dioxide is a toxic gas and reacts immediately with water to sulfurous acid.
4.3.4.2 Elemental sulfur
NOTE Elemental sulfur is used as a protecting compound on herbal surfaces.
4.3.4.2.1 Sample preparation
In the case of declaration on the product documents or suspicion based on yellow powder on the
surfaces, an analytical measurement shall be used.
An appropriate amount of test sample of minimum 50 g shall be used and washed with cold water.
The resulting suspension shall be separated from the test material and then filtered over an appropriate
typical laboratory folded filter.
The resulting residue shall be dried.
4.3.4.2.2 Reagents
Reagents are not needed.
4.3.4.2.3 Apparatus
Test tube or melting pot: bunsen burner or other appropriate heating source with a minimum
temperature of about 150 °C.
4.3.4.2.4 Analytical instrumentation
None.
4.3.4.2.5 Analytical procedure
The dried test residue shall be heated with air contact until melting under appropriate conditions.
4.3.4.2.6 Measurement and reporting
If the test sample contains elemental sulfur or other sulfur derivatives in the reaction with air, the
colourless gas SO with a characteristic sticky o
...