EN ISO 11238:2012

SLOVENSKI STANDARD
01-februar-2013
Zdravstvena informatika - Identifikacija medicinskih izdelkov - Elementi in zgradba
podatkov za enotno identifikacijo in izmenjavo predpisanih informacij o
substancah (ISO 11238:2012)
Health informatics - Identification of medicinal products - Data elements and structures
for the unique identification and exchange of regulated information on substances (ISO
11238:2012)
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Ta slovenski standard je istoveten z: EN ISO 11238:2012
ICS:
11.020 0HGLFLQVNHYHGHLQ Medical sciences and health
]GUDYVWYHQRYDUVWYHQL care facilities in general
SULSRPRþNLQDVSORãQR
35.240.80 Uporabniške rešitve IT v IT applications in health care
zdravstveni tehniki technology
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 11238
NORME EUROPÉENNE
EUROPÄISCHE NORM
November 2012
ICS 35.240.80
English Version
Health informatics - Identification of medicinal products - Data
elements and structures for the unique identification and
exchange of regulated information on substances (ISO
11238:2012)
Informatique de santé - Identification des médicaments - Medizinische Informatik - Identifikation von Arzneimitteln -
Éléments de données et structures pour l'identification Struktur und kontrollierte Vokabularien zur Identifikation
unique et l'échange d'informations réglementées sur les und Beschreibung von Substanzen und Inhaltsstoffen (ISO
substances (ISO 11238:2012) 11238:2012)
This European Standard was approved by CEN on 24 May 2012.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same
status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2012 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11238:2012: E
worldwide for CEN national Members.

Contents Page
Foreword .3

Foreword
This document (EN ISO 11238:2012) has been prepared by Technical Committee ISO/TC 215 "Health
informatics" in collaboration with Technical Committee CEN/TC 251 “Health informatics” the secretariat of
which is held by NEN.
This European Standard shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by May 2013, and conflicting national standards shall be withdrawn at the
latest by May 2013.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
According to the CEN/CENELEC Internal Regulations, the national standards organisations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech
Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.
Endorsement notice
The text of ISO 11238:2012 has been approved by CEN as a EN ISO 11238:2012 without any modification.

INTERNATIONAL ISO
STANDARD 11238
First edition
2012-11-01
Health informatics — Identification of
medicinal products — Data elements and
structures for the unique identification
and exchange of regulated information
on substances
Informatique de santé — Identification des médicaments — Éléments
de données et structures pour l’identification unique et l’échange
d’informations réglementées concernant les substances
Reference number
ISO 11238:2012(E)
©
ISO 2012
ISO 11238:2012(E)
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISO’s
member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2012 – All rights reserved

ISO 11238:2012(E)
Contents Page
Foreword .iv
Introduction . v
1 Scope . 1
2 Terms, definitions, symbols and abbreviated terms . 1
2.1 Terms and definitions . 1
2.2 Symbols and abbreviated terms . 8
3 Requirements . 9
3.1 General . 9
3.2 Concepts required for the unique identification and description of substances . 9
3.3 Concepts required for the description of specified substances . 11
3.4 Naming of substances .12
3.5 Requirements for unique identifiers .13
3.6 Types of substances .14
3.7 Defining specified substances .27
Annex A (informative) Existing identifiers and molecular structure representations .35
Bibliography .38
ISO 11238:2012(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 11238 was prepared by Technical Committee ISO/TC 215, Health informatics.
iv © ISO 2012 – All rights reserved

ISO 11238:2012(E)
Introduction
This International Standard was developed in response to a worldwide demand for internationally harmonized
specifications for medicinal products. It is one of a group of five standards which together provide the basis for
the unique identification of medicinal products. The group of standards comprises:
ISO 11615, Health informatics — Identification of medicinal products — Data elements and structures for the
unique identification and exchange of regulated medicinal product information;
ISO 11616, Health informatics — Identification of medicinal products — Data elements and structures for the
unique identification and exchange of regulated pharmaceutical product information;
ISO 11238, Health informatics — Identification of medicinal products — Data elements and structures for the
unique identification and exchange of regulated information on substances;
ISO 11239, Health informatics — Identification of medicinal products — Data elements and structures for
the unique identification and exchange of regulated information on pharmaceutical dose forms, units of
presentation, routes of administration and packaging;
ISO 11240, Health informatics — Identification of medicinal products — Data elements and structures for the
unique identification and exchange of units of measurement.
These standards for the identification of medicinal products (IDMP) support the activities of medicines
regulatory agencies worldwide by jurisdiction. These include a variety of regulatory activities related to
development, registration and life cycle management of medicinal products, as well as pharmacovigilance and
risk management.
To meet the primary objectives of the regulation of medicines and pharmacovigilance, it is necessary to reliably
exchange medicinal product information in a robust and reliable manner. The IDMP standards therefore support
the following interactions:
— between one medicine regulatory agency and another, e.g. European Medicines Agency to the US Food
and Drug Administration (FDA), or vice versa;
— between pharmaceutical companies and medicine regulatory agencies, e.g. “Pharma Company A” to
Health Canada;
— between the sponsor of a clinical trial to a medicine regulatory agency, e.g. “University X” to the Austrian
Medicines Agency;
— between a medicine regulatory agency and other stakeholders, e.g. UK Medicines and Health Care
Products Regulatory Agency (MHRA) to the National Health Service (NHS);
— between medicine regulatory agencies and worldwide-maintained data sources, e.g. the Pharmaceutical
and Medical Device Agency (PMDA) and the organization responsible for assigning substance identifiers.
The necessary messaging specifications are included as an integral part of the IDMP standards to secure the
interactions listed above.
Unique identifiers produced in conformance with the IDMP standards will support applications for which it is
necessary to reliably identify and trace the use of medicinal products and the materials within medicinal products.
This International Standard provides a structure that enables the assignment and maintenance of unique
identifiers for all substances in medicinal products or in packaging materials in which medicinal products are
contained. This International Standard sets out the general rules for defining and distinguishing substances,
and provides a high-level model that structures substances and specified substances for the organization and
capturing of data.
This International Standard has been developed using HL7’s Common Product Model, and detailed modelling of
substances and specified substances has been undertaken in that domain. It is anticipated that implementation
will use the HL7 substances implementation guide and messaging to deliver a strong, non-semantic unique
identifier for every substance present in a medicinal product. It is anticipated that a single organization will be
ISO 11238:2012(E)
responsible for the generation of identifiers for every substance and that such an organization would retain the
defining elements upon which the substance identifier was based. At the specified substance level, a more
regional approach may be necessary because of the proprietary nature of much of the information.
The use of the identifier is essential for the description of substances in medicinal products on a global scale.
This International Standard does not involve developing nomenclature for substances or specified substances,
but common and official substance names in current use can be mapped to each identifier.
Materials used in medicinal products range from simple chemicals to gene-modified cells to animal tissues.
To unambiguously define these substances is particularly challenging. This International Standard defines
substances based on their scientific identity (i.e. what they are) rather than on their use or method of production.
Molecular structure or other immutable properties, such as taxonomic, anatomical and/or fractionation
information, are used to define substances. This International Standard contains five groups of elements that
are sufficient to define all substances. Although it is certainly possible to define or classify substances in other
ways, this International Standard uses a minimalist structured scientific concept approach focusing on the
critical elements necessary to distinguish two substances from one another. There are frequently interactions
between substances when they are mixed together, but this International Standard has intentionally not
included these supramolecular interactions at the substance level because of the variable nature and strength
of such interactions. This International Standard also allows for the capture of multiple terms which refer to a
given substance and a variety of reference information that could be used to classify substances or relate one
substance to another.
In addition to the substance level, this International Standard also provides elements for the capture of further
information on substances, such as grade, manufacturer, manufacturing specifications, and also to capture
information on substances that are frequently combined together in commerce but are not strictly a medicinal
product. At the specified substance level, four groups of elements provide information essential to the tracking
and description of substances in medicinal products.
The basic concepts in the regulatory and pharmaceutical standards development domain use a wide variety
of terms in various contexts. The information models presented in this International Standard depict elements
and the relationship between elements that are necessary to define substances. The terms and definitions
described in this International Standard are to be applied for the concepts that are required to uniquely identify,
characterize and exchange information on substances in regulated medicinal products.
The terms and definitions adopted in this International Standard are intended to facilitate the interpretation and
application of legal and regulatory requirements, but they are without prejudice to any legally binding document.
In case of doubt or potential conflict, the terms and definitions contained in legally binding documents prevail.
vi © ISO 2012 – All rights reserved

INTERNATIONAL STANDARD ISO 11238:2012(E)
Health informatics — Identification of medicinal products —
Data elements and structures for the unique identification and
exchange of regulated information on substances
1 Scope
This International Standard provides an information model to define and identify substances within medicinal
products or substances used for medicinal purposes, including dietary supplements, foods and cosmetics. Other
standards and external terminological resources are referenced that are applicable to this International Standard.
2 Terms, definitions, symbols and abbreviated terms
2.1 Terms and definitions
For the purposes of this document, the following terms, definitions and abbreviations apply.
2.1.1
active marker
constituent, or groups of constituents, of an herbal substance, herbal preparation or herbal medicinal product
which are of interest for control purposes and are generally accepted to contribute to therapeutic activity
NOTE Active markers are not equivalent to analytical or signature markers that serve solely for identification or
control purposes.
2.1.2
analytical data
set of elements to describe and capture methods and reference material used to determine purity, potency or
identity in a specified substance
2.1.3
chemical bond
condition that occurs when forces acting between two atoms or groups of atoms lead to the formation of a
stable discrete molecular entity
2.1.4
chemical substance
type of substance that can be described as a stoichiometric or non-stoichiometric single molecular entity and
is not a protein or nucleic acid substance
NOTE Chemical substances are generally considered “small” molecules which have associated salts, solvates or
ions and may be described using a single definitive or representative structure.
2.1.5
chiral substance
substance whose molecular structure is not superimposable on its mirror image
2.1.6
component
intended constituent of a specified substance
EXAMPLE Dimethicone and silicon dioxide are components of simethicone. Human insulin protamine and zinc are
the components in human insulin isophane.
NOTE Components are used to describe the substances and specified substances that form a multi-substance material.
ISO 11238:2012(E)
2.1.7
composition stoichiometry
quantitative relationships between the chemical elements or moieties that make up a substance
EXAMPLE Sodium phosphate dibasic heptahydrate and sodium phosphate dibasic dihydrate are defined as
different substances.
2.1.8
constituent
substance present within a specified substance
NOTE Constituents can be impurities, degradants, active markers or signature substances, or single substances
mixed together to form a product. Constituents shall have an associated role and amount. Constituent specifications shall
be used to describe components as well as limits on impurities or related substances for a given material.
2.1.9
controlled vocabulary
finite set of values that represent the only allowed values for a data item
NOTE 1 The allowed values can be codes, text or numeric.
NOTE 2 Adapted from CDISC Clinical Research Glossary V8.0, 2009.
2.1.10
copolymer
polymer with more than one type of structural repeating unit linked through covalent bonds
NOTE Copolymers are obtained by copolymerization or sequential polymerization of two or more monomers.
Copolymers can be random, alternating, block or graft.
2.1.11
critical process step
manufacturing step necessary for production of a specified substance
2.1.12
degree of polymerization
number of structural repeating units in a polymeric block or chain
NOTE Applies to both homopolymers and block copolymers where it refers to the degree of polymerization within a block.
2.1.13
diverse origin
substances that are not isolated together or the result of the same chemical synthetic process
NOTE Material containing multiple substances is defined either as a mixture substance or a multi-substance (group 1)
specified substance based on origin. Two substances brought together that do not undergo a chemical reaction resulting
in the formation or breakage of specific chemical bonds would be defined as separate substances, even if there are non-
bonding interactions between the substances.
2.1.14
enhancer
cis-acting sequence of DNA that increases the utilization of some eukaryotic promoters and which can function
in either orientation and in any location (upstream or downstream) relative to the promoter
2.1.15
fraction
distinct portion of material derived from a complex matrix, the composition of which differs from antecedent material
NOTE This concept is used to describe source material and is recursive in that a subsequent fraction can be derived
from an antecedent fraction, which is implied in the order of listing.
EXAMPLE Serum immunoglobulins to polyclonal IgG is an example of recursive fractionation.
2 © ISO 2012 – All rights reserved

ISO 11238:2012(E)
2.1.16
gene
basic unit of hereditary material that encodes and controls the expression of a protein or protein subunit
2.1.17
gene element
individual element within a gene such as a promoter, enhancer, silencer or coding sequence
2.1.18
glycosylation
enzymatic process that links saccharides or oligosaccharides to proteins, lipids or other organic molecules
2.1.19
glycosylation type
significant differences in glycosylation between different types of organisms
NOTE This distinguishes the pattern of glycosylation across organism types, e.g. human, mammalian and avian. The
glycosylation type is a defining element when polydisperse organism-based glycosylation exists in a substance.
2.1.20
grade
set of specifications indicating the quality of a specified substance
2.1.21
homopolymer
polymer containing a single structural repeating unit
2.1.22
isotope
variants of a chemical element that differ by molecular mass
NOTE Radionuclides or nuclides with a non-natural isotopic ratio are shown in the structural representation with the
nuclide number displayed. Natural abundance isotopes are represented by an elemental symbol without a nuclide number.
EXAMPLE C refers to a carbon atom that has an atomic mass of 13.
2.1.23
manufacturing
process of production for a substance or medicinal product from the acquisition of all materials through all
processing stages
NOTE The critical process, starting and processing materials, and critical production parameters are included.
2.1.24
material
any entity that has mass, occupies space and consists of one or more substances
2.1.25
medicinal product
any substance or combination of substances which may be administered to human beings or animals for
treating or preventing disease, with the view to making a medical diagnosis or to restore, correct or modify
physiological functions
NOTE 1 A medicinal product may contain one or more manufactured items and one or more pharmaceutical products.
NOTE 2 In certain jurisdictions, a medicinal product may also be defined as any substance or combination of substances
which may be used to make a medical diagnosis.
ISO 11238:2012(E)
2.1.26
microheterogeneity
substances isolated together that contain minor differences in glycosylation, or post-translational modification
such as glycosylation or sequence heterogeneity
NOTE 1 Microheterogeneity is not a defining characteristic of either substances or specified substances.
NOTE 2 Microheterogeneity consists of variability in the type of glycosylation (biantennary, triantennary), extent of
glycosylation at a given site (site occupancy), sequence heterogeneity due to polymorphism in source material, translation
errors, variable proteolytic processing or other.
2.1.27
mixture substance
type of polydisperse substance that is a combination of single substances isolated together or produced in the
same synthetic process
NOTE Single substances of diverse origin that are brought together and do not undergo a chemical transformation
as a result of that combination are defined as multi-substance materials (Group 1 specified substances) and not as
mixture substances.
EXAMPLE Gentamicin is defined as a mixture substance of Gentamicin C1A, Gentamicin C1 and Gentamicin C2.
Glyceryl monoesters are defined as mixture substances of two single substances which differ in the position of esterification.
Simethicone, which consists of dimethicone and silicon dioxide, is not defined as a mixture substance since these are
diverse materials brought together to form a product.
2.1.28
moiety
entity within a substance that has a complete and continuous molecular structure
EXAMPLE The strength of a medicinal product is often based on what is referred to as the active moiety and should
be defined in a consistent manner across all products. To avoid ambiguity, the free acid and/or free base should be used
as the moiety upon which strength is based.
NOTE In this International Standard, moiety shall be used in the context of non-stoichiometric chemical substances
and in modification of nucleic acid, proteins, polymers and structurally diverse substances. Moieties shall be single
substances, ions or solvate molecules.
2.1.29
molecular fragment
portion of a molecule that has one or more sites of attachment to other fragments or moieties
NOTE Molecular fragments are used in the description of polymers to represent substituents and in structural
modifications to a substance.
2.1.30
molecular structure
unambiguous representation of the arrangement of atoms
NOTE 1 For the purposes of defining substances, the three dimensional conformations are not captured. Individual
conformations or conformers of substances would only be captured in either a general sense for proteins (i.e. denatured)
or when a given rotation about a single bond is restricted in such a way that the two different conformers are isolatable
from each other and do not interconvert at room temperature (e.g. substituted biphenyls).
NOTE 2 This representation should be generally translatable into a graphical representation.
2.1.31
molecular weight
mass of one molecule of a homogenous substance or the average mass of molecules that comprise a
heterogeneous substance
NOTE 1 The unified atomic mass unit is the unit of molecular weight. The type of molecular weight should always be captured.
NOTE 2 For polymers, there are several different types of molecular weight (weight average, number average, etc.).
4 © ISO 2012 – All rights reserved

ISO 11238:2012(E)
2.1.32
multi-substance material
multiple substances and/or specified substances of diverse origin used as a component in the formulation of
a medicinal product
EXAMPLE Materials such as human insulin isophane, simethicone, aluminium lakes, nicotine polacrilex, and
phosphate buffered saline are all multi-substance ingredients.
NOTE Multi-substance materials are Group 1 specified substances. Any medicinal product used to formulate another
medicinal product could also be considered a multi-substance material.
2.1.33
nucleic acid substance
type of substance that can be defined by a linear sequence of nucleosides typically linked through phosphate esters
NOTE The type of nucleic acid substance (RNA, DNA) is also identified. Oligonucleotides and gene elements (i.e.
promoters, enhancers, coding sequences and silencers) are defined as nucleic acid substances.
2.1.34
official name
name given by an official registration authority
2.1.35
parent organism
organism from which biological source material is derived
2.1.36
part
anatomical origin and location of source material within an organism
2.1.37
pharmaceutical product
qualitative and quantitative composition of a medicinal product in the dose form approved for administration in
line with the regulated product information
NOTE 1 A medicinal product may contain one or more pharmaceutical products.
NOTE 2 In many instances, the pharmaceutical product is equal to the manufactured item. However, there are
instances where the manufactured item must undergo a transformation before being administered to the patient (as the
pharmaceutical product) and the two are not equal.
2.1.38
physical form
physical state, either gas, liquid or solid, and the type of organization for solid matter
NOTE Solids can be either crystalline or amorphous. Polymorphism can also be captured.
2.1.39
polydisperse substance
substance containing multiple related molecular components
NOTE Polydisperse substances include polymers and structurally diverse material isolated from a single source.
Chemical substances, proteins and nucleic acids with defined sequences are not described as polydisperse substances.
2.1.40
polydispersity
measure of the range of molecular masses in a polymer substance
NOTE The polydispersity index of polymers is typically calculated by the ratio of weight average molecular weight to
number average molecular weight.
ISO 11238:2012(E)
2.1.41
polymer substance
type of polydisperse substance that contains structural repeating units linked by covalent bonds
NOTE Monodisperse proteins and nucleic acids with defined sequences shall not be defined using the polymer
substance elements.
2.1.42
post-translational modification
modification of a protein that typically occurs in vivo during or after translation
NOTE Post-translational modification is described within the structural representation and not as a modification
of a protein.
2.1.43
processing material
type of material essential to the manufacturing process that is not incorporated into the resultant material
2.1.44
protein substance
type of substance with a defined sequence of alpha-amino-acids connected through peptide bonds
NOTE Synthetic peptides and proteins with defined sequences, recombinant proteins and highly purified proteins
extracted from biological matrices are described as protein substances. Sites of glycosylation, disulfide linkages and
glycosylation type (e.g. fungal, plant, arthropod, avian, mammalian, human) are defining elements of protein substances,
when known. A graphical molecular structure is also included in the definition of all peptides of 15 amino acid residues or less.
2.1.45
protein sequence
order and identity of amino acids within a protein sub-unit
NOTE Protein sequences will be represented by single letter Dayhoff codes and listed from the N-terminus to
the C-terminus.
2.1.46
protein sub-unit
linear sequence of amino acid residues connected through peptide bonds
NOTE Repeated sub-units in proteins are captured.
EXAMPLE Monoclonal antibodies typically consist of four sub-units.
2.1.47
resultant material
material that is the result of a critical process
NOTE Resultant material may be the starting material of the next process or the final material or actual specified substance.
2.1.48
salt
ionic substances formed from the neutralization reaction of an acid and base
NOTE Salts are ionic compounds composed of cations (positive ions) and anions (negative ions).
2.1.49
silencer
DNA sequence that suppresses transcription
2.1.50
single substance
substance that can be described by a single representation or set of descriptive elements
NOTE 1 A single substance can be described using one or more of five types of elements: chemical, protein, nucleic
acid, polymer and structurally diverse substances.
6 © ISO 2012 – All rights reserved

ISO 11238:2012(E)
NOTE 2 Racemates and substances with unknown, epimeric or mixed chirality can be defined as single substances
because a single structural representation may be generated and the stereochemistry indicated as descriptive text.
2.1.51
solvate
substance formed through association of a solvent molecule (e.g. water, alcohol) with another moiety.
NOTE Solvates can be either stoichiometric or non-stoichiometric and are predominately present when substances
exist in a solid form.
2.1.52
source material
material from which a substance is derived, which is defined based on taxonomic and anatomical origins
NOTE This class is used to define structurally diverse and polymer substances isolated from biological matrices.
2.1.53
specified substance
group of elements which describe multi-substance materials and specify further information on substances
and multi-substance materials relevant to the description of medicinal products
EXAMPLE This could include grade, units of measure, physical form, constituents, manufacturer, critical manufacturing
processes (i.e. extraction, synthetic, recombinant processes), specification and the analytical methods used to determine
that a substance is in compliance with a specification.
NOTE There are four different groups of elements that can be used to define a given specified substance and specific
relationships between each group of elements.
2.1.54
starting material
type of material that is modified through a manufacturing process
2.1.55
stoichiometric
substances that contain moieties in simple integral ratios
NOTE 1 Defined composition stoichiometry shall be represented in the structural representation of a given substance.
Moieties shall be represented using the lowest common factors such that a fractional representation is avoided. Substances
will either be defined as stoichiometric or non-stoichiometric.
NOTE 2 Chemicals have defined composition stoichiometry when the ratio of all moieties (ion, counter ion and solvate)
can be represented as simple integral ratios.
2.1.56
stereochemistry
relative spatial arrangement of atoms within molecules
2.1.57
structurally diverse substance
type of polydisperse substance isolated from a single source that is a complex mixture which cannot be
described as a mixture of a limited number of single substances
NOTE Structurally diverse substances are defined based on immutable properties of a given material. Modifications
that irreversibly alter the structure of the material, distinctive physical properties or components subsumed into the material,
e.g. a gene in gene therapy substances, are defining elements for structurally diverse substances. Fractions derived from
source material (oils and juices) are also captured in the definition. Protein mixtures containing a large number of diverse
sequences such as polyclonal immunoglobulins are defined as structurally diverse substances.
ISO 11238:2012(E)
2.1.58
substance
any matter of defined composition that has discrete existence, whose origin may be biological, mineral or chemical
NOTE 1 Substances can be single substances, mixture substances or one of a group of specified substances. Single
substances are defined using a minimally sufficient set of data elements divided into five types: chemical, protein, nucleic
acid, polymer and structurally diverse. Substances may be salts, solvates, free acids, free bases or mixtures of related
compounds that are either isolated or synthesized together. Pharmacopoeial terminology and defining characteristics will
be used when available and appropriate. Defining elements are dependent on the type of substance.
NOTE 2 Discrete existence refers to the ability of a substance to exist independently of any other substance. Substances
can either be well-defined entities containing definite chemical structures, synthetic (i.e. isomeric mixtures) or naturally-
occurring (i.e. conjugated oestrogens) mixtures of chemicals containing definite molecular structures, or materials derived
from plants, animals, microorganisms or inorganic matrices for which the chemical structure may be unknown or difficult
to define. Substances may be salts, solvates, free acids, free bases and mixtures of related compounds that are either
isolated or synthesized together.
2.1.59
substituent
molecular fragment attached to a structural repeat unit of a polymer that typically replaces a hydrogen atom
NOTE This information is captured as part of the structural repeat unit when the position of substitution is fully
occupied. When occupancy of a site is incomplete, the amount of a substituent is specified as either a fragment or moiety
structural modification.
2.1.60
tautomer
molecular structure capable of interconversion with an isomeric molecular structure that typically involves
facile migration of a hydrogen atom between two adjacent atoms
NOTE It is anticipated that a single tautomeric form will be associated with each substance and detailed rules will be
developed within the implementation guide to indicate the tautomeric form associated with each chemical substance. If
individual isomers may be isolated under normal conditions and are known to have distinct molecular properties, they are
defined as separate substances.
2.1.61
taxonomy
scientific organism classification system needed to describe the origin of source material in substances isolated
from biological matrices
NOTE Taxonomic information is captured to the species level for all polydisperse substances isolated from biological
matrices, if such information is available and the source material is consistently derived from the species. Taxonomic
family, genus and species along with the taxon author are necessary to identify the source organism. Kingdom, phylum,
class and order are also captured when available. Intraspecific information (e.g. subspecies, strain or variety) is captured
when the forms exhibit consistent differences in either material content or function.
2.2 Symbols and abbreviated terms
2.2.1
ACS
American Chemical Society
2.2.2
ASK Number
ID of a substance in German “Arzneistoffkatalog” (Pharmaceutical Substance Dictionary)
2.2.3
BAN
British Approved Name
2.2.4
DCF
Dénominations Communes Françaises (French approved drug name)
8 © ISO 2012 – All rights reserved

ISO 11238:2012(E)
2.2.5
EP
European Pharmacopoeia
2.2.6
INCI
International Nomenclature of Cosmetic Ingredients
2.2.7
INN
International Non-proprietary Name [also known as rINN (recommended International Non-proprietary Name)
or pINN (proposed International Non-proprietary Name)].
2.2.8
JAN
Japanese Approved Name
2.2.9
JP
Japanese Pharmacopoeia
2.2.10
UCUM
Unified Code for Units of Measure
2.2.11
USAN
United States Adopted Name
2.2.12
USP
United States Pharmacopeia
3 Requirements
3.1 General
Substances and specified substances shall be defined in a manner consistent with the elements and
relationships present in the figures within this clause. An implementation guide shall further define these
elements and relationships.
3.2 Concepts required for the unique identification and description of substances
Substances shall be single substances, mixture substances or specified substances.
NOTE 1 The term “substance” as used below generally refers to a single substance or mixture substance. A specified
substance is generally a further specification of a substance that captures information on manufacture, specifications,
physical form and multi-substance materials that are components of a medicinal product formulation.
This International Standard defines the concepts required for the unique identification of substances at an international
level, whenever such recognition is required. Such identification shall be based on the following principles:
a) a substance shall generally be defined based on what the material is rather than on how it is made or used;
b) a substance shall be defined based on immutable properties independent of physical form, grade or
level of purity;
c) substances can be single molecular entities or mixtures of single molecular entities either synthesized or
isolated together;
d) to avoid ambiguity and facilitate implementation, a mixture shall be defined as a combination of single substances;
ISO 11238:2012(E)
e) substances shall not be diverse materials brought together to form a medicinal product or multi-
substance material.
EXAMPLE 1 Simethicone would not be defined as a substance because it consists of two substances, dimethicone
and silicon dioxide, which are of diverse origin and typically not isolated together.
Complex materials from biological matrices and mixtures that cannot be defined or represented by a limited
number of chemical structures are defined based on source taxonomy, part and fraction. Materials containing
interactions of an indefinite nature and indefinite composition stoichiometry shall not be defined as substances.
NOTE 2 Because of the difficulties in determining the extent, strength and composition stoichiometry of non-covalent
interactions, these types of interactions are not taken into account when defining a substance. The only exceptions would
be ionic (salt) and solvate (hydrate) interactions of simple chemicals and well-defined polymers. Materials that contain
moieties that interact with polymers, complex matrices or cyclodextrins will typically not be defined as substances. Simple
polymeric salts such as sodium polystyrene sulfonate would be defined as a single substance.
EXAMPLE 2 Nicotine polacrilex is defined as two distinct substances: nicotine and polacrilex. Human insulin isophane
would also be defined as two distinct substances: protamine and human insulin. Nicotine polacrilex and human insulin
isophane, however, could be defined as single specified substances. Liposomal doxorubicin would be defined as a
specified substance that contains doxorubicin and the components that make up the liposome.
Substances shall be defined using one or more of the following groups of elements:
— chemical;
— protein;
— nucleic acid;
— polymer;
— structurally diverse;
— mixture.
All types of substances shall have the ability to capture official names, synonyms, isotopic and other
reference information.
10 © ISO 2012 – All rights reserved

ISO 11238:2012(
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