CEN ISO/TS 5499:2024

Health informatics - Clinical particulars - Core principles for the harmonization of therapeutic indications terms and identifiers (ISO/TS 5499:2024)

The objective of this document is to establish common principles for the creation, assessment, selection and maintenance of maps between terminological resources used to describe and code IDMP therapeutic indications for investigational and medicinal products, medical devices, combination products, biologics and companion diagnostics. Core maintenance principles, such as reliability, reproducibility and quality assurance of the maps for future indication terminology use, are also discussed. The intended audience for this document includes:
a)       Global regulators, pharmaceutical/biopharmaceutical companies, Clinical Research Organizations (CROs) and universities/scientific institutes involved in the development, authorization and marketing of medicinal products
b)       Implementers of IDMP seeking more information about coding of Therapeutic Indications
c)        Healthcare providers
d)       Standards Organizations
e)       Implementers and software vendors developing and implementing terminology map sets
f)         Patients

Medizinische Informatik - Klinische Besonderheiten - Grundprinzipien für die Harmonisierung von therapeutischen Indikationsbegriffen und -bezeichnungen (ISO/TS 5499:2024)

Informatique de santé - Spécificités cliniques - Principes fondamentaux pour l'harmonisation des termes et identifiants des indications thérapeutiques (ISO/TS 5499:2024)

Zdravstvena informatika - Klinični podatki - Temeljna načela za uskladitev izrazov in identifikatorjev terapevtskih indikacij (ISO/TS 5499:2024)

Cilj tega dokumenta je določiti skupna načela za ustvarjanje, ocenjevanje, izbiro in vzdrževanje preslikav med terminološkimi viri, ki se uporabljajo za opisovanje in šifriranje terapevtskih indikacij za identifikacijo medicinskih izdelkov (IDMP) za izdelke v postopku preiskave in medicinske izdelke, medicinske pripomočke, kombinirane izdelke ter biološko in dopolnilno diagnostiko. Obravnavana so tudi osnovna načela vzdrževanja, kot so zanesljivost, ponovljivost in zagotavljanje kakovosti preslikav za prihodnjo uporabo indikacijske terminologije. Ta dokument je namenjen:
a)       globalnim regulatorjem, farmacevtskim/biofarmacevtskim podjetjem, organizacijam za klinične raziskave (CRO) in univerzam/znanstvenim inštitutom, vključenim v razvoj, odobritev in trženje medicinskih izdelkov;
b)       izvajalcem identifikacije medicinskih izdelkov, ki iščejo dodatne informacije o šifriranju terapevtskih indikacij;
c)       izvajalcem zdravstvenih storitev;
d)       organizacijam za standardizacijo;
e)       izvajalcem in prodajalcem programske opreme, ki razvijajo in izvajajo sklope terminoloških preiskav;
f)        pacientom.

General Information

• Status: Published
• Publication Date: 06-Feb-2024
• ICS: 35.240.80 - IT applications in health care technology
• Technical Committee: CEN/TC 251 - Medical informatics
• Drafting Committee: CEN/TC 251 - Medical informatics
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 07-Feb-2024
• Completion Date: 07-Feb-2024
• Ref Project: SIST-TS CEN ISO/TS 5499:2024 - Health informatics - Clinical particulars - Core principles for the harmonization of therapeutic indications terms and identifiers (ISO/TS 5499:2024)

Overview

CEN ISO/TS 5499:2024 - Health informatics: Core principles for harmonizing therapeutic indications terms and identifiers defines common principles for creating, assessing, selecting and maintaining maps between terminological resources used to describe and code IDMP therapeutic indications. The Technical Specification focuses on harmonization, map quality, reliability, reproducibility and long‑term maintenance to support interoperable exchange of indication data across regulators, industry, healthcare and research.

Key topics and requirements

• Scope and audience: Guidance intended for global regulators, pharmaceutical/biopharma companies, CROs, implementers of IDMP, healthcare providers, standards organizations, software vendors and patients.
• Terminologies covered: Practical considerations for mapping between commonly used vocabularies such as SNOMED CT, MedDRA, ICD, MeSH and other national/regional term sets.
• Mapping principles: Requirements for map creation and validation, including prerequisites, mapping processes, best practice conventions, documentation and stakeholder engagement aligned to specific use cases.
• Use‑case driven mapping: Emphasis that maps must be developed and evaluated against clear use cases (e.g., regulatory submissions, coded labelling, clinical trials, pharmacovigilance, registries, EHR integration).
• Maintenance principles: Core maintenance topics such as quality assurance, reproducibility, governance, versioning and reliability of map sets to ensure ongoing utility.
• Implementation guidance: Practical annexes and examples for implementing the IDMP therapeutic indications data model and for exchanging coded indication data between regulators and industry.

Applications and practical value

• Regulatory exchange and submissions: Enables consistent coding of therapeutic indications for IDMP data exchange between regulators and manufacturers, improving automated review and label harmonization.
• Clinical trials & drug development: Supports standardized capture of indication concepts used in protocol design, trial registries and evidence synthesis (PICO).
• Pharmacovigilance & safety monitoring: Improves signal detection and assessment by linking adverse event data to coded therapeutic indications across datasets.
• EHR and real‑world evidence: Facilitates mapping between clinical problem lists and medicinal product indications to support prescribing decisions, off‑label detection and registries.
• Software and terminology implementers: Provides governance and quality principles for vendors building terminology map sets, APIs, and IDMP‑compliant systems.

Related standards

• ISO 11615 (Identification of Medicinal Products - IDMP): conceptual data model referenced throughout for clinical particulars and therapeutic indications.
• Other ISO/CEN health informatics standards (e.g., terminology and interoperability guidance) are complementary for full implementation.

This Technical Specification is essential for anyone implementing IDMP‑based indication coding, developing terminology maps, or managing cross‑system exchange of therapeutic indication data. Keywords: IDMP, therapeutic indications, terminology mapping, SNOMED CT, MedDRA, pharmacovigilance, regulatory submission, EHR.

Standards Content (Sample)

SLOVENSKI STANDARD
01-junij-2024
Zdravstvena informatika - Klinični podatki - Temeljna načela za uskladitev izrazov
in identifikatorjev terapevtskih indikacij (ISO/TS 5499:2024)
Health informatics - Clinical particulars - Core principles for the harmonization of
therapeutic indications terms and identifiers (ISO/TS 5499:2024)
Medizinische Informatik - Klinische Besonderheiten - Grundprinzipien für die
Harmonisierung von Indikationsbegriffen und -bezeichnungen (ISO/TS 5499:2024)
Informatique de santé - Spécificités cliniques - Principes fondamentaux pour
l'harmonisation des termes et identifiants des indications thérapeutiques (ISO/TS
5499:2024)
Ta slovenski standard je istoveten z: CEN ISO/TS 5499:2024
ICS:
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.

CEN ISO/TS 5499
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
February 2024
TECHNISCHE SPEZIFIKATION
ICS 35.240.80
English Version
Health informatics - Clinical particulars - Core principles
for the harmonization of therapeutic indications terms and
identifiers (ISO/TS 5499:2024)
Informatique de santé - Spécificités cliniques - Medizinische Informatik - Klinische Besonderheiten -
Principes fondamentaux pour l'harmonisation des Grundprinzipien für die Harmonisierung von
termes et identifiants des indications thérapeutiques Indikationsbegriffen und -bezeichnungen (ISO/TS
(ISO/TS 5499:2024) 5499:2024)
This Technical Specification (CEN/TS) was approved by CEN on 28 January 2024 for provisional application.

The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to
submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standard.

CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS
available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in
parallel to the CEN/TS) until the final decision about the possible conversion of the CEN/TS into an EN is reached.

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

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2024 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN ISO/TS 5499:2024 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (CEN ISO/TS 5499:2024) 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.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to announce this Technical Specification: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO/TS 5499:2024 has been approved by CEN as CEN ISO/TS 5499:2024 without any
modification.
Technical
Specification
ISO/TS 5499
First edition
Health informatics — Clinical
2024-01
particulars — Core principles for
the harmonization of therapeutic
indications terms and identifiers
Informatique de santé — Spécificités cliniques — Principes
fondamentaux pour l'harmonisation des termes et identifiants
des indications thérapeutiques
Reference number
ISO/TS 5499:2024(en) © ISO 2024

ISO/TS 5499:2024(en)
© ISO 2024
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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
ISO/TS 5499:2024(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions .1
3.2 Abbreviated terms .3
4 Terminologies used for the coding of Therapeutic Indications . 4
4.1 General .4
4.2 SNOMED CT .4
4.3 MedDRA .4
4.4 ICD .4
4.5 MeSH .5
5 Use Cases for Coding of Therapeutic Indications . 5
5.1 General .5
5.2 IDMP data exchange between global regulators and bio/pharmaceutical companies
during regulatory processes .6
5.2.1 Clinical Trials (Medicinal Product Development Lifecycle) .6
5.2.2 Regulatory Submission and Coded Labelling Information .6
5.2.3 Clinical protocol .8
5.2.4 Risk Management.8
5.3 Pharmacovigilance .9
5.3.1 General .9
5.3.2 Clinical information in the EHR supporting regulation for Pharmacovigilance .9
5.3.3 Identify potentially inappropriate prescribing/off-label use .10
5.4 Registries.10
6 Mapping principles specific to therapeutic indications .10
6.1 Maps between Terminologies .10
6.1.1 General .10
6.1.2 Mapping Prerequisites .10
6.1.3 Required Processes . .11
6.2 Therapeutic Indications - Mapping best practice principles and conventions .11
6.3 General mapping guidance . 13
6.3.1 General . 13
6.3.2 Mapping of national and regional terms . 13
6.3.3 Regulatory agencies . 13
Annex A (informative) Implementations of the IDMP Therapeutic Indications Data Model .16
Bibliography .22

iii
ISO/TS 5499:2024(en)
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 document 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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
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 215, Health informatics, in collaboration with
the European Committee for Standardization (CEN) Technical Committee CEN/TC 251, Health informatics, in
accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
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/TS 5499:2024(en)
Introduction
The need for improved communication between health agencies, hospitals, pharmacies, pharmaceutical
companies and the general public about drug safety and efficacy information requires migration from manual
text entry and unstructured data that cannot be coded, to a structured data model that is interoperable
[1]
across the health care ecosystem . The clinical particulars conceptual class of the ISO 11615 Identification
of Medicinal Products (IDMP) data model captures information about a medicinal product’s indication(s),
contraindication(s), undesirable effect(s) and interactions. Within this conceptual class, the Therapeutic
Indication subclass captures information about the therapeutic indication for the target disease or condition
for which a medicinal product is authorized, under investigation, or utilized in clinical practice. Therapeutic
indications can be described using free text as presented in approved product labelling documents, and as
terms and codes from standard terminologies. Consistent and accurate coding of therapeutic indication
terms is needed to support a variety of processes and is found in various terminological resources and
official documents, which include epidemiological and real-world databases, electronic health records and
health authority reporting processes. Therefore, a key principle for terminology mapping is that maps are
based on specific use cases, and stakeholders who can provide feedback on the form, content and scope of
the mapping should be engaged from the beginning of and throughout the mapping exercise.
A universally accepted terminology for coding therapeutic indications does not yet exist and is not feasible
due to differing international medicinal product and healthcare regulations and reporting requirements.
There is a difference between the therapeutic indication of a specific medicinal product and the diseases,
conditions or problems listed in an electronic health record (EHR). While most EHRs will manage a problem
list and/or a list of findings and diagnoses and a medication list, it is less frequent that the indication (or
indications) for each specific medication is specified for a particular patient.
In medicinal product labels, a range of authorized indications is listed, often with qualifiers (diagnostic,
preventive, curative, disease-modifying) or specified patient target groups. Sometimes, diseases or
conditions are explicitly listed as not being indications for a specific drug. For example, “drug x” is not
indicated in von Willebrand disease, or “drug y” is contraindicated with Haemophilia A. Use of medicinal
products outside the authorized indications is considered off-label.
The indication wording, and thus the related coding, is based on a highly complex process over the years-long
development of a pharmaceutical product. The relationship between a medicinal product and an indication
is based on evidence from clinical trials, which are often comparative in nature (e.g. placebo versus active
substance, or active substance A versus active substance B). Evidence synthesis in systematic reviews is
often constrained by a Patient/intervention/comparator/outcome (PICO) statement, which results in a
clinical recommendation to prefer or not to prefer the use of a particular medicinal product over another
intervention for a particular patient (with a specific disease or condition), aiming at a specific outcome.
In a regulatory document, this information is often reduced to a statement that “this medicinal product is
indicated for ….”.
In regulatory documents, the relationship is specified between a particular medicinal product (with specific
substance(s), dose form(s), strength(s) and pack sizes), on the one hand and the indication(s), which are
often specified in a detailed form. The formulation of this detailed indication often results from strong
and intricate debate between the medical department of a pharmaceutical company, medical experts and
regulators. The finesse of such formulation is often difficult to catch by any of the existing terminologies. For
example, the therapeutic indications for a preparation that is licensed for over-the-counter (OTC) use can be
more restrictive than the indications for the same preparation when prescribed by a clinician. For example,
treatment of candidiasis in pregnancy using a clotrimazole must be under the direction of a physician; an
OTC preparation is not authorized for this indication.
In handbooks of pharmacology and in drug classifications, indications might be formulated at a higher level
of aggregation, and substances can be aggregated to drug classes. Hence, relationships between high level
indications and drug classes (rather than individual substances) can be described.

v
ISO/TS 5499:2024(en)
Terminologies describing drug classes (e.g. the Anatomical Therapeutic Chemical (ATC) codes, SNOMED
1)
CT® , Standard Drug Groups from WHO Drug, etc.) are built using different principles and dimensions
(chemical class, anatomical target, therapeutic intent, mechanism of action, molecular target site), and
exhibit variable levels of granularity. The same is true for terminologies describing diseases, conditions and
signs and symptoms as proxies for indications. Therefore, using different terminologies (and maps between
these terminologies) to establish relationships between medicinal products/drug classes and specific
indications/high level indications can be bewilderingly complex. Hence, harmonization of terminologies
for therapeutic indications should account for both the specific level of regulatory listing of authorized
indications for specific medicinal products, as well as the relationship between high level aggregations of
indications and substances.
The most common standard terminological resources used to describe and code medicinal product
2)
indication terms are the Medical Dictionary for Regulatory Activities (MedDRA® ), SNOMED CT, the
3)
International Statistical Classification of Diseases and Related Health Problems (ICD™ ) and Medical Subject
Headings (MeSH). Mappings between these terminological resources are necessary for documentation and
reporting purposes; however, the different hierarchy levels and variation in the number of terms for each
resource introduce significant complexity in the creation and maintenance of terminology maps. Map usage
is often restricted by the limited availability of centrally provided and approved map sets and contributes
to inefficiencies and redundant manual curation by individual stakeholders for specific use cases. Creation
and maintenance of comprehensive maps between clinical terminologies to support coding of indication
terms will thus liberate workforce effort and enable more efficient processes, responses and comprehensive
reporting.
There are safety and maintenance implications when creating and applying maps that directly impact clinical
care and decision-making. Therefore, a key principle is the requirement to identify the use case for any map
before creating or using mappings. For example, there is an allowable semantic shift during mapping such as
for statistics and billing because of aggregation to a group level, whereas in use cases to support clinical care
at the individual (patient) level, no semantic shift can be tolerated because of potential safety issues. Thus,
mappings between e.g. SNOMED CT and MedDRA are semantic maps of total meaning focused on adverse
events. However, additional maps between these two terminologies with use cases focused on therapeutic
indications are possibly needed, so a use case will need to be developed and tested against existing maps
before deciding on next steps.
This document describes use cases and principles that are applicable for creation, assessment and selection
of maps specific to Therapeutic Indications. This document thus refers to and builds on the following
documents regarding terminologies and mapping:
— ISO/TR 14872 on core principles for maintenance of identifiers and terms
— ISO/TR 12300 on principles of mapping between terminological systems
— ISO/TS 21564 on terminology resource map quality measures (MapQual)
1) SNOMED CT® is the registered trademark of a product supplied by the International Health Terminology Standards
Organization (IHTSDO). This information is given for the convenience of users of this document and does not constitute
an endorsement by ISO of the product named.
2) MedDRA is the registered trademark of a product supplied by the International Federation of Pharmaceutical
Manufacturers & Associations (IFPMA) on behalf of the International Council for Harmonization of Technical Requirements
for Pharmaceuticals for Human Use (ICH). This information is given for the convenience of users of this document and
does not constitute an endorsement by ISO of the product named.
3) ICD™ (International Classification of Diseases) maintained by the World Health Organization is an example of a
suitable product available commercially. This information is given for the convenience of users of this document and does
not constitute an endorsement by ISO of this product.

vi
Technical Specification ISO/TS 5499:2024(en)
Health informatics — Clinical particulars — Core principles
for the harmonization of therapeutic indications terms and
identifiers
1 Scope
The objective of this document is to establish common principles for the creation, assessment, selection
and maintenance of maps between terminological resources used to describe and code IDMP therapeutic
indications for investigational and medicinal products, medical devices, combination products, biologics
and companion diagnostics. Core maintenance principles, such as reliability, reproducibility and quality
assurance of the maps for future indication terminology use, are also discussed. The intended audience for
this document includes:
a) Global regulators, pharmaceutical/biopharmaceutical companies, Clinical Research Organizations
(CROs) and universities/scientific institutes involved in the development, authorization and marketing
of medicinal products
b) Implementers of IDMP seeking more information about coding of Therapeutic Indications
c) Healthcare providers
d) Standards Organizations
e) Implementers and software vendors developing and implementing terminology map sets
f) Patients
2 Normative references
There are no normative references in this document.
3 Terms, definitions and abbreviated terms
3.1 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/
3.1.1
comorbidity
concurrent condition or co-infection described as part of the indication
3.1.2
electronic health record
EHR
repository of information regarding the health status of a subject of care, in computer processable form
[SOURCE: ISO/TR 20514:2005, 2.11, modified]

ISO/TS 5499:2024(en)
3.1.3
electronic health record system
EHR system
system for recording, retrieving and manipulating information in electronic health record
3.1.4
individual map
map
cross map
index from one term to another, sometimes using rules that allow translation from one representation to
another indicating degree of equivalence
Note 1 to entry: Entry in a map which indicates how to translate from an individual source concept to a target concept.
The term map is often used to indicate a table of individual map entries. It is for this reason that the individual and
map tables are being differentiated.
Note 2 to entry: The use of this term is often used in ways which are confusing. It is essential to always make it clear
whether you are referring to an individual map or a map table (or set).
Note 3 to entry: In SNOMED CT, each individual map is represented as a row or group of rows in a map Reference Set.
It links a single map source concept code (e.g. SNOMED CT Concept ID) to one or more codes in a map target (e.g. ICD
Code).
Note 4 to entry: A map is often computable and is the outcome of the mapping process.
[SOURCE: ISO/TR 12300:2014, 2.1.9]
3.1.5
maintenance organization
formal and recognized group or legal business entity involved in the direct or indirect provision of
terminology services such as the creation, reconciliation, maintenance and distribution of IDMP controlled
vocabularies
[SOURCE: ISO/TR 14872:2019, 3.7]
3.1.6
mapping
process of defining a relationship between concepts in one coding system to concepts in another coding
system, in accordance with a documented rationale, for a given purpose
Note 1 to entry: Quality mapping will produce a usable map table, be a reproducible and understandable process.
[SOURCE: ISO/TR 12300:2014, 2.1.12]
3.1.7
map set
map table
map reference set
group of individual maps used to convert a range of entries from source to target code system
[SOURCE: ISO/TR 12300:2014, 2.1.11]
3.1.8
real-world data
RWD
data collected in a non-experimental, non-virtual situation
[SOURCE: ISO/TR 21934-1:2021, 3.9]

ISO/TS 5499:2024(en)
3.1.9
structured product labelling
SPL
document markup standard that specifies the structure and semantics of the content of authorized published
information that accompanies any medicine licensed by a medicines licensing authority
[SOURCE: Reference [10]]
3.1.10
target population
type of patients or consumers for which the indication of a medicinal product is authorized or is under
investigation
[SOURCE: ISO 11615:2017, 3.1.81]
3.1.11
term
linguistic representation of a concept
Note 1 to entry: A term can contain symbols and have variants, e.g. different forms of spelling
[SOURCE: ISO/TR 12300:2014, 2.2.8]
3.1.12
terminology
structured, human readable and machine-readable representation of concepts
Note 1 to entry: This includes the relationship of the terminology to the specifications for organizing, communicating
and interpreting such a set of concepts.
[SOURCE: ISO/TS 23541-1:2021, 3.1.5, modified — Note added.]
3.1.13
therapeutic indication
definition of the target disease or condition for which the Medicinal Product is authorized or under
investigation
[SOURCE: ISO 11615:2017, 3.1.82]
3.1.14
vocabulary
terminological dictionary which contains designations and definitions from one or more domains or subjects
[SOURCE: ISO 1087:2019, 3.7.5, modified]
3.1.15
off-label
prescribing of a medicinal product for an unapproved/unauthorized indication when a health care provider
determines that it is medically appropriate for their patient
3.2 Abbreviated terms
ADR Adverse Drug Reaction
CT Clinical Trials
ERP Enterprise resource planning
ICSR Individual Case Safety Report
PSUR Periodic Safety Update Reports

ISO/TS 5499:2024(en)
PV Pharmacovigilance
RIM Regulatory Information Management
4 Terminologies used for the coding of Therapeutic Indications
4.1 General
The following terminologies are commonly used in various jurisdictions and are required by regulatory
agencies for coding medicinal product therapeutic indications.
4.2 SNOMED CT
SNOMED CT is a comprehensive, multilingual clinical healthcare terminology, used in more than eighty
countries. It is a resource with comprehensive, scientifically validated clinical content that enables consistent
representation of clinical content in electronic health records and is mapped to other international
standards. SNOMED CT is owned, administered and developed by SNOMED International, a not-for-profit
organization.
The primary purpose of SNOMED CT is to encode the meanings that are used in health information and to
support the effective clinical recording of data with the aim of improving patient care. SNOMED CT provides
the core general terminology for electronic health records. SNOMED CT provides for consistent information
interchange and is fundamental to an interoperable electronic health record. It allows a consistent way to
index, store, retrieve and aggregate clinical data across specialties and sites of care. SNOMED CT is used
to represent Medical Condition in Structured Product Labelling to facilitate informed decision-making and
support long-term patient care. Thus, it is the required terminology for the coding of indications reported to,
[14]
e.g. the U.S. FDA .
4.3 MedDRA
The Medical Dictionary for Regulatory Activities (MedDRA), which is owned by the International Council
for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and maintained
and distributed by the MedDRA Maintenance and Support Services Organization (MSSO) and the Japanese
Maintenance Organization (JMO), is an international standardized terminology used to exchange regulatory
information on medical products in both pre- and post-authorization phases. In developing and continuously
maintaining MedDRA, the ICH endeavours to provide a single standardized international, multi-lingual
medical terminology which can be used for regulatory communication and evaluation of data pertaining to
medicinal products for human use. As a result, MedDRA is designed for use in the registration, documentation
and safety monitoring of medicinal products through all phases of the development cycle (i.e. from clinical
trials to post-marketing surveillance). Furthermore, MedDRA supports ICH electronic communication
within the ICH’s Electronic Common Technical Document (eCTD) and the E2B Individual Case Safety Report.
[15] [16]
MedDRA is the required terminology for the coding of indications for EMA .
4.4 ICD
The International Statistical Classification of Diseases and Related Health Problems (ICD) is a global
standard classification for reporting diseases and health conditions that is developed and maintained by
the World Health Organization (WHO). It is used worldwide in systems such as patient registries, insurance
claims systems, mortality and morbidity statistics, and patient health records. ICD is the foundation for the
identification of health trends and statistics globally, and the international standard for reporting diseases
and health conditions. It is the diagnostic classification standard for all clinical and research purposes.
ICD defines the universe of diseases, disorders, injuries and other related health conditions, listed in a
[17]
comprehensive, hierarchical fashion .
In addition, the International Classification of Primary Care (ICPC) is accepted within the WHO Family of
nd
International Classifications (FIC) as a classification for primary care or general practice. ICPC, 2 edition
(ICPC-2) classifies patient data and clinical activity in the domains of General/Family Practice and primary

ISO/TS 5499:2024(en)
care; it allows classification of the patient’s reason for encounter (RFE), the problems/diagnosis managed,
[18]
interventions, and the ordering of these data in an episode of care structure .
Since the diagnosis and interventions assigned by the healthcare provider and coded with ICD and ICPC
are related to the indications of a pharmaceutical product, mappings between disease terms within these
classifications to those used for coding the therapeutic indications are useful in the healthcare domain.
4.5 MeSH
The Medical Subject Headings (MeSH) thesaurus is a controlled and hierarchically organized vocabulary
produced by the National Library of Medicine (NLM). It is used for indexing, cataloguing, and searching of
biomedical and health-related information. The usage of appropriate descriptors from NLM's Medical Subject
Headings (MeSH)-controlled vocabulary thesaurus or terms from another vocabulary, such as SNOMED
CT, that has been mapped to MeSH within the Unified Medical Language System (UMLS) Metathesaurus,
is required when posting the primary disease or condition being studied in a clinical trial at clinicaltrials.
[19][20]
gov .
5 Use Cases for Coding of Therapeutic Indications
5.1 General
Medicinal product therapeutic indications are initially proposed for clinical trials and can be further
detailed and refined for regulatory submissions, and, if successful, will be included in product labels as part
of the marketing authorization process. Details of the indications are recorded and exchanged as text and
codes, via regulator and pharmaceutical company systems. Once authorized for distribution, the medicinal
products enter the supply chain along with the authorized indication information. This information can then
be used within the healthcare domain, including during the prescribing, dispensing, administering cycle,
with data stored and processed in clinical support systems, medicinal product dictionaries and electronic
health records. If adverse reactions to a medication are encountered, indication information can be sent
back to regulators and pharmaceutical companies in reports as part of the pharmacovigilance process.
Indication data are also be used as part of the reimbursement process and for pharmaco-epidemiological or
other statistical analyses. A high-level view of the flow of indication data is shown in Figure 1. This section
describes some of the use cases for indications and the need for harmonization of indication-related data.
Figure 1 — Processes & Systems Involving Product Indication Data Across Regulatory &
Healthcare4
ISO/TS 5499:2024(en)
5.2 IDMP data exchange between global regulators and bio/pharmaceutical companies
during regulatory processes
5.2.1 Clinical Trials (Medicinal Product Development Lifecycle)
During the development lifecycle of a medicinal product, clinical trials must be conducted to prove the
safety and efficacy of the medicine, and indications must be submitted by the pharmaceutical company to
the regulator as part of the clinical trial application process (e.g. clinical trial application (CTA) in Europe,
Investigational new drug (IND) application for the US). Clinical trials for the same medicinal product are
often conducted in multiple countries. Requirements for the description of the indication text and how
it is coded vary between regions, so the indication data for the same medicinal product can be recorded
differently between regions. The availability of maps between terminologies would facilitate exchange of
this data between regions.
5.2.2 Regulatory Submission and Coded Labelling Information
After the successful completion of clinical trials, a regulatory submission for authorization of the medicinal
product can be submitted to the regulator. The data submitted will include details of the therapeutic
indication(s) to be approved/authorized and to be included in the product label as well as coding of the
indication terms.
According to health authority guidance for labelling documents used as the basis for information to health
care professionals and patients, therapeutic indications should be clearly stated to reflect in which disease/
condition and target population the benefit-risk balance was established to be positive.
Nevertheless, defining the therapeutic indication is quite complex and requires a multidimensional analysis
of aspects that influence the benefit/risk assessment with respect to the interpretation of wording in
different therapeutic areas. The therapeutic indication is the primary information on the use of a medicine,
and it should clearly state the disease/condition and population that a medicine is intended to treat.
Examples of such areas of common interest refer to the description of the target population, the severity
of the disease, the aim of the treatment (diagnostic indication, prevention, or treatment), the place of the
medicinal product in the therapy, the use in combination therapy, as well as the consistency of wording
within and across therapeutic areas.
Study data standards describe principles for the exchange of clinical and nonclinical research data between
computer systems and provide a framework for the organization of study data. For example, the Clinical
Data Interchange Standards Consortium-Study Data Tabulation Model (CDISC-SDTM) provides a standard
for organizing and formatting data to streamline processes in collection, management, analysis and
reporting. CDISC SDTM is a required standard in certain regulatory regions (i.e. US, Japan) and promotes the
use of common dictionaries to be utilized across clinical studies adverse events, concomitant medications,
procedures, indications, study drug names, and medical history. More specifically, SDTM requires SNOMED
CT to identify the medical condition or problem that the investigational product in a clinical study is intended
[21]
to affect (treat, diagnose or prevent, i.e. the indication) .
5.2.2.1 Coded Labelling Information
Maps between the terminologies commonly used for coding therapeutic indications within each domain, i.e.
SNOMED CT in the clinical space, MedDRA for safety reporting, and ICD in the healthcare domain, enable the
transformation of unstructured information, e.g. in labelling documents, to structured (coded) information.
In this way, by making that data interoperable, further use cases can be supported, from the tracking of off-
label usage to identification of unmet medical needs.
5.2.2.2 Use Case: Structured Electronic Product Information
Clinical particulars such as indications and contra-indications are key for enabling clinical decision support
systems to be able to use product information and the patient’s health records to alert the prescriber or
dispenser to potential issues or harm with the chosen medicines for a specific patient.

ISO/TS 5499:2024(en)
Structured electronic product information (ePI) enables the easy checking of product information for
products concerning the same substances and linkage to other systems.
Online repositories of product information and linkage to this data through use of barcodes on packaging
will enable patients to benefit from the latest information for their medicines and translations of this
information into other languages.
Certain health authorities have implemented or have current initiatives to structure electronic product
information. These initiatives have leveraged data standards to structure and code medicinal product
information that includes therapeutic indications. For example, in 2005 the U.S. FDA implemented HL7
[22]
Structured Product Labeling to structure and code medicinal product information (i.e. ePI). In 2019,
Health Canada initiated their transition to a structured XML format for their product monograph templates
[23]
also utilizing HL7 SPL. The European Medicines Agency (EMA) have also initiated an ePI initiative
utilizing HL7 Fast Healthcare Interoperability Resources (FHIR), which also lends itself to the coding of
[24]
medicinal product information to include therapeutic indications. Of note, U.S. FDA and Health Canada
have identified SNOMED CT as the terminology for the identification of therapeutic indications whereby EMA
has identified MedDRA. This introduces an additional use case in the application of the general principles
identified within this document for additional mapping between SNOMED CT and M
...