ISO/TR 11147:2023

ISO/DTR 11147:####(X:2022(E)
ISO TC 215/WG 11
Date: 2022-MM-DD09-20
Health informatics –— Personalized digital health –— Digital therapeutics health software
systems

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ISO/DTR 11147:2022(E)



DTR stage


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ISO/DTR 11147:2022(E)
© 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.orgwww.iso.org
Published in Switzerland
© ISO 2022 – All rights reserved iii

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ISO/DTR 11147:2022(E)
Contents
Foreword . v
Introduction . vi
1 Scope . 2
2 Normative references . 2
3 Terms and definitions . 2
4 Context . 9
5 Considerations . 10
5.1 DTx Attributes . 10
5.1.1 Impact on patient care .10
5.1.2 Relationship to SiMD .10
5.1.3 DTx Software in context of a DTx System .10
Figure 1 — Use of DTx system in clinical practice . 13
5.2 Future considerations for standardization . 13
6 DTx in relation to ecosystem constructs . 14
6.1 Ecosystem overview . 14
Figure 2 — Relationship of industry categorizations . 15
6.2 Medical device . 15
6.3 Software as a Medical Device (SaMD) . 15
6.4 Software in a Medical Device (SiMD) . 16
6.5 Digital Health Technology (DHT) . 17
6.5.1 DHT Overview .17
6.5.2 Digital Therapeutics Alliance (DTA) .17
6.5.3 National Institute for Health and Care Excellence (NICE) .17
6.5.4 European Commission DG communications networks, content, and technology . 18
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ISO/DTR 11147:2022(E)
6.6 Artificial Intelligence as a Medical Device (AIaMD) . 20
7 Medical device software standards . 20
Annex A (informative) Landscape analysis . 24
Annex B (informative) DTx use cases . 31
Bibliography . 35
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ISO/DTR 11147:2022(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national
standards bodies (ISO member bodies). The work of preparing International Standards is normally
carried out through ISO technical committees. Each member body interested in a subject for which a
technical committee has been established has the right to be represented on that committee.
International organizations, governmental and non-governmental, in liaison with ISO, also take part
in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all
matters of electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for
the different types of ISO documents should be noted. This document was drafted in accordance with
the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject
of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details
of any patent rights identified during the development of the document will be in the Introduction
and/or on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 215, Health informatics.

A list of all parts in the ISO 11147 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.
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ISO/DTR 11147:2022(E)
Introduction
As the healthcare sector evolves, there is an increasing demand for the production and appropriate
use of digital health technologies (DHTs) across patient care settings. DHTs represent a broad
spectrum of products ranging from clinician-facing electronic prescribing systems, telemedicine
platforms, and decision support systems, to patient-facing wellness apps, diagnostic tools,
monitoring products, biomarkers, and therapeutics.
Given the diversity of digital product types available, it is important for patients, clinicians, and
healthcare decision makers to have the ability to clearly distinguish between the numerous types of
DHTs on the market. Without harmonized internationally recognized guidance, users are often
unable to differentiate between DHTs based on products’ intended use.
Digital therapeutics (DTx) - as defined in this document - represent a decade-old category of medicine
that can be used as standalone therapies or integrate into clinical care pathways alongside
pharmaceuticals, clinician-delivered therapies, and other medical devices.

ISO Standards exist for various non-DTx DHT product categories and varying DTx product definitions
and best practices are emerging at the industry level (see Annex A), yet no DTx-specific international
standardspublication exist. This document serves as an internationally recognisable reference for
patients, clinicians, healthcare decision makers, and product manufacturers to identify DHTs that
qualify as a DTx. It centres on DTx’s use of software to generate and deliver validated and measurable
medical interventions directly to patients. It is relevant to patients, clinicians, healthcare decision
makers, and product manufacturers
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TECHNICAL REPORT ISO/DTR 11147:2022(E)



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ISO/DTR 11147:2022(E)
Digital Therapeutics (DTx) — Health informatics –— Personalized
digital health –— Digital therapeutics health software systems

21 1  Scope
This document lists characteristics of a category of health software: digital therapeutics (DTx). DTx
provides medical interventions that are based on clinical evidence and produce real-world outcomes.
Product use cases (see Annex B) demonstrate the variety of products represented in this quickly
growing industry.
This document provides an overview of how DTx relates to other ecosystem constructs, including
medical devices, software as a medical device (SaMD), software in a medical device (SiMD), and
digital health technologies (DHT). It also addresses relevant health and medical device software
standards that have various degrees of applicability to DTx.
The focus of this document is on therapeutic products for human use and that are used in the context
of a disease, disorder, condition, or injury. It does not address products that are intended for
veterinary uses or for general wellbeing. Additional exclusions of this document include DTx market
access pathways (i.e.,. prescription, non-prescription pathways), medical device requirements,
product risk assessment, clinical evidence requirements, data security and patient privacy
considerations, and product authorization pathways.

42 2  Normative references
There are no normative references in this document.

63 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
digital health technology
DHT
system that uses computing platforms, connectivity, software, and sensors for healthcare and related
uses
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ISO/DTR 11147:2022(E)
Note 1 to entry: These technologies span a wide range of uses, from applications in general wellness to
applications as a medical device. They include technologies intended for use as a medical product, in a medical
product, or as an adjunct to other medical products (devices, drugs, and biologics). They can also be used to
develop or study medical products.
[1]
[SOURCE: BEST (Biomarkers, EndpointS, and other Tools) Resource ]
3.2
user
person using the system for a health-related purpose
Note 1 to entry: The user can be the subject of care directly, or an individual assisting (as proxy for) the subject
of care.
[SOURCE: ISO 81001-1:2021 [2]]

, 3.1.14]
3.3
intended use
intended purpose
use for which a product, process, or service is intended according to the specifications, instructions
and information provided by the manufacturer
Note 1 to entry: The intended medical indication, patient population, part of the body or type of tissue
interacted with, user profile, use environment, and operating principle are typical elements of the intended use.
[SOURCE: ISO/IEC Guide 63:2019, 3.4, modified — Added admitted term "intended purpose. [3]]".]
3.4
digital therapeutic
DTx
health software intended to treat or alleviate a disease, disorder, condition, or injury by generating
and delivering a medical intervention that has a demonstrable positive therapeutic impact on a
patient’s health
Note 1 to entry: DTx software can integrate with ancillary components to form a DTx system by:
— using general purpose hardware (i.e.,. smartphone, tablet, computer, watch, headset), input or output
components (i.e.,. wearables, sensors, platforms), or pharmaceuticals necessary for DTx functioning;
— using patient- and context-specific data to generate a medical intervention;
— integrating with tandem medical interventions (i.e.,. clinician-delivered therapies, pharmaceuticals, SiMD,
other DHT components).
Note 2 to entry: DTx can function independently or in addition to other interventions.
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ISO/DTR 11147:2022(E)
Note 3 to entry: Includes secondary prevention and tertiary prevention.
Note 4 to entry: DTx is produced in compliance with good product life cycle (PLC) management practices,
through use of a quality management system which encompasses demonstrated safety and effectiveness, and
post-market surveillance.
3.5
medical device
instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software,
material or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings, for one of more of the specific medical purpose(s) of
— diagnosis, prevention, monitoring, treatment or alleviation of disease,
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
— investigation, replacement, modification, or support of the anatomy or of a physiological process,
— supporting or sustaining life,
— control of conception,
— disinfection of medical devices,
— providing information by means of in vitro examination of specimens derived from the human
body,
and which does not achieve its primary intended action by pharmacological, immunological or
metabolic means, in or on the human body, but which can be assisted in its intended function by such
means
Note 1 to entry: Products which can be considered to be medical devices in some jurisdictions but not in others
include:
— disinfection substances,
— aids for persons with disabilities,
— devices incorporating animal and human tissues,
— devices for in-vitro fertilization or assisted reproductive technologies.
[SOURCE: ISO/IEC Guide 63:2019 [, 3]].7]
3.6
medical intervention
activity intended to maintain or to improve an individual’s health or functioning, or to alter the course
of a disease, disorder, or condition for the better, or to restore function lost through disease or injury,
or to assist an individual with activities of daily living, or to support physical and mental well-being
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3.7
health software
software intended to be used specifically for managing, maintaining, or improving health of
individual persons, or the delivery of care
Note 1 to entry: Health software fully includes what is considered software as a medical device.

Note 2 to entry: The scope of this document refers to the subset of health software that is intended to run on
general computing platforms.

[SOURCE: IEC 82304-1:2016 [4]], 3.6, modified — Note 2 to entry deleted.]
3.8
evidence
directly measurable characteristics of a process or product that represent objective, demonstrable
proof that a specific activity satisfied a specified requirement
[SOURCE: ISO/IEC 21827:2008 [5]], 3.19]
3.9
software as a medical device
SaMD
software intended to be used for one or more medical purposes that performs these purposes
without being part of a hardware medical device
Note 1 to entry: SaMD is a medical device and includes in-vitro diagnostic (IVD) medical device
Note 2 to entry: SaMD is capable of running on general purpose (non-medical purpose) computing platforms
Note 3 to entry: “without being part of” means software not necessary for a hardware medical device to achieve
its intended medical purpose
Note 4 to entry: Software does not meet the definition of SaMD if its intended purpose is to drive a hardware
medical device
Note 5 to entry: SaMD can be used in combination (e.g.,. as a module) with other products including medical
devices
Note 6 to entry: SaMD can be interfaced with other medical devices, including hardware medical devices and
other SaMD software, as well as general purpose software
Note 7 to entry: Mobile apps that meet the definition above are considered SaMD
[6]
[SOURCE: IMDRF 2013 – , modified — ‘may’ changed to ‘can’ [6]].]
3.10
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ISO/DTR 11147:2022(E)
software in a medical device
SiMD
software that is used as an integral part of a specified hardware medical device or is intended to drive
a hardware medical device
3.11
health
state of complete physical, mental and social well-being and not merely the absence of disease or
infirmity
[7]
[SOURCE: WHO 1948 ]
3.12
risk
combination of the probability of occurrence of harm and the severity of that harm
Note 1 to entry: The probability of occurrence includes the exposure to a hazardous situation and the possibility
to avoid or limit the harm.
[SOURCE: ISO/IEC Guide 63:2019 [, 3]].10]
3.13
cybersecurity
state where information and systems are protected from unauthorized activities, such as access, use,
disclosure, disruption, modification, or destruction to a degree that the risks related to violation of
confidentiality, integrity, and availability are maintained at an acceptable level throughout the life
cycle
[SOURCE: ISO 81001-1:2021 [, 3.2]].13]
3.14
privacy
freedom from intrusion into the private life or affairs of an individual when that intrusion results
from undue or illegal gathering and use of data about that individual
[SOURCE: ISO/TS 27790:2009 [8]], 3.56]
3.15
positive therapeutic impact
favourable or useful response to, effect resulting from, or outcome of a medical intervention
3.16
digital therapeutic software
DTx software
software intended to be used specifically for treating or alleviating a disease, disorder, condition, or
injury of individual persons
3.17
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ISO/DTR 11147:2022(E)
component
collection of system resources that (a) forms a physical or logical part of the system, (b) has specified
functions and interfaces, and (c) is treated (e.g.,. by policies or specifications) as existing
independently of other parts of the system
[9]
[SOURCE: IETF RFC 4949, , modified — Note 1 deleted. [9]].]
3.18
digital therapeutic system
digital therapeutic (DTx) software plus general purpose computer platform and any inputs or
outputs necessary for DTx functioning
3.19
tandem medical intervention
two or more medical interventions, each capable of producing a positive therapeutic benefit, when
implemented together are expected to produce a higher level of benefit than either one alone
3.20
secondary prevention
includes procedures that detect and treat preclinical pathological changes and thereby control
disease progression
[10]
[SOURCE: PANDVE, Harshal T. 2014. ]
3.21
tertiary prevention
seeks to soften the impact caused by the disease on the patient's function, longevity, and quality-of-
life once the disease has developed and has been treated in its acute clinical phase
[10]
[SOURCE: PANDVE, Harshal T. 2014. ]
3.22
product life-cycle management
PLC management

process of managing the life-cycle of a product through every stage, including concept/design,
manufacture, launch, sales/acquisition, integration/implementation, use, etc, to decommissioning

[SOURCE: AAMI HIT1000-1: 2022 [11]]

3.23quality management system
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part of a management system with regard to quality
Note 1 to entry: Requirements for a quality management systemssystem are given in ISO 9001 [12].
[SOURCE: ISO 9000:2015 [13]], 3.3.4, modified — Note 1 to entry replaced with new note 1 to entry.]
3.23
3.24safety
freedom from unacceptable risk
[SOURCE: ISO/IEC Guide 63:2019 [, 3]].16]

3.25
3.24
effectiveness
ability to produce the intended result
[SOURCE: ISO 81001-1:2021 [2]]

, 3.26 2.5]
post-market surveillance
systematic process to collect and analyse experience gained from medical devices that have been
placed on the market

[SOURCE: ISO 13485:2016 [14]]

3.27 25
primary prevention
prevent the onset of specific diseases via risk reduction by altering behaviours or exposures that can
lead to disease or by enhancing resistance to the effects of exposure to a disease agent
[10]
[SOURCE: PANDVE, Harshal T. 2014. ]
3.28 26
system
combination of interacting elements organized to achieve one or more stated purposes
[SOURCE: ISO/IEC/IEEE 15288: 2015, 4.1.46, modified — Notes to entry deleted. [15]].]
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ISO/DTR 11147:2022(E)
3.2927
combination medical intervention
two or more medical interventions that are necessary and, which, in combination are sufficient to
produce a positive therapeutic benefit
3.3028
artificial intelligence inas a medical device
AIaMD
subset of SaMDsoftware as a medical device that incorporates artificial intelligence or machine
learning
[16]
[SOURCE: MHRA 2022 ]

84 4  Context
The digital health landscape encompasses a broad range of technologies, with each serving a specific
purpose. While some DHTs are used for wellness, medication adherence, monitoring, or patient
diagnosis, others use software to deliver a medical intervention that directly impacts a disease,
disorder, condition, or injury. Without a common internationally recognizable definition of a DTx,
healthcare decision makers are not able to appropriately identify DTx products and distinguish them
from other DHTs to determine which products will best meet patients’ needs and expectations.
National regulatory and reimbursement frameworks for DHT and DTx are increasingly emerging.
While most national frameworks reference some version of a DHT framework, under which various
subsets of DTx products can fall, one nation has alreadycountry (the Republic of Korea) has
developed a DTx-specific framework:
— In South Korea, the Ministry of Food and Drug Safety established a regulatory framework for DTx
[17 ]
as a subcategory of SaMD [, ], largely based on the International Medical Device Regulators
[6]
Forum’s (IMDRF) SaMD definition .
— The National Institute for Health and Care Excellence (NICE) Evidence for Effectiveness
functional classification of DHTs includes three tiers of DHTs based on potential risk to users.
The top tier includes the categories of inform clinical management, drive clinicial management,
treat a specific condition, and diagnose a specific condition. DTx products are not specifically
[18]
categorized .
— In Germany’s Fast-Track Process for Digital Health Applications [digitale
[19 ]
Gesundheitsanwendungen (DiGA)] [)], ], DTx products that are classified under the European
Union’s Medical Device Regulation (MDR) Class I and Class IIa can qualify as a subset of DiGA,
but Class IIa and Class III DTx products do not currently qualify under this framework.
Without a consistent, internationally recognized definition of a DTx and eventual corresponding
quality standards, it is difficult for policymakers and other healthcare decision makers to develop
appropriate frameworks that properly distinguish DTx from other software categories and establish
harmonized expectations related to DTx function, reliability, and real-world impact.
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105 5  Considerations
10.15.1 5.1 DTx Attributes
10.1.15.1.1 5.1.1 Impact on patient care
Digital therapeutic software (DTx software) is responsible for the directly attributable impact on
patient health, similarly to pharmaceuticals and clinician-delivered therapies are responsible for
their own clinical impact.
DTx products include indications for secondary prevention and tertiary prevention. Primary
prevention does not qualify based on a disease, disorder, condition, or injury not being present.
DTx products are generally able to operate with little or no clinician control or intervention. While
DTx therapies can be supplemented with clinician-delivered interventions, DTx software is classified
differently from clinical decision support (CDS) tools and is therefore not intended to solely augment
a human decision.
DTx products are autonomous and differ from Medical Device Data Systems (MDDS), a class of
systems that has no intelligence and serves as an accessory to other regulated technology that do
have intelligence.
10.1.25.1.2 5.1.2 Relationship to SiMD
DTx software typically forms a subset of Software as a Medical Device (SaMD). Software whose sole
intent is to operate a medical purpose device (SiMD), regardless of whether the software is embedded
or remote, does not qualify as a DTx. However, if DTx software is hosted on general purpose hardware
(i.e.,. VR headset), even if the hardware is customized, branded, or locked for a specific function, it
qualifies as a DTx since the headset is general purpose and not a medical purpose device.
For example, if a virtual reality (VR) headset is branded and used exclusively with DTx software, the
headset is still considered to be general purpose hardware, as opposed to a medical purpose
hardware. In this case, VR software is loaded on the headset, but this software is not "embedded" in
the hardware to control a medical purpose device, as defined for SiMD devices. Further discussion is
warranted related to the relationship between VR, SaMD, and SiMD since in this example, the VR
software controls the headset hardware only to the extent needed for visual display. Yet, since the
VR software needs to be paired with a headset to function and will not be effective if displayed on
another platform such as a smartphone, it cannot be strictly classified as SaMD.
10.1.35.1.3 5.1.3 DTx Software in context of a DTx System
While this document focuses on DTx software, it is important to recognize thethere are other
components that can be incorporated into a digital therapeutic system (DTx system).
Two levels of a DTx system include, as shown in Figure 1:
The first level of a DTx system includes any structural elements that are necessary to facilitate and
enable the DTx software to generate and deliver its medical intervention. This includes components
such as hardware (i.e.,. smartphone, tablet, computer, watch, headset, sensors), software (i.e.,.
operating system), or pharmaceuticals that are necessary in order for the DTx software to function.
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ISO/DTR 11147:2022(E)
It can also include other required components, such as a quality management system. While
hardware components are general purpose in nature, as discussed above, it is still possible for the
hardware to be customized, branded, or locked for a specific function.
The second level of a DTx system includes any elements that work alongside DTx software as a
tandem medical intervention (this couldcan exclude combination medical interventions) to deliver a
cohesive therapy. Components that can form this level of a DTx system include other therapeutic
categories (i.e.,. clinician-delivered therapies, pharmaceuticals, SiMD), in addition to other digital
health technology components (i.e.,. monitoring, diagnostic, clinical decision support features).
For both levels of DTx systems, it is important to understand the intended use and functionality of
each individual component. While a product can be regulated at the system level, as opposed to the
standalone component level, it is important for evaluators to understand the intent, performance,
and outcomes associated with each component.
For example, a patient oughtwould need to know whether a product intends to monitor a condition,
diagnose a condition, or treat a condition, or any combination of these. Clinicians and policy makers
can provide patients with clarity by clearly distingu
...

FINAL
TECHNICAL ISO/DTR
DRAFT
REPORT 11147
ISO/TC 215
Health informatics – Personalized
Secretariat: ANSI
digital health – Digital therapeutics
Voting begins on:
2022-10-26 health software systems
Voting terminates on:
2022-12-21
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/DTR 11147:2022(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS. © ISO 2022

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ISO/DTR 11147:2022(E)
FINAL
TECHNICAL ISO/DTR
DRAFT
REPORT 11147
ISO/TC 215
Health informatics – Personalized
Secretariat: ANSI
digital health – Digital therapeutics
Voting begins on:
health software systems
Voting terminates on:
COPYRIGHT PROTECTED DOCUMENT
© 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.
RECIPIENTS OF THIS DRAFT ARE INVITED TO
ISO copyright office
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
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THEY ARE AWARE AND TO PROVIDE SUPPOR TING
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DOCUMENTATION.
Phone: +41 22 749 01 11
IN ADDITION TO THEIR EVALUATION AS
Reference number
Email: copyright@iso.org
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO­
ISO/DTR 11147:2022(E)
Website: www.iso.org
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
Published in Switzerland
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN­
DARDS TO WHICH REFERENCE MAY BE MADE IN
ii
  © ISO 2022 – All rights reserved
NATIONAL REGULATIONS. © ISO 2022

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ISO/DTR 11147:2022(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Context . 6
5 Considerations .6
5.1 DTx Attributes . 6
5.1.1 Impact on patient care . 6
5.1.2 Relationship to SiMD . . 6
5.1.3 DTx Software in context of a DTx System . 7
5.2 Future considerations for standardization . 8
6 DTx in relation to ecosystem constructs . 9
6.1 Ecosystem overview . 9
6.2 Medical device . 9
6.3 Software as a Medical Device (SaMD). 9
6.4 Software in a Medical Device (SiMD) . 10
6.5 Digital Health Technology (DHT) . 10
6.5.1 DHT Overview . 10
6.5.2 Digital Therapeutics Alliance (DTA) . 10
6.5.3 National Institute for Health and Care Excellence (NICE) . 11
6.5.4 European Commission DG communications networks, content, and
technology .12
6.6 Artificial Intelligence as a Medical Device (AIaMD) . 13
7 Medical device software standards . .13
Annex A (informative) Landscape analysis .15
Annex B (informative) DTx use cases .16
Bibliography .20
iii
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ISO/DTR 11147:2022(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 non­governmental, 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 215, Health informatics.
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
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ISO/DTR 11147:2022(E)
Introduction
As the healthcare sector evolves, there is an increasing demand for the production and appropriate use
of digital health technologies (DHTs) across patient care settings. DHTs represent a broad spectrum
of products ranging from clinician-facing electronic prescribing systems, telemedicine platforms,
and decision support systems, to patient-facing wellness apps, diagnostic tools, monitoring products,
biomarkers, and therapeutics.
Given the diversity of digital product types available, it is important for patients, clinicians, and
healthcare decision makers to have the ability to clearly distinguish between the numerous types of
DHTs on the market. Without harmonized internationally recognized guidance, users are often unable
to differentiate between DHTs based on products’ intended use.
Digital therapeutics (DTx) as defined in this document represent a decade-old category of medicine that
can be used as standalone therapies or integrate into clinical care pathways alongside pharmaceuticals,
clinician­delivered therapies, and other medical devices.
Standards exist for various non-DTx DHT product categories and varying DTx product definitions and
best practices are emerging at the industry level (see Annex A), yet no DTx-specific publication exist.
This document centres on DTx’s use of software to generate and deliver validated and measurable
medical interventions directly to patients. It is relevant to patients, clinicians, healthcare decision
makers, and product manufacturers
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TECHNICAL REPORT ISO/DTR 11147:2022(E)
Health informatics – Personalized digital health – Digital
therapeutics health software systems
1 Scope
This document lists characteristics of a category of health software: digital therapeutics (DTx). DTx
provides medical interventions that are based on clinical evidence and produce real­world outcomes.
Product use cases (see Annex B) demonstrate the variety of products represented in this quickly
growing industry.
This document provides an overview of how DTx relates to other ecosystem constructs, including
medical devices, software as a medical device (SaMD), software in a medical device (SiMD), and digital
health technologies (DHT). It also addresses relevant health and medical device software standards
that have various degrees of applicability to DTx.
The focus of this document is on therapeutic products for human use and that are used in the context
of a disease, disorder, condition, or injury. It does not address products that are intended for veterinary
uses or for general wellbeing. Additional exclusions of this document include DTx market access
pathways (i.e. prescription, non-prescription pathways), medical device requirements, product risk
assessment, clinical evidence requirements, data security and patient privacy considerations, and
product authorization pathways.
2 Normative references
There are no normative references in this document.
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
digital health technology
DHT
system that uses computing platforms, connectivity, software, and sensors for healthcare and related
uses
Note 1 to entry: These technologies span a wide range of uses, from applications in general wellness to
applications as a medical device. They include technologies intended for use as a medical product, in a medical
product, or as an adjunct to other medical products (devices, drugs, and biologics). They can also be used to
develop or study medical products.
[1]
[SOURCE: BEST Resource ]
3.2
user
person using the system for a health-related purpose
Note 1 to entry: The user can be the subject of care directly, or an individual assisting (as proxy for) the subject
of care.
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ISO/DTR 11147:2022(E)
[SOURCE: ISO 81001­1:2021, 3.1.14]
3.3
intended use
intended purpose
use for which a product, process or service is intended according to the specifications, instructions and
information provided by the manufacturer
Note 1 to entry: The intended medical indication, patient population, part of the body or type of tissue interacted
with, user profile, use environment, and operating principle are typical elements of the intended use.
[SOURCE: ISO/IEC Guide 63:2019, 3.4, modified — Added admitted term "intended purpose".]
3.4
digital therapeutic
DTx
health software intended to treat or alleviate a disease, disorder, condition, or injury by generating and
delivering a medical intervention that has a demonstrable positive therapeutic impact on a patient’s
health
Note 1 to entry: DTx software can integrate with ancillary components to form a DTx system by:
— using general purpose hardware (i.e. smartphone, tablet, computer, watch, headset), input or output
components (i.e. wearables, sensors, platforms), or pharmaceuticals necessary for DTx functioning;
— using patient- and context-specific data to generate a medical intervention;
— integrating with tandem medical interventions (i.e. clinician­delivered therapies, pharmaceuticals, SiMD,
other DHT components).
Note 2 to entry: DTx can function independently or in addition to other interventions.
Note 3 to entry: Includes secondary prevention and tertiary prevention.
Note 4 to entry: DTx is produced in compliance with good product life cycle (PLC) management practices,
through use of a quality management system which encompasses demonstrated safety and effectiveness, and
post­market surveillance.
3.5
medical device
instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software,
material or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings, for one of more of the specific medical purpose(s) of
— diagnosis, prevention, monitoring, treatment or alleviation of disease,
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
— investigation, replacement, modification, or support of the anatomy or of a physiological process,
— supporting or sustaining life,
— control of conception,
— disinfection of medical devices,
— providing information by means of in vitro examination of specimens derived from the human body,
and which does not achieve its primary intended action by pharmacological, immunological or metabolic
means, in or on the human body, but which can be assisted in its intended function by such means
Note 1 to entry: Products which can be considered to be medical devices in some jurisdictions but not in others
include:
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— disinfection substances,
— aids for persons with disabilities,
— devices incorporating animal and human tissues,
— devices for in­vitro fertilization or assisted reproductive technologies.
[SOURCE: ISO/IEC Guide 63:2019, 3.7]
3.6
medical intervention
activity intended to maintain or to improve an individual’s health or functioning, or to alter the course
of a disease, disorder, or condition for the better, or to restore function lost through disease or injury, or
to assist an individual with activities of daily living, or to support physical and mental well-being
3.7
health software
software intended to be used specifically for managing, maintaining or improving health of individual
persons, or the delivery of care
Note 1 to entry: Health software fully includes what is considered software as a medical device.
[SOURCE: IEC 82304-1:2016, 3.6, modified — Note 2 to entry deleted.]
3.8
evidence
directly measurable characteristics of a process or product that represent objective, demonstrable
proof that a specific activity satisfied a specified requirement
[SOURCE: ISO/IEC 21827:2008, 3.19]
3.9
software as a medical device
SaMD
software intended to be used for one or more medical purposes that performs these purposes without
being part of a hardware medical device
Note 1 to entry: SaMD is a medical device and includes in-vitro diagnostic (IVD) medical device
Note 2 to entry: SaMD is capable of running on general purpose (non-medical purpose) computing platforms
Note 3 to entry: “without being part of” means software not necessary for a hardware medical device to achieve
its intended medical purpose
Note 4 to entry: Software does not meet the definition of SaMD if its intended purpose is to drive a hardware
medical device
Note 5 to entry: SaMD can be used in combination (e.g. as a module) with other products including medical
devices
Note 6 to entry: SaMD can be interfaced with other medical devices, including hardware medical devices and
other SaMD software, as well as general purpose software
Note 7 to entry: Mobile apps that meet the definition above are considered SaMD
[6]
[SOURCE: IMDRF 2013 , modified — ‘may’ changed to ‘can’.]
3.10
software in a medical device
SiMD
software that is used as an integral part of a specified hardware medical device or is intended to drive
a hardware medical device
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3.11
health
state of complete physical, mental and social well-being and not merely the absence of disease or
infirmity
[7]
[SOURCE: WHO 1948 ]
3.12
risk
combination of the probability of occurrence of harm and the severity of that harm
Note 1 to entry: The probability of occurrence includes the exposure to a hazardous situation and the possibility
to avoid or limit the harm.
[SOURCE: ISO/IEC Guide 63:2019, 3.10]
3.13
cybersecurity
state where information and systems are protected from unauthorized activities, such as access, use,
disclosure, disruption, modification, or destruction to a degree that the risks related to violation of
confidentiality, integrity, and availability are maintained at an acceptable level throughout the life cycle
[SOURCE: ISO 81001­1:2021, 3.2.13]
3.14
privacy
freedom from intrusion into the private life or affairs of an individual when that intrusion results from
undue or illegal gathering and use of data about that individual
[SOURCE: ISO/TS 27790:2009, 3.56]
3.15
positive therapeutic impact
favourable or useful response to, effect resulting from, or outcome of a medical intervention
3.16
digital therapeutic software
DTx software
software intended to be used specifically for treating or alleviating a disease, disorder, condition, or
injury of individual persons
3.17
component
collection of system resources that a) forms a physical or logical part of the system, b) has specified
functions and interfaces, and c) is treated (e.g. by policies or specifications) as existing independently of
other parts of the system
[9]
[SOURCE: IETF RFC 4949 , modified — Note 1 deleted.]
3.18
digital therapeutic system
digital therapeutic (DTx) software plus general purpose computer platform and any inputs or outputs
necessary for DTx functioning
3.19
tandem medical intervention
two or more medical interventions, each capable of producing a positive therapeutic benefit, when
implemented together are expected to produce a higher level of benefit than either one alone
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3.20
secondary prevention
includes procedures that detect and treat preclinical pathological changes and thereby control disease
progression
[10]
[SOURCE: PANDVE 2014 ]
3.21
tertiary prevention
impact caused by the disease on the patient's function, longevity, and quality-of-life once the disease
has developed and has been treated in its acute clinical phase
[10]
[SOURCE: PANDVE 2014 ]
3.22
quality management system
part of a management system with regard to quality
Note 1 to entry: Requirements for a quality management system are given in ISO 9001.
[SOURCE: ISO 9000:2015, 3.3.4, modified — Note 1 to entry replaced with new note 1 to entry.]
3.23
safety
freedom from unacceptable risk
[SOURCE: ISO/IEC Guide 63:2019, 3.16]
3.24
effectiveness
ability to produce the intended result
[SOURCE: ISO 81001­1:2021, 3.2.5]
3.25
primary prevention
prevent the onset of specific diseases via risk reduction by altering behaviours or exposures that can
lead to disease or by enhancing resistance to the effects of exposure to a disease agent
[10]
[SOURCE: PANDVE 2014 ]
3.26
system
combination of interacting elements organized to achieve one or more stated purposes
[SOURCE: ISO/IEC/IEEE 15288: 2015, 4.1.46, modified — Notes to entry deleted.]
3.27
combination medical intervention
two or more medical interventions that are necessary, which, in combination are sufficient to produce a
positive therapeutic benefit
3.28
artificial intelligence as a medical device
AIaMD
subset of software as a medical device that incorporates artificial intelligence or machine learning
[16]
[SOURCE: MHRA 2022 ]
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ISO/DTR 11147:2022(E)
4 Context
The digital health landscape encompasses a broad range of technologies, with each serving a specific
purpose. While some DHTs are used for wellness, medication adherence, monitoring, or patient
diagnosis, others use software to deliver a medical intervention that directly impacts a disease,
disorder, condition, or injury. Without a common internationally recognizable definition of a DTx,
healthcare decision makers are not able to appropriately identify DTx products and distinguish them
from other DHTs to determine which products will best meet patients’ needs and expectations.
National regulatory and reimbursement frameworks for DHT and DTx are increasingly emerging. While
most national frameworks reference some version of a DHT framework, under which various subsets
of DTx products can fall, one country (the Republic of Korea) has developed a DTx-specific framework:
— In South Korea, the Ministry of Food and Drug Safety established a regulatory framework for DTx
[17]
as a subcategory of SaMD, largely based on the International Medical Device Regulators Forum’s
[6]
(IMDRF) SaMD definition .
— The National Institute for Health and Care Excellence (NICE) Evidence for Effectiveness functional
classification of DHTs includes three tiers of DHTs based on potential risk to users. The top tier
includes the categories of inform clinical management, drive clinicial management, treat a specific
[18]
condition, and diagnose a specific condition. DTx products are not specifically categorized .
— In Germany’s Fast-Track Process for Digital Health Applications [digitale Gesundheitsanwendungen
[19]
(DiGA)], DTx products that are classified under the European Union’s Medical Device Regulation
(MDR) Class I and Class IIa can qualify as a subset of DiGA, but Class IIa and Class III DTx products
do not currently qualify under this framework.
Without a consistent, internationally recognized definition of a DTx and eventual corresponding quality
standards, it is difficult for policymakers and other healthcare decision makers to develop appropriate
frameworks that properly distinguish DTx from other software categories and establish harmonized
expectations related to DTx function, reliability, and real-world impact.
5 Considerations
5.1 DTx Attributes
5.1.1 Impact on patient care
Digital therapeutic software (DTx software) is responsible for the directly attributable impact on
patient health, similarly to pharmaceuticals and clinician-delivered therapies are responsible for their
own clinical impact.
DTx products include indications for secondary prevention and tertiary prevention. Primary prevention
does not qualify based on a disease, disorder, condition, or injury not being present.
DTx products are generally able to operate with little or no clinician control or intervention. While
DTx therapies can be supplemented with clinician-delivered interventions, DTx software is classified
differently from clinical decision support (CDS) tools and is therefore not intended to solely augment a
human decision.
DTx products are autonomous and differ from Medical Device Data Systems (MDDS), a class of
systems that has no intelligence and serves as an accessory to other regulated technology that do have
intelligence.
5.1.2 Relationship to SiMD
DTx software typically forms a subset of Software as a Medical Device (SaMD). Software whose sole
intent is to operate a medical purpose device (SiMD), regardless of whether the software is embedded
or remote, does not qualify as a DTx. However, if DTx software is hosted on general purpose hardware
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(i.e. VR headset), even if the hardware is customized, branded, or locked for a specific function, it
qualifies as a DTx since the headset is general purpose and not a medical purpose device.
For example, if a virtual reality (VR) headset is branded and used exclusively with DTx software, the
headset is still considered to be general purpose hardware, as opposed to a medical purpose hardware.
In this case, VR software is loaded on the headset, but this software is not "embedded" in the hardware
to control a medical purpose device, as defined for SiMD devices. Further discussion is warranted
related to the relationship between VR, SaMD, and SiMD since in this example, the VR software controls
the headset hardware only to the extent needed for visual display. Yet, since the VR software needs to
be paired with a headset to function and will not be effective if displayed on another platform such as a
smartphone, it cannot be strictly classified as SaMD.
5.1.3 DTx Software in context of a DTx System
While this document focuses on DTx software, there are other components that can be incorporated
into a digital therapeutic system (DTx system).
Two levels of a DTx system include, as shown in Figure 1:
The first level of a DTx system includes any structural elements that are necessary to facilitate and
enable the DTx software to generate and deliver its medical intervention. This includes components
such as hardware (i.e. smartphone, tablet, computer, watch, headset, sensors), software (i.e. operating
system), or pharmaceuticals that are necessary in order for the DTx software to function. It can also
include other required components, such as a quality management system. While hardware components
are general purpose in nature, as discussed above, it is still possible for the hardware to be customized,
branded, or locked for a specific function.
The second level of a DTx system includes any elements that work alongside DTx software as a tandem
medical intervention (this can exclude combination medical interventions) to deliver a cohesive therapy.
Components that can form this level of a DTx system include other therapeutic categories (i.e. clinician-
delivered therapies, pharmaceuticals, SiMD), in addition to other digital health technology components
(i.e. monitoring, diagnostic, clinical decision support features).
For both levels of DTx systems, it is important to understand the intended use and functionality of
each individual component. While a product can be regulated at the system level, as opposed to the
standalone component level, it is important for evaluators to understand the intent, performance, and
outcomes associated with each component.
For example, a patient would need to know whether a product intends to monitor a condition, diagnose
a condition, or treat a condition, or any combination of the
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