ISO/TR 11147

Health informatics — Personalized digital health — Digital therapeutics health software systems

This document lists characteristics of a category of health software: digital therapeutics (DTx). DTx products generate and deliver medical interventions that are based on clinical evidence, have demonstrable positive therapeutic impacts on patient health, 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 other 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 that are used in the context of a disease, disorder, condition, or injury for human use. It does not address products that are intended for veterinary use 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, patient privacy considerations, and product authorization pathways.

Informatique de santé — Santé numérique personnalisée — Systèmes logiciels de santé pour la thérapeutique numérique

General Information

• Status: Not Published
• ICS: 35.240.80 - IT applications in health care technology
• Technical Committee: ISO/TC 215 - Health informatics
• Drafting Committee: ISO/TC 215 - Health informatics
• Current Stage: 6000 - International Standard under publication
• Completion Date: 04-May-2023

Standards Content (Sample)

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: [phone]
Email: [e-mail]
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.
vi © ISO 2022 – All rights reserved
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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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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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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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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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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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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:
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© ISO 2022

All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may

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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
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SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
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LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
Published in Switzerland
OCCASION HAVE TO BE CONSIDERED IN THE
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DARDS TO WHICH REFERENCE MAY BE MADE IN
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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.
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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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ISO/DTR 11147:2022(E)
— 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
...