ISO/TR 17302:2015
(Main)Nanotechnologies — Framework for identifying vocabulary development for nanotechnology applications in human healthcare
Nanotechnologies — Framework for identifying vocabulary development for nanotechnology applications in human healthcare
ISO/TR 17302:2015 will not attempt a formal, comprehensive definition of "nanomedicine". Instead, it will provide a taxonomic framework for the development of vocabulary for clinical applications of nanotechnologies in human healthcare. While it is understood that the origins of nanotechnologies for healthcare applications emerge from pre-clinical and translational research, the interest of this Technical Report is to determine where these technologies will impact the clinical value chain and the practice of medicine. ISO/TR 17302:2015 is intended to facilitate communications between developers and users of nanotechnologies, deliverers and users of medicine including the pharmaceutical, research and medical communities, regulatory professionals, and additional organizations and individuals who might interact with these groups, including biotechnology, diagnostic, and medical device companies, the life sciences, patent attorneys and patent offices, institutional review boards, ethics review boards, and accreditation organizations.
Nanotechnologies — Cadre pour le développement d'un vocabulaire d'identification des applications de nanotechnologies en santé humaine
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Standards Content (Sample)
TECHNICAL ISO/TR
REPORT 17302
First edition
2015-12-15
Nanotechnologies — Framework for
identifying vocabulary development
for nanotechnology applications in
human healthcare
Nanotechnologies — Cadre pour le développement d’un vocabulaire
d’identification des applications de nanotechnologies en santé humaine
Reference number
ISO/TR 17302:2015(E)
©
ISO 2015
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ISO/TR 17302:2015(E)
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ISO/TR 17302:2015(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Symbols and abbreviated terms . 1
3 Framework . 1
3.1 General . 1
3.2 The clinical value chain . 2
3.2.1 General. 2
3.2.2 Prediction and prevention . 3
3.2.3 Diagnosis . 4
3.2.4 Therapy . 5
3.2.5 Monitoring . 5
4 Terminology development within the clinical value chain . 6
4.1 General . 6
4.2 Identifying terms in need of definition in the clinical value chain . 7
4.2.1 General. 7
4.2.2 Prediction and prevention . 8
4.2.3 Diagnosis . 8
4.2.4 Therapy . 9
4.2.5 Monitoring . 9
4.2.6 Further identification of potential terms . 9
Annex A (informative) Nanomedicine terms as defined in current literature .10
Annex B (informative) Nanomedicine ontology and terminology resources .16
Bibliography .18
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ISO/TR 17302:2015(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 on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 229, Nanotechnologies.
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ISO/TR 17302:2015(E)
Introduction
Terminology related to the use of nanotechnologies in human healthcare is on the rise as research
in the field continues to intensify. The heightened focus in medical research on nanotechnologies is
reflected by the number of medical and related scientific journals that are reporting on this research.
The number of publications mentioning both nanotechnology and biology or medicine has increased
[1]
logarithmically since approximately the year 2000.
This Technical Report explains current concepts related to human healthcare in the clinical setting
and identifies pertinent and timely categories most likely to be advanced by nanotechnologies.
Certain aspects of human healthcare are expected to be advanced by nanotechnologies more than
others, and standardization needs unique vocabulary to support the development of applications of
nanotechnologies within it. It is recognized, for example, that physical chemists use the term “substrate”
to describe a material surface supporting adsorption processes; this differs from a biologist’s use of the
term “substrate” to describe a substance that an enzyme acts upon.
Due to the keen public interest in the advancement of human healthcare, a common vocabulary is
particularly relevant to the development of research proposals to gain funding and to communicate
findings and results. This Technical Report provides a taxonomic framework to serve as the basis for
the development of terminology related to the application of nanotechnologies in human healthcare.
The framework identifies categories associated with the clinical value chain most likely to be advanced
by nanotechnologies and describes some of the promising technologies being developed and utilized
within the clinical workflow. It is intended that terms will be identified and harmonized definitions will
be developed for them within the framework offered by this Technical Report.
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TECHNICAL REPORT ISO/TR 17302:2015(E)
Nanotechnologies — Framework for identifying
vocabulary development for nanotechnology applications
in human healthcare
1 Scope
This Technical Report will not attempt a formal, comprehensive definition of “nanomedicine”. Instead,
it will provide a taxonomic framework for the development of vocabulary for clinical applications of
nanotechnologies in human healthcare. While it is understood that the origins of nanotechnologies
for healthcare applications emerge from pre-clinical and translational research, the interest of this
Technical Report is to determine where these technologies will impact the clinical value chain and the
practice of medicine.
This Technical Report is intended to facilitate communications between developers and users of
nanotechnologies, deliverers and users of medicine including the pharmaceutical, research and medical
communities, regulatory professionals, and additional organizations and individuals who might
interact with these groups, including biotechnology, diagnostic, and medical device companies, the life
sciences, patent attorneys and patent offices, institutional review boards, ethics review boards, and
accreditation organizations.
2 Symbols and abbreviated terms
nm nanometer
3 Framework
3.1 General
The term “nanomedicine” is used by the scientific community and government agencies to describe a
field that is relatively undefined in terms of the affected health care segments and the specific advances
in nanotechnologies for biomedical applications.
In addition, the relevant mechanisms currently associated with diagnosis and treatment in biological
processes can be larger than approximately 100 nm (e.g. endocytosis). Several participants from
the biological sciences work with 400 nm diameter particles as drug carriers, while others consider
<1 000 nm or <500 nm as pertinent in exploring emerging applications. Overall, the products currently
enabled by nanotechnologies that are available for commercial clinical use are characterized by in vitro
bulk properties or systemic effects. Examples of nanosize objects of interest in healthcare applications
are depicted in Figure 1.
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a) Polymer-drug b) Polymeric c) Solid lipid
d) Dendrimer
conjugate nanoparticle nanoparticle
e) Liposome f) Micelle g) Gold nanoparticle h) Carbon nanotube
Key
therapeutic agent hydrophilic linker
diagnostic agent targeting moiety
[ ]
Figure 1 — Examples of nanosize objects of interest in healthcare applications 2
In contrast, the current ISO definition of the term “nanoscale” stems from materials science and
expresses in part the size range associated with quantum effects. The broad, enabling nature of
nanotechnologies means that convergence with the biological sciences will continue to intensify.
However, this Technical Report does not seek to suggest that current definitions in nanotechnologies,
[3]
such as the approximately 100 nm upper boundary found in the ISO definition of the term “nanoscale”,
be normalized to account for all size relationships in biological systems.
3.2 The clinical value chain
3.2.1 General
In recognition of the advancements that are anticipated in the clinical practice of medicine associated
with nanotechnologies, relevant applications of nanotechnologies in human healthcare can be identified
by their location in the clinical value chain (see Figure 2).
Figure 2 — The clinical value chain
The clinical value chain suggested for use in this Technical Report consists of 4 segments. The
prediction and prevention segment includes nanotechnologies that are used to predict, or prevent
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disease, conduct disease screening, and which are used in disease surveillance. The diagnosis segment
includes nanotechnologies that are used for in vitro and in vivo detection, classification, grading, etc. of
disease. The therapy segment includes nanotechnologies that are associated with therapy for disease.
This includes drugs and other medicines (e.g. biopharmaceuticals), surgical implants, materials,
devices, and surgical aids, and alternative therapies (e.g. stem cells). The monitoring segment includes
nanotechnologies that are used to monitor disease after therapy to evaluate the efficacy of treatment
and the progression or remission of disease, recurrence, side effects, etc.
Underlying these segments are pre-clinical and translational activities. That is, fundamental
nanotechnology developments in academia, life science, and the biopharmaceutical industry are
undertaken with the objective of having an eventual impact or application in one or more of the clinical
value chain segments. These might be nanotechnologies used to understand basic life processes or
nanotechnologies that support products used in a clinical setting (see Figure 3).
Figure 3 — Illustrative example of the general stages of development for nanotechnologies used
[ ]
in medicine, which highlights the European Union’s approach 4
3.2.2 Prediction and prevention
Prediction and prevention inlcudes technologies that permit accurate screening to identify the risk or
susceptibility to disease or disease recurrence, prognosis based on one or more indicators, public health
surveillance of disease and immunization to prevent disease. Products enabled by nanotechnologies in
this value chain segment include sprays, coatings, antiseptics and vaccines.
Two application areas that are useful to highlight the contribution of nanotechnologies to this segment
of the clinical value are the prevention of surgical site infections and the use of informatics to predict and
reduce drug side effects by identifying patients at risk. Surgical site infections encompass inadvertent
infections occurring inside the hospital or physician’s office, the prevention of which can include the
use of disinfectants, sterile surfaces, protective gowns, air handling, and appropriate waste disposal.
The use of nanotechnologies for preventing adventitious infections might be the source of new terms,
e.g. “nanotextured surface” to describe a product designed by the coating industry to ensure a sterile
environment. Bioinformatics and nano-informatics might be used to evaluate disease prevalence, drug
design, acceptable test protocols, dose metrics, and toxicity.
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3.2.3 Diagnosis
Nanotechnologies for diagnostics encompass in vivo as well as ex vivo/in vitro evaluations.
Nanotechnologies can be used to advance sensing systems to improve the accurate and early detection
and diagnosis of disease. There are multiple components in the diagnostic process ranging from the
manufacturing setting (e.g. reagent and detection systems) to the selection of target analytes (e.g. cells,
proteins, tissue structures) and the organism setting (in vitro/ex vivo or in vivo) (see Figure 4).
Figure 4 — Overview of nanotechnologies in diagnostics
For example, when a new nanoparticle is developed for in vivo imaging, this diagram approach could be
applied to understand the application area and technology as follows (Figure 5):
— Manufacture — Method of synthesis of the nanoparticle. Further details could be added, such as
additional nanotechnology that is required for the manufacturing process.
— Source — Context of use of the nanoparticle. In this case, the nanoparticle is designed to image a
living patient.
— Measurand — This nanoparticle is designed to be delivered into and enhance the visualization of
the patient’s lymphatics.
— Sensing System — The actual diagnostic action occurs with placement of the patient in the MRI
device and detecting the nanoparticles with the lymphatics.
— Application — The goal of the use of the nanoparticle is for the detection of metastatic cancer in the
patient’s lymphatics.
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Figure 5 — Example of understanding a diagnostic application for terminology development
3.2.4 Therapy
Applications of nanotechnologies in the therapy segment of the clinical value chain include the delivery
selective and targeted drug therapies, material modifications, and medical devices. Specific areas of
therapy that could be advanced by the use of nanotechnologies in this clinical value chain segment
include clinical indication tools, understanding of route of administration, reduced inter and intra-
subject variability, improved dose-response relationship(s), faster achievement of maximum amount of
drug in blood stream, and limiting the effect on pharmacokinetics of a drug once absorbed.
Cancer therapy is a dominant field that leverages advancements in nanotechnology. In this area,
nano-objects of interest include nanowires, gold (functional metallic), magnetic nanoparticles, viral
nanoparticles, polysaccharide nanocarriers, nanobiosensors, nanomicelles, nanoscale liposomes, nano-
arrays, nanobioconjugates, nanochannels, stealth nano-objects, nanomembranes, DNA complexes,
molecular motors, and protein coronas.
For material modification and manufacture applications, key classes of nano-objects include synthetic
nanoparticles, dendrimers (e.g. hyperbranched polymers, dendigrafts, and dendronised polymers),
nanogels, nanosuspensions, solid lipid nanoparticles, nano shells, nanopores, nanocapsule, nanoneedle,
nanoporous membrane, and nanofilms.
In the area of medical devices, applications of nanotechnologies include the development of artificial
muscles, nanoscale knee and lymph sleeves, nanowire and needle scaffolds, tissue and vessel re-
enforcement, dental applications, drug delivery devices, and nano-coatings on medical devices, such as
ball and socket joints in hip joint replacements.
3.2.5 Monitoring
Post-therapy applications being advanced with nanotechnologies show promise regarding the ability
to accurately monitor the progress of disease treatment, recovery, and recurrence. Nanotechnologies
of interest can fall into the categories of microchip sensors or nanoparticles, ligands, and reagents that,
depending on the intended use, can interact with human systems in vivo or ex vivo (see Figure 6).
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Figure 6 — Nanomedicine monitoring applications
Examples of technologies and applications in this value chain segment include electrochemical sensors,
biomarker and neurological monitoring, disease monitoring, and optical tracking of drug delivery.
Analytical lab-on-a-chip miniaturized sensor technology designed to be ingested or implanted can be
[6]
used to monitor and record details of medication, metabolism, and vital signs. Sensors for monitoring
purposes can be incorporated in wearable and mobile applications such as textiles and cellular phones,
[7] [8]
or implanted (e.g. an integrated glucose monitor and insulin dispenser).
4 Terminology development within the clinical value chain
4.1 General
There is inherent inter-dependence between the clinical value chain segments and the nanotechnologies
[9] [10] [15]
that could be employed. This can be viewed in the emerging field of theranostics, which tightly
integrates diagnostic and therapeutic components. All value chain segments could make use of sensor
technologies; however, the measurands are focused on the particular objective of each value chain
segment. For example, in the case of diagnosis, a nano-based imaging agent could be used to detect
and localize cancer within the body in order to classify and grade the extent of disease. In the context
of monitoring, this same or a similar agent and imaging methodology could be used to determine the
effect that a drug or other therapy is having in combating disease.
A method for determining the appropriate segment or segments in which nanotechnologies targeted
toward human healthcare fit into the clinical value chain, in order to identify associated terminology, is
illustrated in Figure 6.
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Figure 7 — Placement of nanotechnologies into a corresponding clinical value chain segment(s)
As shown in Figure 7, a nanotechnology component can be placed within the appropriate clinical
value chain segment based on its intended use(s). This determination can be made during preclinical
development or anytime thereafter. Responses to the following questions can be used to guide the
placement of nanotechnologies in the value chain and identify associated terminology.
— What is the intended use of the nanotechnology component?
— What is the investigation or treatment objective?
— What is the intended result of the investigation or treatment?
4.2 Identifying terms in need of definition in the clinical value chain
4.2.1 General
A review of the current literature on nanomedicine and related terms has found many areas where
there are suggested definitions of terms as defined in the literature. A summary of these is provided in
Annex A. The entries are divided into the following areas:
— clinical indication;
— generic clinical terms;
— route of administration;
— class of nano-object;
— modification and manufacture;
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— other.
The first three areas are covered by well-established terms in the medical literature. It is therefore
appropriate to focus on the class of nano-object and modification and manufacture.
As noted at the outset of this Technical Report, the term “nanomedicine” is increasingly used by the
scientific community and government agencies to describe the applications of nanotechnologies in
human health care. However, no single definition for this term is actively promoted. Additional terms
are identified for each clinical value chain segment from the published literature or using the method
offered by this Technical Report. Consistent with the purpose of the clinical value chain, identified
terms look outward toward integrating nanotechnologies with existing medical applications, rather
than emphasizing that they are sourced from nanotechnologies.
There is also a lack of clarity around the use of nanotechnology related to medical devices. For example,
in Australia there is no available definition of nano-specific devices, and the requirement to do so is
only a recommendation to have “lists of available nanotechnology infrastructure and equipment”
within the following 2009 report: “Nanotechnology in Australia, Trends, Applications and Collaborative
[5]
Opportunities” . This is an area that requires the application of standardization principles, especially
[35]
as labelling can be confusing. For example, the “Accu-chek” blood glucose monitoring machine which
uses a nano descriptor on the product packaging does not contain nanomaterial. The term “nano” is used
to emphasize the very small amount of blood that the equipment requires in order to perform its analysis.
Perhaps due to this confusion, some countries are proposing the use of product databases. For example,
Denmark intends to create a database of products containing nanomaterials. Specifically, under a draft
amendment to the Danish Chemicals Act, the Minister of the Environment would have the authority to
write a detailed order establishing the rules for a national database of mixtures and articles containing
or releasing nanomaterials. The order would also require producers and importers to report products
containing or releasing nanomaterials. The information in the database is intended to form the basis of
an evaluation of whether the content of nanomaterials in products on the Danish market poses a risk
[11]
for consumers and the environment. The Ministry plans for the first reports to be due in early 2014.
The current conclusion is that discovering what nano-enabled or nano-enhanced medical devices are
currently available in the market place is almost an impossibility given that to date, no country appears
to have a system in place to record them. Based on literature review, while research is being done, this
appears to be mainly in the field of drug delivery systems.
4.2.2 Prediction and prevention
There are relative merits associated with the use of bio-, bionano-, nanobio-, and nano- when modifying
root nouns such as “material”. A specific example is in defining a reinforced polymer that consists of a
30 nm nanoparticle mesh for organ repair procedures. In addition, common definitions for terms such
as nano-informatics, bionano-informatics, nanomedicine informatics, nanodelivery, nano-ontologies,
and nanobiosystem could be useful.
4.2.3 Diagnosis
For any given diagnostic nanotechnology, basic characteristics can be evaluated for the identification
of terminology development using the diagram provided in Figure 7. An example of how this approach
can be used to identify associated terminology is illustrated in Figure 8 using the diagnostics segment
of the clinical value chain.
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Figure 8 — Terminology development process related to diagnostics value chain segment
4.2.4 Therapy
Certain terms in therapy have existing ISO definitions including nanotoxicology, nanobiotechnology,
[3] [12] [13]
nanoscience, and stealth nano-object. Others can lend themselves to common terminology
development, including gene therapy, nanotherapeutics, imaging agents, nanoneurotechnology,
nanoneuroprotection, transfection, wrapping, and functional agent.
4.2.5 Monitoring
Terminology associated with sensing technologies bears study for evaluating definition needs for the
monitoring segment of the clinical value chain. Possible candidates for consideration include nanosensor
and nanobiosensor. In the area of nanoparticles, ligands and reagents, the term nanoparticle has an
[14]
existing ISO definition.
4.2.6 Further identification of potential terms
A list of references for several sourcing terms that are being actively used in healthcare applications
of nanotechnologies is provided in Annex B. In this regard, it should be recognized that there is a
relationship between standard terminologies that is captured in informatics. Lexical semantics,
the meaning of words when combined into sentences and phrases, will differ among groups and
it is prudent and valuable to understand that these nuances exist when conducting broad spectrum
keyword searches.
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ISO/TR 17302:2015(E)
Annex A
(informative)
Nanomedicine terms as defined in current literature
Note that the definitions listed in this Table have not been agreed through an ISO body. Therefore, at
present, they are simply a source of information and opportunities for term standardization in the
future. Furthermore, the definitions are just examples and are not meant to be all-inclusive of terms
used in the field.
Table A.1 — Nanomedicine terms as defined in current literature
Nanotechnology
Definition from the external Example literature
Area term or branch of
literature reference
medicine
Clinical indication Of or relating to the heart and blood
Cardiovascular Oxforddictionaries.com
vessels.
N.B. Only those The disease caused by an uncontrolled
reported for Cancer division of abnormal cells in a part of the Oxforddictionaries.com
”nanomedicine” body.
applications are
(Chiefly of a drug) used to reduce
included. Anti-inflammatory Oxforddictionaries.com
inflam
...
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