Special Report

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Device safety and effectiveness

in the pediatric population:
aUS FDA perspective
Expert Rev. Med. Devices 6(2), 131135 (2009)

Joy Samuels-Reid,
Judith U Cope and
Audrey E Morrison

Author for correspondence

Division of Anesthesiology,
General Hospital, Infection
Control and Dental Devices/
ODE/CDRH/FDA, Rockville,
MD20850, USA
joy.samuels-reid@fda.hhs.gov

The US FDA recognizes that there are many challenges to ensuring that medical devices are used
responsibly and safely in the pediatric population. Education plays a key role, and manufacturers
and healthcare providers must be informed of medical device issues unique to the pediatric
population. Healthcare workers and device manufacturers must recognize that adverse events
may differ between the adult and pediatric population and among pediatric subpopulations.
Risk mitigation may also differ, and heightened awareness will reduce the potential for adverse
events and promote the safe use of medical devices in children.
Keywords : children device classification diagnostic test human factor implanted device medical device
pediatric safety US FDA

The Center for Devices and Radiological

Health (CDRH), in the US FDA, specifically
reviews all device submissions, including those
devices targeted for the pediatric population.
The CDRH defines the pediatric population to include birth through to the age of
21years [101] . There are important factors to
consider for each subpopulation within this
age group in terms of safety and effectiveness
of the medical device, including issues of size,
weight, growth and development. Diagnostic
blood tests, implanted artificial joints, infusion pumps and thermometers are just a few
examples of the wide array of medical devices.
Careful evaluation of which designs would best
support the pediatric users needs and developing the device in accordance with these considerations are crucial in the development and
approval of medical devices that will be used
by pediatric patients. This article highlights
the information that the FDA considers when
reviewing medical devices that are intended for
use in the pediatric population.
The world of medical devices has skyrocketed
with technological advancement in the treatment of medical conditions, and device use has
become widespread in pediatric patients. The
pediatric population and its subpopulations
interface with a multitude of devices on a daily
basis. Devices can range from the simple, such
as tongue depressors, to the complex, such as
ventilators. Safety issues may arise and it may
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10.1586/17434440.6.2.131

not be apparent what role the device played in

the adverse outcome. In other situations, effectiveness may have only been demonstrated or
studied in the adult population.
How does the US FDA define children
with respect to devices?

The CDRH is responsible for the approval of

medical devices within the FDA. The CDRH
defines the pediatric population as birth
through to 21years of age. It further recognizes
the unique differences among the pediatric subpopulations, dividing this population into the
following age subgroups:
Neonate: birth28days
Infant: 28days2years
Child: 212years
Adolescent: 1221years
The CDRH recommends that these various
pediatric subpopulations be considered when
reviewing medical device applications.
What is the legal definition of a
medicaldevice?

A medical device is an instrument, apparatus,

implement, machine, contrivance, implant,
in vitro reagent or similar article that is not
metabolized in the body; it is not a biologic,
drug or food; and, it is used to treat, diagnose
or prevent a disease or condition [1] .

2009 Expert Reviews Ltd

ISSN 1743-4440

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Samuels-Reid, Cope & Morrison

The wide range of devices that are processed through various

FDA regulatory pathways often requires scrutiny to assess whether
or not there is a pediatric indication, that is, use of the device
in the pediatric population or any of its subpopulations. There
are various regulatory pathways for marketed devices, including
premarket application (PMA) for complex devices that may pose
significant risk and may require data from clinical trials, and
premarket notification (510[k]), where a predicate device exists
with previously cleared indications with which a new device can
be compared [102,103] .
The FDA further classifies devices into Class I, II and III,
according to risk, complexity and prior experience with use of the
devices. Class I devices are simple with low risk; Class II includes
devices that are more complex and may have a higher risk; and
Class III involves high-risk devices with greater complexity, which
may require implantation or life-altering procedures (Table 1) .
Pediatric use & indication

The FDA considers pediatric use if the device has a primary indication or a more general indication in which pediatric application
is indicated. Typically, data are needed to support the use of the
device in the age range indicated, depending on the device, its
intended use and the regulatory pathway being used, as well as
the results of any prior investigations, if they exist. Although it is
preferable to have data for the particular subpopulations in which
the device is to be used, if none exist, data from other pediatric
subpopulations may be helpful. These may provide some indication of safety and effectiveness, but may not be sufficient to
answer questions that may be unique to the pediatric population
or a particular subpopulation. Thus, the information necessary
to demonstrate safety and effectiveness will depend on the type
of the device, its indication and the subpopulation(s) in which
it will be used.
Consideration of risk

The evaluation of any device in the pediatric population must take

into account inter- and intrapopulation variability and unique characteristics of children, such as different developmental milestones,
anatomical, physiological and metabolic changes, and the various
stages of growth and development. This knowledge, together with
an age-appropriate risk assessment, will help to minimize adverse
events and ensure adequate safety outcomes for each subpopulation. It is not clear how many marketed devices are currently being
used in the pediatric population in manners for which they have
not been approved (off-label use). Off-label use may occur either to
fill an unmet need for which no pediatric device exists or because
of a lack in adequate education regarding the contraindications for
pediatric use of the device. Therefore, risk mitigation is a major
component of efforts to ensure the safety of medical devices. For
example, additional labeling may be needed in order to provide
age-appropriate instructions for use. In some cases, adequate labeling concerning safety issues in children may be enough, in others,
more proactive intervention may be necessary to provide adequate
safeguards. In some cases, information from clinical trials will be
necessary to ensure safe and effective use.
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Table 1. Examples of devices used in the

pediatricpopulation.
Device
Types of device
classification
Class I

Pediatric stethoscope
Infant heel warmer to aid in blood collection
First-aid kit without drugs

Class II

Phototherapy device for newborns

Newborn incubator
Cerebrospinal fluid shunt
Infusion pump
Newborn screening test for inborn errors
ofmetabolism
Pediatric sphygmomanometer
Pediatric umbilical catheter

Class III

Atrial septal defect occluder

Fetal pulse oximeter
Cochlear implant
HIV test

In the realm of medical devices, the clich that children are

not little adults applies on every level. In its review of medical
device submissions and applications, the CDRH considers the
following issues as important factors: size, growth and development, hormonal and physiological changes, and psychosocial and
behavioral factors.
Size differences

One size does not necessarily fit all children. The rate of growth
and unique characteristics of the pediatric population must be considered. Each subgroup is different and there is not only intergroup
but also intragroup variability. For example, vascular access will be
dependent on the size of blood vessels, which tend to be smaller
in the pediatric population, particularly in neonates and infants,
as can be demonstrated when choosing intravascular catheters.
Anthropometric parameters also vary among children, with differences in skin thickness between a newborn and an adolescent;
skin permeability will also vary. Devices that have contact with the
skin of children, such as barrier products, must be assessed in terms
of the differences among the various subgroups. Considerations
should include the sensitivity of the area of skin to which the device
will be applied, the integrity of the skin and the activity level of
the child. Dermatological changes must be quantified from skin
types ranging from healthy and intact to abraded or severely excoriated skin. The safety of the product must be evaluated in terms of
the different behavioral characteristics of children, depending on
their ages. For instance, since children tend to have more handto-mouth contact, transfer of material from the device to the oral
mucosa may occur [2] . Similarly, the increased surface area and
skin permeability in newborns may pose special concerns regarding
exposure to products, such as barrier dressings, adhesive materials,
exposure to light and heat during use of phototherapy devices, and
infant radiant warmers. Other instances in which size matters
involve intubation procedures in children. In these cases, the size
and contour of the airway of the child are important factors to
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Pediatric device safety & effectiveness

Special Report

consider when selecting endotracheal tubes. The unique pediatric

anatomy and size of the trachea may influence tube selection and
will vary within each pediatric subpopulation.

component of a device system, or used concomitantly. Therefore,

all components of devices should be evaluated for safety and
effectiveness in children.

Growth & development

Human factors engineering

The impact of growth and development is a major consideration

in the selection and use of medical devices in children. When
examining safety and effectiveness within this population, special consideration should be given to unique aspects of growth
and development, such as prematurity, small for gestational age,
large for gestational age, very low birthweight, body mass, height,
weight and head circumference, as well as local and systemic
effects. For example, a child may outgrow a device, particularly
those devices that require surgical intervention or implantation
(e.g., spinal rods), or need readjustment or revision surgery. These
devices require consideration of skeletal development and rapid
growth spurts to avoid poor orthopedic outcomes.
During orthopedic procedures, the clinician must determine
whether a staged approach will be necessary and if further intervention is required, for example, limb-lengthening procedures.
The stage of development and the impact of the device on the
achievement of normal growth should be assessed.
Devices that are recommended for children must be evaluated
with the following considerations:

Most devices used for pediatric patients at home require adult

supervision. Pediatric users of devices are usually children aged
7years or older, but most often are adolescents. Neonates, infants
and children below 7years of age will not have sufficient capabilities to use medical devices. The design of devices to be used
in a pediatric population should consider the unique qualities of
the pediatric user and should support those users. This can be
achieved by evaluating how children use the device early in and
throughout the design process, culminating in the validation of
safe use by simulated-use testing that involves children as users.
Human factors considerations are important for designing medical devices that can be used safely. A central part of this process
involves ensuring that the device can be used by the population of
users for which it is intended. This is, of course, true in the case of
pediatric device users since there can be differences in the abilities
of children and adults to use devices. These differences include
the physical size and strength of children being generally less than
that of adults; therefore, the design should be appropriate for the
size of the user. Another area of concern is the degree of understanding pediatric users have regarding device operation, and
the written and spoken instructions and precautions regarding
use of devices. Carefully considering and evaluating how design
alternatives can best support these user needs, and developing
the device in accordance with these considerations and evaluations, constitutes good human factors engineering for all devices,
including those intended for use by pediatric patients [104] .

The physical nature of the activities that they may participate in

The level of interaction needed
The impact of the device on the child
The effect of the sport or activity on the device
Possible risks to health
Whenever possible, the selection of the device should be based
on the particular developmental stage and age group of the child.
For instance, a child who is ambulatory may have different device
needs and issues compared with a nonambulatory child. The
impact of the device on the child and, conversely, the impact of
the child on the device must be assessed. For example, activity level
should be considered when determining the level of wear and tear
on the device and must be evaluated from the outset. Devices for
children who are involved in sports may be particularly challenged
and will need to adapt to the wear and tear of the sport.
Since children are constantly experiencing hormonal changes
as they grow, especially during adolescence, these influences may
play a role in determining how a device may affect a child. As
children grow and mature, the various organ systems, if healthy,
will also undergo maturation. In chronic disease states, various
organs may not develop and mature to their full potential, or
may function poorly owing to the disease or condition. Medical
devices that are used in these circumstances must be evaluated
with the development and maturation of not only the child, but
also the growth of the organs. Use of medical devices in children
must consider the short- and long-term effects and the potential
exposure to different materials. These may include biomaterials, chemicals, drugs and biologics that may be either a part or
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Behavioral, neurocognitive & psychosocialconsiderations

When medical devices are used by, rather than on, pediatric
users, differences in behavioral and neurocognitive capabilities,
and psychosocial factors can require special consideration and
design. This includes not only the device itself, but also training
materials and labeling, such as the user guides. Safe device use
by pediatric patients often involves assistance and training by
parents, siblings, guardians, healthcare providers or professional
educators at the onset, but users later begin to use the device
independently or with minimal supervision. Beyond design considerations, it is necessary for healthcare providers to understand
the family dynamics and whether adequate support exists for
the safe use of devices by children, and the individual needs and
abilities of each child who will use a device. The types of setting
for the use of the device must also be considered; for instance,
home versus hospital use.
The optimal choice of a medical device for children with special
needs, physical handicaps or neurocognitive disorders may require
additional considerations regarding training and guidance. It may
be necessary to ensure that these users can manage safe device
use independently. A suitable device may not exist for every type
of special need, and some pediatric patients may not be capable
of safely using certain devices.
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Samuels-Reid, Cope & Morrison

Diagnostic tests & medical devices

With the use of diagnostic tests and medical devices, such as

x-rays and other radiological devices, one must consider dose
exposure, size, weight and the long-term cumulative effects of
repeat procedures. Many radiologic devices are not calibrated
for children.
Sampling methods may also differ. Each pediatric subpopulation may reflect differences in laboratory indices, and these may
vary widely from adults. Many laboratory tests for renal function,
liver function and hematology indices will have different norms
for different ages. For example, normal values for hemoglobin and
hematocrit will vary from the neonate to the adolescent. Variations
may occur within each age subgroup, and the criteria for normal
range cut-off will differ. If use of the device is determined by these
indices, these differences must be considered.
Implanted devices & surgical procedures

Implanted medical devices in the pediatric population may

have different implications from those seen in adults. Many
devices require surgical procedures, which may range from a
simple incision to a more complex procedure. For each pediatric subpopulation, the risks will vary and must be evaluated in
terms of the following: implant site, anatomical landmark, level
of activity, growth and development. These are important as
children transition through the various stages of physical and
sexual maturation.
Devices implanted in pediatric patients must take into consideration the lifetime of the device and the need for future revisions.
For example, a growing child with a hip implant may require more
frequent revisions to adjust for growth and development over their
lifespan. In the pediatric population, assessment of immunization
status and antibiotic prophylaxis are important factors to consider
owing to increased susceptibility and developing immunity.
Children with devices that require invasive techniques, such
as surgical implantation (e.g., tunneling of catheters), should
be evaluated carefully. These factors may influence the need for
prophylactic antibiotics, updated immunization coverage or special vaccines [3,4] . Risk will vary by age subgroups. This awareness will help to anticipate the most common types of infection
seen for each group and facilitate any necessary intervention.
For example, the association between cochlear implants and the

occurrence of bacterial meningitis led to recommendations that

patients who are undergoing surgery for cochlear implants should
receive the pneumococcal vaccine [4] .
Expert commentary

There is a paucity of medical devices on the market that address

the needs of the pediatric population and its subpopulations.
Many factors have contributed to this problem, including, but
not limited to, the following: reluctance to study children; ethical concerns regarding children in clinical trials; and the expense
that manufactures believe they will incur because of the smaller
market. However, recently, legislation was passed to encourage
medical device development in the pediatric population. Through
the Pediatric Medical Device Safety Act of 2007, manufacturers
are being encouraged, via incentives, to address unmet pediatric
needs. There is growing concern that too many devices for adults
are being makeshifted for use in the pediatric population. Novel
ways of thinking are necessary to address the unmet needs of the
pediatric population.
Five-year view

The world of medical devices has skyrocketed with technological

advancements in the treatment of medical conditions and use of
medical devices, and this use will become widespread in pediatric
patients. The FDA has made a concerted effort to encourage device
submissions that target the pediatric population. It is anticipated
that, in the next 5years, these advancements will encompass the
entire pediatric population and should be evident in the manufacturing of pediatric devices. With the advent of new legislation,
there is added impetus to address the unmet needs of children.
Information submitted to FDA on both known and potential uses
of medical devices in pediatric patients will provide further insight
regarding where to direct future pediatric device research.
Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any

organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Key issues
The focus of this paper is to highlight information that FDA considers in its reviews of safety and effectiveness of medical devices
unique to the pediatric population.
The definition used by the Center for Devices and Radiological Health to define the pediatric population is birth to 21 years.
Medical device applications that involve the pediatric population are addressed with respect to the types of information necessary to
ensure safety and effectiveness.
Regulatory definitions are highlighted with respect to medical devices. Unique host characteristics and other considerations for each
pediatric subpopulation are reviewed.
The evaluation of any device in the pediatric population must take into account all of the intra- and interpopulation variability and
unique characteristics. The importance of human factors is described with special emphasis on the use of medical devices in various
pediatric subpopulations.
Human factors are a major component of medical device design and interaction. For the pediatric population, the importance of
human factors is heightened, since the device design must consider all the different age groups.

134

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Pediatric device safety & effectiveness

References

Websites

Papers of special note have been highlighted as:

of interest

101

Guidance for industry and FDA staff:

Premarket Assessment of Pediatric Medical
Devices. Issued May 14 (2004).
www.fda.gov/cdrh/mdufma/
guidance/1220.pdf

Addresses the elements that FDA

considers in its review of
pediatricdevices.

102

FDA device advice premarket notification

510(k)
www.fda.gov/cdrh/devadvice/314.
html#intro

Describes one of the regulatory pathways

to market.

FDA Device Definition. 1998 US Congress

Federal Food, Drug, & Cosmetic Act Section
201(321), (1998).

Gives the legal definition of a

medicaldevice.

Mancini AJ. Skin. Pediatrics 113(4 Suppl.),

11141119 (2004).

Outlines differences in the characteristics

of the skin between children and adults.

Hirsch BE, Blikas A, Whitaker M.

Antibiotic prophylaxis in cochlear implant
surgery. Laryngoscope 117, 864867 (2007).

Discusses the use of antibiotic

prophylaxisin the perioperative period to
prevent infections.

103

FDA Device Advice Premarket Approval

(PMA)
www.fda.gov/cdrh/devadvice/pma

Centers for Disease Control and Prevention

(CDC); Advisory Committee on
Immunization Practices. Pneumococcal
vaccination for cochlear implant candidates
and recipients: updated recommendations
of the Advisory Committee on
Immunization Practices. MMWR Morb.
Mortal Wkly Rep. 52, 739740 (2003).

Describes another regulatory pathway

tomarket.

104

Guidance for industry and FDA staff:

medical device use safety: incorporating
human factors engineering into risk
management.
www.fda.gov/cdrh/humfac/1497.pdf

Addresses the importance of human

factors engineering in riskmanagement.

Highlights the need for special vaccines to

prevent meningitis in children following
cochlear implantation.

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Special Report

Affiliations

Joy Samuels-Reid, MD, FAAP

Chief Medical Officer/Pediatrician,
Division of Anesthesiology,
GeneralHospital;
and, Infection Control and Dental Devices;
and, Center for Devices and Radiological
Health, Office of Device Evaluation, FDA,
9200 Corporate Blvd. Rockville,
MD20857, USA
Tel.: +1 240 276 3700
Fax: +1 240 276 3789
joy.samuels-reid@fda.hhs.gov

Judith U Cope, MD, MPH

Pediatric Epidemiologist, Office of the
Commissioner and Office of Pediatric
Therapeutics, FDA, 5600 Fishers Lane,
Rockville, MD 20857, USA
Tel.: +1 301 827 7866
Fax: +1 301 827 1017
judith.cope@fda.hhs.gov

Audrey E Morrison, RN, BSN

Nurse Consultant, Division of Postmarket
Surveillance, Office of Surveillance and
Biometrics,Center for Devices and
Radiological Health, FDA, Rockville,
MD20857, USA
Tel.: +1 240 276 341
Fax: +1 240 276 3301
audrey.morrison@fda.hhs,gov

135

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