This is the accessible text file for GAO report number GAO-12-225 
entitled 'Pediatric Medical Devices: Provisions Support Development, 
but Better Data Needed for Required Reporting' which was released on 
December 20, 2011. 

This text file was formatted by the U.S. Government Accountability 
Office (GAO) to be accessible to users with visual impairments, as 
part of a longer term project to improve GAO products' accessibility. 
Every attempt has been made to maintain the structural and data 
integrity of the original printed product. Accessibility features, 
such as text descriptions of tables, consecutively numbered footnotes 
placed at the end of the file, and the text of agency comment letters, 
are provided but may not exactly duplicate the presentation or format 
of the printed version. The portable document format (PDF) file is an 
exact electronic replica of the printed version. We welcome your 
feedback. Please E-mail your comments regarding the contents or 
accessibility features of this document to Webmaster@gao.gov. 

This is a work of the U.S. government and is not subject to copyright 
protection in the United States. It may be reproduced and distributed 
in its entirety without further permission from GAO. Because this work 
may contain copyrighted images or other material, permission from the 
copyright holder may be necessary if you wish to reproduce this 
material separately. 

United States Government Accountability Office: 
GAO: 

Report to Congressional Committees: 

December 2011: 

Pediatric Medical Devices: 

Provisions Support Development, but Better Data Needed for Required 
Reporting: 

GAO-12-225: 

GAO Highlights: 

Highlights of GAO-12-225, a report to congressional committees. 

Why GAO Did This Study: 

Medical devices can significantly improve, and save, the lives of 
children. Yet according to the Department of Health and Human Services’
(HHS) Food and Drug Administration (FDA), the development of pediatric 
devices lags years behind the development of devices for adults. The 
FDA Amendments Act of 2007 (FDAAA) provided incentives to develop 
devices for children, particularly devices that receive FDA’s 
humanitarian device exemption (HDE), a process for devices that treat 
or diagnose rare diseases or conditions. FDAAA also authorized 
demonstration grants for nonprofit consortia to facilitate pediatric 
device development and required FDA to annually report the number of 
approved devices labeled for use in pediatric patients. Finally, FDAAA 
required GAO to report on pediatric device development. This report 
(1) describes barriers to developing pediatric devices, (2) describes 
how pediatric device consortia have contributed to the development of 
pediatric devices, and (3) examines FDA data on the number of 
pediatric devices approved since FDAAA was enacted. GAO examined FDA 
data and documents related to device approvals, reviewed relevant laws 
and regulations, and interviewed and reviewed documents from 
stakeholders and FDA officials. 

What GAO Found: 

Certain characteristics unique to pediatric populations—including 
physiological differences from adult patients and challenges with 
recruiting pediatric participants for clinical trials—are barriers to 
developing medical devices for pediatric use cited by stakeholders. 
Given the unique characteristics of the pediatric population, and 
because the market for pediatric devices is smaller than the market 
for adult devices, there are limited economic incentives for 
manufacturers to develop pediatric medical devices. 

FDAAA provisions authorized demonstration grants for pediatric device 
consortia—these consortia reported assisting over 100 pediatric device 
projects in the first 2 years of the program, fiscal years 2009 and 
2010. FDA awarded grants totaling about $5 million to four pediatric 
device consortia in these 2 years. Of the device projects assisted by 
the consortia, many projects were in early stages of development, such 
as the creation of a prototype and the preclinical testing of that 
prototype. Activities performed by the consortia included regularly 
scheduled forums where innovators could discuss new device ideas with 
a group of experts. 

FDA lacks reliable internal data with which to identify all pediatric 
devices. FDAAA required FDA to annually report to congressional 
committees on the number of devices approved in the preceding year 
that were labeled for use in pediatric patients. While FDA created an 
electronic flag in its internal tracking system to identify such 
devices, FDA has not consistently used this flag and therefore lacks 
reliable and timely information needed for reporting. GAO’s review of 
the indication for use statements of devices approved since FDAAA was 
enacted identified 18 devices—including 3 HDE devices and 15 premarket 
approval (PMA) devices—that were explicitly indicated for use in 
pediatric patients (patients age 21 or younger). However, the approved 
indication for use statements for most (72 percent) of the devices 
approved through the HDE or PMA processes did not specify the age of 
the intended patient population, so additional pediatric devices could 
exist. 

Figure: PMA and HDE Devices Approved in Fiscal Years 2008 through 2011 
by Indicated Population: 

[Refer to PDF for image: 3 pie-charts] 

PMA (n = 110): 
Pediatric (explicitly indicated for use in pediatric patients-—
patients age 21 or younger-—or pediatric and adult patients): 14%; 
Adult (explicitly indicated for use in only adult patients—patients 
age 22 or older): 12%; 
Silent (patient age not specified): 74%. 

HDE (n = 8): 
Pediatric (explicitly indicated for use in pediatric patients-—
patients age 21 or younger-—or pediatric and adult patients): 38%; 
Adult (explicitly indicated for use in only adult patients—patients 
age 22 or older): 25%; 
Silent (patient age not specified): 38%. 

Total (n = 118): 
Pediatric (explicitly indicated for use in pediatric patients-—
patients age 21 or younger-—or pediatric and adult patients): 15%; 
Adult (explicitly indicated for use in only adult patients—patients 
age 22 or older): 13%; 
Silent (patient age not specified): 72%. 

Source: GAO. 

Note: Totals do not add to 100 percent because of rounding. 

[End of figure] 

What GAO Recommends: 

GAO recommends that FDA collect reliable information to report data on 
pediatric medical devices by consistently using its existing pediatric 
electronic flag in its tracking system or otherwise developing 
internal controls. HHS concurred with GAO’s recommendations. 

View [hyperlink, http://www.gao.gov/products/GAO-12-225]. For more 
information, contact Marcia Crosse at (202) 512-7114 or 
crossem@gao.gov. 

[End of section] 

Contents: 

Letter: 

Background: 

Characteristics of the Population and Limited Economic Incentives 
Cited as Barriers to Pediatric Device Development: 

Pediatric Device Consortia Have Assisted over 100 Device Projects; 
Many Were in Early Development: 

FDA Lacks Reliable Information to Readily Identify All Pediatric PMA 
and HDE Devices: 

Conclusions: 

Recommendation for Executive Action: 

Agency Comments: 

Appendix I: Summary of HDE Devices Granted Exemption from the HDE 
Profit Prohibition: 

Appendix II: PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients since Fiscal Year 2006: 

Appendix III: PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients, Fiscal Years 2008 through 2011: 

Appendix IV: Comments from the Department of Health and Human Services: 

Appendix V: GAO Contact and Staff Acknowledgments: 

Related GAO Products: 

Tables: 

Table 1: Pediatric Subpopulations for Medical Devices and Related Ages: 

Table 2: Summary of Pediatric Device Consortia Grant Amounts and 
Funded Activities, Fiscal Years 2009 and 2010: 

Table 3: Number of Device Projects by Development Phase That Were 
Mentored or Supported by the Pediatric Device Consortia: 

Table 4: Medical Device Projects Presented in Consortia Grant 
Applications and Funded in Fiscal Years 2009 and 2010: 

Table 5: Approved PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients since FDAAA Was Enacted, by Pediatric Subpopulation: 

Table 6: Characteristics of the Two Pediatric HDE Devices Granted 
Exemption from the HDE Profit Prohibition: 

Table 7: Number of Physicians Reporting Difficulty Obtaining Insurance 
Coverage for Melody TPV Device, by Insurance Type and Extent of 
Difficulty Experienced: 

Table 8: PMA and HDE Devices Explicitly Indicated for Use in Pediatric 
Patients, Fiscal Years 2006 through 2011: 

Figures: 

Figure 1: PMA and HDE Devices Approved in Fiscal Years 2008 through 
2011 by Indicated Patient Population: 

Figure 2: HUD Requests, HUD Designations, and Approved HDE Devices 
Explicitly Indicated for Use in Pediatric Patients, Fiscal Years 2001 
through 2011: 

Abbreviations: 

ADN: annual distribution number: 

CDRH: Center for Devices and Radiological Health: 

CHIP: Children's Health Insurance Program: 

CPT: current procedural terminology: 

CTS: Center Tracking System: 

FDA: Food and Drug Administration: 

FDAAA: FDA Amendments Act of 2007: 

HDE: humanitarian device exemption: 

HHS: Department of Health and Human Services: 

HUD: humanitarian use device: 

IRB: institutional review board: 

PMA: premarket approval: 

RVOT: right ventricular outflow tract: 

[End of section] 

United States Government Accountability Office: 
Washington, DC 20548: 

December 20, 2011: 

The Honorable Tom Harkin: 
Chairman: 
The Honorable Michael B. Enzi: 
Ranking Member: 
Committee on Health, Education, Labor, and Pensions: United States 
Senate: 

The Honorable Fred Upton: 
Chairman: 
The Honorable Henry A. Waxman: 
Ranking Member: 
Committee on Energy and Commerce: 
House of Representatives: 

Medical devices prevent premature death and significantly improve the 
quality of life for many children each year.[Footnote 1] However, 
stakeholders from the pediatric community have raised concerns about 
the availability of devices developed and approved for pediatric use. 
In particular, concerns have been raised about challenges to 
developing and marketing pediatric medical devices. Designing and 
developing pediatric medical devices can be challenging because 
children's bodies are often smaller, are structured differently than 
adults, and change throughout childhood. According to the Food and 
Drug Administration (FDA), in 2011 the development of medical devices 
for children lagged 5 to 10 years behind the development of devices 
for adults. Some medical devices are designed specifically for 
pediatric patients and some are designed for patients above a certain 
age. Frequently, providers modify devices designed for adults for use 
in their pediatric patients. 

FDA, an agency within the Department of Health and Human Services 
(HHS), is responsible for ensuring that medical devices, including 
pediatric medical devices, sold in the United States provide 
reasonable assurance of safety and effectiveness and do not pose a 
threat to public health. Before medical devices may be legally 
marketed in the United States, they are generally subject to FDA 
premarket review unless exempt by FDA regulations.[Footnote 2] Under 
FDA's premarket approval (PMA) process, manufacturers must supply 
evidence providing reasonable assurance of safety and effectiveness to 
obtain FDA approval to market a device in the United States; we refer 
to devices approved through this process as PMA devices. To encourage 
development of devices that treat or diagnose rare diseases or 
conditions, devices that receive a humanitarian device exemption (HDE) 
are exempt from the effectiveness requirement of the PMA process. 
Under FDA's HDE process, manufacturers are instead required to show 
that the probable benefit outweighs the risk of using the device. In 
general, manufacturers of devices approved through the HDE process are 
allowed to recover certain development and production costs but may 
not make a profit on their device; we refer to devices approved 
through this process as HDE devices. 

To encourage the development of pediatric medical devices, the FDA 
Amendments Act of 2007 (FDAAA) removed the profit prohibition for HDE 
devices that are used to treat children and meet other requirements, 
[Footnote 3] and established a demonstration grant program for 
nonprofit consortia to stimulate pediatric medical device development. 
[Footnote 4] Pediatric device consortia receiving these grants, 
administered by FDA, are expected to facilitate the development, 
production, and distribution of pediatric medical devices through 
activities such as connecting innovators and physicians to existing 
federal resources, assessing the scientific merit of proposed 
pediatric device projects, and providing assistance and advice as 
needed on business development. In addition, FDAAA required FDA to 
annually report to the Senate Committee on Health, Education, Labor, 
and Pensions and the House Committee on Energy and Commerce on 
pediatric medical devices, including the number of devices approved in 
the preceding year that were labeled for use in pediatric patients. 
[Footnote 5] 

FDAAA also required GAO to report on pediatric medical device 
development.[Footnote 6] In this report, we (1) describe barriers to 
developing pediatric medical devices, (2) describe how the 
demonstration grants for pediatric device consortia have contributed 
to the development of pediatric medical devices, and (3) examine FDA's 
data on the number of pediatric PMA and HDE devices approved since 
FDAAA was enacted.[Footnote 7] 

To describe the barriers to developing pediatric medical devices, we 
interviewed officials and reviewed documents from key pediatric 
medical device stakeholders, including the pediatric device consortia; 
manufacturer organizations, including the Medical Device Manufacturers 
Association and the Advanced Medical Technology Association; 
professional associations, such as the American Academy of Pediatrics, 
the Pediatric Orthopaedic Society of North America, and the American 
Thoracic Society; advocacy organizations, such as the Elizabeth Glaser 
Pediatric AIDS Foundation and the National Organization for Rare 
Disorders; and the two manufacturers of HDE devices approved for use 
in pediatric patients and exempted from the HDE profit prohibition. In 
addition, we interviewed officials from FDA and the National 
Institutes of Health who conduct work related to medical devices. We 
also conducted a literature review of government and independent 
reports and peer-reviewed publications and reviewed stakeholder 
testimonies and summaries regarding barriers to pediatric medical 
device development.[Footnote 8] In addition, we examined policy papers 
written by key stakeholders, including FDA and professional 
associations. 

To describe the contributions of the pediatric device consortia, we 
reviewed pediatric device consortia quarterly and annual reports 
submitted to FDA to assess the type and amount of assistance the 
consortia provided to device innovators and manufacturers described in 
the reports.[Footnote 9] We also reviewed additional information 
provided by FDA and interviewed officials from FDA and the consortia 
and other relevant stakeholders. 

To examine FDA's data on the number of pediatric PMA and HDE devices 
approved since FDAAA was enacted, we reviewed FDA procedures for 
tracking and reporting information on pediatric medical devices and 
analyzed FDA data and documents for approved PMA and HDE devices. 
[Footnote 10] We compared FDA's procedures for tracking and reporting 
information on pediatric medical devices to standards described in 
Standards for Internal Control in the Federal Government--which 
specifies that information should be communicated to those who need it 
in a form and within a time frame that enables them to carry out their 
operational responsibilities.[Footnote 11] Specifically, we examined 
the agency's ability to readily identify approved PMA and HDE devices 
labeled for use in pediatric patients and report on them in a timely 
manner. To do this and to determine the reliability of FDA's data on 
PMA and HDE devices labeled for use in pediatric patients, we 
interviewed FDA officials; reviewed laws, regulations, and guidance; 
and reviewed FDA data systems.[Footnote 12] Based on our examination, 
we generally found the data that FDA maintains on the number of 
approved PMA and HDE devices labeled for use in pediatric patients not 
to be sufficiently reliable for our purposes and, as a result, in 
order to identify pediatric devices, we reviewed FDA documents--the 
approval order, approved labeling, and summary of safety and 
effectiveness data--that FDA makes publicly available for each 
approved PMA and HDE device.[Footnote 13] Each document contains the 
approved indication for use statement, which specifies the disease and 
population the device is intended to treat. However, the indication 
for use statement may not explicitly state if a device can be used in 
pediatric patients; in these cases, FDA may still consider the device 
to be labeled for use in pediatric patients based on other information 
in the labeling or summary documents. Given the extent of information 
and expertise needed to determine if a device is labeled for use in 
pediatric patients, for our analysis we considered pediatric devices 
to be those explicitly indicated for use in pediatric patients when 
the indication for use statement in these approval documents (1) 
specified a population that included patients age 21 years or younger, 
(2) stated that the device was for pediatric patients, or (3) stated 
that it was for skeletally immature patients.[Footnote 14] We reviewed 
approval documents for PMA devices, including PMA supplements called 
panel-track supplements,[Footnote 15] approved in fiscal years 2006 
through 2011 and HDE devices approved in fiscal years 2001 through 
2011.[Footnote 16] 

In addition, to determine how many humanitarian use device (HUD) 
designations--a required first step for FDA approval to market an HDE 
device--FDA granted for devices used to treat diseases that occur in 
pediatric populations since FDAAA was enacted, we analyzed data 
provided by FDA for all HUD requests submitted and designated in 
fiscal years 2001 through 2011. We interviewed FDA officials regarding 
methods for tracking HUD requests and designations and determined that 
the data were sufficiently reliable for our purposes. We also 
interviewed FDA officials and reviewed FDA data to identify the HDE 
devices exempted from the HDE profit prohibition and determined that 
these data were sufficiently reliable for our purposes. 

We conducted this performance audit from February 2011 through 
December 2011 in accordance with generally accepted government 
auditing standards. Those standards require that we plan and perform 
the audit to obtain sufficient, appropriate evidence to provide a 
reasonable basis for our findings and conclusions based on our audit 
objectives. We believe that the evidence obtained provides a 
reasonable basis for our findings and conclusions based on our audit 
objectives. 

Background: 

Medical devices include items used for the diagnosis, cure, 
mitigation, treatment, or prevention of a disease. These devices range 
from simple tools like bandages and surgical clamps to complicated 
devices like pacemakers; unless exempt by FDA regulations, devices are 
generally subject to FDA premarket review. Pediatric patients may be 
among those a device is intended to treat and generally are defined as 
those age 21 years or younger. FDAAA included provisions to support 
and track pediatric device development. 

Medical Device Premarket Review Process: 

Unless exempt by regulation, medical devices are generally subject to 
FDA premarket review before they may be legally marketed in the United 
States. The extent of the premarket review is generally correlated 
with the level of risk the device poses.[Footnote 17] Applications to 
market medical devices are primarily submitted to and reviewed by 
FDA's Center for Devices and Radiological Health (CDRH).[Footnote 18] 

Under the PMA premarket review process, FDA reviews and makes approval 
decisions on applications for class III devices.[Footnote 19] Among 
other things, PMA applications must include the indication for use--
including the disease and population the medical device is intended to 
treat--and evidence (typically clinical data) providing reasonable 
assurance that the device is safe and effective. After an initial 
screening of an application and determination that the review should 
proceed, FDA's reviewers conduct a scientific review of the 
application and may refer applications to an external advisory 
committee composed of individuals with expertise in a particular 
medical specialty, such as cardiovascular or neurology--known as a 
medical specialty panel. FDA charges manufacturers a fee to review PMA 
applications, but PMA applications for devices intended solely for 
pediatric use are exempt from any fees.[Footnote 20] 

For devices that have been approved through the PMA process, a 
manufacturer that wants to add a pediatric population (or otherwise 
significantly change the approved indication for use) must submit and 
receive FDA approval for a PMA panel-track supplement.[Footnote 21] 
FDA charges manufacturers a fee to review PMA panel-track supplements, 
but those intended solely for pediatric use are exempt.[Footnote 22] 

In 1990, Congress authorized FDA to exempt from the premarket review 
requirement to demonstrate effectiveness certain medical devices in 
order to provide an incentive for the development of devices that 
treat or diagnose rare diseases or conditions, including those in 
children.[Footnote 23] Manufacturers of such devices still must show 
that the probable benefit outweighs the risk of using the device and 
that the device will not expose patients to unreasonable or 
significant risk of illness or injury. These devices, called HUDs, are 
intended to treat or diagnose a disease or condition that affects 
fewer than 4,000 individuals in the United States. In order to market 
an HUD in the United States, an HDE application must be submitted to 
and approved by FDA. 

Obtaining HDE approval is a two-part process: 

* A manufacturer must first request and obtain HUD designation from 
FDA's Office of Orphan Product Development. A device manufacturer 
requests HUD designation by providing a description of the rare 
disease or condition for which the device is to be used, the proposed 
indication or indications for use of the device, the reasons why such 
therapy is needed, and a description of the intended patient 
population along with data to support that there are fewer than 4,000 
of these patients within the United States. The device manufacturer 
must also provide a description of the device and scientific rationale 
for the use of the device for the rare disease or condition. 

* Once the HUD designation is granted, the manufacturer can then seek 
device approval by submitting an HDE application. In addition to 
including the indication for use, the HDE application must include a 
detailed description of the device, along with evidence demonstrating 
device safety, and data and a rationale supporting the probable 
benefit of the device. Device labeling is also reviewed and must 
include a statement indicating that the device is a humanitarian 
device.[Footnote 24] According to FDA guidance, criteria for HDE 
approval are focused on safety, probable benefit, and lack of a 
comparable device. FDA does not charge manufacturers a fee to review 
HDE applications.[Footnote 25] 

Manufacturers of HDE devices are allowed to recover certain 
development and production costs but are generally prohibited from 
making a profit on their device. Unless exempt, HDE applications must 
include a cost assessment to demonstrate that the amount charged for 
the HDE device does not exceed the cost of research and development, 
fabrication, and distribution. After FDA approval, in order for an HDE 
device to be used in patient care, it must be reviewed and approved by 
an institutional review board (IRB) to assess the safety of the 
device.[Footnote 26] 

If FDA review results in premarket approval, FDA issues an approval 
order to the manufacturer, which includes the approved indication for 
use statement. FDA also approves all printed material accompanying the 
device--known as the device labeling. The approval order, labeling, 
and a summary of safety and effectiveness data are available on FDA's 
website; all three documents contain the approved indication for use 
statement. 

Pediatric Populations for Medical Devices: 

Although the upper age limit experts use to define the pediatric 
population varies, for purposes of certain statutory provisions for 
PMA and HDE device applications, FDA considers pediatric patients as 
those who are age 21 years or younger at the time of diagnosis or 
treatment.[Footnote 27] FDA issued guidance in 2004 that specifies age 
ranges for four main pediatric subpopulations: neonate, infant, child, 
and adolescent (see table 1).[Footnote 28] According to FDA officials, 
the agency defined an additional subpopulation, transitional 
adolescents, for its internal application review purposes. These 
officials noted that in some cases patients in this age range may not 
require special considerations compared to adults.[Footnote 29] A 
pediatric medical device may be indicated for use in more than one 
pediatric subpopulation. 

Table 1: Pediatric Subpopulations for Medical Devices and Related Ages: 

Pediatric subpopulation: Neonate (newborn); 
FDA guidance on approximate age range for this subpopulation: Birth to 
1 month. 

Pediatric subpopulation: Infant; 
FDA guidance on approximate age range for this subpopulation: Greater 
than 1 month to 2 years. 

Pediatric subpopulation: Child; 
FDA guidance on approximate age range for this subpopulation: Greater 
than 2 years to 12 years. 

Pediatric subpopulation: Adolescent; 
FDA guidance on approximate age range for this subpopulation: Greater 
than 12 years to 21 years[A]. 

Source: GAO analysis of FDA information. 

Notes: This table presents FDA's guidance on the approximate age 
ranges for four main pediatric subpopoulations as reported in FDA's 
Guidance for Industry and FDA Staff: Premarket Assessment of Pediatric 
Medical Devices (2004). According to FDA officials, for internal 
application review purposes, FDA uses slightly different age ranges 
for these main subpopulations--for example, 2 years to less than 12 
years for children. 

[A] For internal application review purposes, FDA identified another 
subpopulation, transitional adolescent, to include those age 18 to 21 
years. 

[End of table] 

According to FDA officials, some pediatric devices are indicated for 
use in both pediatric and adult patients, such as devices with an 
indication for all patients with a given condition above a certain 
age. Additionally, a device's indication for use statement might not 
specify the age of the intended population, but based on additional 
clinical information that may be included in the approval documents, 
FDA might consider a device labeled for pediatric use. For example, 
the indication for use statement for an influenza diagnostic test 
might not specify a pediatric population, but FDA could consider the 
device labeled for patients of all ages. In addition, a device's 
indication for use statement might specify a minimum blood vessel size 
or body weight rather than a certain patient age, and if pediatric 
patients meet the criteria, the device could be considered labeled for 
pediatric use. 

FDAAA Provisions on Pediatric Medical Device Development: 

To stimulate pediatric medical device development, FDAAA exempted HDE 
devices labeled for use in pediatric patients (including those for 
both pediatric and adult patients) from the HDE profit prohibition for 
applications approved on or after September 27, 2007, when FDAAA was 
signed into law.[Footnote 30] In order to receive the exemption from 
the profit prohibition, HDE applications must include data to prove 
that the device can safely be used in a pediatric population and to 
support the number of individuals likely to use the device each year. 
Based on this information, FDA determines an upper limit on the number 
of devices that can be distributed or sold each year--to treat both 
pediatric and adult patients--known as the annual distribution number 
(ADN). Manufacturers may only receive profits from the sale of HDE 
devices exempt from the profit prohibition and indicated for pediatric 
or pediatric and adult use up to the ADN. In addition, FDAAA requires 
that FDA's Pediatric Advisory Committee annually review all HDE 
devices granted exemption from the profit prohibition to ensure that 
the exemption remains appropriate for the pediatric populations for 
which it is granted.[Footnote 31] 

FDAAA also required PMA and HDE applications to include, if readily 
available, a description of any pediatric population or 
subpopulation(s) that suffer from the disease or condition that the 
device is intended to treat, diagnose, or cure and the number of 
affected pediatric patients. FDAAA further required FDA to annually 
report to congressional committees on the number of PMA and HDE 
devices approved in the preceding year (1) for which there is a 
pediatric subpopulation that suffers from the disease or condition 
that the device is intended to treat, diagnose, or cure; (2) labeled 
for use in pediatric patients; and (3) exempt from user fees because 
the device was intended solely for pediatric use.[Footnote 32] 

To help connect individuals with ideas for pediatric medical devices 
with experienced professionals to assist them through the medical 
device development process, FDAAA also authorized demonstration grants 
for pediatric device consortia to promote pediatric device 
development.[Footnote 33] Pediatric device consortia receive 2-year 
grants, administered by FDA, to conduct certain activities for device 
projects, such as mentoring and managing the development process, 
assessing the scientific merit of a proposed device, and providing 
assistance and advice as needed on business development and navigating 
the regulatory process. In their demonstration grant applications, 
consortia were not only required to demonstrate their capability to 
develop pediatric devices--by having members with medical and 
scientific expertise in device development and relationships with 
manufacturers--but they were also required to identify two to five 
device projects that the consortia would directly support under the 
demonstration grant.[Footnote 34] Grantees must submit quarterly and 
annual reports to FDA describing how they have used grant funds to 
support innovation and the phase of development for the devices for 
which they provided assistance.[Footnote 35] Phases of development 
include, for example, concept, prototype (during which a model is 
developed), clinical (during which the device is tested), and 
marketing (during which the device goes through the regulatory 
process).[Footnote 36] 

Characteristics of the Population and Limited Economic Incentives 
Cited as Barriers to Pediatric Device Development: 

Certain characteristics unique to pediatric populations--including 
physiological differences in pediatric patients and challenges with 
recruiting pediatric participants for clinical trials--are barriers to 
developing pediatric medical devices that were cited by stakeholders. 

* Pediatric patients are composed of different subpopulations with 
differences in size, growth rate, metabolism, heart rate, activity 
level, and other differences. For example, younger pediatric patients--
neonates, infants, and children--have higher heart rates or 
respiratory rates than adults. This difference, as cited by some 
stakeholders, makes some devices used for adults, such as certain 
heart valves, not appropriate for use in young children; thus a device 
that has already been developed for an adult may have to be redesigned 
for a pediatric population. Another unique characteristic cited is the 
range of pediatric subpopulations and the difficulty in developing 
potentially different devices for each of these subpopulations. For 
example, a device that is developed for a toddler may not be 
appropriate for use in an adolescent, even if they have the same 
disease or condition. As a result, manufacturers may have to develop 
and test a different device for each subpopulation although the 
disease or condition may be the same. 

* Recruiting pediatric patients to participate in clinical trials has 
also been cited as a challenge for manufacturers. Performing 
experimental procedures on children naturally raises concern for their 
safety, and it may be difficult to obtain parental consent on behalf 
of the child to conduct experimental procedures. This issue is 
compounded because the pediatric population is not just one population 
but rather many subpopulations. Therefore, manufacturers find it 
difficult to recruit enough children for each pediatric subpopulation 
over a reasonable time frame and within a manageable number of 
investigational sites to ensure enough test subjects to meet clinical 
trial requirements. 

Given these unique characteristics of the pediatric population, as 
well as the fact that the market for pediatric devices is generally 
smaller than the market for adult devices, there are limited economic 
incentives for manufacturers to develop pediatric medical devices. 
Stakeholders indicated that the cost of developing pediatric medical 
devices relative to the potential revenue generated by sales in a 
small market is a significant barrier to the development of new 
pediatric medical devices. Stakeholders also noted that the cost of 
research and development for pediatric medical devices can be the same 
as for adult devices while the market size is often smaller. Given 
these factors, stakeholders report that the return on the investment 
to develop and test pediatric medical devices usually falls below the 
profit goals of most medical device manufacturers. 

Stakeholders noted that the FDAAA provision allowing pediatric HDE 
devices to earn a profit is one helpful step to encourage pediatric 
medical device development; however, they indicated that this 
provision is not enough to address the small market for pediatric 
devices and the resources necessary to study a device in a pediatric 
population. An official from one device manufacturer that had a 
pediatric HDE device approved since FDAAA was enacted told us that the 
ability to earn a profit for the HDE device, while helpful, was not 
part of this manufacturer's decision to develop and market it. 
Stakeholders noted that the maximum number of 4,000 individuals for 
HDEs limited the effectiveness of this incentive for development of 
devices for larger pediatric populations. Stakeholders also noted that 
incentives used for pediatric drug development would not necessarily 
work for pediatric medical device development. For example, patent 
protection for medical devices is not as meaningful an incentive as it 
is for the development of pediatric drugs because the typical life 
cycle for medical devices (about 18 months) is significantly shorter 
than the typical life cycle for a drug.[Footnote 37] 

Other barriers identified by stakeholders included an incomplete 
understanding of unmet pediatric device needs and issues related to 
the medical device regulatory process. 

* Several stakeholders commented that there is no consistent inventory 
of the devices that need to be developed for pediatric populations. 
Although it is unclear who should maintain this inventory, FDAAA did 
require FDA to annually report on the number of devices approved in 
the preceding year that were labeled for use in pediatric patients or 
for which there is a pediatric subpopulation that suffers from the 
disease or condition that the device is intended to treat, diagnose, 
or cure. FDA has reported to Congress that the pediatric device data 
contained in these reports may help identify areas of pediatric device 
research and development that need to be addressed.[Footnote 38] 
However, FDA has issued only one of these reports to date.[Footnote 
39] Furthermore, some of the information from which FDA would develop 
these reports may not be as useful as possible in determining unmet 
need. Specifically, manufacturers are to include the information on 
pediatric subpopulations in their premarket approval applications if 
readily available; however, one manufacturer organization stated that 
it was unclear about the specific information requirements, and thus 
manufacturers may not be submitting useful information for tracking 
unmet pediatric device needs.[Footnote 40] 

* Stakeholders also cited as barriers to pediatric device development 
certain issues related to the medical device regulatory process in 
general. For instance, it was reported that the amount of time that it 
will take to get through the regulatory process cannot always be 
predicted, which limits the ability to appropriately budget for 
development. One manufacturer organization also noted that FDAAA 
authorized FDA to consider published data from adult studies and 
studies in different age groups when determining effectiveness for 
pediatric device approvals; this manufacturer organization commented 
that where appropriate, FDA should also use scientific evidence other 
than randomized controlled studies, such as well-documented case 
histories, to show probable benefit or demonstrate effectiveness. 
[Footnote 41] Recognizing the need to discuss the ways scientific 
research data can be used for pediatric medical device applications, 
FDA announced in November 2011 that it would hold a public workshop to 
discuss the use of scientific research data, including published 
scientific literature, to support and establish pediatric indications 
for medical devices.[Footnote 42] 

Stakeholders also noted barriers that were unique to HDE devices, 
including pediatric HDE devices. One manufacturer organization stated 
that FDA has provided no general guidance to manufacturers regarding 
the type or level of evidence that must be developed to demonstrate 
that an HDE device meets the probable benefit standard. According to 
the organization, this lack of guidance ultimately hinders the use of 
the HDE program as a pathway to market devices that treat or diagnose 
diseases and conditions that affect fewer than 4,000 patients, 
including pediatric patients. According to stakeholders, difficulties 
in obtaining insurance coverage for HDE devices are also a barrier to 
development because HDE devices are approved by demonstrating safety 
but not effectiveness. Although the two manufacturers' representatives 
we spoke with reported experiencing frustration with the HDE approval 
process, they noted that overall, their interaction with FDA reviewers 
was positive in that FDA responded to their questions in a timely 
manner and provided specific guidance where necessary. 

Finally, stakeholders stated that individuals with innovative ideas 
for new pediatric medical devices do not necessarily know what steps 
to take to bring their ideas for pediatric medical devices to the 
market, and it would be helpful to connect these individuals with 
manufacturers and to help them navigate the device development and 
regulatory process. Individuals with ideas for medical devices range 
from engineers to clinicians, who often need to work together to 
develop and manufacture a pediatric medical device. In addition, it is 
necessary to have funds to sustain development and an understanding of 
how to navigate the regulatory process. A commonly cited example of 
the challenges faced by pediatric device innovators is the experience 
developing the titanium rib, which took about 14 years to develop 
before it was approved for the market in part because its inventor, a 
physician who saw the need for such a device, did not have the 
information or resources to navigate the development and regulatory 
process.[Footnote 43] FDA officials and other stakeholders reported 
that the pediatric device consortia have helped to address this 
barrier. In addition, FDA officials reported that other efforts by FDA 
to organize early meetings before device manufacturers submit 
applications to clarify required clinical information and meetings 
with groups such as the pediatric orthopedic surgeons have also helped 
device innovators navigate the device development and regulatory 
process. 

Pediatric Device Consortia Have Assisted over 100 Device Projects; 
Many Were in Early Development: 

The pediatric device consortia reported assisting 107 pediatric device 
projects--that is, projects to develop new pediatric devices--in the 
first 2 years of the demonstration grant program. In order to 
facilitate the development and approval of pediatric medical devices, 
FDA awarded grants totaling about $5 million to four pediatric device 
consortia in fiscal years 2009 and 2010 (see table 2).[Footnote 44] 
The consortia receiving these grants provided assistance that included 
review of projects by clinical experts to evaluate the devices' 
usefulness in a clinical environment and help connecting innovators 
with manufacturers as well as potential sources of additional federal 
grant funding.[Footnote 45] The consortia also conducted other 
activities to support pediatric medical device development and connect 
individuals who have ideas for medical devices with information and 
resources, such as lectures, forums, and relevant conferences. 
[Footnote 46] 

Table 2: Summary of Pediatric Device Consortia Grant Amounts and 
Funded Activities, Fiscal Years 2009 and 2010: 

Pediatric device consortia grantees (location): Michigan Pediatric 
Device Consortium (Ann Arbor, MI); 
Grant amounts[A](in thousands): $2,311; 
Number of device projects assisted: 63; 
Examples of activities to facilitate pediatric device development: 
Hired postgraduate professionals with medical, dental, doctorate, or 
masters degrees for a 1-year fellowship to focus on bringing device 
innovations to the market. 

Pediatric device consortia grantees (location): MISTRAL Device 
Consortium[B](Menlo Park, CA); 
Grant amounts[A](in thousands): $500; 
Number of device projects assisted: 17; 
Examples of activities to facilitate pediatric device development: 
Organized two teleconferences on issues surrounding neonatal intensive 
care units for the purposes of developing new devices. 

Pediatric device consortia grantees (location): Pediatric 
Cardiovascular Device Consortium (Boston, MA); 
Grant amounts[A](in thousands): $1,102; 
Number of device projects assisted: 9; 
Examples of activities to facilitate pediatric device development: 
Held monthly forums for device innovators to discuss new device 
innovations with experts such as engineers and scientists. 

Pediatric device consortia grantees (location): University of 
California at San Francisco Pediatric Device Consortium (San 
Francisco, CA); 
Grant amounts[A](in thousands): $1,087; 
Number of device projects assisted: 18; 
Examples of activities to facilitate pediatric device development: 
Held weekly forums to discuss new device innovations[C]. 

Pediatric device consortia grantees (location): Total; 
Grant amounts[A](in thousands): $5,000; 
Number of device projects assisted: 107. 

Source: GAO analysis of FDA information. 

Notes: The total number of device projects assisted by the consortia 
is not proportional to the amount each consortium received in grant 
funding. Some device projects were more complex and needed more 
consortium resources than others. In addition, some consortia received 
funding outside of the demonstration grants to support their projects. 
This table presents grant funding for fiscal years 2009 and 2010 and 
the number of device projects assisted using those funds. 

[A] Grant award amounts were rounded to the nearest thousand. 

[B] Information presented for MISTRAL Device Consortium is for 
activities supported with funds from a grant made in fiscal year 2010. 

[C] This innovator forum is scheduled two times per week and is open 
to anyone with a device idea or who wants to learn about device 
development. A 1-hour agenda is created where ideas are heard and 
consulted on. In addition, expert speakers are also brought in who can 
speak on manufacturing a device or taking a device through the 
regulatory process. 

[End of table] 

For the device projects assisted by the consortia, the phase of 
development varied. Although the consortia assisted a total of 107 
device projects, 34 were inactive or were device projects that the 
consortia were no longer assisting at the time of our review.[Footnote 
47] Of the 73 active device projects, about half (36) were in the 
prototype phase (see table 3).[Footnote 48] In order to monitor the 
progress of the device projects the pediatric consortia assisted, FDA 
requires each consortium to report on the development phase of each 
device project--including the directly supported device projects 
included in the grantees' applications as well as other device 
projects that received consortia assistance--on a quarterly and annual 
basis. Throughout the grant period, device projects were presented to 
the consortia and consortia members determined the kind of assistance 
to provide for development of these devices. The assistance provided 
depended on the device's phase of development. For example, for a 
device in the concept phase a consortium could assess its scientific 
merit to see if there is a need for the device or if it makes sense to 
develop it; for devices that were further along, a consortium could 
help produce prototypes. For devices in the marketing phase, the 
consortia could consult on next steps, including working with FDA, a 
step which the developer needs to take to market a device. As of the 
most recent grantee reports available in September 2011, 3 of the 107 
devices that were assisted by the consortia were commercially 
available and 1 had received HUD designation. 

Table 3: Number of Device Projects by Development Phase That Were 
Mentored or Supported by the Pediatric Device Consortia: 

Phase of development: Active; 

Phase of development: Active; Concept (development of an idea for a 
device); 
Total: 8. 

Phase of development: Active; Prototype (the design and development 
phase where a model is used to conceive the concept); 
Total: 36. 

Phase of development: Active; Preclinical (testing a prototype in 
laboratories or animals); 
Total: 20. 

Phase of development: Active; Clinical (testing the device in humans); 
Total: 4. 

Phase of development: Active; Manufacturing (production of the device); 
Total: 2. 

Phase of development: Active; Marketing (includes the regulatory 
process and putting the device on the market); 
Total: 0. 

Phase of development: Active; Commercial use (use of the device by the 
general public); 
Total: 3. 

Active total[A]: 
Total: 73. 

Inactive total[B]: 
Total: 34. 

Total inactive and active: 
Total: 107. 

Source: GAO analysis of FDA information. 

Notes: The table presents the total number of device projects assisted 
by all four consortia. Data presented cover device projects that were 
assisted with funds from grants made in fiscal years 2009 and 2010. 

[A] Active projects were those that were reported as supported with 
funds from grants made in fiscal year 2010 in the most recent 
consortia reports available at the time of our review in 2011, 
supplemented by additional information provided by FDA. 

[B] Projects that we considered inactive were those that the consortia 
had mentored or supported at some point during their grant periods but 
that were no longer receiving consortia assistance with fiscal year 
2010 funds. In some cases, inactive device projects stopped receiving 
consortia support because they could not obtain outside funding or 
there were complex development challenges. 

[End of table] 

Of the 107 device projects assisted by the consortia, 13 were directly 
supported--that is, they were identified in the grant awards to 
receive a portion of the grantee's demonstration grant funding. Table 
4 lists these directly supported device projects, which were 
identified by the grantees in their applications and selected by FDA 
to receive support through the consortia grants. FDA's evaluation 
criteria included (1) the significance of the device to address 
pediatric needs, (2) how well the project was designed, (3) the 
likelihood for marketing success, (4) the expertise and training of 
project leaders, and (5) evidence that the institution where the 
consortium was located supported the project. 

Table 4: Medical Device Projects Presented in Consortia Grant 
Applications and Funded in Fiscal Years 2009 and 2010: 

Pediatric device consortia grantees: Michigan Pediatric Device 
Consortium: 

Device project: Bowel lengthening device; 
Condition treated or use: Treats short bowel syndrome[A]. 

Device project: Nonthrombogenic and antiseptic catheters for infants; 
Condition treated or use: Treats clotting and infection problems with 
catheters in children. 

Pediatric device consortia grantees: MISTRAL Device Consortium: 

Device project: Pyloromyotomy surgical tool; 
Condition treated or use: Used in making laparoscopic pyloromyotomy 
safer and easier[B]. 

Device project: Esophageal atresia surgical tool; 
Condition treated or use: Treats esophageal atresia[C]. 

Device project: Neurosurgical articulated tools; 
Condition treated or use: Used in pediatric brain surgery. 

Device project: NICU dashboard; 
Condition treated or use: Used to monitor and synthesize multiple 
pediatric vital sign inputs. 

Device project: Catheter for peripheral nerve blocks; 
Condition treated or use: Used to secure catheter placement in 
pediatric pain management. 

Pediatric device consortia grantees: Pediatric Cardiovascular Device 
Consortium: 

Device project: Septal cincher; 
Condition treated or use: Used to reduce the opening of a cardiac 
valve. 

Device project: Biodegradable valve ring for children; 
Condition treated or use: Used in repair of cardiac valve. 

Device project: Pediatric ultrasound imaging for diagnostics and 
surgical planning; 
Condition treated or use: Used for cardiac imaging. 

Device project: PediVAS pediatric circulatory assist device; 
Condition treated or use: Used in acute and temporary life support for 
infants and small children. 

Pediatric device consortia grantees: University of California at San 
Francisco Pediatric Device Consortium: 

Device project: Magnetic Mini-Mover for pectus excavatum: 3rd 
generation magnimplant device; 
Condition treated or use: Treats pectus excavatum (sunken chest)[D]. 

Device project: Roboimplant (remotely operated bionic ortho implant) 
for scoliosis; 
Condition treated or use: Treats congenital and acquired spine 
disorders, such as early onset scoliosis. 

Source: GAO analysis of FDA information. 

Notes: This table presents information on the device projects that 
were directly supported under the pediatric device consortia grants--
that is, they were proposed in the grantees' applications and selected 
by FDA to receive support under the grants. All device projects were 
developing devices for use in pediatric patients. 

[A] Short bowel syndrome represents a loss of sufficient length of 
intestine to allow for the absorption of nutrients. 

[B] Laparoscopic pyloromyotomy is a minimally invasive surgery that 
makes an incision in the pylorus--the region of the stomach that 
connects to the small intestine. 

[C] Esophageal atresia is a congenital medical condition that causes 
the esophagus to end rather than connecting normally to the stomach. 

[D] Pectus excavatum is also known as sunken chest and is a congenital 
chest wall deformity in which several ribs and the sternum grow 
abnormally, producing a concave, or caved-in, appearance in the 
anterior chest wall. 

[End of table] 

FDA Lacks Reliable Information to Readily Identify All Pediatric PMA 
and HDE Devices: 

FDA Has Not Consistently Collected Reliable and Timely Information 
Needed to Report on Pediatric Devices: 

Although FDAAA required FDA to annually report to congressional 
committees on the number of PMA and HDE devices approved in the 
preceding year that were labeled for use in pediatric patients, the 
agency lacks reliable information to readily identify all such 
pediatric devices. Under standards for internal control in the federal 
government, relevant, reliable, and timely information should be 
available for external reporting purposes; however, FDA has not 
consistently collected reliable and timely information needed to 
report on pediatric devices.[Footnote 49] In response to FDAAA, FDA 
developed an electronic flag within its Center Tracking System (CTS) 
in 2008, to help CDRH internally identify PMA and HDE devices that 
were labeled for use in pediatric patients.[Footnote 50] According to 
FDA officials, the agency's medical device reviewers should check the 
pediatric flags during the PMA and HDE process based on all of the 
information available in the application. However, FDA officials 
reported that these electronic flags are not consistently applied, and 
that the agency does not provide formal training or guidance to its 
device reviewers regarding proper implementation of the pediatric 
flags. Therefore, information from FDA's tracking system is not 
sufficiently reliable to identify PMA and HDE devices labeled for use 
in pediatric patients. 

In the absence of reliable information from its internal tracking 
system that could be retrieved in a timely manner to identify approved 
PMA and HDE devices labeled for use in pediatric patients, FDA 
reported that staff completed labor-intensive file reviews--which 
included examining voluminous application files as well as discussion 
with FDA reviewers--to complete its first annual report.[Footnote 51] 
This report, which covered devices approved in fiscal year 2008, did 
not specify the criteria FDA used to identify devices labeled for use 
in pediatric patients in its manual data collection process. An FDA 
official involved in the preparation of the fiscal year 2008 report 
told us that FDA staff considered devices to be labeled for pediatric 
patients if FDA officials determined that the devices were for 
patients younger than 18 years of age; however, this criterion was not 
explicit in the report. Instead, FDA's report noted that a committee 
report described pediatric medical devices as those used to treat or 
diagnose diseases or conditions in patients from birth through age 21. 
[Footnote 52] Further, in the absence of documented criteria used to 
prepare the fiscal year 2008 report, FDA officials involved in 
preparing the combined fiscal years 2009-2010 report at the time of 
our review were not aware of the specific criteria used for the fiscal 
year 2008 report and, as a result, created their own criteria and 
labor-intensive file review for identifying and reporting on approved 
PMA and HDE devices labeled for use in pediatric patients. As of 
October 2011, the combined fiscal years 2009-2010 report had not been 
issued; FDA officials reported that it was in the agency's internal 
review and clearance process. 

In addition, FDA does not have readily available, reliable information 
to identify other pediatric information that FDAAA required the agency 
to report annually. Specifically, FDA officials said that the agency 
does not have reliable information to readily identify and report on 
the number of PMA and HDE devices approved each year for which there 
is a pediatric subpopulation that suffers from the disease or 
condition that the device is intended to treat, diagnose, or 
cure.[Footnote 53] Furthermore, FDAAA required FDA to annually report 
the number of PMA devices exempt from a user fee because they were 
solely intended for pediatric use. Although the agency reported that 
none of the devices approved in fiscal year 2008 were exempt from a 
user fee for this reason, FDA officials stated that as a result of our 
inquiry they reevaluated some of the PMA applications for which user 
fees were paid and identified certain PMA applications from other 
years that may not have properly received the user fee exemption. FDA 
officials said they were in the process of providing refunds to 
applicants that should have been exempt from the user fee. 

Without readily available information on the approved PMA and HDE 
devices labeled for use in pediatric patients or the number of 
approved devices for which a pediatric subpopulation might be 
indicated, FDA cannot easily identify and aggregate data to complete 
statutorily required reporting in a consistent and timely manner. The 
inconsistent information presented in these reports makes it more 
difficult for policymakers, industry stakeholders, and innovators to 
identify what opportunities and needs exist for devices to diagnose 
and treat pediatric patients. 

Fifteen PMA and 3 HDE Devices Have Been Explicitly Indicated for Use 
in Pediatric Patients since FDAAA Was Enacted: 

While the indication for use statement for most approved PMA and HDE 
devices did not identify the age of the intended population, our 
review identified 18 devices approved since FDAAA was enacted that 
were explicitly indicated for use in pediatric patients.[Footnote 54] 
Specifically, our review found that 15 PMA and 3 HDE devices approved 
since FDAAA was enacted have indication for use statements explicitly 
stating that the devices are for patients that include patients age 21 
or younger, pediatric patients, or skeletally immature patients. 
However, the approved indication for use statements for most of the 
118 PMA and HDE devices approved since FDAAA was enacted do not 
specify the age of the intended patient population. Specifically, the 
indication for use statement was silent on the age of the intended 
patient population for 75 percent of PMA devices and 38 percent of HDE 
devices approved during that time (see fig. 1). Given that a device's 
indication for use statement may not explicitly state the age of the 
intended patient population or specify if it is for pediatric 
patients, additional pediatric devices could exist because other 
labeling and clinical information can be used to determine if the 
device can be used in pediatric patients.[Footnote 55] 

Figure 1: PMA and HDE Devices Approved in Fiscal Years 2008 through 
2011 by Indicated Patient Population: 

Figure: PMA and HDE Devices Approved in Fiscal Years 2008 through 2011 
by Indicated Population: 

[Refer to PDF for image: 3 pie-charts] 

PMA (n = 110)[A]: 
Pediatric (pediatric only or pediatric and adult: 14%; 
Adult only: 12%; 
Silent (age not specified): 74%. 

HDE (n = 8): 
Pediatric (pediatri conly or pediatric and adult: 38%; 
Adult only: 25%; 
Silent (age not specified): 38%. 

Total (n = 118): 
Pediatric (pediatric only or pediatric and adult: 15%; 
Adult only: 13%; 
Silent (age not specified): 72%. 

Source: GAO. 

Notes: Totals do not add to 100 percent because of rounding. 

In this figure, devices approved through FDA's premarket approval 
(PMA) and humanitarian device exemption (HDE) processes were 
considered to be for pediatric patients if they were explicitly 
indicated for use in pediatric patients--that is, if the approved 
indication for use statement (1) specified a population that included 
patients age 21 years or younger, (2) specifically stated it was for 
pediatric use, or (3) stated it was for skeletally immature patients. 
Devices explicitly indicated for use in pediatric patients include 
those explicitly indicated for use in pediatric patients or those for 
both pediatric and adult patients. 

Adult only devices are those explicitly indicated for use in adult 
patients--that is, (1) if the indication for use statement specified a 
population that only included patients age 22 or older or (2) if the 
indication for use statement did not specify an age, but specifically 
stated it was for adult use. 

Silent means devices for which the indication for use statement did 
not specify the age of the intended patient population. 

[A] PMA devices include original and panel-track supplement devices. 

[End of figure] 

Of the 18 PMA and HDE devices explicitly indicated for use in 
pediatric patients since FDAAA was enacted, most were explicitly 
indicated for adolescents. The majority of those indicated for 
adolescents were indicated for patients age 18 and older. Nine devices 
(50 percent) were indicated solely for patients age 18 or older--the 
age group FDA considers to be transitional adolescents for internal 
application review purposes--and 2 of those were indicated solely for 
patients age 21 or older.[Footnote 56] Two devices were explicitly 
indicated for children and none were explicitly indicated for neonates 
or infants (see table 5). In addition, the most common medical 
specialties of devices explicitly indicated for use in pediatric 
patients were microbiology (39 percent); cardiovascular (22 percent); 
anesthesiology and ear, nose, and throat (11 percent each); and 
clinical chemistry, ophthalmology, and gastroenterology (6 percent 
each).[Footnote 57] 

Table 5: Approved PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients since FDAAA Was Enacted, by Pediatric Subpopulation: 

Pediatric subpopulation[A]: Pediatric subpopulation[A]Device type: 0: 
[Empty]. 

Pediatric subpopulation[A]: Adolescent: PMA (n=15): [Empty]. 

Device type: PMA (n=15); 
Pediatric subpopulation[A]: 
Neonate: 0; 
Infant: 0; 
Child: 2; 
Adolescent: 
Twelve years to less than 18 years: 4; 
Transitional adolescent (18 to 21 years)[B]: 12; 
Pediatric subpopulation not specified[C]: 3. 

Device type: HDE (n=3); 
Pediatric subpopulation[A]: 
Neonate: 0; 
Infant: 0; 
Child: 0; 
Adolescent: 
Twelve years to less than 18 years: 1; 
Transitional adolescent (18 to 21 years)[B]: 2; 
Pediatric subpopulation not specified[C]: 1. 

Device type: Total (n=18); 
Pediatric subpopulation[A]: 
Neonate: 0; 
Infant: 0; 
Child: 2; 
Adolescent: 
Twelve years to less than 18 years: 5; 
Transitional adolescent (18 to 21 years)[B]: 14; 
Pediatric subpopulation not specified[C]: 4. 

Source: GAO analysis of FDA documents. 

Notes: This table presents PMA and HDE devices approved in fiscal 
years 2008 through 2011. FDAAA was enacted September 27, 2007; no 
devices approved through FDA's premarket approval (PMA) and 
humanitarian device exemption (HDE) processes were approved in fiscal 
year 2007 after FDAAA was enacted. We considered PMA and HDE devices 
to be for pediatric patients if they were explicitly indicated for use 
in pediatric patients--that is, if the approved indication for use 
statement (1) specified a population that included patients age 21 
years or younger, (2) specifically stated it was for pediatric use, or 
(3) stated it was for skeletally immature patients. Devices explicitly 
indicated for use in pediatric patients include those explicitly 
indicated for use in pediatric patients or those for both pediatric 
and adult patients. 

[A] A device can be indicated for more than one pediatric 
subpopulation. For purposes of this table, pediatric subpopulation 
ages are those that FDA uses for internal tracking purposes: neonate 
(birth to 28 days), infant (29 days to <2 years), child (2 years to 
<12 years), adolescent (12 years to <18 years), and transitional 
adolescent (18 years to <=21 years). 

[B] Nine of the devices were explicitly indicated solely for 
transitional adolescents and adults, seven of which were indicated for 
patients age 18 or older and two of which were indicated for patients 
age 21 or older. 

[C] The indication for use statement for four devices did not specify 
the pediatric subpopulation, but one was indicated solely for 
pediatric patients and three were indicated for both pediatric and 
adult patients according to the approved indication for use statement. 

[End of table] 

Although three HDE devices approved since FDAAA was enacted were 
explicitly indicated for use in pediatric patients, the number per 
year may increase in the future, as the number of HUD requests and 
designations per year for devices intended to treat diseases that 
occur in pediatric patients increased after FDAAA was 
enacted.[Footnote 58] Because HUD designation is the first step to 
obtaining HDE approval, increasing HUD designations indicate potential 
for future pediatric HDE devices.[Footnote 59] According to FDA, the 
agency received about one HUD request per year on average for devices 
intended to treat a disease that occurs in pediatric patients before 
FDAAA was enacted and about five requests per year on average in the 
years after the law was enacted. Likewise, FDA granted about one HUD 
designation for devices intended to treat a disease that occurs in 
pediatric patients per year prior to FDAAA and almost five such HUD 
designations per year in the years after (see figure 2). 

Figure 2: HUD Requests, HUD Designations, and Approved HDE Devices 
Explicitly Indicated for Use in Pediatric Patients, Fiscal Years 2001 
through 2011: 

[Refer to PDF for image: multiple line graph] 

Year: 2001; 
HUD requests for pediatrics: 1; 
HUD designations for pediatrics: 1; 
HDE explicitly indicated for use in pediatric patients: 0. 

Year: 2002; 
HUD requests for pediatrics: 1; 
HUD designations for pediatrics: 1; 
HDE explicitly indicated for use in pediatric patients: 0. 

Year: 2003; 
HUD requests for pediatrics: 1; 
HUD designations for pediatrics: 1; 
HDE explicitly indicated for use in pediatric patients: 1. 

Year: 2004; 
HUD requests for pediatrics: 2; 
HUD designations for pediatrics: 1; 
HDE explicitly indicated for use in pediatric patients: 4. 

Year: 2005; 
HUD requests for pediatrics: 0; 
HUD designations for pediatrics: 0; 
HDE explicitly indicated for use in pediatric patients: 0. 

Year: 2006; 
HUD requests for pediatrics: 2; 
HUD designations for pediatrics: 2; 
HDE explicitly indicated for use in pediatric patients: 1. 

Year: 2007; 
HUD requests for pediatrics: 1; 
HUD designations for pediatrics: 1; 
HDE explicitly indicated for use in pediatric patients: 0. 

Year: 2008; 
HUD requests for pediatrics: 4; 
HUD designations for pediatrics: 3; 
HDE explicitly indicated for use in pediatric patients: 1. 

Year: 2009; 
HUD requests for pediatrics: 4; 
HUD designations for pediatrics: 4; 
HDE explicitly indicated for use in pediatric patients: 0. 

Year: 2010; 
HUD requests for pediatrics: 9; 
HUD designations for pediatrics: 6; 
HDE explicitly indicated for use in pediatric patients: 1. 

Year: 2011; 
HUD requests for pediatrics: 7; 
HUD designations for pediatrics: 8; 
HDE explicitly indicated for use in pediatric patients: 1. 

Source: GAO analysis of FDA data. 

Notes: Some humanitarian use device (HUD) designations during a 
particular fiscal year may be from HUD requests submitted in an 
earlier fiscal year. FDA identified HUD requests and designations for 
pediatrics based on each device's indication for use statement, which 
includes the disease the device is intended to treat, diagnose, or 
cure. 

We considered devices approved through FDA's humanitarian device 
exemption (HDE) process to be for pediatric patients if they were 
explicitly indicated for use in pediatric patients--that is, if the 
approved indication for use statement (1) specified a population that 
included patients age 21 years or younger, (2) specifically stated it 
was for pediatric use, or (3) stated it was for skeletally immature 
patients. Devices explicitly indicated for pediatric use include those 
explicitly indicated for use in pediatric patients or those for both 
pediatric and adult patients. 

[End of figure] 

Since FDAAA was enacted, two of the three HDE devices explicitly 
indicated for use in pediatric patients (patients age 21 years or 
younger) were granted the exemption from the HDE profit prohibition. 
[Footnote 60] One of these two exempted devices, the Medtronic Melody® 
Transcatheter Pulmonary Valve and Ensemble® Transcatheter Valve 
Delivery System (Melody® TPV) was approved in January 2010 for use in 
treating pediatric and adult patients with a blocked or leaky 
pulmonary heart valve that has previously been replaced to correct 
congenital (birth) heart defects and with a vessel size above a 
certain threshold.[Footnote 61] In September 2011, FDA's Pediatric 
Advisory Committee reviewed the Melody TPV and determined that the HDE 
profit prohibition exemption remained appropriate.[Footnote 62] The 
ELANA (Excimer Laser Assisted Non-Occlusive Anastamosis) Surgical 
KitHUD was approved in March 2011 for use in neurosurgery during 
intracranial vascular bypass procedures in patients 13 years of age or 
older who meet certain criteria. (See appendix I for more information 
on the two devices.) 

Conclusions: 

It is too early to determine if the FDAAA provisions authorizing 
demonstration grants for pediatric device consortia or allowing 
manufacturers to earn a profit on pediatric HDE devices have had a 
substantial impact on the number of approved pediatric devices; 
however, the provisions show potential for more pediatric devices in 
future years. Although stakeholders identified barriers to developing 
and receiving FDA approval to market pediatric medical devices, 
programs such as the pediatric device consortia can foster an 
environment for device innovators to share ideas and advance the 
development of pediatric medical devices. The number of devices that 
the pediatric device consortia have supported through the early phases 
of development and the positive feedback from stakeholders indicate 
that pediatric devices are being developed. Further, the increase in 
the number of HUD requests and designations for devices that treat 
pediatric populations since FDAAA was enacted indicate potential for 
development of additional pediatric HDE devices in the near future. 
Over the past 10 years, it has taken a few years for a manufacturer to 
submit an HDE application and receive FDA market approval after 
receiving HUD designation; therefore the profit eligibility incentive 
for pediatric HDE devices may have induced an increase in the number 
of pediatric HUD requests. 

Although the future for pediatric device development may be promising, 
FDA lacks reliable and timely information on pediatric devices 
approved for the U.S. market. To meet statutory reporting 
requirements, FDA must have data systems in place to produce timely, 
reliable information to readily identify and track devices the agency 
has approved for use in pediatric patients. Without a systematic 
database to identify medical devices approved for use in pediatric 
patients, FDA cannot provide data so that policymakers, innovators, 
and physicians may understand the extent of medical device 
availability and needs for further development. 

Recommendation for Executive Action: 

We recommend that the Commissioner of FDA collect reliable information 
to report data related to pediatric medical devices. Specifically, FDA 
should take steps to consistently collect information using its 
existing pediatric electronic flag or otherwise develop internal 
controls to readily and reliably collect and report information on 
devices for pediatric use. 

Agency Comments: 

We received comments on a draft of this report from HHS, which are 
reproduced in appendix IV. The department agreed with our 
recommendation that FDA collect reliable information related to 
pediatric medical devices and commented that FDA is in the process of 
modifying and updating its current tracking system, related data 
quality controls, and training program requirements for pediatric 
medical device premarket submissions. The department further stated 
that when this process is complete, FDA's pediatric information 
collection efforts will satisfy the department's pediatric device 
operations and oversight needs, including the development of the 
annual pediatric report. 

We are sending copies of this report to the Secretary of Health and 
Human Services, the Commissioner of FDA, and other interested parties. 
In addition, the report will be available at no charge on the GAO 
website at [hyperlink, http://www.gao.gov]. 

If you or your staff have any questions about this report, please 
contact me at (202) 512-7114 or crossem@gao.gov. Contact points for 
our Offices of Congressional Relations and Public Affairs may be found 
on the last page of this report. GAO staff who made major 
contributions to this report are listed in appendix V. 

Signed by: 

Marcia Crosse: 
Director, Health Care: 

[End of section] 

Appendix I: Summary of HDE Devices Granted Exemption from the HDE 
Profit Prohibition: 

The Food and Drug Administration Amendments Act of 2007 (FDAAA) also 
required that we describe the key characteristics of devices approved 
through the humanitarian device exemption (HDE) process that were 
granted exemptions from the HDE profit prohibition because they were 
labeled for use in pediatric patients. This appendix describes the 
conditions and the indicated patient populations of the two pediatric 
medical devices that were granted exemption from the HDE profit 
prohibition--Medtronic Melody® Transcatheter Pulmonary Valve and 
Ensemble® Transcatheter Valve Delivery System (Melody® TPV) and ELANA 
(Excimer Laser Assisted Non-Occlusive Anastamosis) Surgical KitHUD. 
[Footnote 63] We also describe when each device was approved for the 
U.S. market and what is known about profits made by the manufacturers 
of each device. In addition, we describe what is known about the costs 
and insurance coverage and off-label use of the Melody TPV device--the 
one HDE device exempt from the HDE profit prohibition that was sold 
and in use in the United States at the time of our review. 

Summary of Pediatric HDE Devices Exempt from the HDE Profit 
Prohibition: 

To describe the key characteristics of each device, we interviewed 
officials from Medtronic, Inc., and Elana, Inc.--manufacturers of the 
Melody TPV and ELANA devices, respectively--and examined manufacturer-
provided documentation, such as billing code information, related to 
the Melody TPV device. We also interviewed officials from the Food and 
Drug Administration (FDA) who manage the HDE process and examined FDA 
documents for each device, including approval documents and an annual 
report for the Melody TPV--which manufacturers granted exemption from 
the HDE profit prohibition are required to submit annually to FDA. 
(Table 6 provides key characteristics of the two pediatric HDE devices 
granted exemption from the HDE profit prohibition.) 

Table 6: Characteristics of the Two Pediatric HDE Devices Granted 
Exemption from the HDE Profit Prohibition: 

Device: Medtronic Melody® Transcatheter Pulmonary Valve and Ensemble® 
Transcatheter Valve Delivery System (Melody TPV); 
Manufacturer: Medtronic, Inc., United States; 

Summary of indication for use: The Melody device is used to repair a 
blocked or leaky pulmonary heart valve that has previously been 
replaced to correct congenital (birth) heart defects. The Melody 
device is put in place without using open heart surgery and while the 
heart is beating, and can delay the need for more invasive open heart 
surgery; 

Approved indication for use -including population: Indicated for use 
as an adjunct to surgery in the management of pediatric and adult 
patients with the following clinical conditions: Existence of a full 
(circumferential) Right Ventricular Outflow Tract (RVOT) conduit that 
was equal to or greater than 16 mm in diameter when originally 
implanted and Dysfunctional RVOT conduits with a clinical indication 
for intervention, and either Regurgitation: moderate regurgitation, or 
Stenosis: mean RVOT gradient 35 mmHg; 

Medical specialty: Cardiovascular; 
HUD designation date: 7/10/2007; 
HDE application: date filed and date approved: HDE application filed: 
8/29/2008; HDE approved: 1/25/2010; 
Annual distribution number[B]: 2,996; 
Number of devices sold in the United States since HDE approval: 695[C]; 
Marketing in other countries: European Union: September 2006 Canada: 
December 2006; 
U.S. list price: $30,500 (combined) $24,000 (valve) $6,500 (delivery 
system); 
Profit from device: Not available. 

Device: ELANA (Excimer Laser Assisted Non-Occlusive Anastamosis) 
Surgical KitHUD; 
Manufacturer: Elana, Inc., Netherlands; 

Summary of indication for use: The ELANA device is intended to allow 
neurosurgeons to reroute blood flow around an aneurysm or a tumor in 
the brains of patients at greater risk of stroke during standard 
bypass surgery. (Standard bypass surgery in the brain requires 
clipping the artery to halt blood flow during the procedure, and this 
standard surgery is not considered safe for about 1,000 patients 
annually for whom temporarily shutting off their blood flow would put 
them at high risk of stroke). 

Approved indication for use - including population: Indicated for 
creating arteriotomies during an intracranial vascular bypass 
procedure in patients 13 years of age or older with an aneurysm or a 
skull base tumor affecting a large (> 2.5 mm), intracranial artery 
that failed balloon test occlusion, cannot be sacrificed, or cannot be 
treated with conventional means due to local anatomy or complexity. 

Medical specialty: Cardiovascular[A]; 
HUD designation date: 9/26/2003; 
HDE application: date filed and date approved: 12/5/2008; HDE 
approved: 3/10/2011; 
Annual distribution number[B]: 1,000; 
Number of devices sold in the United States since HDE approval: 4[D]; 
Marketing in other countries: European Union: January 2006 Canada: 
November 2007; 
U.S. list price: Not available; 
Profit from device: Not available. 

Source: GAO analysis of FDA and manufacturer information. 

Notes: Humanitarian use devices (HUD) are approved for the U.S. market 
through FDA's humanitarian device exemption (HDE) process. 

[A] We identified each device's medical specialty based on data from 
FDA's product code classification database--which contains device 
names and product codes assigned based upon the medical device product 
classification designated under 21 C.F.R. Parts 862-892. Although the 
database indicated a medical specialty of cardiovascular for the ELANA 
Surgical KitHUD, FDA officials reported that upon further review they 
determined that the product code assigned for the device is 
technically inaccurate. To correct this technical inconsistency, FDA 
will issue a corrected product code for this product in the near 
future. The corrected medical specialty for the device should be 
neurology, according to FDA officials. 

[B] FDA determines an upper limit on the number of devices that can be 
distributed each year--to treat both pediatric and adult patients--
known as the annual distribution number (ADN). Manufacturers may only 
receive profits on devices exempt from the profit prohibition up to 
the ADN. 

[C] Number of Melody TPV devices sold from January 26, 2010, through 
August 31, 2011. According to the manufacturer, 386 devices (56 
percent) were sold for use in patients age 21 or younger. 

[D] According to the manufacturer, the ELANA Surgical KitHUD was first 
sold in the U.S. market in November 2011. 

[End of table] 

Survey of Physicians and Hospitals That Have Used the Melody TPV: 

To obtain information regarding costs of the Melody TPV device as well 
as insurance coverage for and off-label use of the device, we surveyed 
36 physicians at the 25 children's hospitals and pediatric units of 
medical centers (which we collectively refer to as children's 
hospitals) that according to the device's manufacturer, had used the 
Melody TPV at least 10 times.[Footnote 64] We received complete 
responses from 27 physicians at 20 children's hospitals for an overall 
response rate of 75 percent of physicians and 80 percent of hospitals 
in our sample.[Footnote 65] 

Almost all (93 percent) of the 27 respondents reported that their 
hospital purchased the Melody TPV at the manufacturer's list price of 
$30,500.[Footnote 66] All but 2 physicians reported that their 
hospital purchased the two components--the valve and the delivery 
system--of the Melody TPV device separately. A physician that we spoke 
with said his hospital kept several valves and several of each size 
delivery system in stock and purchased more as needed. Twenty-four of 
the 25 physicians at children's hospitals that purchased the 
components separately reported paying the list price for each 
component--$24,000 for each Melody Transcatheter Pulmonary Valve and 
$6,500 for each Ensemble Transcatheter Valve Delivery System. 

Many physicians we surveyed reported that they experienced at least 
some difficulty obtaining health insurance coverage for the Melody TPV 
device regardless of the type of insurance held by the patient (see 
table 7).[Footnote 67] Twenty-five of the 27 responding physicians 
reported experiencing difficulty obtaining coverage for patients with 
private health insurance at least some of the time, with 3 of those 
physicians reporting that it was always difficult.[Footnote 68] For 
Medicaid and Children's Health Insurance Program (CHIP) coverage, 4 
physicians reported that the device was not covered at all by this 
type of insurance. Additionally, 18 of the 22 responding physicians 
who reported receiving reimbursement for the device through Medicaid 
or CHIP also reported difficulty obtaining that coverage at least some 
of the time, with 4 of those reporting that it was always difficult. 
Most responding physicians (19 of 27) reported not treating any 
patients covered by Medicare, but 4 of those who did treat patients 
with Medicare coverage said that obtaining Medicare coverage for the 
device was always difficult.[Footnote 69] Further, 7 of the 27 
responding physicians reported that health insurance coverage 
influenced their clinical decision to use the device. For example, 3 
physicians reported that delay or denial of insurance coverage for the 
Melody TPV device has led them to conduct open heart surgery in 
patients for whom use of the device would otherwise have allowed them 
to delay this more invasive surgery. 

Table 7: Number of Physicians Reporting Difficulty Obtaining Insurance 
Coverage for Melody TPV Device, by Insurance Type and Extent of 
Difficulty Experienced: 

Type of health insurance: Private health insurance; 
Number of physicians reporting difficulty obtaining insurance coverage 
for Melody TPV: 
Melody TPV not covered by this type of insurance: 0; 
No patients with this type of insurance: 0; 
Never difficult: 2; 
Sometimes difficult: 11; 
About half the time difficult: 9; 
Most of the time difficult: 2; 
Always difficult: 3; 
At least sometimes difficult: 25. 

Type of health insurance: Medicaid/Children's Health Insurance Program; 
Number of physicians reporting difficulty obtaining insurance coverage 
for Melody TPV: 
Melody TPV not covered by this type of insurance: 4; 
No patients with this type of insurance: 1; 
Never difficult: 4; 
Sometimes difficult: 10; 
About half the time difficult: 2; 
Most of the time difficult: 2; 
Always difficult: 4; 
At least sometimes difficult: 18. 

Type of health insurance: Medicare[A]; 
Number of physicians reporting difficulty obtaining insurance coverage 
for Melody TPV: 
Melody TPV not covered by this type of insurance: 0; 
No patients with this type of insurance: 19; 
Never difficult: 2; 
Sometimes difficult: 0; 
About half the time difficult: 0; 
Most of the time difficult: 0; 
Always difficult: 4; 
At least sometimes difficult: 4. 

Source: GAO. 

Notes: This table presents the responses from 27 physicians who 
responded to GAO's 2011 Survey of Physicians Who Use the Melody TPV 
device. 

[A] Two physicians did not respond to the question regarding Medicare 
insurance. 

[End of table] 

Consistent with what stakeholders reported about challenges to 
obtaining insurance coverage for HDE devices in general, physicians we 
surveyed reported challenges obtaining health insurance coverage for 
the Melody TPV device. These included comments about the time required 
to discuss coverage with the insurers to obtain reimbursement, 
insurers' lack of familiarity with the medical device, challenges 
because insurers consider the medical device experimental, and 
problems because the Melody TPV procedure did not have a current 
procedural terminology (CPT) code at the time of our survey.[Footnote 
70] 

About half (52 percent) of physician respondents reported that they 
have implanted the Melody TPV device in a pediatric or adult patient 
for an indication other than the indication on the label of the 
device--an off-label indication--since it was approved for the U.S. 
market in February 2010. However, all but 1 of those physicians said 
they used it off-label 20 percent of the time or less across instances 
when they implanted the device in pediatric patients. Further, 29 
percent of responding physicians stated that they never used the 
device for an off-label indication in pediatric patients. In addition, 
each instance of off-label use should have been for an indication 
approved by the hospital's institutional review board (IRB). For 
example, 1 physician reported that he routinely implanted the Melody 
TPV for one of three IRB-approved protocols, two of which were for an 
off-label indication but all were for pediatric patients.[Footnote 71] 

[End of section] 

Appendix II: PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients since Fiscal Year 2006: 

Of the 118 devices approved through FDA's premarket approval (PMA) and 
HDE processes in the 4 years since FDAAA was enacted, 18 (15 percent) 
were explicitly indicated for use in only pediatric patients--those 
age 21 or younger--or both pediatric and adult patients. Of the 86 PMA 
and HDE devices approved in the 2 years before FDAAA was enacted, 21 
were explicitly indicated for use in only pediatric patients or both 
pediatric and adult patients (see table 8). Of these, few devices were 
explicitly indicated for use in patients under age 18--that is, in 
each fiscal year, most devices that explicitly indicated a pediatric 
population were indicated for use in patients age 18 years and older. 
[Footnote 72] 

Table 8: PMA and HDE Devices Explicitly Indicated for Use in Pediatric 
Patients, Fiscal Years 2006 through 2011: 

Device type: PMA[B]: Pediatric only; 
Pre-FDAAA: 
FY2006: 1; 
FY2007: 1; 
Post-FDAAA[A]: 
FY2008: 0; 
FY2009: 1; 
FY2010: 0; 
FY2011: 0; 
Total pre-FDAAA: 2; 
Total post-FDAAA: 1. 

Device type: PMA[B]: Pediatric and adult; 
Pre-FDAAA: 
FY2006: 13; 
FY2007: 5; 
Post-FDAAA[A]: 
FY2008: 2; 
FY2009: 2; 
FY2010: 3; 
FY2011: 7; 
Total pre-FDAAA: 18[C]; 
Total post-FDAAA: 14[D]. 

Device type: PMA[B]: All pediatric PMA; 
Pre-FDAAA: 
FY2006: 14; 
FY2007: 6; 
Post-FDAAA[A]: 
FY2008: 2; 
FY2009: 3; 
FY2010: 3; 
FY2011: 7; 
Total pre-FDAAA: 20; 
Total post-FDAAA: 15. 

Device type: HDE: Pediatric only; 
Pre-FDAAA: 
FY2006: 1[E]; 
FY2007: 0; 
Post-FDAAA[A]: 
FY2008: 0; 
FY2009: 0; 
FY2010: 0; 
FY2011: 0; 
Total pre-FDAAA: 1; 
Total post-FDAAA: 0. 

Device type: HDE: Pediatric and adult; 
Pre-FDAAA: 
FY2006: 0; 
FY2007: 0; 
Post-FDAAA[A]: 
FY2008: 1; 
FY2009: 0; 
FY2010: 1; 
FY2011: 1; 
Total pre-FDAAA: 0; 
Total post-FDAAA: 3[F]. 

Device type: HDE: All pediatric HDE; 
Pre-FDAAA: 
FY2006: 1; 
FY2007: 0; 
Post-FDAAA[A]: 
FY2008: 1; 
FY2009: 0; 
FY2010: 1; 
FY2011: 1; 
Total pre-FDAAA: 1; 
Total post-FDAAA: 3. 

Device type: Total pediatric; 
Pre-FDAAA: 
FY2006: 15; 
FY2007: 6; 
Post-FDAAA[A]: 
FY2008: 3; 
FY2009: 3; 
FY2010: 4; 
FY2011: 8; 
Total pre-FDAAA: 21; 
Total post-FDAAA: 18. 

Source: GAO analysis of FDA documents. 

Notes: We considered pediatric devices approved through FDA's 
premarket approval (PMA) and humanitarian device exemption (HDE) 
processes to be those explicitly indicated for use in pediatric 
patients when the approved indication for use statement (1) specified 
a population that included patients age 21 years or younger, (2) 
specifically stated it was for pediatric use, or (3) stated it was for 
skeletally immature patients. Devices explicitly indicated for use in 
pediatric patients include those explicitly indicated for use in 
pediatric patients or those for both pediatric and adult patients. 
Additional medical devices for which the indication for use was silent 
on the age of the patient population may have been approved for 
pediatric use during this time period. 

[A] The FDA Amendments Act of 2007 (FDAAA) was enacted September 27, 
2007, but no PMA or HDE devices were approved after FDAAA was enacted 
in fiscal year 2007. 

[B] PMA devices include original and panel-track supplement devices. 

[C] Five of the PMA devices approved in the 2 years before FDAAA was 
enacted were indicated solely for use in patients age 18 or older. An 
additional six were indicated solely for use in patients age 21 or 
older. We consider these to be explicitly indicated for use in 
pediatric patients because the minimum age includes patients age 21 
years or younger. 

[D] Six of the PMA devices approved in the 4 years after FDAAA was 
enacted were indicated solely for use in patients age 18 or older. An 
additional two PMA devices were indicated solely for use in patients 
age 21 or older. We consider these to be explicitly indicated for use 
in pediatric patients because the minimum age includes patients age 21 
years or younger. 

[E] The HDE device approved in fiscal year 2006 was indicated for 
fetuses whose gestational age is between 16 and 26 weeks. We 
considered this device to be explicitly indicated for use in pediatric 
patients. 

[F] One of the HDE devices approved in the 4 years after FDAAA was 
enacted was indicated solely for use in patients age 18 or older. 

[End of table] 

[End of section] 

Appendix III: PMA and HDE Devices Explicitly Indicated for Use in 
Pediatric Patients, Fiscal Years 2008 through 2011: 

Devices approved through the Food and Drug Administration's (FDA) 
premarket approval (PMA) process: 

Device name, number[A]: Propel sinus implant, P100044; 
Date approved: 8/11/2011; 
Summary of indication for use: Indicated for use in patients 18 years 
of age or older following ethmoid sinus surgery to reduce the need for 
postoperative intervention; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Ear, nose, and throat. 

Device name, number[A]: Vitros Immunodiagnostic Products Anti-HBe 
Reagent Pack, Calibrator and Controls, P100001; 
Date approved: 7/20/2011; 
Summary of indication for use: Indicated for the in vitro qualitative 
detection of antibodies to hepatitis B e antigen (anti-HBe) in human 
adult and pediatric (2 to 21 years old) serum from individuals who 
have symptoms of chronic hepatitis and those who have recovered from 
hepatitis B infection; 
Pediatric subpopulation (if available)[B]: Child, adolescent, 
transitional adolescent, adult; 
Medical specialty: Microbiology. 

Device name, number[A]: Solseta Injectable Gel, P100014; 
Date approved: 5/27/2011; 
Summary of indication for use: Indicated for the treatment of fecal 
incontinence in patients 18 years and older who have failed 
conservative therapy (e.g., diet, fiber therapy, and antimotility 
medications); 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Gastroenterology/Urology. 

Device name, number[A]: Vitros Immunodiagnostic Products HBeAg Reagent 
Pack, Calibrator and Controls, P090028; 
Date approved: 5/11/2011; 
Summary of indication for use: Indicated for the in vitro qualitative 
detection of hepatitis B e antigen (HBeAg) in human adult and 
pediatric (2 to 21 years old) serum from individuals who have symptoms 
of hepatitis or who may be at risk for hepatitis B virus infection; 
Pediatric subpopulation (if available)[B]: Child, adolescent, 
transitional adolescent, adult; 
Medical specialty: Microbiology. 

Device name, number[A]: Cobas HPV Test, P100020; 
Date approved: 4/19/2011; 
Summary of indication for use: Indicated to screen patients 21 years 
and older with ASC-US (atypical squamous cells of undetermined 
significance) cervical cytology test results to determine the need for 
referral to colposcopy or to assess the presence or absence of high-
risk Human Papillomavirus genotypes 16 and 18, and for other uses in 
women 30 years and older; 
Pediatric subpopulation (if available)[B]: Transitional adolescent,[C] 
adult; 
Medical specialty: Microbiology. 

Device name, number[A]: Oraquick HCV Rapid Antibody Test, P080027[D]; 
Date approved: 6/25/2010; 
Summary of indication for use: Indicated for the qualitative detection 
of antibodies to hepatitis C virus in venipuncture whole blood 
specimens from individuals 15 years or older; 
Pediatric subpopulation (if available)[B]: Adolescent, transitional 
adolescent, adult; 
Medical specialty: Microbiology. 

Device name, number[A]: Alair Bronchial Thermoplasty System, P080032; 
Date approved: 4/27/2010; 
Summary of indication for use: Indicated for the treatment of severe 
persistent asthma in patient 18 years and older whose asthma is not 
well controlled with inhaled corticosteroids and long-acting beta 
agonists; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Anesthesiology. 

Device name, number[A]: Esteem Totally Implantable Hearing System, 
P090018; 
Date approved: 3/17/2010; 
Summary of indication for use: Indicated for patients with hearing 
loss who meet the following criteria: (1) 18 years of age or older, 
(2) stable bilateral sensorineural hearing loss, (3) moderate to 
severe sensorineural hearing loss defined by Pure Tone Average, (4) 
unaided speech discrimination test score greater than or equal to 40 
percent, (5) normally functioning eustachian tube, (6) normal middle 
ear anatomy, (7) normal tympanic membrane, (8) adequate space for 
Esteem implant determined via a high resolution computerized 
tomography (CT) scan, and (9) minimum 30 days of experience with 
appropriately fit hearing aids; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Ear, nose, and throat. 

Device name, number[A]: Architect Core Reagent Kit, Architect Core 
Calibrator and Architect Core Controls, P080023; 
Date approved: 4/10/2009; 
Summary of indication for use: Indicated for the qualitative detection 
of antibodies to hepatitis B core antigen in human adult and pediatric 
serum and plasma and neonatal serum. It is intended as an aid in the 
diagnosis of acute, chronic, or resolved hepatitis B virus infection 
in conjunction with other laboratory results and clinical information; 
Pediatric subpopulation (if available)[B]: (No age provided, indicated 
for pediatric and adult patients); 
Medical specialty: Microbiology. 

Device name, number[A]: REPEL-CV Bioreabsorbable Adhesion Barrier, 
P070005; 
Date approved: 3/6/2009; 
Summary of indication for use: Indicated for reducing the severity of 
postoperative cardiac adhesions in pediatric patients who are likely 
to require reoperation via sternotomy; 
Pediatric subpopulation (if available)[B]: (No age provided, indicated 
for pediatric patients); 
Medical specialty: Cardiovascular. 

Device name, number[A]: Freestyle Navigator Continuous Glucose 
Monitor, P050020; 
Date approved: 3/12/2008; 
Summary of indication for use: Indicated for continually recording 
interstitial fluid glucose levels in people ages 18 and older with 
diabetes mellitus for the purpose of improving diabetes management; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Clinical chemistry. 

Device name, number[A]: Architect Core-M Reagent Kit, Architect Core 
Calibrator and Architect Core Controls, P060035; 
Date approved: 11/6/2007; 
Summary of indication for use: Indicated for the qualitative detection 
of IgM antibodies to hepatitis B core antigen in human adult and 
pediatric serum and plasma and neonatal serum. It is intended as an 
aid in the diagnosis of acute, chronic, or resolved hepatitis B virus 
infection in conjunction with other laboratory results and clinical 
information; 
Pediatric subpopulation (if available)[B]: (No age provided, indicated 
for pediatric and adult patients); 
Medical specialty: Microbiology. 

PMA panel-track supplement devices: 

Device name, number[A]: Meditec MEL 80 Excimer Laser, P060004-S001; 
Date approved: 3/28/2011; 
Summary of indication for use: Indicated for primary lasik treatments 
for (1) the reduction or elimination of naturally occurring hyperopia, 
(2) in patients who are 21 years of age or older, and (3) with 
documentation of stable manifest refraction over the past year; 
Pediatric subpopulation (if available)[B]: Transitional adolescent,[C] 
adult; 
Medical specialty: Ophthalmic. 

Device name, number[A]: Oraquick HCV Rapid Antibody Test, P080027-
S001[D]; 
Date approved: 2/18/2011; 
Summary of indication for use: A single-use immunoassay for the 
qualitative detection of antibodies to hepatitis C virus in 
fingerstick whole blood specimens and venipuncture whole blood 
specimens from individuals 15 years or older; 
Pediatric subpopulation (if available)[B]: Adolescent, transitional 
adolescent, adult; 
Medical specialty: Microbiology. 

Device name, number[A]: Navistar & Celsius Thermacool Catheters, 
P030031-S011; 
Date approved: 2/6/2009; 
Summary of indication for use: Indicated for catheter-based cardiac 
electrophysiological mapping (stimulating and recording), for the 
treatment of (1) type I atrial flutter in patients age 18 or older, 
(2) recurrent drug/device refractory sustained monomorphic ventricular 
tachycardia due to prior myocardial infarction in adults, and (3) drug 
refractory recurrent symptomatic paroxysmal atrial fibrillation; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Cardiovascular. 

Devices approved through FDA's humanitarian device exemption process 
(HDE): 

Device name, number[A]: ELANA Surgical KitHUD, H080005; 
Date approved: 3/10/2011; 
Summary of indication for use: Indicated for creating arteriotomies 
during an intracranial vascular bypass procedure in patients 13 years 
of age or older with an aneurysm or a skull base tumor affecting a 
large (> 2.5 mm), intracranial artery that failed balloon test 
occlusion, cannot be sacrificed, or cannot be treated with 
conventional means due to local anatomy or complexity; 
Pediatric subpopulation (if available)[B]: Adolescent, transitional 
adolescent, adult; 
Medical specialty: Cardiovascular[E]. 

Device name, number[A]: Medtronic Melody Transcatheter Pulmonary Valve 
and Ensemble Transcatheter Valve Delivery System, H080002; 
Date approved: 1/25/2010; 
Summary of indication for use: Indicated for use as an adjunct to 
surgery in the management of pediatric and adult patients with the 
following clinical conditions: Existence of a full (circumferential) 
Right Ventricular Outflow Tract (RVOT) conduit that was equal to or 
greater than 16 mm in diameter when originally implanted and 
Dysfunctional RVOT conduits with a clinical indication for 
intervention, and either Regurgitation: moderate regurgitation, or 
Stenosis: mean RVOT gradient 35 mmHg; 
Pediatric subpopulation (if available)[B]: (No age provided, indicated 
for pediatric and adult patients); 
Medical specialty: Cardiovascular. 

Device name, number[A]: NeuRx RA/4, H070003; 
Date approved: 6/17/2008; 
Summary of indication for use: Indicated for use in patients with 
stable, high spinal cord injuries with stimulatable diaphragms, but 
who lack control of their diaphragms. The device is indicated to allow 
the patients to breathe without the assistance of a mechanical 
ventilator for at least 4 continuous hours a day. For use only in 
patients 18 years of age or older; 
Pediatric subpopulation (if available)[B]: Transitional adolescent, 
adult; 
Medical specialty: Anesthesiology. 

Source: GAO analysis of FDA data and documents. 

Notes: We considered pediatric devices to be those explicitly 
indicated for use in pediatric patients when the approved indication 
for use statement (1) specified a population that included patients 
age 21 years or younger, (2) specifically stated it was for pediatric 
use, or (3) stated it was for skeletally immature patients. Devices 
explicitly indicated for use in pediatric patients include those 
explicitly indicated for use in pediatric patients or those for both 
pediatric and adult patients. 

[A] FDA assigns a number to each device application that denotes the 
type of device (P=PMA, H=HDE), year the application was received, and 
number assigned chronologically in the order it was received. FDA also 
assigns PMA supplements, including panel-track supplements, a 
supplement number (S). 

[B] For purposes of this table, pediatric subpopulation ages are those 
that FDA uses for internal tracking purposes: neonate (birth to 28 
days), infant (29 days to <2 years), child (2 years to <12 years), 
adolescent (12 years to <18 years), and transitional adolescent (18 
years to <=21 years). 

[C] Two PMA devices are indicated solely for use in patients age 21 or 
older--we consider these devices to be indicated for use in pediatric 
patients because the minimum age includes pediatric patients. 

[D] The original application and a panel-track supplement for the 
Oraquick HCV Rapid Antibody Test were both approved for use in 
pediatric patients after the FDA Amendments Act of 2007 was enacted. 

[E] We identified each device's medical specialty based on data from 
FDA's product code classification database--which contains device 
names and product codes assigned based upon the medical device product 
classification designated under 21 C.F.R. Parts 862-892. Although the 
database indicated a medical specialty of cardiovascular for the ELANA 
Surgical KitHUD, FDA officials reported that upon further review they 
determined that the product code assigned for the device is 
technically inaccurate. To correct this technical inconsistency, FDA 
will issue a corrected product code for this product in the near 
future. The corrected medical specialty for the device should be 
neurology, according to FDA officials. 

[End of table] 

[End of section] 

Appendix IV: Comments from the Department of Health and Human Services: 

Department Of Health & Human Services: 
Office Of The Secretary: 
Assistant Secretary for Legislation: 
Washington, 20201: 

December 9, 2011: 

Marcia Crosse, Director: 
Health Care: 
U.S. Government Accountability Office: 
441 G Street NW: 
Washington, DC 20548: 

Dear Ms. Crosse: 

Attached are comments on the U.S. Government Accountability Office's 
(GAO) draft report entitled, "Pediatric Medical Devices: Provisions 
Support Development, but Better Data Needed for Required Reporting” 
(GAO-12-225). 

The Department appreciates the opportunity to review this report prior 
to publication. 

Sincerely, 

Signed by: 

Jim R. Esquea: 
Assistant Secretary for Legislation: 

Attachment: 

[End of letter] 

General Comments Of The Department Of Health And Human Services (HHS) 
On The Government Accountability Office's (GAO) Draft Report Entitled, 
"Pediatric Medical Devices: Provisions Support Development, But Better 
Data Needed For Required Reporting" (GAO-12-225): 

The Department appreciates the opportunity to review and comment on 
this draft report. 

GAO Recommendation: 

We recommend that the Commissioner of the Food and Drug Administration 
(FDA) collect reliable information to report data related to pediatric 
medical devices. Specifically, FDA should take steps to consistently 
collect information using its existing pediatric electronic flag or 
otherwise develop internal controls to readily and reliably collect 
and report information on devices for pediatric use. 

FDA Response: 

We recognize that medical devices—including devices designed for the 
pediatric population—are critical to the improvement and advancement 
of healthcare, often serving as life-saving delivery systems. We agree 
with the GAO recommendation that FDA collect reliable information to 
report data related to pediatric medical devices. FDA is in the 
process of modifying and updating its current tracking system, related 
data quality controls, and training program requirements for pediatric 
medical device premarket submissions. When this process is complete, 
FDA's pediatric information collection efforts will satisfy our 
pediatric device operations and oversight needs, including the 
development of the annual Pediatric Report to Congress. 

[End of section] 

Appendix V: GAO Contact and Staff Acknowledgments: 

GAO Contact: 

Marcia Crosse, (202) 512-7114 or crossem@gao.gov: 

Staff Acknowledgments: 

In addition to the contact named above, Kim Yamane, Assistant 
Director; Rebecca Abela; Carolyn Fitzgerald; Cathleen Hamann; Shirin 
Hormozi; Lisa Motley; and Dan Ries made key contributions to this 
report. 

[End of section] 

Related GAO Products: 

Medical Devices: FDA Should Enhance Its Oversight of Recalls. 
[hyperlink, http://www.gao.gov/products/GAO-11-468]. Washington, D.C.: 
June 14, 2011. 

Medical Devices: FDA's Premarket Review and Postmarket Safety Efforts. 
[hyperlink, http://www.gao.gov/products/GAO-11-556T]. Washington, 
D.C.: April 13, 2011. 

High-Risk Series: An Update. [hyperlink, 
http://www.gao.gov/products/GAO-11-278]. Washington, D.C.: February 
2011. 

Food and Drug Administration: Overseas Offices Have Taken Steps to 
Help Ensure Import Safety, but More Long-Term Planning Is Needed. 
[hyperlink, http://www.gao.gov/products/GAO-10-960]. Washington, D.C.: 
September 30, 2010. 

Food and Drug Administration: Opportunities Exist to Better Address 
Management Challenges. [hyperlink, 
http://www.gao.gov/products/GAO-10-279]. Washington, D.C.: February 
19, 2010. 

Food and Drug Administration: FDA Faces Challenges Meeting Its Growing 
Medical Product Responsibilities and Should Develop Complete Estimates 
of Its Resource Needs. [hyperlink, 
http://www.gao.gov/products/GAO-09-581]. Washington, D.C.: June 19, 
2009. 

Medical Devices: Shortcomings in FDA's Premarket Review, Postmarket 
Surveillance, and Inspections of Device Manufacturing Establishments. 
[hyperlink, http://www.gao.gov/products/GAO-09-370T]. Washington, 
D.C.: June 18, 2009. 

High-Risk Series: An Update. [hyperlink, 
http://www.gao.gov/products/GAO-09-271]. Washington, D.C.: January 
2009. 

Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device 
Types Are Approved through the Most Stringent Premarket Review 
Process. [hyperlink, http://www.gao.gov/products/GAO-09-190]. 
Washington, D.C.: January 15, 2009. 

Health-Care-Associated Infections in Hospitals: Number Associated with 
Medical Devices Unknown, but Experts Report Provider Practices as a 
Significant Factor. [hyperlink, 
http://www.gao.gov/products/GAO-08-1091R]. Washington, D.C.: September 
26, 2008. 

Medical Devices: FDA Faces Challenges in Conducting Inspections of 
Foreign Manufacturing Establishments. [hyperlink, 
http://www.gao.gov/products/GAO-08-780T]. Washington, D.C.: May 14, 
2008. 

Reprocessed Single-Use Medical Devices: FDA Oversight Has Increased, 
and Available Information Does Not Indicate That Use Presents an 
Elevated Health Risk. [hyperlink, http://www.gao.gov/products/GAO-08-
147]. Washington, D.C.: January 31, 2008. 

Medical Devices: Challenges for FDA in Conducting Manufacturer 
Inspections. [hyperlink, http://www.gao.gov/products/GAO-08-428T]. 
Washington, D.C.: January 29, 2008. 

Medical Devices: FDA's Approval of Four Temporomandibular Joint 
Implants. [hyperlink, http://www.gao.gov/products/GAO-07-996]. 
Washington, D.C.: September 17, 2007. 

Food and Drug Administration: Methodologies for Identifying and 
Allocating Costs of Reviewing Medical Device Applications Are 
Consistent with Federal Cost Accounting Standards, and Staffing Levels 
for Reviews Have Generally Increased in Recent Years. [hyperlink, 
http://www.gao.gov/products/GAO-07-882R]. Washington, D.C.: June 25, 
2007. 

Medical Devices: Status of FDA's Program for Inspections by Accredited 
Organizations. [hyperlink, http://www.gao.gov/products/GAO-07-157]. 
Washington, D.C.: January 5, 2007.
[End of section] 

Footnotes: 

[1] Generally, medical devices include items used for the diagnosis, 
cure, mitigation, treatment, or prevention of a disease. See 21 U.S.C. 
§ 321(h). Throughout this report, the term device refers to a medical 
device that is not being regulated as a drug or a biological product. 

[2] Devices are generally subject to one of two types of FDA premarket 
review--the 510(k) premarket notification process and the more 
stringent premarket approval process--unless exempt by FDA 
regulations. Under the 510(k) premarket review process, a medical 
device may be marketed in the United States after being cleared by FDA 
if FDA determines that the device is substantially equivalent to a 
legally marketed device that is not required to go through the 
premarket approval (PMA) process. 

[3] Pub. L. No. 110-85, § 303(a)(3), 121 Stat. 823, 860-62 (2007) 
(codified in part at 21 U.S.C. § 360j(m)(6)). 

[4] Pub. L. No. 110-85, § 305, 121 Stat. 823, 863-64 (2007). 

[5] Pub. L. No. 110-85, § 302, 121 Stat. 823, 859-60 (2007) (codified 
at 21 U.S.C. § 360e-1). 

[6] Pub. L. No. 110-85, § 303(b), 121 Stat. 823, 862 (2007). 

[7] In addition, FDAAA required that we describe the key 
characteristics of pediatric HDE devices granted exemption from the 
HDE profit prohibition. We discuss these devices in app. I. 

[8] Reports we reviewed included, for example, Institute of Medicine, 
Rare Diseases and Orphan Products: Accelerating Research and 
Development (Washington, D.C.: The National Academies Press, October 
2010), and American Academy of Pediatrics, Summary of Pediatric 
Stakeholder Meetings (Washington, D.C.: November 2004). 

[9] We reviewed quarterly and annual consortia reports available 
through September 2011. These reports included information on the 
device projects assisted by the consortia that could be developed to 
enter the U.S. market through one of FDA's premarket review processes--
PMA, HDE, or the 510(k) premarket review process. 

[10] FDAAA required that we focus our report on medical devices that 
were approved for the U.S. market through the PMA and HDE processes. 
For additional information on devices cleared through the 510(k) 
premarket review process, see GAO, Medical Devices: FDA Should Take 
Steps to Ensure That High-Risk Device Types Are Approved through the 
Most Stringent Premarket Review Process, [hyperlink, 
http://www.gao.gov/products/GAO-09-190] (Washington, D.C.: Jan. 15, 
2009), and the Related GAO Products section at the end of this report. 

[11] These standards provide an overall framework for establishing and 
maintaining internal controls and for identifying and addressing major 
performance and management challenges and areas at greatest risk of 
fraud, waste, abuse, and mismanagement. See GAO, Standards for 
Internal Control in the Federal Government, [hyperlink, 
http://www.gao.gov/products/GAO/AIMD-00-21.3.1] (Washington, D.C.: 
November 1999), and its supplemental guide, Internal Control 
Management and Evaluation Tool, [hyperlink, 
http://www.gao.gov/products/GAO-01-1008G] (Washington, D.C.: August 
2001). 

[12] We also examined FDA's ability to readily identify additional 
information that FDAAA required FDA to annually report to 
congressional committees, including the number of approved devices for 
which there is a pediatric subpopulation that suffers from the disease 
or condition that the device is intended to treat, diagnose, or cure 
and the number of approved devices that were exempted from the fee 
charged by FDA to review a PMA application because the device was 
intended solely for a pediatric population. 

[13] To the extent possible, we compared FDA data on pediatric devices 
that the agency generated from its Center Tracking System with data 
generated from our PMA and HDE document review to corroborate or 
provide perspective on the data FDA provided. 

[14] A device's approved indication for use statement describes the 
disease and population the medical device is intended to treat. 
Although the upper age limit used to define the pediatric population 
varies among experts, FDA issued guidance in 2004 stating that 
including adolescents up to the age of 21 years in the pediatric 
population is consistent with the definition found in several sources. 
We counted patients age 21 years or younger as pediatric patients in 
our review of the indication for use statements because the Food, 
Drug, and Cosmetic Act (as amended by FDAAA) defines pediatric 
patients, for purposes of provisions related to HDE devices, as those 
who are age 21 years or younger at the time of diagnosis or treatment. 
See 21 U.S.C. § 360j(m)(6)(E)(i). FDA has also concluded that for 
purposes of a provision requiring sponsors to submit information with 
PMA and HDE device applications, the term "pediatric patients" refers 
to patients who are age 21 years or younger at the time of diagnosis 
or treatment. See 75 Fed. Reg. 16,365, 16,366-67 (Apr. 1, 2010). 

[15] A PMA panel-track supplement is required if substantial clinical 
data are necessary to provide reasonable assurance of the safety and 
effectiveness to change the indication of an approved PMA device--for 
example, to add a pediatric population to a PMA device already 
approved for use in adults. 

[16] We reviewed information for PMA devices (including PMA panel-
track supplements) approved since fiscal year 2006 in order to include 
information for 2 years prior to enactment of FDAAA on September 27, 
2007. This included a total of 81 devices approved before FDAAA was 
enacted and 110 devices approved after FDAAA was enacted. Because a 
much smaller number of HDE devices are approved each year, we included 
information for HDE devices approved since fiscal year 2001 listed on 
FDA's website as of October 2011, for a total of 23 HDE devices 
approved before FDAAA was enacted and 8 devices approved after FDAAA 
was enacted. 

[17] FDA categorizes medical devices into three classes based on the 
level of risk the device poses and the controls necessary to provide 
reasonable assurance of its safety and effectiveness. Class I devices 
include those with the lowest risk (such as forceps) and class III 
devices include those with the greatest risk (such as pacemakers). See 
21 U.S.C. § 360c; 21 C.F.R. pts. 862-892 (2011). 

[18] Although FDA's Center for Biologics Evaluation and Research also 
reviews medical device applications, including those for devices used 
in the testing and manufacturing of biological products, FDA officials 
noted that the majority of pediatric medical device applications are 
reviewed by CDRH and no pediatric HDE applications had, at the time of 
our review, been reviewed by the Center for Biologics Evaluation and 
Research. 

[19] Some class III device types on the market before the enactment of 
the Medical Device Amendments of 1976 do not currently require PMA 
approval for marketing. FDA has been taking steps to address these 
device types; once this process is completed, all class III devices 
will be required to go through the PMA review process. For additional 
information, see GAO, Medical Devices: FDA's Premarket Review and 
Postmarket Safety Efforts, [hyperlink, 
http://www.gao.gov/products/GAO-11-556T] (Washington, D.C.: Apr. 13, 
2011). 

[20] For fiscal year 2012, the standard fee for a PMA application is 
$220,050. 

[21] Although FDA reviews and approves other types of PMA supplements, 
a panel-track supplement is required if the manufacturer wants to 
change the indication for use of an approved PMA device to add a 
pediatric population, according to FDA officials. 

[22] For fiscal year 2012, the standard fee for a PMA panel-track 
supplement is $165,038. 

[23] Pub. L. No. 101-629, § 14(a), 104 Stat. 4511, 4524-25 (1990) 
(codified as amended at 21 U.S.C. § 360j(m)). 

[24] The HDE device label must include the following statement: 
"Humanitarian Device. Authorized by Federal law for use in the 
[treatment or diagnosis] of [specify disease or condition]. The 
effectiveness of this device for this use has not been demonstrated." 

[25] See 21 U.S.C. § 379j(a)(2)(B)(i). 

[26] The IRB is a committee that has been formally designated to 
approve, monitor, and review biomedical and behavioral research 
involving humans with the aim to protect the rights and welfare of the 
research subjects. Although IRBs generally oversee clinical 
investigations, for HDE devices IRBs are required to review and 
approve the use of the device. The IRB may review each use of an HDE 
device or use discretion to determine general rules for use of the HDE 
device after initial review. If an HDE device is used in an emergency 
situation, subsequent written notice to the IRB must be provided. See 
21 U.S.C. § 379j(m)(4). 

[27] 21 U.S.C. § 360j(m)(6)(E)(i) and (ii) define pediatric patients 
as age 21 years or younger at the time of diagnosis or treatment and 
specifies categories of pediatric subpopulations. 21 U.S.C. § 360e-
1(a), which requires sponsors of PMA and HDE applications and 
supplements to submit information on pediatric subpopulations and 
pediatric patients, uses the same definition of "pediatric 
subpopulations" but does not include a definition of "pediatric 
patients." Because no other definition of "pediatric patients" is 
included in statute and because the definitions of "pediatric 
patients" and "pediatric subpopulations" in section 360j are 
consistent, FDA has concluded that the term "pediatric patients" for 
purposes of required information for PMA and HDE applications refers 
to patients who are 21 years of age or younger at the time of 
diagnosis or treatment. See 75 Fed. Reg. 16,365, 16,366-67 (Apr. 1, 
2010). 

[28] See FDA, Guidance for Industry and FDA Staff: Premarket 
Assessment of Pediatric Medical Devices. (Rockville, Md.: 2004). FDA, 
in its guidance, recognized that factors other than a patient's 
numerical age may often be appropriate to consider in defining a 
pediatric population. 

[29] FDA developed this subpopulation for determining if certain 
devices indicated for patients in the age range should be considered 
differently than adults. FDA officials stated that they will issue 
guidance on pediatric subpopulations that will include the 
transitional adolescent category. 

[30] To qualify for the exemption from the HDE profit prohibition, the 
sponsor must submit an HDE application on or before October 1, 2012. 

[31] Pub. L. No. 110-85, § 303(a)(3), 121 Stat. 823, 861-62 (2007) 
(codified at 21 U.S.C. § 360j(m)(8)). 

[32] Pub. L. No. 110-85, § 302, 121 Stat. 823, 859-60 (2007) (codified 
at 21 U.S.C. § 360e-1). The third requirement applies only to PMA 
devices since HDE devices are already exempt from user fees. In 
addition, the report is required to include the FDA review times for 
these devices. 

[33] FDAAA also authorized the use of contracts. Pub. L. No. 110-85, § 
305, 121 Stat. 823, 863-64 (2007). 

[34] Directly supported device projects received a portion of the 
demonstration grant funding. 

[35] Grantees are required to report on the directly supported 
projects that were proposed in the grant applications as well as on 
other device projects for which the consortia provided assistance, 
such as developing a prototype or assessing the scientific merit of a 
device project. 

[36] FDA officials stated that the phases of development used in 
consortia reporting come from CDRH's Total Product Lifecycle approach 
to reviewing medical devices. 

[37] Generally, it is possible to design a medical device in a number 
of different ways that could be marketed by different manufacturers. 
As noted by the medical device industry, the typical "life cycle" or 
the amount of time before competitors begin selling an alternative 
product of a device is 18 months. The Best Pharmaceuticals for 
Children Act authorizes FDA to provide an incentive of an additional 6 
months of market exclusivity to drug manufacturers that conduct 
pediatric studies requested by FDA. See 21 U.S.C. § 355a; 42 U.S.C. § 
284m. 

[38] See Department of Health and Human Services, Agency for 
Healthcare Research and Quality, Food and Drug Administration, and 
National Institutes of Health, Report to Congress on the Plan for 
Expanding Pediatric Medical Device Research and Development 
(Washington, D.C.: 2009). 

[39] FDA issued a report for PMA and HDE devices approved in fiscal 
year 2008. 

[40] FDA officials stated that the agency was working on draft 
guidance for tracking pediatric device information; however, at the 
time of our review, FDA had not issued this guidance. In addition, FDA 
is working to finalize a proposed rule regarding the requirement for 
submission of information on pediatric subpopulations that suffer from 
a disease or condition that a device is intended to treat, diagnose, 
or cure. See 75 Fed. Reg. 16,365 (Apr. 1, 2010). 

[41] Pub. L. No. 110-85, § 302, 121 Stat. 823, 860 (codified at 21 
U.S.C. § 360e-1(b)). 

[42] See 76 Fed. Reg. 67,463 (Nov. 1, 2011). 

[43] FDA approved the Vertical Expandable Prosthetic Titanium Rib for 
market through the HDE process in August 2004. 

[44] Although the pediatric device consortia grant program was 
authorized as a demonstration grant program under FDAAA, 
appropriations were not designated for the program in committee 
reports until fiscal year 2009. 

[45] Federal grant funding included grants through the National 
Institutes of Health. 

[46] In 2011, FDA awarded grants for fiscal years 2011 and 2012 
totaling $5 million to three pediatric device consortia; the grant 
period for these awards had not yet started at the time of our review. 
Two of the grantees--Michigan Pediatric Device Consortium-PMDI and 
University of California at San Francisco Pediatric Device Consortium--
had previously received pediatric device consortia grants; the third 
grantee--Atlanta Pediatric Device Consortium--had not previously 
received a pediatric device consortium grant. FDA also awarded an 
additional $500,000 to MISTRAL Device Consortium. 

[47] In some cases inactive device projects stopped receiving 
consortia support because they could not obtain outside funding or 
there were complex development challenges. 

[48] Active projects were those that were reported in the most recent 
consortia reports available at the time of our review, supplemented by 
additional information provided by FDA. Projects that we considered 
inactive were those that the consortia had mentored or supported at 
some point with grant funds but that were no longer receiving 
consortia assistance at the time of our review. 

[49] See [hyperlink, http://www.gao.gov/products/GAO/AIMD-00-21.3.1] 
and [hyperlink, http://www.gao.gov/products/GAO-01-1008G]. 

[50] CTS is a web-based system used by CDRH for tracking premarket 
documents through the review process. According to FDA officials, the 
agency started using CTS in 2004 and implemented the pediatric flags 
in 2008. 

[51] See FDA, Report to Congress: Premarket Approval of Pediatric Uses 
of Devices--FY2008 (March 2009), accessed October 31, 2011, 
[hyperlink, www.fda.gov/downloads/MedicalDevices/.../UCM268801.pdf]. 

[52] The report, H.R. Rep No. 110-225, was associated with a version 
of FDAAA that did not become law. 

[53] In April 2010, FDA issued a proposed rule and a direct final rule 
implementing the FDAAA requirement for HDE and PMA device applications 
and supplements to include this information, if readily available. 
However, FDA withdrew the direct final rule after receiving 
significant adverse comments. According to FDA officials, the agency 
is in the process of reviewing the comments before issuing a final 
rule. See 75 Fed. Reg. 16,347 (Apr. 1, 2010); 75 Fed. Reg. 16,365 
(Apr. 1, 2010); 75 Fed. Reg. 41,986 (July 20, 2010). 

[54] See appendices II and III for additional information on PMA and 
HDE devices approved before and after FDAAA was enacted that were 
explicitly indicated for use in pediatric patients. 

[55] Based on our review of additional labeling information, at least 
1 HDE device and 8 original PMA devices approved since fiscal year 
2008 with indication for use statements that were silent on the age of 
the intended patient population were approved based on clinical 
studies that included one or more subjects age 21 or younger and did 
not include contraindications stating that the device should not be 
used in pediatric patients. At least 12 additional devices with 
indication for use statements that were silent on the age of the 
intended patient population included contraindication statements 
stating that the device should not be used in or was not tested in 
patients under age 18--that is, the device could potentially be used 
in patients age 18 to 21 years and older. 

[56] FDA officials told us that during their premarket review they 
consider some devices indicated for patients age 18 to 21 years--
transitional adolescents--the same as adult devices. However, because 
patients age 21 years or younger are considered pediatric under the 
definition in 21 U.S.C. § 360j(m)(6)(E)(i), devices labeled for 
patients age 19, 20, or 21 are considered pediatric devices for 
certain purposes. 

[57] We identified each device's medical specialty based on data from 
FDA's product code classification database--which contains device 
names and product codes assigned based upon the medical device product 
classification designated under 21 C.F.R. Parts 862-892. The database 
did not include the medical specialty for some device product codes; 
for these we used information on the medical specialty provided by FDA. 

[58] These three HDE devices explicitly indicated for use in pediatric 
patients--those age 21 or younger--or both pediatric and adult 
patients accounted for 38 percent of HDE devices approved after FDAAA 
was enacted. In the 7 fiscal years before FDAAA was enacted, six HDE 
devices (26 percent of approved HDE devices) were explicitly indicated 
for use in pediatric patients or both pediatric and adult patients. 

[59] The length of time between HUD designation and HDE device 
approval for HDE devices approved in the past decade ranged from 4 
months to 7.5 years, with an average across the decade of about 2 
years. However, to qualify for exemption from the HDE profit 
prohibition, the sponsor must submit an HDE application on or before 
October 1, 2012. 

[60] An additional HDE device was approved for use in patients age 18 
years and older (and therefore includes pediatric patients age 18 
through 21 years), but the manufacturer did not request and receive 
exemption from the HDE profit prohibition for a pediatric device. FDA 
officials reported that the agency internally tracks HDE devices that 
have been approved for use in pediatric patients and granted exemption 
from the profit prohibition. 

[61] The Melody TPV includes two parts--the Melody Transcatheter 
Pulmonary Valve (the valve) and Ensemble Transcatheter Valve Delivery 
System (the delivery system). The manufacturer refers to both parts 
together as Melody TPV. 

[62] FDAAA requires that FDA's Pediatric Advisory Committee annually 
review all HDE devices granted exemption from the profit prohibition 
to ensure that the exemption remains appropriate for the pediatric 
populations for which it is granted. See Pub. L. No. 110-85, § 
303(a)(3), 121 Stat. 823, 861-62 (2007) (codified at 21 U.S.C. § 
360j(m)(8)). 

[63] The Melody TPV includes two parts--the Melody Transcatheter 
Pulmonary Valve (the valve) and Ensemble Transcatheter Valve Delivery 
System (the delivery system). The manufacturer refers to both parts 
together as Melody TPV. 

[64] We also interviewed officials from the Centers for Medicare & 
Medicaid Services and America's Health Insurance Plans regarding 
public and private health insurance coverage of HDE devices, 
respectively. 

[65] We fielded our survey from August 19, 2011, through October 3, 
2011. At this time, the Melody TPV device was the only HDE device 
exempt from the HDE profit prohibition that was on the U.S. market. 
For questions regarding cost and insurance coverage for the device, 
someone other than the physician--such as a purchasing department 
representative--may have provided information on behalf of the 
physician. 

[66] Thirty-three percent of respondents stated that they were not 
sure if the price they reported included all rebates or discounts 
their institution received for their most recent Melody TPV order. We 
did not further examine whether the reported prices included all 
rebates or discounts, and therefore additional rebates or discounts 
for these devices may have existed. 

[67] We did not determine if issues in obtaining coverage were 
specifically related to off-label use. 

[68] According to officials from America's Health Insurance Plans, 
private health insurers often determine coverage for HDE devices on a 
case-by-case basis. 

[69] According to officials at the Centers for Medicare & Medicaid 
Services, the agency has not issued any national guidance to state 
Medicaid programs regarding coverage of HDE devices. In addition, 
officials reported that in most cases Medicare coverage for HDE 
devices is determined on a case-by-case basis. 

[70] CPT is a uniform coding system maintained by the American Medical 
Association used to identify and bill for medical procedures and 
services under public and private health insurance programs. Officials 
from the device manufacturer said they implemented new CPT codes for 
outpatient and inpatient use of the Melody TPV device in July and 
October 2011. 

[71] The three protocols approved by the hospital's IRB were (1) in 
accordance with the approved indication for use, (2) transcatheter use 
outside the parameters of the approved indication for use, and (3) for 
surgical use instead of a conduit. The physician reported that the 
hospital used the second two off-label protocols in a small percentage 
of cases. 

[72] Five of the PMA devices approved in the 2 years before FDAAA was 
enacted were indicated solely for use in patients age 18 or older. An 
additional six PMA devices approved before FDAAA was enacted were 
indicated solely for use in patients age 21 or older. Six of the PMA 
devices and one of the HDE devices approved in the 4 years after FDAAA 
was enacted were indicated solely for use in patients age 18 or older. 
An additional two PMA devices approved after FDAAA was enacted were 
indicated solely for use in patients age 21 or older. We consider 
these to be explicitly indicated for use in pediatric patients because 
the minimum age includes patients age 21 years or younger. 

[End of section] 

GAO’s Mission: 

The Government Accountability Office, the audit, evaluation, and 
investigative arm of Congress, exists to support Congress in meeting 
its constitutional responsibilities and to help improve the 
performance and accountability of the federal government for the 
American people. GAO examines the use of public funds; evaluates 
federal programs and policies; and provides analyses, recommendations, 
and other assistance to help Congress make informed oversight, policy, 
and funding decisions. GAO’s commitment to good government is 
reflected in its core values of accountability, integrity, and 
reliability. 

Obtaining Copies of GAO Reports and Testimony: 

The fastest and easiest way to obtain copies of GAO documents at no 
cost is through GAO’s website [hyperlink, http://www.gao.gov]. Each 
weekday afternoon, GAO posts on its website newly released reports, 
testimony, and correspondence. To have GAO e mail you a list of newly 
posted products, go to [hyperlink, http://www.gao.gov] and select “E-
mail Updates.” 

Order by Phone: 

The price of each GAO publication reflects GAO’s actual cost of 
production and distribution and depends on the number of pages in the 
publication and whether the publication is printed in color or black 
and white. Pricing and ordering information is posted on GAO’s 
website, [hyperlink, http://www.gao.gov/ordering.htm]. 

Place orders by calling (202) 512-6000, toll free (866) 801-7077, or 
TDD (202) 512-2537. 

Orders may be paid for using American Express, Discover Card, 
MasterCard, Visa, check, or money order. Call for additional 
information. 

Connect with GAO: 

Connect with GAO on facebook, flickr, twitter, and YouTube.
Subscribe to our RSS Feeds or E mail Updates. Listen to our Podcasts.
Visit GAO on the web at [hyperlink, http://www.gao.gov]. 

To Report Fraud, Waste, and Abuse in Federal Programs: 

Contact: 
Website: [hyperlink, http://www.gao.gov/fraudnet/fraudnet.htm]; 
E-mail: fraudnet@gao.gov; 
Automated answering system: (800) 424-5454 or (202) 512-7470. 

Congressional Relations: 

Ralph Dawn, Managing Director, dawnr@gao.gov, (202) 512-4400
U.S. Government Accountability Office, 441 G Street NW, Room 7125
Washington, DC 20548. 

Public Affairs: 
Chuck Young, Managing Director, youngc1@gao.gov, (202) 512-4800
U.S. Government Accountability Office, 441 G Street NW, Room 7149 
Washington, DC 20548.