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entitled 'National Preparedness: Efforts to Address the Medical Needs 
of Children in a Chemical, Biological, Radiological, or Nuclear 
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United States Government Accountability Office: 
GAO: 

Report to the Committee on Energy and Commerce, House of 
Representatives: 

April 2013: 

National Preparedness: 

Efforts to Address the Medical Needs of Children in a Chemical, 
Biological, Radiological, or Nuclear Incident: 

GAO-13-438: 

GAO Highlights: 

Highlights of GAO-13-438, a report to the Committee on Energy and 
Commerce, House of Representatives. 

Why GAO Did This Study: 

The nation remains vulnerable to terrorist and other threats posed by 
CBRN agents. Medical countermeasures—-drugs, vaccines, and medical 
devices-—can prevent or treat the effects of exposure to CBRN agents, 
and countermeasures are available in the SNS for some of these agents. 
Children, who make up 25 percent of the population in the United 
States, are especially vulnerable because many of the countermeasures 
in the SNS have only been approved for use in adults. HHS leads the 
federal efforts to develop and acquire countermeasures. 

GAO was asked about efforts to address the needs of children in the 
event of a CBRN incident. This report examines (1) the percentage of 
CBRN medical countermeasures in the SNS that are approved for 
pediatric use; (2) the challenges HHS faces in developing and 
acquiring CBRN medical countermeasures for the pediatric population, 
and the steps it is taking to address them; and (3) the ways that HHS 
has addressed the dispensing of pediatric medical countermeasures in 
its emergency response plans and guidance, and ways that state and 
local governments have addressed this issue. To address these 
objectives, GAO reviewed relevant laws, agency documents, and reports, 
and interviewed HHS officials, industry representatives, and subject-
matter experts. GAO also reviewed a stratified sample of emergency 
response plans from seven state and seven local governments, based on 
geographic location and population size, to assess how these 
governments address pediatric dispensing. 

What GAO Found: 

According to the Department of Health and Human Services (HHS), about 
60 percent of the chemical, biological, radiological, and nuclear 
(CBRN) medical countermeasures in the Strategic National Stockpile 
(SNS) have been approved for children, but in many instances approval 
is limited to specific age groups. In addition, about 40 percent of 
the CBRN countermeasures have not been approved for any pediatric use. 
Furthermore, some of the countermeasures have not been approved to 
treat individuals for the specific indications for which they have 
been stockpiled. For example, ciprofloxacin is stockpiled in the SNS 
for the treatment of anthrax, plague, and tularemia, but is not 
approved for these indications. Countermeasures may be used to treat 
unapproved age groups or indications under an emergency use 
authorization (EUA) or an Investigational New Drug (IND) application 
submitted to the Food and Drug Administration (FDA). 

HHS faces a variety of economic, regulatory, scientific, and ethical 
challenges in developing and acquiring pediatric CBRN medical 
countermeasures. High costs and the high risk of failure associated 
with testing and research of pharmaceutical products on children, 
difficulties in meeting regulatory requirements for approving CBRN 
countermeasures, and scientific and ethical obstacles to safely 
evaluating countermeasures for children all pose challenges to 
developing pediatric countermeasures. Despite these challenges, HHS 
has taken steps to focus agency efforts on the pediatric population, 
adapt pediatric formulations from existing medical countermeasures, 
and prepare and review materials for EUAs and INDs in advance of 
public health emergencies. 

HHS addresses dispensing of pediatric medical countermeasures in more 
than half of its 12 response plans and in its guidance, and seven 
state and seven local government plans that GAO reviewed included 
details about pediatric dispensing. Seven of the 12 HHS plans include 
information about pediatric medical countermeasures; however, HHS 
officials stated that these plans are intended to provide guidance for 
emergency response at the federal level, and not at the state or local 
levels, which is where dispensing would occur. CDC and FDA also 
provide guidance on pediatric dispensing that state and local 
governments can use in their planning. For example, CDC developed 
guidance about receiving, distributing, and dispensing contents from 
the SNS to help state and local emergency management and public health 
personnel plan for the use of countermeasures from the SNS. Response 
plans for all 14 of the state and local governments that GAO reviewed 
also included details about dispensing to the pediatric population 
during an emergency. For example, these seven states and seven local 
governments all adopted some version of a “family member pick-up” 
policy—-sometimes referred to as a “head of household” policy—-which 
would allow adults to pick up medicines for other family members, 
including children, during an event. 

In commenting on a draft of this report, HHS concurred with our 
findings. HHS emphasized that the needs of the pediatric population 
have been a priority for HHS and that the department is continuously 
progressing in this area. 

View [hyperlink, http://www.gao.gov/products/GAO-13-438]. For more 
information, contact Marcia Crosse at (202) 512-7114 or 
crossem@gao.gov. 

[End of section] 

Contents: 

Letter: 

Background: 

More than Half of CBRN Medical Countermeasures Have Been Approved for 
at Least Some Children: 

HHS Faces Challenges in Developing and Acquiring Pediatric Medical 
Countermeasures but Is Taking Steps to Address the Needs of the 
Pediatric Population: 

HHS and State and Local Governments Address Dispensing of Pediatric 
Medical Countermeasures in Their Response Plans: 

Agency Comments: 

Appendix I: Pediatric CBRN Medical Countermeasures in the Strategic 
National Stockpile: 

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

Appendix III: GAO Contact and Staff Acknowledgments: 

Related GAO Products: 

Table: 

Table 1: Overview of Certain Types of Chemical, Biological, 
Radiological, and Nuclear (CBRN) Medical Countermeasures Available in 
the Strategic National Stockpile (SNS) and Their Regulatory Status for 
the Pediatric Population: 

Figure: 

Figure 1: Processes for Medical Countermeasure Development and 
Acquisition: 

Abbreviations: 

ASPR: Office of the Assistant Secretary for Preparedness and Response: 

AVA: anthrax vaccine adsorbed: 

BARDA: Biomedical Advanced Research and Development Authority: 

CBRN: chemical, biological, radiological, and nuclear: 

CDC: Centers for Disease Control and Prevention: 

CHILD: Children's HHS Interagency Leadership on Disasters: 

DHS: Department of Homeland Security: 

EUA: Emergency Use Authorization: 

FDA: Food and Drug Administration: 

HHS: Department of Health and Human Services: 

IND: Investigational New Drug: 

NIH: National Institutes of Health: 

PHEMCE: Public Health Emergency Medical Countermeasures Enterprise: 

POD: point of dispensing: 

SNS: Strategic National Stockpile: 

[End of section] 

United States Government Accountability Office: 
Washington, DC 20548: 

April 30, 2013: 

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

The 2001 anthrax attacks and the 2011 earthquake and tsunami in Japan 
raised concerns that the United States is vulnerable to intentional 
and unintentional threats from chemical, biological, radiological, and 
nuclear (CBRN) agents.[Footnote 1] Rapid diagnosis, treatment, and 
prevention could mitigate the public health impact of a release of 
CBRN agents, and there are medical countermeasures available for some 
of these agents.[Footnote 2] Members of Congress, federal commissions, 
and other experts have noted the need for the United States to develop 
and acquire medical countermeasures to protect the public, and 
children in particular, from public health emergencies involving CBRN 
agents. In 2010, the National Commission on Children and Disasters 
reported that children, who make up nearly 25 percent of the U.S. 
population, are more susceptible to CBRN threats and require different 
countermeasures, dosages, and delivery systems than adults.[Footnote 3] 

The Department of Health and Human Services (HHS) is responsible for 
leading federal efforts to prepare for and respond to public health 
and medical CBRN incidents, including identifying needed medical 
countermeasures to diagnose, treat, prevent, or mitigate potential 
health effects from exposure, as well as engaging with industry to 
develop and acquire the countermeasures.[Footnote 4] Because desired 
CBRN medical countermeasures may not be developed to a point where 
they are available for acquisition, HHS's responsibility extends to 
overseeing and supporting research, as well as the development of 
these countermeasures by manufacturers. In 2006, HHS established the 
Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), a 
federal interagency body that includes various HHS agencies and 
offices, as well as other federal departments, to provide 
recommendations to the Secretary of HHS on medical countermeasure 
priorities and development and acquisition activities. HHS's Centers 
for Disease Control and Prevention (CDC) manages the U.S. Strategic 
National Stockpile (SNS)--the national repository of medications, 
medical supplies, and equipment for HHS's use in mitigating the 
potential effects of exposure to CBRN agents and other public health 
emergencies. PHEMCE annually reviews the contents of the SNS to help 
HHS prioritize the maintenance and acquisition of medical 
countermeasures. CDC is responsible for distributing medical 
countermeasures from the SNS to states. In most instances, states are 
in turn responsible for distributing the countermeasures to local 
governments to dispense to affected populations. In addition, HHS's 
Food and Drug Administration (FDA) reviews safety, efficacy, and 
product quality data on medical countermeasures and approves, 
licenses, or clears them for specific indications and for use by 
various populations, including children. 

You raised questions concerning pediatric medical countermeasures that 
are available in HHS's SNS, as well as medical and public health 
preparedness and response activities that are in place at the federal, 
state, and local levels to address the needs of the pediatric 
population in the event of a CBRN incident. This report addresses (1) 
the percentage of CBRN medical countermeasures in the SNS that are 
approved for pediatric use; (2) the challenges HHS faces in developing 
and acquiring CBRN medical countermeasures for the pediatric 
population, and the steps it is taking to address them; and (3) the 
ways that HHS has addressed the dispensing of pediatric medical 
countermeasures in its emergency response plans and guidance, and ways 
that state and local governments have addressed this issue. 

To determine the percentage of CBRN medical countermeasures in the SNS 
that are approved for pediatric use, we reviewed and analyzed HHS 
documentation, such as the PHEMCE annual reviews of the contents in 
the SNS, and determined that the information was sufficiently 
reliable.[Footnote 5] We interviewed officials from the HHS agencies 
and offices that are responsible for CBRN emergency preparedness--
including the Office of the Assistant Secretary for Preparedness and 
Response (ASPR), the Biomedical Advanced Research and Development 
Authority (BARDA), the National Institutes of Health (NIH), CDC, FDA, 
the Children's HHS Interagency Leadership on Disasters (CHILD) Working 
Group, as well as officials from PHEMCE. We also analyzed BARDA and 
CDC reports on their investments and interviewed HHS officials. 
[Footnote 6] 

To identify challenges that HHS faces in developing and acquiring CBRN 
medical countermeasures for the pediatric population and steps it is 
taking to address those challenges, we reviewed relevant laws, our 
earlier reports,[Footnote 7] HHS documents, and other reports and 
information from subject-matter experts on emergency preparedness and 
pediatric health. We also interviewed officials from ASPR, BARDA, CDC, 
FDA, NIH, and PHEMCE, as well as industry officials and other expert 
groups, such as the American Academy of Pediatrics, Trust for 
America's Health, the Center for Infectious Disease Research and 
Policy, and state and local organizations, such as the Association of 
State and Territorial Health Officials and the National Association of 
County and City Health Officials. 

To determine the ways that HHS has addressed the dispensing of 
pediatric medical countermeasures in its emergency response plans and 
guidance, and to assess how state and local governments have addressed 
pediatric dispensing, we reviewed HHS documents, such as the 
department's 12 emergency response plans for specific CBRN threats and 
CDC's emergency operations plan and guidance on dispensing medical 
countermeasures. In addition, we reviewed a sample of emergency 
response plans[Footnote 8] from seven states and seven local 
governments to assess how state and local governments address 
pediatric dispensing.[Footnote 9] Our findings related to the 
documentation and responses from the state and local governments are 
for illustrative purposes only and are not generalizable to other 
state and local governments' emergency response plans. We interviewed 
HHS and CDC officials responsible for addressing information in 
emergency response plans and providing guidance to state and local 
governments on dispensing pediatric medical countermeasures. We also 
interviewed state and local health officials and interest groups, such 
as the Association of State and Territorial Health Officials and the 
National Association of County and City Health Officials, to confirm 
our understanding about how dispensing CBRN medical countermeasures to 
children is handled during emergencies. 

We conducted this performance audit from July 2012 through March 2013 
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: 

Since the terrorist attacks of 2001, HHS has worked to prepare for and 
mitigate potential consequences resulting from the intentional or 
unintentional release of CBRN agents. This work has involved the 
efforts of various agencies, industry, and subject-matter experts to 
develop, acquire, and store medical countermeasures. 

The development of medical countermeasures generally begins with 
research on able-bodied adults, according to the National Commission 
on Children and Disasters.[Footnote 10] However, children have unique 
anatomical, physiological, and psychological differences that can 
predispose them in some circumstances to more serious or different 
adverse effects during public health emergencies compared to adults. 
HHS classifies children as part of the "at-risk population" and 
evaluates CBRN medical countermeasures for this group after developing 
them for the general adult population.[Footnote 11] The at-risk 
population generally has unique characteristics that may interfere 
with an individual's ability to access or receive medical 
countermeasures. For example, individuals who have a limited ability 
to receive or respond to information because of hearing, vision, 
speech, or cognitive limitations would need to have information 
provided in such a way that they could understand it. In addition, 
before, during, and after an emergency, individuals may lose the 
support of caregivers, family, or friends. If separated from their 
caregivers, young children may be unable to identify themselves, and 
may lack the cognitive ability to assess situations and react 
appropriately. The National Commission on Children and Disasters and 
other experts in the field of pediatrics and emergency preparedness 
have reported that a disparity exists in the quality of adult and 
pediatric emergency care, especially in HHS's efforts to acquire FDA-
approved pediatric medical countermeasures.[Footnote 12] 

Roles and Responsibilities of HHS's Agencies and Offices: 

HHS leads the federal public health and medical response to potential 
CBRN incidents, including identifying needed medical countermeasures 
to prevent or mitigate potential health effects from exposure and 
engaging with industry to develop and acquire the countermeasures. The 
following agencies and offices within HHS have responsibilities 
related to medical countermeasures. 

* ASPR is responsible for leading federal government efforts to 
research, develop, evaluate, and acquire medical countermeasures to 
diagnose, prevent, treat, or mitigate the potential health effects 
from exposure to CBRN agents. Within ASPR, BARDA, which was 
established by the Pandemic and All-Hazards Preparedness Act of 2006, 
is responsible for overseeing and funding advanced development and 
acquisition of CBRN medical countermeasures. 

* NIH is responsible for conducting and coordinating basic and applied 
research to develop new or enhanced medical countermeasures for CBRN 
agents. 

* FDA is responsible for regulating the development and approval of 
drugs, biologics, diagnostics, and devices, which includes assessing 
the safety, efficacy, and quality of CBRN medical countermeasures 
before approval and postmarket. 

* CDC is responsible for maintaining the SNS and supporting state and 
local public health departments in their efforts to respond to public 
health emergencies, including providing guidance and recommendations 
for the mass distribution and use of medical countermeasures. 

CBRN Threats and Medical Countermeasures: 

Since 2004, the Department of Homeland Security (DHS), in consultation 
with the Secretary of HHS, has determined that certain CBRN agents 
pose a threat to the nation that could affect national security. 
[Footnote 13] HHS has used these material threat determinations to 
assess the potential public health and medical consequences of the 
CBRN agents, and to establish specific medical requirements for 
developing countermeasures. Assessing the medical consequences and 
establishing medical requirements are both interim steps in 
determining the types and quantities of medical countermeasures 
required to respond to the agents. 

CBRN agents differ from one another in their potential to cause 
widespread illness and death. In the event of a release of a CBRN 
agent, medical countermeasures may be needed for rapid diagnosis, 
treatment, and prevention of infection, illness, and injury, but the 
dose and formulation of the countermeasures needed for an individual 
may vary according to traits such as the individual's age and weight, 
especially when considering the needs of children.[Footnote 14] For 
example, in some cases, it is desirable to have multiple formulations 
of countermeasures available--such as oral liquid suspensions and 
tablets--to facilitate patient compliance. There are an increasing 
number of available medical countermeasures to protect the nation 
against CBRN agents. Supplies of countermeasures that are available 
are generally held in the SNS for use in a public health emergency. 
The SNS is designed to supplement and resupply state and local public 
health departments in the event of a national public health emergency 
such as a CBRN incident.[Footnote 15] 

To acquire medical countermeasures for use during a CBRN incident 
where there is a lack of a significant commercial market, Congress 
authorized the appropriation of approximately $5.6 billion and the use 
of a Special Reserve Fund for the procurement of certain 
countermeasures.[Footnote 16] The Special Reserve Fund has been used 
to acquire CBRN medical countermeasures for the SNS. The Pandemic and 
All-Hazards Preparedness Reauthorization Act of 2013 reauthorizes the 
Special Reserve Fund and authorizes $2.8 billion over 5 years, from 
fiscal year 2014 through fiscal year 2018.[Footnote 17] 

FDA Approval and Emergency Authorization of Medical Countermeasures: 

In general, drugs, devices, diagnostics, and biologics such as 
vaccines, including CBRN countermeasures, cannot be marketed legally 
in the United States without FDA approval. To approve a 
countermeasure, FDA requires manufacturers to sufficiently demonstrate 
the safety, efficacy, and product quality of the countermeasure for 
the intended indication and population specified in the application. 
[Footnote 18] When products are approved, clinicians might prescribe 
them for unapproved indications or to unapproved populations, also 
referred to as "off-label use." Generally, a doctor-patient 
relationship should exist for off-label dispensing of a medical 
countermeasure. In a CBRN incident, dispensing of countermeasures for 
approved or off-label indications may have to occur outside of the 
doctor-patient relationship.[Footnote 19] According to HHS, many 
medicines and vaccines used in normal, standard medical care for the 
pediatric population are prescribed using this off-label practice. 
However, one possible consequence of off-label use of countermeasures 
by children is that some children, depending on weight or growth 
rates, may not receive the most appropriate dose of a medical 
countermeasure. In addition, some children may be at risk for side 
effects that are unique to children, including adverse effects on 
their growth and development.[Footnote 20] To encourage the study of 
more drugs for pediatric use, Congress passed the Best Pharmaceuticals 
for Children Act in 2002, which provides financial incentives to 
product sponsors, and the Pediatric Research Equity Act of 2003. These 
laws encourage or require product sponsors to conduct pediatric 
studies, and also include labeling requirements, including labeling 
updates that result from pediatric drug studies.[Footnote 21] 

Although FDA regulates the use of medical countermeasures by approving 
their use by specific populations and for specific indications, during 
a public health emergency--such as a CBRN incident--FDA can authorize 
the use of those countermeasures by populations or for indications for 
which they have not been approved. This can occur in one of two ways. 
First, FDA can authorize the use of countermeasures that are 
unapproved, or approved but for a different indication, in a declared 
emergency to diagnose, treat, or prevent serious or life-threatening 
diseases or conditions caused by CBRN agents, when there are no 
adequate, approved, and available alternatives, and other criteria are 
met.[Footnote 22] This is referred to as an Emergency Use 
Authorization (EUA). In order for FDA to authorize the emergency use 
of a countermeasure, it must be reasonable to believe that, based on 
the evidence available, the product may be effective in diagnosing, 
treating, or preventing such disease or condition. In addition, the 
known and potential benefits of the product must outweigh the known 
and potential risks.[Footnote 23] 

Second, if a countermeasure's safety and efficacy are not sufficiently 
documented, FDA may allow its use under an Investigational New Drug 
(IND) application, which allows for expanded access to medical 
countermeasures during an emergency[Footnote 24] while the safety and 
efficacy are being investigated. In order for children to receive 
investigational medical countermeasures under an IND, written, 
informed consent is required. Documentation of informed consent is not 
required when children receive countermeasures through an EUA; 
however, to the extent practicable given the circumstances of the 
emergency, patients are to be informed about the known and potential 
benefits and risks of the countermeasure and the right to refuse the 
countermeasure. 

Medical Countermeasure Research, Development, Acquisition, and Support: 

HHS's and PHEMCE's medical countermeasure acquisition strategy is 
based on a multistep process. This process includes assessing the 
threat and public health consequences of CBRN agents, determining the 
type and quantity of needed medical countermeasures, evaluating the 
public health response capability, and developing and acquiring 
countermeasures against CBRN agents for the SNS. Because desired CBRN 
medical countermeasures may not be developed to a point where they are 
available for acquisition, HHS oversees and supports research and 
development of these countermeasures. (See fig. 1.) NIH and BARDA 
oversee and support CBRN medical countermeasure research and 
development, which is conducted in several stages: (1) basic research, 
(2) applied research, (3) early development, and (4) advanced 
development.[Footnote 25] NIH typically provides federal funding to 
academic centers and small biotechnology companies for basic and 
applied research and early development.[Footnote 26] Once an 
organization's research is at the advanced development stage and 
moving toward the development of a product that will meet HHS's 
specific requirements, it may partner with an established 
pharmaceutical or manufacturing company to continue the advanced 
development. Within HHS, the product transitions from NIH to BARDA to 
support its advanced development.[Footnote 27] If a countermeasure is 
not FDA-approved or licensed, its acquisition into the SNS is 
typically funded by the Project BioShield Special Reserve Fund. 
[Footnote 28] If a countermeasure is FDA-approved or licensed, CDC 
generally purchases the countermeasure for the SNS. 

Figure 1: Processes for Medical Countermeasure Development and 
Acquisition: 

[Refer to PDF for image: process illustration] 

Processes for countermeasure priority setting: 

PHEMCE: 
Assess CBRN threats and medical consequences. 

PHEMCE: 
Establish countermeasure requirements. 

PHEMCE: 
Prioritize development and acquisition. 

Processes for countermeasure development and acquisition: 

PHEMCE: 
Determine if existing products can serve as countermeasures. 

NIH: 
Support basic research. 

NIH: 
Support applied research. 

NIH: 
Support early development. 

BARDA: 
Support advanced development. 

Acquisition & licensure: 
PHEMCE, BARDA, FDA, CDC[A]. 

BARDA: Biomedical Advanced Research and Development Authority; 
CBRN: chemical, biological, radiological, and nuclear; 
CDC: Centers for Disease Control and Prevention; 
FDA: Food and Drug Administration; 
NIH: National Institutes of Health; 
PHEMCE: Public Health Emergency Medical Countermeasures Enterprise. 

Source: GAO analysis of Department of Health and Human Services 
information. 

[A] In addition to approving, licensing, or clearing medical 
countermeasures, FDA works with researchers throughout the development 
stages to review safety and efficacy test results and provide 
technical assistance to help ensure that research meets FDA's 
regulatory requirements. 

[End of figure] 

Planning for Medical Countermeasure Distribution and Dispensing: 

Public health emergency response planning for CBRN incidents requires 
efforts at the federal, state, and local levels. Governments at each 
level have developed emergency response plans that outline their 
respective responsibilities during public health emergencies, which 
include responsibilities for distributing and dispensing medical 
countermeasures to the public. The federal government is responsible 
for planning the federal response to CBRN incidents. HHS has developed 
response plans for specific CBRN agents to help coordinate the federal 
response to such emergencies.[Footnote 29] Federal assistance to state 
and local governments would be provided if resources were unavailable 
or if state and local governments were overwhelmed and requested 
public health or medical assistance from the federal government. HHS 
would then direct CDC to distribute medical countermeasures from the 
SNS to the states. 

Once CDC distributes medical countermeasures from the SNS to a state, 
in most instances the state then distributes the countermeasures to 
local governments, based on established plans. State and local 
governments are responsible for developing plans for receiving, 
distributing, and dispensing medical countermeasures from the SNS. 
These plans are intended to describe all functions that are required 
to accomplish these tasks, in order to get medical countermeasures to 
the affected population as quickly and efficiently as possible. Some 
states plan to receive countermeasures and immediately turn them over 
to a local jurisdiction for staging, distributing, and dispensing 
during an emergency. Other states plan to receive medical 
countermeasures at a state warehouse facility and then deliver them 
directly to points of dispensing (POD) or hospitals. Each state is 
responsible for determining the best method for its circumstances and 
resources. Local governments, in turn, are responsible for receiving 
and dispensing medical countermeasures in a timely and efficient 
manner. 

More than Half of CBRN Medical Countermeasures Have Been Approved for 
at Least Some Children: 

About 60 percent of CBRN medical countermeasures in the SNS have been 
approved for children, but in many instances approval is limited to 
specific age groups. Specifically, PHEMCE officials stated that about 
38 percent of the CBRN medical countermeasures in the SNS have been 
approved for children of all ages for treatment of certain CBRN 
threats. For example, ciprofloxacin and doxycycline as antimicrobials 
indicated for postexposure prophylaxis of inhalational anthrax, 
atropine as a treatment for exposure to nerve gas, and raxibacumab as 
an anthrax antitoxin have all been approved for use in the pediatric 
population for these indications. In addition, 22 percent of the CBRN 
medical countermeasures in the SNS have been approved for use by some, 
but not all, pediatric age groups for treatment of certain CBRN 
threats. For example, Prussian blue--a medical countermeasure that 
removes certain internalized radiological particles from the body--is 
approved for children ages 2 and above for that indication, but has 
not been approved for those less than 2 years of age. PHEMCE officials 
stated that the remaining 40 percent of the CBRN countermeasures have 
not been approved for any pediatric use.[Footnote 30] For example, 
anthrax vaccine adsorbed (AVA) has not been approved for use by any 
children.[Footnote 31] Furthermore, some of the CBRN medical 
countermeasures in the SNS have not been approved to treat individuals 
of any age for the specific indications for which they have been 
stockpiled. For example, ciprofloxacin is stockpiled in the SNS for 
the treatment of anthrax, plague, and tularemia, but is not approved 
for these indications. It is, however, approved for postexposure 
prophylaxis of inhalational anthrax in all age groups. In addition, 
for certain CBRN threats, there are no countermeasures available in 
the SNS because treatments for the conditions do not exist beyond 
supportive care. 

According to HHS officials, almost all medical countermeasures in the 
SNS can be used by children in an emergency if already approved for 
children or if FDA authorizes their use through an EUA or if an IND 
protocol is in effect. Even products that are not approved for a CBRN 
indication may be used in a public health emergency under an EUA--
after an emergency has been declared--or under an IND protocol. HHS 
officials told us that almost all medical countermeasures that are not 
approved for use by the pediatric population can be used in an 
emergency under an EUA. However, some countermeasures, such as AVA 
vaccine, lack sufficient data to support their use by the pediatric 
population under an EUA. This vaccine would need to be administered to 
the pediatric population under an IND protocol. HHS officials 
explained that two different IND protocols for AVA have been developed 
in preparation for a potential anthrax-related public health 
emergency. The first protocol is designed to provide children access 
to the vaccine. It would require parents or guardians to sign consent 
forms to allow their children to receive anthrax vaccine during an 
emergency. The second IND protocol would require parents or guardians 
to sign consent forms to allow their children to participate in a 
research study after receiving the vaccine.[Footnote 32] (See appendix 
I for additional information on the regulatory status of types of CBRN 
medical countermeasures in the SNS for the pediatric population.) 

Although HHS can provide information on the proportion of SNS 
countermeasures that can be used by children, it cannot provide 
information on the funds invested in procuring these countermeasures. 
HHS does not separately track the funds that it has invested in the 
acquisition and development of pediatric medical countermeasures 
because it does not account separately for investments related to the 
different populations. HHS procures CBRN medical countermeasures for 
the SNS based on, among other things, the list of material threats to 
the nation, public health response and medical consequence 
assessments, and available resources. Since 2004, BARDA has invested 
over $4 billion of Project BioShield's Special Reserve Fund, which 
supports advanced development and manufacturing of potential CBRN 
medical countermeasures, in contracts to support medical 
countermeasure development in healthy and at-risk populations, 
including the pediatric population. In addition, between 2009 and 
2012, CDC's budget to maintain or acquire licensed CBRN medical 
countermeasures for the SNS was over $1.5 billion; however, no funds 
were specifically designated exclusively for products to be used only 
by the pediatric population. 

HHS Faces Challenges in Developing and Acquiring Pediatric Medical 
Countermeasures but Is Taking Steps to Address the Needs of the 
Pediatric Population: 

HHS faces economic, regulatory, scientific, and ethical challenges in 
its efforts to develop and acquire CBRN medical countermeasures for 
children in an emergency. Despite these challenges, HHS is taking 
steps to focus on the pediatric population and develop pediatric 
formulations of existing medical countermeasures. 

HHS Faces Economic, Regulatory, Scientific, and Ethical Challenges in 
Developing and Acquiring Pediatric Medical Countermeasures: 

HHS faces a variety of interrelated challenges in developing and 
acquiring pediatric CBRN medical countermeasures, including economic, 
regulatory, scientific, and ethical issues that impede the ability of 
HHS to address the needs of children during a CBRN incident.[Footnote 
33] Economic challenges facing HHS include the high failure rate of 
research, development, approval, and licensure of most drugs, 
vaccines, and diagnostic devices. Agency and industry officials told 
us that the risk of failure in developing countermeasures for children 
is even higher than the risk in developing them for the adult 
population. This risk, as well as a lack of a commercial market for 
most CBRN medical countermeasures, has made it difficult for HHS to 
attract companies willing to invest in such development and has 
therefore impeded HHS's ability to acquire the needed countermeasures. 
In addition, various reports have stated that insufficient economic 
incentives are available to encourage the private sector to invest 
millions of dollars to develop potential new pediatric medical 
countermeasures.[Footnote 34] According to CDC officials, while it is 
desirable to have oral liquid formulations available for young 
children who cannot swallow pills, it is not always practical to 
develop and acquire them for the SNS because such countermeasures for 
children can be more costly to procure and maintain, have shorter 
shelf lives, and may exceed manufacturer capability, as opposed to 
alternatives such as pill crushing and mixing that can be explored for 
all but the youngest children. CDC estimated that it would cost 
approximately $3 billion to purchase sufficient quantities of oral 
liquid formulations of countermeasures for the SNS to support the 
needs of all children--an amount well over CDC's approximately $600 
million annual budget for CBRN medical countermeasures over the past 5 
years. Further, because the shelf life of liquids is shorter than that 
of tablets, oral liquid formulations would require more frequent 
investments. Finally, even if such funds were available, the 
manufacturing capacity to meet such acquisition requests may not be 
available. 

The FDA regulatory pathway for developing pediatric CBRN medical 
countermeasures also poses unique challenges making it more difficult 
than for adult countermeasures. The Institute of Medicine, the 
National Biodefense Science Board, HHS, and FDA have stated that it is 
difficult to meet FDA's requirements for data from adequate and well-
controlled clinical investigations to support the approval of 
pediatric medical countermeasures because large, complex clinical 
trials are needed to prove safety and efficacy. As a result of this 
regulatory challenge, FDA has increasingly relied on alternative 
sources of data in order to approve, license, or authorize the use of 
medical countermeasures by children. For example, FDA allows 
researchers to submit evidence of efficacy obtained from historical 
inferences and appropriate studies in animals in accordance with FDA's 
Animal Rule.[Footnote 35] Another challenge to developing 
countermeasures for children is that manufacturers are permitted, 
under certain circumstances, to avoid testing drugs for use by 
children. For example, manufacturers of CBRN countermeasures often 
seek an orphan drug designation for a new countermeasure,[Footnote 36] 
which, if granted, exempts the manufacturer from the requirement to 
conduct pediatric studies under the Pediatric Research Equity Act. 
[Footnote 37] 

There are scientific challenges in obtaining sufficient pediatric 
safety and efficacy information to appropriately inform the use of 
CBRN medical countermeasures for children. For example, FDA officials 
told us that extrapolating data to support efficacy information on a 
medical countermeasure from animal studies presents not only 
regulatory, but also complex scientific challenges to understanding 
how children would react to exposure to CBRN agents. NIH and industry 
officials told us that exposure in juvenile animal models is also not 
well understood. For example, extrapolating data from animal studies 
presents other scientific challenges in understanding the response to 
the medical countermeasures used to prevent or treat the disease or 
condition. Appropriate animal models have not yet been developed for 
many CBRN agents. In addition, the presentation of the disease or 
condition that humans manifest following exposure to a CBRN agent may 
not be the same as that for animals following exposure to the same 
CBRN agent, thus complicating the task of researchers that are relying 
on animal models. Further, there is an initial hurdle of extrapolating 
data from animal models for adults first; only after those data have 
been extrapolated and applied to the adult population can researchers 
extrapolate to children. For example, in order to develop or indicate 
a countermeasure for use in children, scientists generally take an 
existing countermeasure that has already been developed for adults and 
then adjust certain variables such as weight-based dosing and delivery 
mechanisms to test the safety and efficacy of the countermeasure in 
children. This is not straightforward because children may have 
special susceptibilities to the CBRN agent and special age-and weight-
dependent responses to the medical countermeasures. 

Finally, HHS faces ethical challenges in its efforts to develop and 
acquire pediatric medical countermeasures because, absent a CBRN 
event, it is generally not ethical or feasible to obtain dosing, 
safety, and efficacy data for children when there is no potential 
direct benefit to them in the context of a clinical trial. FDA-
regulated clinical trials that include children as subjects must 
consider both the risks to which a child may be exposed in a clinical 
investigation and whether the proposed intervention offers a prospect 
of direct benefit to the child.[Footnote 38] Because children can be 
enrolled as subjects in research only when directly necessary and when 
the research is ethically sound, industry officials we met with stated 
that researching CBRN medical countermeasures' effect on children is 
nearly impossible. Industry officials told us that knowing that CBRN 
medical countermeasure research has a clear, direct benefit to a child 
participating in a study would always be unlikely because diseases 
caused by CBRN agents do not generally occur naturally. 

HHS Is Taking Steps to Focus on the Pediatric Population and Develop 
Pediatric Formulations of Existing Medical Countermeasures: 

Although challenges persist in developing and acquiring pediatric 
medical countermeasures, HHS is beginning to address gaps in the SNS 
for pediatric medical countermeasures by focusing agency efforts on 
children, developing pediatric formulations of medical countermeasures 
in the SNS, and preparing and reviewing EUA and IND application 
materials in advance of emergencies. 

Focusing Department-wide Efforts: 

HHS is taking steps to focus department-wide efforts on children's 
CBRN medical countermeasure needs. In 2010, FDA announced its Medical 
Countermeasures Initiative, which is intended to foster the 
development and availability of medical countermeasures, including 
those intended to be used by children.[Footnote 39] FDA officials said 
the initiative has improved the regulatory pathway for advancing the 
development and acquisition of medical countermeasures, for example, 
by clarifying and streamlining its review process and countermeasure 
requirements, which may entice manufacturers to develop new, novel 
medical countermeasures, including countermeasures with pediatric 
applicability. In addition, in 2010, HHS increased its focus on 
children's needs with the establishment of the CHILD Working Group, 
which was formed to identify and integrate activities related to the 
needs of children across all HHS inter- and intragovernmental disaster 
planning activities and operations. The CHILD Working Group has 
developed recommendations for how HHS can improve the delivery of care 
to children who are affected by disasters. In 2011, in the area of 
medical countermeasures, the CHILD Working Group recommended that HHS 
provide clarity in the regulatory pathway for pediatric medical 
countermeasures; obtain the appropriate data, when available, to 
provide clinical pediatric dosing and use guidance for existing 
medical countermeasures; and gather safety and efficacy data from 
nontraditional sources to support the use of pediatric medical 
countermeasures under EUAs and for eventual FDA approval.[Footnote 40] 
According to HHS officials, many of the recommendations from the CHILD 
Working Group are being adopted by HHS. For example, in 2011, HHS 
developed the Pediatric Obstetric Integrated Program Team, which 
includes pediatric and obstetric subject-matter experts who advise 
PHEMCE on pediatric and obstetric medical countermeasure issues. This 
integrated program team is intended to recommend that pediatric 
medical countermeasure needs are consistently considered throughout 
the entire medical countermeasure development process and that 
pediatric subject-matter experts help consider complex ethical, 
scientific, and legal issues associated with studies that are 
necessary for the licensure and approval of medical countermeasures 
for children. In 2012 the integrated program team conducted a review 
of the contents of the SNS to determine the suitability of the 
contents for use by children, and it subsequently used the review to 
make recommendations to PHEMCE, and to petition for new medical 
countermeasure development. The content of the review is a work 
product of the integrated program team, and HHS has no plans to 
formally issue it. According to HHS, the findings and recommendations 
were considered during the 2012 SNS Annual Review. Further, in 2012, 
BARDA announced that where feasible and appropriate, it would be 
including development of medical countermeasures for the pediatric 
population as part of all base contracts moving forward. 

Adapting Pediatric Formulations of Existing Medical Countermeasures: 

HHS has taken steps to support the development of CBRN medical 
countermeasure formulations for children, and has begun to base the 
pediatric dosing information on other evidence, such as by 
extrapolating from relevant and historical data of the countermeasure. 
Countermeasures are not approved for an indication unless data on the 
safety and efficacy of the countermeasure are available for a 
particular population, such as children. According to FDA officials, 
the agency has determined that in a smallpox emergency, the 
investigational smallpox vaccine under development may be authorized 
for use under an EUA in populations with compromised immune systems, 
including children. Specifically, in 2007 a second-generation smallpox 
vaccine, developed for persons determined to be at high risk for 
infection, was licensed based on data from clinical trials and the 
routine vaccination of infants in the United States through 1972. The 
vaccine was not studied in pediatric populations; however, this second-
generation vaccine was similar to the vaccine that was routinely used 
to vaccinate infants in the United States through 1972 and had been 
demonstrated to be safe and effective in children. Therefore, FDA has 
determined that this vaccine could be used in pediatric populations 
under its license in a smallpox emergency. Similarly, pralidoxime 
chloride, prescribed as an antidote to treat nerve agent poisoning, 
has also been approved for use by children based on the extrapolation 
of efficacy data from both the adult and pediatric populations. In 
addition, FDA has used historical data from other countries to support 
EUAs or product approvals for pediatric indications when analogous 
U.S. data were neither available nor obtainable. For example, 
according to FDA officials, in 1987, a radiological incident in Brazil 
provided the majority of the pediatric data that FDA reviewed to 
assess the safety and efficacy of a radiological countermeasure. The 
data included the use of the countermeasure by both adults and 
children. The review allowed FDA to approve the countermeasure for 
children ages 2 and older in 2003. 

PHEMCE has also encouraged adapting and manufacturing of oral liquid 
formulations of existing medical countermeasures in order to ease 
dispensing of countermeasures in the SNS for children. For example, 
BARDA is contracting with industry partners to manufacture a liquid 
form of a countermeasure that removes certain radioactive particles 
from the body through the intestinal tract.[Footnote 41] Additionally, 
PHEMCE is considering lowering the recommended age at which children 
should be administered oral liquid suspensions of doxycycline in lieu 
of crushed tablets. CDC officials told us that they would like to have 
more oral liquid suspensions considered for the SNS; however, PHEMCE 
officials have reported that crushing tablets would be an acceptable 
alternative and would have benefits for storage, dispensing, and 
dosing. As a result, FDA and CDC have developed instructions for 
crushing certain approved medical countermeasures for use by people 
who cannot swallow tablets or capsules. The crushing instructions 
include instructions for mixing the countermeasures with food or drink 
to make them more palatable to children. Crushing instructions 
generally include weight-based dosing instructions, the number of 
doses required per day, and instructions for how to crush pills and 
mix them.[Footnote 42] 

Preparing and Reviewing EUA and IND Materials in Advance of 
Emergencies: 

Relevant component agencies within HHS collaborate to prepare and 
review materials for EUAs and INDs in advance of public health 
emergencies to ensure that sufficient data are available to support 
authorizations for the use of certain medical countermeasures by 
children. According to CDC officials, the agency assesses, on a 
regular basis, the contents in the SNS and updates and assembles data 
and information for those countermeasures that are not approved for 
use by children so that in the event of a public health emergency, the 
contents can be disseminated to states quickly. Specifically, to 
prepare for such an emergency, CDC collaborates with BARDA, NIH, FDA, 
and manufacturers to develop the EUA and IND submissions in advance of 
an actual incident, so that all medical countermeasures in the SNS can 
be used by children. In addition, they consult with the American 
Academy of Pediatrics on pediatric issues. 

HHS and State and Local Governments Address Dispensing of Pediatric 
Medical Countermeasures in Their Response Plans: 

More than half of HHS's emergency response plans that we examined 
included information about pediatric medical countermeasures. CDC and 
FDA developed guidance on pediatric dispensing for state and local 
government use. The state and local plans we examined also provided 
details about dispensing to the pediatric population during an 
emergency. 

More than Half of HHS's Response Plans We Reviewed Include Information 
about Dispensing Pediatric Medical Countermeasures: 

Of the 12 HHS CBRN response plans we reviewed, more than half included 
information about dispensing pediatric medical countermeasures. 
Specifically, 7 of these threat-specific plans contained information 
about medical countermeasures that could be dispensed for use by 
children in the event of a CBRN incident.[Footnote 43] The type of 
information included varied by plan. For example, two of the plans for 
responding to biological threats identified preferred and alternative 
countermeasures, and the appropriate dosages, that should be dispensed 
to children during an event. For a chemical incident, one of the plans 
indicated a premedication that should be used in pediatric patients 
before intubating them.[Footnote 44] The response plans for nuclear or 
radiological incidents also included information about medical 
countermeasures that could be used by children, although one plan 
noted that an EUA would be required before some of the countermeasures 
could be dispensed to the pediatric population. Although more than 
half of HHS's response plans included information about dispensing 
specific countermeasures to children, HHS officials told us that the 
purpose of these plans is to provide guidance for emergency responses 
at the federal level, and not instructions for use at the state and 
local level, which is where dispensing to children would occur. 
[Footnote 45] While these plans are intended primarily to support the 
federal response, they could also be used by state and local 
governments to inform their activities as part of planning their own 
response to a public health emergency.[Footnote 46] 

HHS officials told us that they were moving away from the use of 
separate, threat-specific response plans and were developing a single 
"all-hazards" response plan.[Footnote 47] This all-hazards plan would 
include sections for responding to specific CBRN events. According to 
HHS officials, these sections would address pediatric dispensing, 
including EUA and IND requirements. Additionally, a briefing paper 
about the pediatric population in disasters would be included in the 
all-hazards plan. 

CDC and FDA Guidance for State and Local Governments Includes 
Information on Pediatric Dispensing: 

Both CDC and FDA developed guidance for the dispensing of CBRN medical 
countermeasures from the SNS to the public, including children. For 
example, CDC developed guidance about receiving, distributing, and 
dispensing contents from the SNS to help state and local emergency 
management and public health personnel plan for the use of 
countermeasures from the SNS.[Footnote 48] The guidance, which could 
be used as a reference document or as a checklist by local and state 
planners, referred to the pediatric population in multiple sections, 
including an appendix about pediatric dispensing considerations. For 
example, the guidance described how the color "pink" is used to 
identify pediatric supplies included in the SNS. Additionally, the 
appendix noted that the SNS has limited amounts of oral suspensions of 
certain countermeasures for use by children and offered potential 
solutions for state and local governments to consider when addressing 
this shortage. These solutions included assigning someone the 
responsibility of mixing suspensions at a POD site or compounding 
tablets of medical countermeasures into oral suspensions.[Footnote 49] 

In addition, CDC and FDA developed other guidance on dispensing 
medical countermeasures, including to the pediatric population, which 
could be shared with and used by state and local governments. For 
example, CDC developed a website and training opportunities for state 
and local governments to use when planning for dispensing medical 
countermeasures. The information shared through the website and 
training addresses dispensing in general, for the most part, although 
a small portion of the training touches on dispensing to the pediatric 
population. FDA also developed guidance on dispensing pediatric 
medical countermeasures. For example, because it can be difficult for 
children to swallow pills, FDA developed instructions for how to crush 
and mix doxycycline with water and then add to food to mask the taste 
of doxycycline. Additionally, FDA, with CDC, developed an information 
sheet about using doxycycline for the prevention of anthrax that state 
and local governments could share with their populations during an 
event. This sheet included dosing instructions for administering 
doxycycline to children. 

CDC and FDA also collaborated to prepare, in advance of an actual CBRN 
incident, information about medical countermeasures that require an 
EUA or IND to have ready to share with state and local governments 
should an emergency occur.[Footnote 50] This included information 
about how a countermeasure would be dispensed to children under an EUA 
or IND protocol, should there be a need. State and local governments 
could then, in turn, share this information with their populations in 
the event of an emergency. For example, CDC and FDA developed an EUA 
fact sheet with instructions for administering doxycycline to children 
at home. CDC officials told us that they have information available 
for all medical countermeasures that could be used by children under 
an EUA. Information about pediatric dispensing under an EUA or IND 
protocol would be sent electronically--rather than in hard copy--to 
state and local governments because dispensing information can change 
and hard copies could become outdated. 

State and Local Government Plans Provide Details about Pediatric 
Dispensing: 

State and local governments have provided details about pediatric 
dispensing in their emergency response plans. All seven of the state 
response plans we reviewed addressed the dispensing of countermeasures 
to the pediatric population during a CBRN incident.[Footnote 51] 
Although the states' plans varied in format, they were consistent with 
one another in terms of the type of information they included about 
dispensing to children. For example, more than half of the states 
included information about pediatric dosing or formulations. 
Additionally, all seven states adopted some version of a "family 
member pick-up" policy--sometimes referred to as a "head of household" 
policy--which would allow adults to pick up medicines for other family 
members, including children, during an event. This policy is intended 
to eliminate disruptions to the dispensing process while 
simultaneously reducing patient numbers and increasing the number of 
persons treated during an incident. In addition, each state's plan 
provided other information about how medical countermeasures would be 
dispensed to children, either under a family member pick-up policy or 
through a POD.[Footnote 52] For example, 

* One state's medical countermeasure dispensing guidance noted that a 
POD should have specialized items for dispensing to children, such as 
scales for weighing children (if they are present and their parents do 
not know their weights) and mixing equipment to make pediatric 
portions. Additionally, the state's Point of Dispensing Field 
Operations Guide suggested that the POD include a staff member who can 
be responsible for ensuring drugs are properly packaged and 
instructions for children are given. 

* One state's plan discussed how oral antibiotic suspensions and 
syrups would be provided for the treatment of children who have 
trouble swallowing tablets, and that converting ciprofloxacin and 
doxycycline tablets into oral suspensions was recommended as an 
alternative for providing additional quantities of pediatric 
prophylactic regimens, due to the limited quantities of oral 
suspensions in the SNS. The plan included instructions for 
reconstituting these medical countermeasures. 

* One state's plan provided information about dispensing 
countermeasures to unaccompanied children who request treatment at 
PODs. The issue of consent for emergency care to a child in a disaster 
was discussed.[Footnote 53] Officials from this state told us that it 
works closely with the state's health care coalitions to ensure that 
the regional guidelines include pediatric-focused strategies.[Footnote 
54] Additionally, because pediatric doses are not stored in the SNS in 
large quantities, the state and local jurisdictions rely on 
partnerships with community and chain pharmacies to compound and 
reconstitute medications for children in an emergency. 

As we found with the states, all seven of the local governments that 
provided us with plans addressed dispensing countermeasures for the 
pediatric population during a CBRN incident.[Footnote 55] Like the 
states' plans, the local governments' plans varied in their format but 
were consistent with one another in terms of the type of information 
they included about dispensing to children. For example, more than 
half of the plans included information about screening children at a 
POD. Additionally, all seven local governments plan to implement 
versions of family member pick-up policies in the event of an 
emergency. The local governments' plans also included other ways to 
address the needs of the pediatric population when dispensing medical 
countermeasures. For example, 

* One local government's POD plan described different types of 
dispensing, one of which is called "slow dispensing." Slow dispensing 
requires children under the age of 9 to pass through medical 
screenings, if they go to the POD. 

* Another local government's plan described the setup of a special 
assistance station at a POD, where individuals could obtain medication 
for children under 9 years of age. Special assistance personnel could 
determine appropriate pediatric dosing by referring to available 
weight charts. 

* Finally, one local government's plan discussed allowing "fast-
tracking protocols," which would allow individuals with children to be 
diverted from the main lines and directed to a Help Desk to receive 
assistance. 

CDC officials noted that state and local governments handle the 
dispensing of countermeasures to children in the same way as for 
adults; that is, the dispensing of countermeasures for both children 
and adults occurs at POD sites. However, CDC officials also told us 
that special considerations can still be made for children--for 
example, by establishing separate family lines in the PODs. We found 
examples of this consideration in some of the plans we reviewed. 

Agency Comments: 

We provided a draft of this report to HHS for comment. In its written 
comments, reproduced in appendix II, HHS concurred with our findings. 
HHS reiterated information provided in our report, including that the 
development, procurement, and dispensing of medical countermeasures 
for the pediatric population is integrated into the PHEMCE's framework 
for public health preparedness across multiple component agencies, 
that state and local jurisdictions play an important role in 
responding to public health emergencies, and that the pace of progress 
in drug development is limited by the complex issues that surround the 
testing of countermeasures in children. In addition, HHS emphasized 
that the needs of the pediatric population have been a priority for 
HHS since the origins of Project Bioshield, and that the department is 
continuously progressing in this area. HHS also provided technical 
comments that we incorporated as appropriate. 

We will send copies of this report to the Secretary of Health and 
Human Services and interested congressional committees. We will also 
make copies available at no charge on GAO's 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. Key contributors to this report are 
listed in appendix III. 

Signed by: 

Marcia Crosse: 
Director, Health Care: 

[End of section] 

Appendix I: Pediatric CBRN Medical Countermeasures in the Strategic 
National Stockpile: 

Table 1 presents additional information about certain types of 
chemical, biological, radiological, and nuclear (CBRN) medical 
countermeasures available in the Strategic National Stockpile (SNS) by 
CBRN threat, as well as their regulatory status, for the pediatric 
population. The information presented is a general overview of 
countermeasures that are available for the pediatric population in the 
event of a CBRN incident, and does not include a complete list of all 
of the variations of each countermeasure. 

Table 1: Overview of Certain Types of Chemical, Biological, 
Radiological, and Nuclear (CBRN) Medical Countermeasures Available in 
the Strategic National Stockpile (SNS) and Their Regulatory Status for 
the Pediatric Population: 

CBRN threat: Anthrax (Bacillus anthracis); 

Types of medical countermeasures available in the SNS: Oral solid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Three oral solid 
antimicrobials are available in the SNS to prevent or treat anthrax. 
One is approved for postexposure prophylaxis and treatment of anthrax 
in all children. Another is approved for postexposure prophylaxis for 
all children, but it is not approved for treatment of anthrax in any 
population. The third is not approved for postexposure prophylaxis or 
treatment of anthrax in any population. The antimicrobials that are 
not approved for postexposure prophylaxis or treatment would need to 
be used under an Emergency Use Authorization (EUA) for unapproved age 
groups, including adults, for these indications. 

Types of medical countermeasures available in the SNS: Oral liquid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Three oral liquid 
antimicrobials are available in the SNS to prevent or treat anthrax. 
One is approved for postexposure prophylaxis and treatment of anthrax 
in all children. Another is approved for postexposure prophylaxis for 
all children, but it is not approved for treatment of anthrax in any 
population. The third is not approved for postexposure prophylaxis or 
treatment of anthrax in any population. The antimicrobials that are 
not approved for postexposure prophylaxis or treatment would need to 
be used under an EUA for unapproved age groups, including adults, for 
these indications. 

Types of medical countermeasures available in the SNS: IV 
antimicrobials; 
Regulatory status for the pediatric population[A]: Seven IV 
antimicrobials are available in the SNS to treat anthrax. Two have 
been approved for use by all children for the treatment of anthrax, 
and five have not been approved for the treatment of anthrax in any 
population. The antimicrobials that are not approved for the treatment 
of anthrax would need to be used under an EUA for all populations for 
this indication. 

Types of medical countermeasures available in the SNS: Vaccine; 
Regulatory status for the pediatric population[A]: One anthrax vaccine 
is available in the SNS, but it has not been approved for 
administration to children. It would need to be administered under an 
Investigational New Drug (IND) protocol. 

Types of medical countermeasures available in the SNS: Antitoxin or 
immunoglobulin[B]; 
Regulatory status for the pediatric population[A]: Two 
antitoxins/immunoglobulins are available in the SNS for the treatment 
of anthrax. One is approved for use by children to treat anthrax, 
while the other is not. The unapproved product would need to be used 
under an EUA in both adults and children. 

CBRN threat: Plague (Yersinia pestis); 

Types of medical countermeasures available in the SNS: Oral solid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Two oral solid 
antimicrobials are available in the SNS for postexposure prophylaxis 
of plague. One is approved for use by some children, while the other 
is not approved for postexposure prophylaxis of plague in any 
population. The first antimicrobial would need to be used under an EUA 
for use by unapproved age groups for postexposure prophylaxis of 
plague, and the second antimicrobial would need to be used under an 
EUA for this indication for all populations. 

Types of medical countermeasures available in the SNS: Oral liquid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Two oral liquid 
antimicrobials are available in the SNS for postexposure prophylaxis 
of plague. One is approved for use by some children, while the other 
is not approved for postexposure prophylaxis of plague in any 
population. The first antimicrobial would need to be used under an EUA 
for use by unapproved age groups for postexposure prophylaxis of 
plague, and the second antimicrobial would need to be used under an 
EUA for this indication for all populations. 

Types of medical countermeasures available in the SNS: IV 
antimicrobials; 
Regulatory status for the pediatric population[A]: Four IV 
antimicrobials are available in the SNS to treat plague. Two are 
approved for use by some children, and two are not approved for the 
treatment of plague in any population. The antimicrobials that are not 
approved for all children would need to be used under EUA for 
unapproved age groups for this indication, and the antimicrobials that 
are not approved for the treatment of plague would need to be used 
under an EUA for all populations. 

CBRN threat: Tularemia (Francisella tularensis); 

Types of medical countermeasures available in the SNS: Oral solid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Two oral solid 
antimicrobials are available in the SNS for postexposure prophylaxis 
of tularemia. One is approved for use by some children for this 
indication, while the other is not approved for postexposure 
prophylaxis of tularemia in any age population. The first 
antimicrobial would need to be used under an EUA for use by unapproved 
age groups for postexposure prophylaxis of tularemia, and the second 
antimicrobial would need to be used under an EUA for this indication 
for all populations. 

Types of medical countermeasures available in the SNS: Oral liquid 
antimicrobials; 
Regulatory status for the pediatric population[A]: Two oral liquid 
antimicrobials are available in the SNS for postexposure prophylaxis 
of tularemia. One is approved for use by some children for this 
indication, while the other is not approved for postexposure 
prophylaxis of tularemia in any age population. The first 
antimicrobial would need to be used under an EUA for use by unapproved 
age groups for postexposure prophylaxis of tularemia, and the second 
antimicrobial would need to be used under an EUA for this indication 
for all populations. 

Types of medical countermeasures available in the SNS: IV 
antimicrobials; 
Regulatory status for the pediatric population[A]: Four IV 
antimicrobials are available in the SNS to treat tularemia. One is 
approved for use by some children for the treatment of tularemia, and 
the other three are not approved for this indication in any age 
populations. The antimicrobial that is approved for use in some 
children for the treatment of tularemia would need to be used under an 
EUA by unapproved age groups. The other three antimicrobials that are 
not approved would need to be used under an EUA for this indication 
for all populations. 

CBRN threat: Typhus (Rickettsia prowazekii); 

Types of medical countermeasures available in the SNS: Oral solid 
antimicrobials; 
Regulatory status for the pediatric population[A]: One oral solid 
antimicrobial is available in the SNS to treat typhus, and it is 
approved for use by some children for this indication. This 
antimicrobial would need to be used under an EUA to treat typhus in 
unapproved populations. 

Types of medical countermeasures available in the SNS: Oral liquid 
antimicrobials; 
Regulatory status for the pediatric population[A]: One oral liquid 
antimicrobial is available in the SNS to treat typhus, and it is 
approved for use by some children for this indication. This 
antimicrobial would need to be used under an EUA to treat typhus in 
unapproved populations. 

Types of medical countermeasures available in the SNS: IV 
antimicrobials; 
Regulatory status for the pediatric population[A]: One IV 
antimicrobial is available in the SNS to treat typhus, and it is 
approved for use by some children for this indication. This 
antimicrobial would need to be used under an EUA to treat typhus in 
unapproved populations. 

CBRN threat: Botulism (Botulinum toxins); 

Types of medical countermeasures available in the SNS: Antitoxin or 
immunoglobulin; 
Regulatory status for the pediatric population[A]: Two antitoxins are 
available in the SNS to treat botulism, and one is approved. The 
unapproved antitoxin would need to be used under an EUA to treat 
botulism. The approved product can be used in all populations, 
including children, under its license. 

CBRN threat: Smallpox (Variola virus); 

Types of medical countermeasures available in the SNS: Vaccine; 
Regulatory status for the pediatric population[A]: Three smallpox 
vaccines are available in the SNS. One vaccine is approved for use by 
all children, and the other two are not approved for any age 
populations. These vaccines would need to be used under an EUA or an 
IND protocol. 

Types of medical countermeasures available in the SNS: Antitoxin or 
immunoglobulin[B]; 
Regulatory status for the pediatric population[A]: One immunoglobulin 
is available in the SNS for treatment of adverse reactions to the 
smallpox vaccine, and it is approved for use by all populations. 

Types of medical countermeasures available in the SNS: IV antivirals; 
Regulatory status for the pediatric population[A]: One IV antiviral is 
available in the SNS to treat adverse reactions to the smallpox 
vaccine, but it has not been approved for this indication for any age 
population. This antiviral would need to be used under an IND protocol 
for this indication. 

CBRN threat: Radiation (Radiological/nuclear agents); 

Types of medical countermeasures available in the SNS: Oral 
chelator[C]; 
Regulatory status for the pediatric population[A]: One oral chelator 
is available in the SNS for treatment of internal radiation 
contamination, and it is approved for use by some children. This 
product would need to be used under an EUA for unapproved age groups 
for this indication. 

Types of medical countermeasures available in the SNS: IV chelator[C]; 
Regulatory status for the pediatric population[A]: Two IV chelators 
are available in the SNS for treatment of internal radiation 
contamination, and both have been approved for use by all children. 

Types of medical countermeasures available in the SNS: Hematopoietic 
growth factors[D]; 
Regulatory status for the pediatric population[A]: One hematopoietic 
growth factor is available in the SNS, but it has not been approved 
for use by any age population for the treatment of acute radiation 
syndrome. This product would need to be used under an EUA or an IND 
protocol for this indication. 

CBRN threat: Chemical (Nerve agents); 

Types of medical countermeasures available in the SNS: Nerve agent 
antidotes; 
Regulatory status for the pediatric population[A]: Three nerve agent 
antidotes are available in the SNS for the treatment of poisoning by 
chemical nerve agents. Two of the antidotes have been approved for use 
by all children for this indication. The third antidote has an 
approved indication for use in seizures, but it has not been approved 
for use by all children and would need to be used under an EUA or an 
IND protocol for unapproved age groups. 

Source: GAO summary of Centers for Disease Control and Prevention 
(CDC) and Food and Drug Administration (FDA) information. 

Notes: According to CDC officials, in general, the same medical 
countermeasures are used for adults and children. The difference may 
be in weight-based dosing, or the need to use the medical 
countermeasures under a regulatory mechanism such as an EUA or IND. 
CDC officials stated that Burkholderia mallei (glanders), Burkholderia 
pseudomallei (melioidosis), and multi-drug resistant Bacillus 
anthracis are currently undergoing discussion for further planning. 
There are no medical countermeasures available for viral hemorrhagic 
fevers--Ebola, Marburg, and Junin viruses. In addition to the CBRN 
medical countermeasures listed, CDC officials told us that the SNS 
contains ventilators in pediatric sizes for all age groups down to 5 
kilograms, as well as thermal burn supplies such as bandages, burn 
creams, and anti-nausea medications. 

[A] FDA determined whether an EUA or IND protocol would be needed; we 
did not evaluate these determinations. 

[B] Immunoglobulins are derived from blood plasma obtained from donors 
who have been immunized with a vaccine, and they contain antibodies 
specific to the disease they are being used to treat. 

[C] Chelators help remove certain radioactive particles from the body. 

[D] Following radiation exposure, bone marrow can be suppressed. This 
reduces circulating white blood cells and increases the chance of 
infection. Infection can be prevented or mitigated by certain 
hematopoietic growth factors that activate bone marrow to protect from 
infection. 

[End of table] 

[End of section] 

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

Department of Health & Human Services: 
Office of the Secretary: 
Assistant Secretary for Legislation: 
Washington. DC 20201: 

April 8, 2013: 

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) report entitled, "National Preparedness: Efforts to Address the 
Medical Needs of Children in a Chemical, Biological, Radiological, or 
Nuclear Incident" (GAO 13-438). 

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

Sincerely, 

Signed by: 

Jim R. Esquea: 
Assistant Secretary for Legislation: 

Attachment: 

General Comments Of The Department Of Health And Human Services (HHS) 
On The Government Accountability Office's (GAO) Draft Report Entitled, 
"National Preparedness: Efforts To Address The Medical Needs Of 
Children In A Chemical, Biological, Radiological, Or Nuclear Incident" 
(GAO-13-438): 

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

HHS greatly values the time and attention that GAO has devoted to this 
important topic and overall we believe that the report does an 
admirable job of compiling a significant amount of information on a 
sensitive and complex subject in addressing the needs of one of the 
most vulnerable sectors of our population, our children. 

The development, procurement, and dispensing of medical 
countermeasures for the pediatric population (and other at-risk 
groups) is integrated into the general framework for public health 
preparedness across the component agencies of the Public Health 
Emergency Medical Countermeasures Enterprise (PHEMCE), which include 
the Office of the Assistant Secretary for Preparedness and Response 
(ASPR), the Food and Drug Administration, the National Institutes of 
Health (NIH), and the Centers for Disease Control and Prevention. The 
PHEMCE recognizes the unique challenges resulting from both the 
regulatory and product formulation issues associated with pediatric 
needs, and has chosen very deliberately to enhance our efforts to 
address these concerns. 

In 2012, PHEMCE released a new Strategy and Implementation Plan, which 
establish meeting the needs of at-risk populations as a central goal 
of the Enterprise. Specifically, the documents call for increasing our 
focus on at-risk populations in medical consequence and public health 
response assessments and requirements setting, supporting medical 
countermeasures development for at-risk populations, and ensuring 
coordinated and equitable access to medical countermeasures across all 
populations. 

One of PHEMCE's key responsibilities is overseeing the requirements-
setting process for medical countermeasures. Our Integrated Product 
Teams (IPTs) are working groups tasked with identifying and 
prioritizing gaps in our capabilities. To ensure that cross-cutting 
pediatric (and obstetric) population issues are addressed, the PHEMCE 
established the Obstetrics and Pediatrics IPT membership is drawn from 
subject matter experts across the component agencies, representing a 
collaborative approach to address pediatric needs, as well as those of 
other at-risk groups. 

Finally, the PHEMCE, through the auspices of the ASPR's role in 
formulating issues for the National Biodefense Science Board (NBSB), 
has recently opined on the difficult question of how best to approach 
the gathering of safety data for biodefense products that do not have 
specific indication for pediatric populations. After careful thought, 
the NBSB concluded that, Weighing the risks to the patient, as well as 
theoretical impacts on post-event operational issues for product use, 
the gathering of safety data prior to an event was preferable to doing 
so after an event. This issue was then given national attention when 
considered by the President's Commission on Bioethics for further 
debate and resolution, as discussed in the Commission's recently 
released report. 

In 2010, ASPR established the Children's HHS Interagency Leadership on 
Disasters (CHILD) Working Group to identify and comprehensively 
integrate the activities related to the needs of children across all 
HHS inter- and intra-governmental disaster planning activities and 
operations. The CHILD Working Group developed six recommendations 
specific to pediatric medical countermeasures, as described in its 
2011 report. 

On the operational side, ASPR is engaged in a number of activities 
that address the unique needs of children during a disaster. The 
Hospital Preparedness Program grants and cooperative agreements 
include guidance to states to assure that written plans and exercises 
include provisions for at-risk populations, including pediatric 
patients. The National Disaster Medical System (NDMS) is directed by a 
pediatrician with advanced fellowship training in pre-hospital and 
disaster medicine. This ensures that NDMS has ongoing perspectives to 
the specific vulnerabilities of children in disaster, and positions 
NDMS well to develop programs to meet these needs. Finally, ASPR has 
developed playbooks for each of the National Planning Scenarios. Each 
of these playbooks specifically integrates operational considerations, 
resources, and action items targeting requirements for pediatric and 
other at-risk populations. 

We would like to emphasize that the unique and complex needs of the 
pediatric population have been a priority for HHS since at least the 
origins of Project Bioshield. This commitment was solidified with the 
passage of the Pandemic and All-Hazards Preparedness Act in 2006 and 
reaffirmed in its recent reauthorization. There has been an enduring 
commitment and products that have been procured to protect this 
population segment, or are in development now, have long been part of 
the national preparedness agenda. 

We would also like to reiterate that the pace of substantial progress 
in drug development and approval for the pediatric population is not a 
matter of HHS policy. Progress is largely limited by the complex 
issues that surround the testing of countermeasures in children. This 
was recently directly demonstrated by the recommendations from the 
President's Commission on Bioethics, which once again re-affirmed the 
very limited allowance given on regulatory issues related to 
developing products for pediatric populations. These ethical issues, 
bound by regulatory language regarding direct benefit for pediatric 
populations in clinical trials, are not directed specifically at 
products associated with the types of public health emergency 
situations confronted by the PHEMCE, but do directly affect its 
ability to easily achieve the desired results. As one example of 
clinical trial progress in medical countermeasures applied to 
pediatric populations, as well as adult populations, the NIH-funded 
RAMPART study was recently recognized as the top clinical trial of 
2012. This trial evaluated midazolam as an effective treatment for 
seizure activity in epilepsy and is directly relevant to the ability 
to treat pediatric patients with this drug following a nerve agent 
exposure. 

In addition, from an operational perspective, it is important to 
recognize the important role that our non-federal partners play in 
responding to emergencies and disasters, including CBRN incidents. The 
federal government is not the sole or major provider for such 
responses. The capabilities and resiliency of state and local 
jurisdictions cannot be underestimated. Particularly for small 
chemical, biological, radiological, and nuclear incidents, the scale 
and timing of the incident have not historically required federal 
intervention beyond providing expertise and supporting coordination. 
While there are some countermeasures that only exist in federal 
caches, the actual use of them relies on local capability and fairly 
robust distribution networks exist. 

We thank you once again for your breadth of coverage on these 
important issues, for your overall assessment that HISS and the PHEMCE 
has devoted considerable attention to this need, and for acknowledging 
that we are continuously progressing in tackling this complex work. 

[End of section] 

Appendix III: 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, Tom Conahan, Assistant 
Director; Kaitlin Coffey; Kelly DeMots; Carolina Morgan; Monica Perez-
Nelson; and Roseanne Price made key contributions to this report. 

[End of section] 

Related GAO Products: 

National Preparedness: Improvements Needed for Measuring Awardee 
Performance in Meeting Medical and Public Health Preparedness Goals. 
[hyperlink, http://www.gao.gov/products/GAO-13-278]. Washington, D.C.: 
March 22, 2013. 

National Preparedness: Countermeasures for Thermal Burns. [hyperlink, 
http://www.gao.gov/products/GAO-12-304R]. Washington, D.C.: February 
22, 2012. 

Chemical, Biological, Radiological, and Nuclear Risk Assessments: DHS 
Should Establish More Specific Guidance for Their Use. [hyperlink, 
http://www.gao.gov/products/GAO-12-272]. Washington, D.C.: January 25, 
2012. 

National Preparedness: Improvements Needed for Acquiring Medical 
Countermeasures to Threats from Terrorism and Other Sources. 
[hyperlink, http://www.gao.gov/products/GAO-12-121]. Washington, D.C.: 
October 26, 2011. 

National Preparedness: DHS and HHS Can Further Strengthen Coordination 
for Chemical, Biological, Radiological, and Nuclear Risk Assessments. 
[hyperlink, http://www.gao.gov/products/GAO-11-606]. Washington, D.C.: 
June 21, 2011. 

Public Health Preparedness: Developing and Acquiring Medical 
Countermeasures Against Chemical, Biological, Radiological, and 
Nuclear Agents. [hyperlink, http://www.gao.gov/products/GAO-11-567T]. 
Washington, D.C.: April 13, 2011. 

National Security: Key Challenges and Solutions to Strengthen 
Interagency Collaboration. [hyperlink, 
http://www.gao.gov/products/GAO-10-822T]. Washington, D.C.: June 9, 
2010. 

Combating Nuclear Terrorism: Actions Needed to Better Prepare to 
Recover from Possible Attacks Using Radiological or Nuclear Materials. 
[hyperlink, http://www.gao.gov/products/GAO-10-204]. Washington, D.C.: 
January 29, 2010. 

Project BioShield Act: HHS Has Supported Development, Procurement, and 
Emergency Use of Medical Countermeasures to Address Health Threats. 
[hyperlink, http://www.gao.gov/products/GAO-09-878R]. Washington, 
D.C.: July 24, 2009. 

Project BioShield: HHS Can Improve Agency Internal Controls for Its 
New Contracting Authorities. [hyperlink, 
http://www.gao.gov/products/GAO-09-820]. Washington, D.C.: July 21, 
2009. 

Project BioShield: Actions Needed to Avoid Repeating Past Problems 
with Procuring New Anthrax Vaccine and Managing the Stockpile of 
Licensed Vaccine. [hyperlink, http://www.gao.gov/products/GAO-08-88]. 
Washington, D.C.: October 23, 2007. 

[End of section] 

Footnotes: 

[1] CBRN agents have the potential to cause widespread illness and 
death. 

[2] Medical countermeasures for CBRN agents include drugs, biologics--
such as vaccines--and devices to diagnose, treat, prevent, or mitigate 
potential effects of exposure. This report focuses on drugs and 
biologics. 

[3] National Commission on Children and Disasters, 2010 Report to the 
President and Congress (Rockville, Md.: October 2010). For the purpose 
of this report, "adults" are individuals 18 years of age and older, 
and the terms "children" and "pediatric population" are equivalent and 
refer to individuals younger than 18 years of age. The Food and Drug 
Administration (FDA) generally defines the pediatric population as 
individuals younger than 16 years of age, but relevant research has 
included children as old as 18. 

[4] For the purposes of this report, we are using the term "industry" 
to include small research companies and manufacturing companies, both 
of which support HHS in efforts to research and develop CBRN medical 
countermeasures. 

[5] We reviewed supporting documentation provided by PHEMCE that 
included the list of CBRN medical countermeasures in the SNS as well 
as its analysis of whether each countermeasure was approved for all 
children, some children, or no children. 

[6] For the purposes of this report, we used the term "investments" to 
mean obligations. 

[7] GAO, National Preparedness: Improvements Needed for Acquiring 
Medical Countermeasures to Threats from Terrorism and Other Sources, 
[hyperlink, http://www.gao.gov/products/GAO-12-121] (Washington, D.C.: 
Oct. 26, 2011), National Preparedness: DHS and HHS Can Further 
Strengthen Coordination for Chemical, Biological, Radiological, and 
Nuclear Risk Assessments, [hyperlink, 
http://www.gao.gov/products/GAO-11-606] (Washington, D.C.: June 21, 
2011), Public Health Preparedness: Developing and Acquiring Medical 
Countermeasures Against Chemical, Biological, Radiological, and 
Nuclear Agents, [hyperlink, http://www.gao.gov/products/GAO-11-567T] 
(Washington, D.C.: Apr. 13, 2011). 

[8] For the purposes of this report, we are using the term "emergency 
response plan" to include any document a state or local government 
provided to us that describes an approach for responding to, or is 
used in the event of, an emergency. 

[9] For the states, we received and reviewed emergency response plans 
from Arkansas, Michigan, Missouri, Oklahoma, Washington, and West 
Virginia, selected by a stratified random sample of the states, based 
on population size. We also received and reviewed documents from 
Virginia, although it was not part of the original sample. For local 
governments, we received and reviewed emergency response plans from 
Chicago (Illinois), Fresno (California), Milwaukee (Wisconsin), 
Nashville and Memphis (Tennessee), New York City (New York), and 
Virginia Beach (Virginia), selected by a stratified random sample of 
local governments that participate in CDC's Cities Readiness 
Initiative, based on the Census regions. 

[10] National Commission on Children and Disasters, 2010 Report to the 
President and Congress. 

[11] In addition to those individuals specifically recognized as "at-
risk individuals" in the Pandemic and All-Hazards Preparedness Act of 
2006--children, senior citizens, and pregnant women--individuals who 
may need additional response assistance include those who have 
disabilities, live in institutionalized settings, are from diverse 
cultures, have limited English proficiency or are non-English 
speaking, are transportation disadvantaged, have chronic medical 
disorders, or have pharmacological dependency. 

[12] Institute of Medicine, Safe and Effective Medicines for Children: 
Pediatric Studies Conducted Under the Best Pharmaceuticals for 
Children Act and the Pediatric Research Equity Act (Washington, D.C.: 
The National Academies Press, 2012). 

[13] Pub. L. No. 108-276. § 3(a)(2), 118 Stat. 835, 844 (2004). The 
Project BioShield Act of 2004 calls for HHS to assess the public 
health consequences of exposure to those CBRN agents that the 
Department of Homeland Security, in consultation with the Secretary of 
HHS, determines are material threats to the nation and to determine 
for which of these agents medical countermeasures are necessary to 
protect the public health. 42 U.S.C. § 247d-6b(c)(2). 

[14] For example, the palatability of a mixture made by crushing solid 
oral doses of a drug into a food or liquid may need to be addressed 
for pediatric formulations. Palatability refers to the taste, texture, 
and smell of a medication, and is considered in the development of 
pediatric formulations. 

[15] Many state and local jurisdictions have purchased their own 
supplies of CBRN medical countermeasures, such as ciprofloxacin and 
doxycycline, to be better prepared to respond to public health 
emergencies. These stockpiles are typically created to ensure early 
access to medicines to protect first responders, among others, so that 
these essential employees can quickly respond to the emergency. 

[16] The 2004 DHS Appropriations Act appropriated approximately $5.6 
billion for biodefense countermeasures to remain available until 2013. 
Pub. L. No. 108-90, 117 Stat. 1137, 1148 (2003). The Project Bioshield 
Act defined the Special Reserve Fund for purposes of the 
countermeasures program to include the Biodefense Countermeasures 
appropriations account. Pub. L. No. 108-276, 118 Stat. 852. 

[17] Pub. L. No. 113-5, title IV, 127 Stat. 161, 193-195 (2013). An 
authorization of appropriations does not constitute an appropriation 
of public funds. Normally, an authorization of appropriations 
legislation is a prerequisite for making appropriations for the given 
programs or agencies. 

[18] FDA requires drug companies, also known as drug manufacturers, to 
specify in their applications for government approval of a product the 
indication intended for their products' use. The indication generally 
describes the disease, condition, or symptoms that the drug is 
intended to treat, prevent, mitigate, cure, or diagnose, as well as 
the populations for which the manufacturer has conducted testing and 
for which it is seeking approval. 

[19] Medical countermeasure dispensing provides medical 
countermeasures in support of treatment or prophylaxis (oral or 
vaccination) to the identified population in accordance with public 
health guidelines and recommendations. 

[20] The Public Readiness and Emergency Preparedness Act provides 
compensation to individuals for serious physical injuries or deaths 
from countermeasures identified in a declaration of a public health 
emergency issued by the Secretary of HHS. The act authorizes HHS to 
issue a declaration that provides immunity from tort liability--except 
for willful misconduct--to certain individuals and organizations 
involved in the development, manufacture, distribution, 
administration, and use of these countermeasures. Pub. L. No. 109-148, 
division C, 119 Stat. 2680, 2818-2832 (2005) (codified at 42 U.S.C. § 
247d-6d). 

[21] The Best Pharmaceuticals for Children Act offers drug sponsors--
typically manufacturers--incentives to conduct pediatric studies, such 
as by extending the company's market exclusivity for that product for 
6 months. Protection from competition under market exclusivity can 
include the marketing of a generic copy. Pub. L. No. 107-109, 115 
Stat. 1408 (2002). The Pediatric Research Equity Act allows FDA to 
require manufacturers of drugs and biological products to submit 
pediatric testing data at the time of new drug applications. Pub. L. 
No. 108-155, 117 Stat. 1936 (2003). Both acts were extended in 2007 
and are now permanent in the Food and Drug Administration Safety and 
Innovation Act of 2012. Pub. L. No. 110-85, §§ 401-404, 501-503, 121 
Stat. 823, 866-890 (2007); Pub. L. No. 112-144, § 501, 126 Stat. 993, 
1039-1040 (2012) (pertinent provisions codified as amended at 21 
U.S.C. §§ 355a, 355c). 

[22] See 21 U.S.C. § 360bbb-3. The Secretary of HHS has delegated 
authority to make such determinations to the Commissioner of FDA. 

[23] If state or local governments dispense countermeasures in a 
manner that is inconsistent with the terms of an EUA, their liability 
protections afforded by the Public Readiness and Emergency 
Preparedness Act may be affected. 

[24] 21 U.S.C. § 360bbb. The Secretary of HHS has delegated authority 
to make such determinations to the Commissioner of FDA. While INDs may 
be submitted for a variety of purposes, in this report we use the term 
IND to refer to only those submitted for expanded access to medical 
countermeasures during an emergency. 

[25] In addition to approving or licensing medical countermeasures, 
FDA works with researchers throughout the development stages to review 
safety and efficacy test results and provide technical assistance to 
help ensure that research meets FDA's regulatory requirements. 

[26] Early, or basic, research is intended to better understand CBRN 
agents and the response of the host organism to the agents through the 
study of the cellular and molecular biology of agents and hosts, their 
physiological processes, and their genome sequences and structures. 
Applied, or translational, research builds on basic research by 
validating and testing concepts in practical settings to identify 
potential products. Successful concepts move from the applied research 
stage into the early development stage, in order to demonstrate basic 
safety, reproducibility, and ability to be used in humans. 

[27] In the advanced development stage, potential medical 
countermeasures are further evaluated to demonstrate safety and 
efficacy for preventing, diagnosing, or treating disease. Successful 
products are then available for development and acquisition. In 
addition, BARDA determines that manufacturing, scale-up production, 
and licensing of countermeasures can be achieved in a timely and 
reliable manner. 

[28] The Project BioShield Act of 2004 provides that the Special 
Reserve Fund may be used to acquire countermeasures for which the HHS 
Secretary determines that sufficient and satisfactory clinical 
experience or research data support a reasonable conclusion that the 
product will qualify for FDA approval or licensing within 8 years. In 
2013, the Pandemic and All-Hazards Preparedness and Reauthorization 
Act extended the timeline for acquisitions, allowing for the use of 
the Special Reserve Fund to acquire countermeasures for which the HHS 
Secretary determines that sufficient and satisfactory clinical 
experience or research data support a reasonable conclusion that the 
product will qualify for FDA approval or licensing within 10 years. 42 
U.S.C. § 247d-6b(c)(1)(B)(i)(III)(bb). 

[29] HHS has developed 12 response plans to address CBRN incidents as 
of December 2012: 8 are For Official Use Only, and 4 are publicly 
available. Officials told us there are fewer publicly available plans 
than For Official Use Only plans because some plans are currently in 
draft form and will be available in public versions once they have 
been cleared by HHS for release. The For Official Use Only response 
plans address some chemical (nerve agent, blister agent, and chlorine 
tank explosion), biological (pneumonic plague, botulism food 
contamination, and aerosolized anthrax), radiological (radiological 
dispersal device), and nuclear (improvised nuclear device) incidents. 
The publicly available response plans address biological (botulinum 
food contamination and aerosolized anthrax), radiological 
(radiological dispersal device), and nuclear (nuclear detonation) 
incidents. 

[30] According to members of PHEMCE, these percentages were derived 
from an analysis of the regulatory status of the contents of the SNS 
performed in June 2012. However, these percentages may not entirely 
reflect the availability of countermeasures to be used by children 
because three items that were counted as not approved for use by 
children are therapeutic ointments that are not labeled by age. An 
official from PHEMCE stated that therapeutic ointments are assumed to 
be safe for use by children unless there is a warning against their 
use. 

[31] In March 2013, the Presidential Commission for the Study of 
Bioethical Issues reported that the federal government would have to 
take multiple steps, including minimal-risk research with adult 
volunteers, before considering pediatric clinical trials to test the 
safety and efficacy of AVA in children. The Presidential Commission 
for the Study of Bioethical Issues, Safeguarding Children: Pediatric 
Medical Countermeasure Research (Washington, D.C.: March 2013). 

[32] HHS officials stated that under this second IND protocol, parents 
would consent to having blood drawn from their children when the 
vaccine was administered during an emergency, as well as submitting 
other health information about their children after they were 
vaccinated in order to follow up on the safety of the vaccine in 
children. Officials stated that these actions could provide FDA with 
some safety and immunogenicity data to inform use of the vaccine in 
children in future emergencies. Officials emphasized that if there are 
no data available in advance of public health emergencies, the gaps in 
the data could be addressed only during an actual event. 

[33] These challenges have been described in past GAO reports, various 
HHS reports, and reports by subject-matter experts. See [hyperlink, 
http://www.gao.gov/products/GAO-12-121], [hyperlink, 
http://www.gao.gov/products/GAO-11-606], and [hyperlink, 
http://www.gao.gov/products/GAO-11-567T]. See also Department of 
Health and Human Services, The Children's HHS Interagency Leadership 
on Disasters (CHILD) Working Group: Summary of Recommendations and 
Implementation Efforts (April 2012); National Commission on Children 
and Disasters, 2010 Report to the President and Congress. 

[34] Institute of Medicine, Advancing Regulatory Science for Medical 
Countermeasure Development (National Academy of Sciences: 2010); 
National Biodefense Science Board, Where Are the Countermeasures? 
Protecting America's Health from CBRN Threats (2010); Department of 
Health and Human Services, The Children's HHS Interagency Leadership 
on Disasters (CHILD) Working Group: Summary of Recommendations and 
Implementation Efforts. 

[35] 21 C.F.R. §§ 314.600-650; 601.90-.95. The Animal Rule states that 
when it is neither ethical nor feasible to conduct human efficacy 
studies, FDA may grant marketing approval of CBRN countermeasures 
based on adequate and well-controlled animal studies when the results 
of those studies establish that the drug or biological product is 
reasonably likely to produce clinical benefit in humans. 

[36] A drug may receive an orphan designation if it is intended for 
conditions or diseases that affect fewer than 200,000 persons in the 
United States. CBRN and non-CBRN drugs that qualify and receive orphan 
designation are exempt from pediatric research requirements under the 
Pediatric Research Equity Act. Orphan designation qualifies the 
sponsor of the product for the tax credit and marketing incentives of 
the Orphan Drug Act. See Pub. L. No. 97-414, 96 Stat. 2049 (1983) 
(codified at 21 U.S.C. §§ 360aa-360cc; 26 U.S.C. § 45C). 

[37] Until 1997, most drugs used to treat children were tested for 
safety and efficacy only in adults. The Pediatric Research Equity Act 
of 2003 requires assessments of safety and efficacy of drugs and 
biological products for pediatric use for the indication for which 
they are approved in the adult population. HHS may grant deferrals and 
full or partial waivers from these requirements. Products with an 
orphan drug designation for a rare disease or condition are exempt 
from the requirements of the Pediatric Research Equity Act. 

[38] 21 C.F.R. part 50, subpart D (Additional Safeguards for Children 
in Clinical Investigations). 

[39] The Medical Countermeasures Initiative is composed of three 
pillars that (1) enhance the medical countermeasure review process; 
(2) advance regulatory science for medical countermeasure development; 
and (3) optimize the legal and policy framework for approving medical 
countermeasures. 

[40] Department of Health and Human Services, 2011 Report of the 
Children's HHS Interagency Leadership on Disasters (CHILD) Working 
Group: Progress and Future Directions (January 2012). 

[41] That countermeasure, Prussian blue, is currently licensed for 
adult and pediatric patients over 2 years of age. 

[42] Department of Health and Human Services, Public Health Emergency 
Medical Countermeasures Enterprise, Pediatric Medical Countermeasure 
Roundtable for National Health Security: Meeting Report (Oct. 13-14, 
2010). Some of the medical countermeasures being considered for 
crushing include Prussian blue, doxycycline, and ciprofloxacin. 

[43] Not all of the plans would necessarily include information about 
which specific medical countermeasure is to be dispensed to children 
during a CBRN incident, according to HHS officials. For example, 
treatment for exposure to certain CBRN agents sometimes only requires 
supportive care, rather than a specific medical countermeasure. 

[44] Intubation is a medical procedure in which a tube is placed into 
the windpipe (trachea), through the mouth or the nose. In most 
emergency situations, it is placed through the mouth. 

[45] The federal government emergency responses are intended to 
provide support, resources, program implementation, and services that 
are most likely needed to save lives, protect property and the 
environment, restore essential services and critical infrastructure, 
and help victims and communities return to normal following domestic 
incidents. HHS is the primary agency responsible for efforts related 
to public health and medical services in order to provide the 
mechanism for coordinated federal assistance to supplement state, 
tribal, and local resources in response to an emergency. 

[46] HHS also developed two web-based resources that can also be used 
to inform CBRN planning at other levels of government--the Chemical 
Hazards Emergency Medical Management and Radiation Emergency Medical 
Management guidance documents. See [hyperlink, 
http://www.chemm.nlm.nih.gov/] and [hyperlink, 
http://www.remm.nlm.gov/], respectively, accessed January 25, 2013. 

[47] HHS officials said that they anticipate releasing this plan by 
August 2013. 

[48] Centers for Disease Control and Prevention, Receiving, 
Distributing, and Dispensing Strategic National Stockpile Assets: A 
Guide for Preparedness, ver.10.02 (August 2006). 

[49] CDC has developed a new version of this guidance, which CDC has 
tentatively scheduled for release during calendar year 2013. 

[50] This information is not shared with state and local governments 
in advance of a CBRN incident because medical countermeasures that are 
dispensed under an EUA or IND protocol have not been FDA-approved for 
use for these indications, according to HHS officials. Information 
about using medical countermeasures for these indications can change 
as new data are made available, and FDA and CDC wait to release such 
information until an emergency occurs to ensure that the information 
reflects the most recent data available. 

[51] Officials from one additional state also provided us with written 
information about its plans, but did not provide us with supporting 
documents to review. 

[52] Despite having a family member pick-up policy in place, there are 
still reasons why a child might go to a POD. For example, parents 
might not want to be separated from their children during a CBRN 
incident, or unaccompanied minors may go to the POD looking for 
medication. 

[53] In general, parental consent is required for the medical 
treatment of children. 

[54] These health care coalitions, which support the state's health 
care preparedness program, work with local partners from different 
regions of the state to prepare hospitals, emergency medical service, 
and supporting health care organizations to deliver coordinated and 
effective care to individuals affected by public health emergencies. 

[55] An official from one additional local government also spoke with 
us about its emergency response plans, but could not provide us with 
supporting documents to review. 

[End of section] 

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