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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.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 According to HHS, many children, including adverse effects on their growth and development. 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. 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. 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. 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. centers and small biotechnology companies for basic and applied research and early development. 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. If a countermeasure is not FDA-approved or licensed, its acquisition into the SNS is typically funded by the Project BioShield Special Reserve Fund. If a countermeasure is FDA-approved or licensed, CDC generally purchases the countermeasure for the SNS. 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 Federal assistance to state and local governments would emergencies.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. 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. For example, anthrax vaccine adsorbed (AVA) has not been approved for use by any children. 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. (See app. 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 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 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. 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.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. According to CDC officials, while it is 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. 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, which, if granted, exempts the manufacturer from the requirement to conduct pediatric studies under the Pediatric Research Equity Act. 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. 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. 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. 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. 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.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. 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. 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. 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. 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. 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. 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.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 The response plans for nuclear or radiological incidents also occur. 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. 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. 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. 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. 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. 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.countermeasure would be dispensed to children under an EUA or IND protocol, should there be a need. State and local governments could This included information about how a 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 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. 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. 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. 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. 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. 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. 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 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. 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. 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. National Preparedness: Improvements Needed for Measuring Awardee Performance in Meeting Medical and Public Health Preparedness Goals. GAO-13-278. Washington, D.C.: March 22, 2013. National Preparedness: Countermeasures for Thermal Burns. 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. GAO-12-272. Washington, D.C.: January 25, 2012. National Preparedness: Improvements Needed for Acquiring Medical Countermeasures to Threats from Terrorism and Other Sources. 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. GAO-11-606. Washington, D.C.: June 21, 2011. Public Health Preparedness: Developing and Acquiring Medical Countermeasures Against Chemical, Biological, Radiological, and Nuclear Agents. GAO-11-567T. Washington, D.C.: April 13, 2011. National Security: Key Challenges and Solutions to Strengthen Interagency Collaboration. 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. 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. GAO-09-878R. Washington, D.C.: July 24, 2009. Project BioShield: HHS Can Improve Agency Internal Controls for Its New Contracting Authorities. 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. GAO-08-88. Washington, D.C.: October 23, 2007.

Summary: 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. 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.