Since 2004, Congress has authorized over $8 billion for medical countermeasure procurement. The Project BioShield Act of 2004 authorized the appropriation of $5.6 billion to be available from fiscal year 2004 through fiscal year 2013 for the Project BioShield Special Reserve The act Fund, and funds totaling this amount were appropriated.facilitated the creation of a government countermeasure market by authorizing the government to commit to making the Special Reserve Fund available to purchase certain medical countermeasures, including those countermeasures that may not yet be approved, cleared, or licensed by the Food and Drug Administration (FDA). In 2013, PAHPRA authorized an additional $2.8 billion to be available from fiscal year 2014 through fiscal year 2018 for these activities, and $255 million was appropriated in fiscal year 2014. Congress has also made funding available through annual and supplemental appropriations to respond to influenza pandemics, including developing vaccines and other drugs. HHS is the primary federal department responsible for public health emergency planning. Within HHS, several offices have specific responsibilities for medical countermeasure development and procurement. HHS’s ASPR leads PHEMCE and the federal medical and public health response to public health emergencies, including strategic planning and support for developing and securing medical countermeasures. As part of these activities, HHS develops priorities for which medical countermeasures are needed. Within ASPR, BARDA—established by the Pandemic and All-Hazards Preparedness Act of 2006—coordinates and supports advanced research and development, manufacturing, and initial procurement of medical countermeasures for CBRN threats, pandemic influenza, and emerging infectious diseases into the Strategic National Stockpile—the national repository for medications, medical supplies, and equipment for use in a public health emergency. As part of these responsibilities, BARDA oversees HHS’s efforts to develop flexible manufacturing capabilities for medical countermeasures. HHS’s PHEMCE, which was established in 2006, is composed of officials from ASPR, BARDA, the Centers for Disease Control and Prevention (CDC), FDA, and the National Institutes of Health (NIH), in addition to officials from other federal departments, including the Departments of Agriculture, Defense, Homeland Security, and Veterans Affairs. In 2007, HHS published the PHEMCE Implementation Plan, which identified HHS’s priorities for CBRN countermeasure procurement using the 2004 Special Reserve Fund appropriation. In December 2012, HHS published an updated PHEMCE Implementation Plan, which describes the capabilities HHS wants to establish to support countermeasure development and procurement, including activities to support flexible manufacturing. The 2012 PHEMCE Implementation Plan also identifies HHS’s priorities for developing and procuring medical countermeasures, such as anthrax vaccine, smallpox antivirals, chemical agent antidotes, and diagnostic devices for radiological and nuclear agents. (See app. I for HHS’s advanced development priorities for CBRN countermeasures.) Flexible manufacturing generally refers to the equipment and technologies that allow a facility to rapidly develop or manufacture a number of products simultaneously or in quick succession. These technologies include the use of disposable equipment, such as growing cell cultures in disposable plastic bag systems rather than in stainless steel tanks that require more time to clean and sterilize prior to the next use and the use of modular sterile rooms to allow for the manufacture of multiple products simultaneously within a given facility. Other technologies include alternatives to more traditional methods of making influenza vaccine, such as using cell-based or recombinant technologies to make vaccine, rather than the traditional egg-based technology, or using adjuvants to enhance the immune response to vaccines. In addition to alternative vaccine development technologies, platform technologies provide flexible systems that have the potential to produce medical countermeasures for multiple threats. The use of flexible manufacturing technologies also has the potential to help provide surge capacity production in a public health emergency. We previously reported on the barriers industry faces in developing and manufacturing CBRN and pandemic influenza medical countermeasures, which create challenges for HHS. In April 2011, we found that the barriers HHS identified in the PHEMCE review continued to exist. Specifically, we found that the lack of a commercial market continued to hinder large pharmaceutical companies from developing medical countermeasures. As a result, less-experienced biotechnology companies became the primary developers of such products, but these companies needed more scientific and regulatory assistance for testing the safety and efficacy of their countermeasures in development. In its 2010 PHEMCE review, HHS stated that new approaches to vaccine manufacturing, such as the use of flexible manufacturing technologies, offered promising ways to meet the demands of pandemic vaccine production while simultaneously meeting needs related to other public health emergency threats. In our June 2011 review, HHS officials told us that the CIADMs are intended to support countermeasure developers by providing needed resources for and expertise about manufacturing and to reduce the technical risks of researching and developing medical countermeasures. In addition, HHS officials indicated that such assistance by the CIADMs could reduce the research and development costs of smaller, less-experienced companies. In fiscal years 2012 and 2013, HHS’s BARDA awarded nearly $440 million to establish its CIADMs and a network of facilities to provide packaging support to ready the product for distribution, known as the Fill Finish Manufacturing Network. The CIADM contractors are required to develop three activities to support flexible manufacturing: pandemic influenza surge capacity, core services for CBRN medical countermeasure developers, and workforce training programs. According to BARDA officials, the Fill Finish Manufacturing Network will supplement the CIADMs’ pandemic influenza surge capacity and CBRN core services activities. HHS’s BARDA awarded approximately $400 million in fiscal year 2012 to three contractors to establish the CIADMs. Under the terms of the CIADM contracts, the three contractors must retrofit existing facilities or build new ones to incorporate flexible, innovative manufacturing equipment and technologies that can be used to develop and manufacture more than one medical countermeasure either simultaneously or in quick succession. BARDA characterizes the CIADMs as public-private partnerships because the contractors are required to provide their own funds to supplement those awarded by HHS under a cost-sharing arrangement. For example, the total investment in pandemic influenza vaccine surge capacity could include up to $194 million in contractor funding to supplement the $400 million government award amount, for a total of about $594 million in public and contractor funding. An option is a unilateral right in a contract by which, for a specified time, the government may elect to purchase additional supplies or services called for by the contract, or may elect to extend the term of the contract. CIADMs are required to design, construct, and commission their facilities. These facilities are intended to establish a warm base for pandemic influenza surge capacity. A warm base refers to facilities that, once constructed and commissioned, would be operationally ready to quickly manufacture vaccine during an influenza pandemic. These facilities are also intended to establish the capacity to provide core services for the development of CBRN countermeasures. (See table 1 for information on the CIADM base period amounts, including the government award and contractor cost-share.) Contractors may be awarded additional amounts beyond the base period award through the issuance of task orders. Under the CIADM contracts, HHS may issue task orders to purchase (1) core services for CBRN medical countermeasure developers, (2) medical countermeasure vaccine production (including vaccine for pandemic influenza), and (3) workforce training activities. The contracts outline the procedures that HHS is to follow to give contractors a fair opportunity to be considered for the award of task orders. BARDA anticipates issuing task orders in the three service areas, including core services for CBRN countermeasures, during the annual option periods. As shown in Table 1, option periods may overlap the base period for the contracts. The filling and finishing of medical countermeasures refers to the process by which individual drugs are packaged for use, such as in vials and syringes, and includes labeling, patient instructions, outside packaging, transport, and promotional materials. contract amount is intended to fund the necessary up front activities (e.g., formulation and technology transfer) to establish warm base facilities that can be used to provide fill and finish services during both pandemic and nonpandemic periods. After the contractors have completed these start-up activities to establish the fill and finish network, BARDA plans to award additional funding through the issuance of task orders. These task orders may include funding for materials, spare parts, equipment, staffing, and fees necessary to complete the task order. BARDA’s CIADMs are intended to provide three activities—surge capacity for manufacturing pandemic influenza vaccine, core services for the development of CBRN medical countermeasures, and workforce training—to support HHS’s flexible manufacturing activities. According to HHS, the primary goal of the CIADMs is to provide core service assistance to CBRN medical countermeasure developers, their ability to provide some core services depends on the retrofitting of existing, or building of new, facilities that are also needed to provide surge capacity. The Fill Finish Manufacturing Network is to supplement the CIADMs’ pandemic influenza surge capacity and CBRN core services activities. The three CIADMs are required under their contracts with BARDA to establish surge capacity to quickly manufacture influenza vaccine in a pandemic and secure a pandemic influenza vaccine candidate currently under development. The CIADMs plan to establish surge capacity as follows: Emergent: Under the CIADM award, Emergent is to design, construct, and commission a biologics development and manufacturing suite in Baltimore, Maryland, intended to support core services for CBRN medical countermeasures on a routine basis and support manufacturing of medical countermeasure vaccines for an influenza pandemic or other public health threats. In addition, Emergent is to design, renovate, and commission a pilot plant at its existing facility in Gaithersburg, Maryland, that is also intended to support core services for CBRN medical countermeasure developers. Novartis Vaccines and Diagnostics (Novartis). Under the CIADM award, Novartis is to design, renovate, and commission a pilot plant to produce and fill clinical investigational lots of CBRN medical countermeasures in its existing plant in Holly Springs, North Carolina. Also, Novartis is to design, construct, and commission a technical services building in Holly Springs, North Carolina, to house administrative staff and provide maintenance services for the pilot plant. Texas A&M University System (TAMUS). Under the CIADM award, TAMUS is to design, construct or renovate, and commission a number of facilities on the Texas A&M campus in College Station, Texas. These facilities are to include a biologics development and manufacturing facility that is intended to provide core services for CBRN medical countermeasures, with the added capability of developing and manufacturing live virus vaccine candidates; a current Good Manufacturing Practices vaccine bulk manufacturing facility dedicated to large-scale surge manufacturing of pandemic influenza vaccines; a laboratory and office building to support process development and technology transfer of CBRN medical countermeasures into the CIADM; and a facility to support the fill and finish requirements for medical countermeasures. The establishment of the TAMUS fill and finish facility is being funded under the CIADM contract and is not a part of BARDA’s Fill Finish Manufacturing Network, for which HHS issued separate contracts. Each of the CIADMs has taken a different approach to acquiring pandemic influenza vaccine candidates: Emergent has partnered with VaxInnate, which is developing a pandemic influenza vaccine using recombinant protein technology. Novartis has developed a pandemic influenza vaccine candidate using cell-based vaccine production, which involves growing flu viruses in mammalian cell cultures instead of the conventional method of making influenza vaccine in chicken eggs. TAMUS has partnered with GlaxoSmithKline to obtain a pandemic influenza vaccine candidate. GlaxoSmithKline plans to grow the vaccine using a proprietary line of cells. A vaccine using the same adjuvant received FDA approval in November 2013 for pandemic response purposes. According to BARDA officials, FDA licensed the vaccine, using this adjuvant, to be manufactured in Canada using egg-based technology. However, the TAMUS CIADM is using GlaxoSmithKline’s cell-based influenza vaccine technology to meet HHS surge manufacturing requirements. The CIADMs are scheduled to have completed construction, acquired an influenza pandemic vaccine candidate, and validated their vaccine surge capacity with FDA by the end of their contract base period (2020, 2016, and 2017, respectively for Emergent, Novartis, and TAMUS). Each of the three CIADMs are to be able and, in the event of an influenza pandemic, be required to produce 50 million doses of vaccine within four months of receipt of the influenza virus strain, with the first doses for the public available to HHS within 12 weeks. BARDA officials told us that they anticipate that at least one CIADM would be able to manufacture pandemic influenza vaccine upon request starting in 2017, and that all of the centers would be capable of manufacturing pandemic influenza vaccine by the end of 2020. BARDA anticipates placing task orders for pandemic influenza vaccine, if needed, during the annual contract option periods available to extend the contracts at the end of the respective base periods. Once the CIADMs’ influenza vaccine surge capacity is operational, the centers are expected to maintain readiness for surge manufacturing, even in nonpandemic periods. According to BARDA officials, in these nonpandemic periods, the CIADMs may use their surge capacity for other activities, including commercial manufacturing, provided they make their influenza vaccine surge capacity available upon request from HHS during an influenza pandemic to produce the required 50 million doses in the specified time period. While surge capacity at the CIADMs is intended for pandemic influenza vaccine production, BARDA officials told us this capacity could be used to manufacture other medical countermeasures, such as an anthrax vaccine, in a public health emergency. BARDA officials told us that based on FDA requirements to maintain the license for the pandemic influenza vaccine, the CIADMs may need to produce one annual lot of the vaccine. BARDA will provide payment for activities required to maintain pandemic readiness. According to BARDA officials, the four companies that were awarded contracts to establish the Fill Finish Manufacturing Network will provide additional fill and finish surge capacity in an influenza pandemic to supplement the CIADMs and allow for the fill and finish of 117 million additional doses of pandemic influenza vaccine in 12 weeks. The companies in the Fill Finish Manufacturing Network are encouraged to collaborate with the three CIADMs as well as partner with domestic influenza vaccine manufacturers in order to transfer the fill and finish technology into the Fill Finish Manufacturing Network contractors’ facilities, which will become alternate locations on the vaccine manufacturers’ licenses for fill finish activities. The network is also expected to provide its services to HHS for production of clinical investigational lots of medical countermeasures that are in development. BARDA anticipates that the Fill Finish Manufacturing Network will be available to receive task orders for core services by the end of fiscal year 2014. For the core services activity, the CIADMs are to provide services for the development and production of CBRN medical countermeasures, such as assisting CBRN medical countermeasure developers in manufacturing small amounts of products that can be used in clinical trials. In the CIADM request for proposals, BARDA outlined a list of core services it expects the CIADMs to provide. (See app. II for a list and description of these core services.) These core services may be provided by the CIADMs directly or by subcontractors. Once the CIADMs are operational, BARDA will issue task orders to the CIADMs for core services using the fair opportunity process outlined in the contracts. For example, BARDA may issue a task order for a CIADM to provide regulatory or technical assistance for a specific CBRN medical countermeasure to a developer with a current BARDA contract. Under the terms of the contracts, the CIADMs are required to make their core services available to HHS for 50 percent of the time, or 6 months per annual contract option period. If HHS does not issue a task order to use a CIADM for core services, or issues a task order for core services for less than 6 months of an annual option period, HHS will provide the CIADM with a facility readiness reimbursement for up to 6 months of that facility’s capacity for that option period. BARDA officials told us that some of the CIADMs may begin providing some core services during 2014, and that each of the CIADMs should be capable of providing each of the core services by the end of 2015. Once the new or retrofitted CIADM facilities are operational, a CIADM may begin providing core services, such as producing sufficient amounts of a specific countermeasure at a small scale to be tested in clinical trials for safety and efficacy. BARDA officials told us that the Fill Finish Manufacturing Network is also intended to provide these fill and finish services to CBRN medical countermeasure developers to supplement the core services provided by the CIADMs. This would be in cases such as when one or more of the CIADMs is at capacity or for countermeasures that may not be eligible for CIADM core services. According to BARDA officials the CIADMs and the Fill Finish Manufacturing Network are part of BARDA’s overall core service assistance programs, which, since 2011, also include an animal studies network and, since 2014, a new clinical studies network to assist developers of CBRN medical countermeasures. For the workforce training activity, the CIADMs are to develop programs to enhance and maintain U.S. capabilities and expertise to develop and produce CBRN medical countermeasures. These workforce training programs are intended to develop a highly-skilled biotechnology and pharmaceutical workforce proficient in bioprocess engineering, production and quality systems, and regulatory affairs. Through these workforce training programs, the CIADMs are to offer training through means such as certificate programs, workshops, industry short courses, and internships. The CIADMs may provide training in subjects such as an introduction to biotechnology, good manufacturing practices procedures and documentation, facility operations and safety, regulatory compliance, and bioprocess control. BARDA officials told us that during the contract base period, the CIADMs are required to develop their workforce training programs, and that the agency may begin to request workforce training activities through task orders in fiscal year 2014. HHS established the CIADMs to provide needed core services to support the development and production through flexible manufacturing of certain CBRN medical countermeasures that were identified as priorities by PHEMCE. The agency followed the recommendation in the PHEMCE review to establish CIADMs capable of providing such core services. However, it is too early to tell how effective this approach will be because HHS has not begun to issue task orders to CIADMs for core services. Of the three flexible manufacturing activities undertaken at the CIADMs, BARDA officials told us that the provision of core services is the primary activity intended to support the development of certain CBRN medical countermeasures. The core services are specifically designed to provide CBRN developers with needed experience, facilities, and technology to help develop and produce certain medical countermeasures that HHS and PHEMCE identified as priorities. According to BARDA, the three CIADM contractors are entities that have experience in developing, manufacturing, and licensing pharmaceutical products in the United States. BARDA officials told us that the core services to be provided by the CIADMs are the types of services that HHS, PHEMCE, and industry representatives identified as necessary. The 2010 PHEMCE review indicated that services such as regulatory support, animal testing, and, if appropriate, clinical trials were needed to help less-experienced countermeasure developers to get through the challenging advanced development phase. Further, the 2012 PHEMCE implementation plan identified, as a programmatic priority, that CIADMs provide experienced biopharmaceutical development staff at the CIADMs to aid in the development of medical countermeasures. Each of the three CIADMs are to provide 24 core services, directly or by subcontract, to assist countermeasure developers in moving their products through advanced development and production. In addition, BARDA officials indicated that each center can provide specific and slightly different expertise in developing products using alternate technologies, such as recombinant proteins or insect cells. For example, Emergent has experience developing products for infectious disease and biodefense. It has developed BioThrax, the only FDA-licensed anthrax vaccine, and has had several medical countermeasure development contracts with U.S. government agencies. Novartis has experience in developing a novel influenza cell culture as well as in other areas, and has an additional contract with BARDA to produce pandemic influenza vaccine. TAMUS is a large university system with access to a network of experienced partners including GlaxoSmithKline and a highly-rated veterinary school. TAMUS officials told us that their flexible manufacturing capabilities include modular “clean” rooms that can be tailored to each biopharmaceutical product’s specifications. According to BARDA officials, the CIADMs are designed to provide developers with access to a variety of core services all in the same facility and the project management experience needed to manage the CBRN medical countermeasure development process. BARDA officials indicated that they envision a countermeasure developer working with a single CIADM on a product’s development. Core services provided by the CAIDMs would have the potential to support only the development of medical countermeasures that are biologics-based, such as vaccines and recombinant proteins, but not small molecule countermeasures, such as antibiotics or antivirals. Examples of biologics-based countermeasures for CBRN threats include anthrax vaccine, recombinant protein chemical antidotes, and products to diagnose or treat the effects of exposure to radiological or nuclear agents. BARDA officials told us that the CIADMs are intended to assist in developing biologics-based countermeasures because a 2008 study commissioned by HHS and DOD examining vaccine manufacturing facility alternatives found that there is a sufficient domestic supply of contract manufacturing organizations that could be called upon in a public health emergency to produce small molecule countermeasures. The CIADMs’ services are intended to support countermeasure developers who have existing contracts with BARDA and countermeasure developers who have contracts with other PHEMCE partners, such as DOD and NIH. based CBRN countermeasure contracts that are eligible, in whole or in part, to receive core services from the CIADMs. BARDA officials indicated that the CBRN medical countermeasures to be developed under these contracts are consistent with the countermeasures identified as HHS priorities in the 2012 PHEMCE implementation plan. For example, the PHEMCE implementation plan identified the development of an anthrax vaccine as a priority, and 4 of the 23 eligible CBRN medical countermeasure projects focus on developing anthrax vaccine. DOD is also developing an advanced development and manufacturing center for medical countermeasure developers. BARDA officials told us that once the DOD facility is built and operational, the HHS and DOD centers’ services will be available under a unified umbrella to provide medical countermeasure development and manufacturing assistance. BARDA has not issued any task orders for core services to date, as the CIADMs are still completing activities associated with the contract base periods. Therefore, it is too early to tell the extent to which countermeasure developers may use CIADM services and how helpful the core services may be to support medical countermeasure development. Under the CIADM contracts, amounts awarded during the contract base period are to fund the construction of physical infrastructure, either the building of new facilities or the retrofitting of existing ones, and other preparations necessary to provide core services to countermeasure developers. As such, the base period of the contract provides a framework to help support countermeasure development, but no direct provision of core services. After the CIADM contractor establishes this framework, BARDA is to award task orders to CIADMs to provide core services to countermeasure developers. Because the CIADMs have not yet completed base period activities, BARDA has not yet issued task orders to provide core services. BARDA officials told us that two CIADMs may be able to provide core services as soon as 2014, a year earlier than planned. According to BARDA officials, once each of the CIADMs have completed construction or retrofitting, so that there is sufficient space to conduct core service activities, BARDA will evaluate and confirm the technical capabilities and capacity of each CIADM to provide core services prior to issuing task orders for these services. Once the CIADMs are operational, BARDA and other agencies that participate in PHEMCE are to select eligible countermeasure development projects for those developers who want to access the CIADMs and issue task orders for core services. In order to select eligible contracts and issue task orders, HHS and PHEMCE have created a CIADM steering committee consisting of senior level officials from BARDA, CDC, FDA, NIH, and DOD. HHS has completed documents that provide governance for this process: a signed charter for the steering committee, preliminary criteria for selecting eligible contracts, and a signed governance document describing how the process will operate. Under the process, the steering committee issues a data call, and in response, medical countermeasure project managers from BARDA, NIH, and DOD are to submit proposals for current medical countermeasure contracts that would benefit from core services provided by the CIADMs to the CIADM steering committee.review the proposals and select the countermeasure projects and developers to which it will offer access to the CIADMs’ core services. Next, HHS plans to issue task order requests for each selected project, and the CIADMs will be required to submit proposals in response to the task order requests. Finally, according to BARDA officials, BARDA plans to issue a task order to the CIADM contractor whose proposal best satisfies the selection factors for award under the task order. BARDA officials told us that the CIADM steering committee met in January 2014 and plans to meet at least semiannually. The steering committee is to then While it is too early to tell how effective HHS’s approach to providing core services to CBRN medical countermeasure developers through the CIADMs will be, some industry stakeholders we interviewed expressed concerns about demand, availability of funding, and communication with BARDA. For example, some stakeholders questioned whether there would be a sufficient number of countermeasure developers who need advanced development support and who might choose to receive those services from the CIADMs. BARDA officials told us that they have conducted surveys of developers with current BARDA contracts about their interest in receiving core services from the CIADMs. As a result, according to officials, BARDA anticipates having a greater demand for core services than the CIADMs will be able to supply. Additionally, industry stakeholders we spoke to expressed concern that insufficient funding for task orders may affect the success of the CIADMs. BARDA officials told us that funding for task orders will either come from BARDA’s budget for specific medical countermeasures, or from other agencies, such as NIH, through interagency agreements, but that the availability of funds for specific development projects would play a role in deciding which projects would receive core services. BARDA officials told us that they expect to have sufficient funding for task orders in fiscal years 2014 and 2015. Some industry stakeholders that we talked to also indicated that BARDA has not yet provided detailed information to industry partners about how countermeasure developers will request and use core services from the CIADMs. BARDA officials told us that BARDA featured the CIADMs and explained CIADM operations at its November 2013 Industry Days. At this time, the eligible countermeasure developers are only those who have current development contracts with BARDA, NIH, and DOD. We provided a draft of this report to HHS, and its comments are reprinted in appendix III. In its comments, HHS acknowledged that it is too early to determine whether the Centers are meeting their prescribed goals because their intended core service activities have not yet begun. However, HHS noted that the CIADMs are nearly a year ahead of schedule in completing construction and ramping up activities in anticipation of providing services once HHS begins issuing task orders in 2014. HHS also noted that the CIADMs are a new model for public- private partnerships, and represent one component of BARDA's comprehensive, integrated approach to supporting advanced research and development, innovation, acquisition, and manufacturing of countermeasures for public health emergency threats. In addition to its overall comments, HHS provided technical comments, which we incorporated as appropriate. We are sending copies of this report to the Secretary of Health and Human Services. In addition, the report is available at no charge on the GAO website at http://www.gao.gov. If you or your staffs have any questions about this report, please contact me at (202) 512-7114 or crossem@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. GAO staff who made key contributions to this report are listed in appendix IV. Developing the appropriate requirements for growing cells upstream (media) and preparing ingredients for downstream purification (buffers) In addition to the contact named above, Sheila K. Avruch, Assistant Director; Matt Byer; Britt Carlson; Shana R. Deitch; Cathy Hamann; and Tracey King made significant contributions to this report. National Preparedness: HHS is Monitoring the Progress of Its Medical Countermeasure Efforts but Has Not Provided Previously Recommended Spending Estimates. GAO-14-90. Washington, D.C.: December 27, 2013. National Preparedness: Efforts to Address the Medical Needs of Children in a Chemical, Biological, Radiological, or Nuclear Incident. GAO-13-438. Washington, D.C.: April 30, 2013. National Preparedness: Countermeasures for Thermal Burns. GAO-12-304R. Washington, D.C.: February 22, 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. Influenza Pandemic: Lessons from the H1N1 Pandemic Should Be Incorporated into Future Planning. GAO-11-632. Washington, D.C.: June 27, 2011. Influenza Vaccine: Federal Investments in Alternative Technologies and Challenges to Development and Licensure. GAO-11-435. Washington, D.C.: June 27, 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.

Summary: Public health emergencies, such as the 2001 anthrax attacks and the 2009 H1N1 influenza pandemic, raise concerns about the nation's vulnerability to threats from CBRN agents and new or reemerging infectious diseases, such as pandemic influenza. HHS is the federal agency primarily responsible for identifying medical countermeasures needed to address the potential health effects from exposure to CBRN agents and emerging infectious diseases. HHS conducted a review to assess how to better address these concerns. Its August 2010 review concluded that the advanced development and manufacture of CBRN medical countermeasures needed greater support. The review recommended that HHS develop centers to provide such support, in part by using flexible manufacturing technologies, such as disposable equipment, to aid in the development and rapid manufacture of products. The Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 requires GAO to examine HHS's flexible manufacturing initiatives and the activities these initiatives will support. This report addresses (1) how much funding HHS has awarded for flexible manufacturing activities for medical countermeasures, and (2) the extent to which these activities will support the development and production of CBRN medical countermeasures. To address these objectives, GAO examined HHS documents and interviewed HHS officials, contractors, and stakeholders. In comments on a draft of the report, HHS agreed with its findings and provided additional information. In fiscal years 2012 and 2013, the Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) awarded nearly $440 million in contracts to establish three Centers for Innovation in Advanced Development and Manufacturing (CIADM) and a network of facilities to provide packaging support for medical countermeasure distribution, known as the Fill Finish Manufacturing Network (FFMN). The contracts require the CIADMs to develop three activities to support flexible manufacturing for medical countermeasure development and production: the manufacture of pandemic influenza vaccines during an emergency; core services to support the development and production of chemical, biological, radiological, and nuclear (CBRN) medical countermeasures; and workforce training. During the contract base periods, each CIADM is to retrofit existing or build new facilities able to produce 50 million doses of pandemic influenza vaccine within 4 months of receipt of the influenza virus strain and to establish the capacity to provide core services, such as assisting countermeasure developers by manufacturing products to be used for clinical trials. The CIADMs are also required to develop workforce training programs, which are intended to increase expertise in CBRN medical countermeasure development. The CIADM base contracts are intended to retrofit or build facilities to stand ready to provide these three activities and maintain this readiness through annual contract option periods. Once the facilities are prepared to provide these activities, BARDA may place task orders for provision of CIADM vaccine surge capacity, core services, or training, and BARDA, through the task orders, would provide additional payments to obtain these services. The FFMN is to supplement CIADMs' pandemic influenza surge capacity, packaging up to 117 million doses of pandemic influenza vaccine in 12 weeks, if needed, and can also provide core services as CIADM subcontractors. HHS's CIADM core services activities are designed to support the development and production of certain CBRN medical countermeasures, but it is too early to tell how effective this approach will be. BARDA's establishment of the CIADMs implements a recommendation from HHS's review of the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE)—a federal interagency body that advises HHS on medical countermeasure priorities. The CIADMs are to support the development of biologics-based countermeasures only, which are products like vaccines that are derived from living sources such as cells, because BARDA considers these countermeasures to need the greatest support. BARDA has identified some of its current biologics-based countermeasure development contracts that could use core services' support and are priorities for PHEMCE. However, the CIADMs are still completing activities associated with their contract base period. Thus, BARDA has not issued any task orders for core services to date, but has created a CIADM steering committee and completed guidance to govern the task order process once the CIADMs are operational. Until the CIADM core services are used, it will be unclear how effectively they will support the development and production of CBRN medical countermeasures. Stakeholders we interviewed were uncertain about the demand for and availability of funding for core services. BARDA officials said that they anticipate having sufficient demand for the services and funding for task orders in fiscal years 2014 and 2015.