National Preparedness: HHS Has Funded Flexible Manufacturing Activities for Medical Countermeasures, but It Is Too Soon to Assess Their Effect
Published: 2014-03-31T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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.
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: Public health emergencies in the new millennium—such as the 2001  anthrax attacks and the 2009 H1N1 influenza pandemic—continue to  raise concerns about our nation’s vulnerability to threats from chemical,  biological, radiological, and nuclear (CBRN) agents and new or  reemerging infectious diseases. The Department of Health and Human  Services (HHS) is the federal agency primarily responsible for identifying  needed medical countermeasures to prevent or mitigate potential health  effects from exposure to such threats. As part of that task, HHS works  with other federal agencies to engage with industry to develop medical  countermeasures through its Public Health Emergency Medical  Countermeasures Enterprise (PHEMCE). PHEMCE is a federal  interagency body—composed of certain HHS agencies and offices, the  Departments of Defense and Homeland Security, and others— established in 2006 and responsible for providing recommendations to  the Secretary of Health and Human Services on medical countermeasure  priorities and development and production needs.
There are some medical countermeasures—drugs, vaccines, and devices  to diagnose, treat, prevent, or mitigate potential health effects of  exposure—available for these agents and diseases. However, as with  drugs and other pharmaceuticals in general, research and development  to create usable countermeasures for CBRN agents and emerging  infectious diseases is a lengthy, complex, and expensive process. The  general lack of a commercial market for some medical countermeasures  may reduce incentives for large pharmaceutical and medical device  manufacturers to invest millions of dollars to develop such products,  instead of others that may be more profitable. Hence, many medical  countermeasure developers are small biotechnology companies with less  experience than larger pharmaceutical companies in developing a  product and bringing it to market.
In addition to the lack of incentives for larger pharmaceutical companies  and the limited experience of smaller biotechnology companies, the 2009  H1N1 influenza pandemic raised particular concerns about the United  States’ ability to rapidly manufacture needed medical countermeasures  for CBRN threats and new or reemerging infectious diseases. As a  result, in August 2010, HHS conducted a review of PHEMCE’s activities  to develop and produce needed medical countermeasures. In its review,  HHS concluded that the United States must have a nimble, flexible  capability to rapidly produce medical countermeasures for CBRN threats  or emerging infectious diseases in a public health emergency and that  this capacity was lacking. The review also highlighted the need for more  support for smaller biotechnology companies conducting advanced  research and development of countermeasures, including assistance in  moving countermeasures through clinical trials and developing and  producing them to the point at which HHS would be able to procure  them. In the PHEMCE review, HHS also recommended that the  department, either alone or in collaboration with the Department of  Defense, establish centers to provide advanced development and  manufacturing capability for medical countermeasures to address national  security and to augment public health needs on a cost-effective, reliable,  and sustainable basis. These centers are intended to support flexible  manufacturing—that is, the use of disposable equipment and alternative  technologies for product development and rapid manufacturing—to aid in  the development and production of medical countermeasures. In its  PHEMCE review, HHS stated that these centers would strengthen  countermeasure development by linking countermeasure developers with  needed expertise, using and improving flexible manufacturing  technologies, augmenting manufacturing surge capacity against emerging  infectious diseases or unknown threats, and helping train future  countermeasure developers. In June 2012, HHS awarded three contracts  to establish three Centers for Innovation in Advanced Development and  Manufacturing (CIADM).
The Pandemic and All-Hazards Preparedness Reauthorization Act of  2013 (PAHPRA) requires that we examine HHS’s flexible manufacturing  initiatives and the activities these initiatives are to support. This report  addresses (1) how much funding HHS has awarded for activities to  support flexible manufacturing for medical countermeasures since fiscal  year 2010, and (2) the extent to which these activities are to support the  development and production of CBRN medical countermeasures.
To answer the first objective, we obtained and analyzed HHS financial  data to calculate how much HHS awarded for flexible manufacturing  capacity since fiscal year 2010, the date of publication of the PHEMCE  review. We also analyzed the three contracts HHS awarded to establish  the CIADMs to determine the amounts awarded under each contract and  the activities each center will carry out. We interviewed officials from  HHS’s Office of the Assistant Secretary for Preparedness and Response  (ASPR), ASPR’s Biomedical Advanced Research and Development  Authority (BARDA), and officials from each of the three CIADMs to  determine the activities these funds are intended to support and the  current status of the CIADMs. Finally, we interviewed two relevant  stakeholder groups for their perspectives on planned center activities. Of  these two stakeholder groups, we interviewed officials from one  association that represents more than 1,000 domestic and international  biotechnology companies and related organizations that develop medical  countermeasures and other pharmaceuticals. We also interviewed  officials from an academic research center that conducts research and  analysis and provides policy recommendations to protect people’s health  from the consequences of public health emergencies.
To answer the second objective, we examined HHS documents, such as  the 2010 PHEMCE review, to identify barriers to advanced research and  development. We also reviewed these documents for recommendations  on overcoming those barriers, such as by supporting and developing  flexible manufacturing capacity. We reviewed HHS’s PHEMCE planning  documents to identify PHEMCE’s CBRN medical countermeasure  priorities. We reviewed HHS’s request for proposals for the CIADMs and  the three CIADM contracts HHS subsequently awarded to identify the  extent to which the CIADM’s activities are to address PHEMCE’s  identified development and production barriers and CBRN  countermeasure priorities. We interviewed the HHS and CIADM officials  and relevant stakeholders identified above to assess how the CIADM’s  activities are to assist in supporting the development of CBRN  countermeasures to fulfill PHEMCE’s priorities.
We conducted this performance audit from September 2013 through  March 2014 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.
subsections: section_title: Background
paragraphs: 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.
subsections: section_title: Federal Roles and Responsibilities Related to Medical Countermeasures
paragraphs: 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.)
section_title: Flexible Manufacturing
paragraphs: 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.
section_title: Addressing Barriers to Developing Countermeasures and Rapid Response to Pandemic Influenza
paragraphs: 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.
section_title: HHS Awarded $440 Million in Fiscal Years 2012 and 2013 in Contracts for Activities to Support Flexible Manufacturing for Medical Countermeasures
paragraphs: 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.
subsections: section_title: HHS Awarded $440 Million in Contracts to Establish Three CIADMs and the Fill Finish Manufacturing Network
paragraphs: 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.
section_title: The CIADMs and the Fill Finish Manufacturing Network Are Intended to Provide Three Activities to Support Flexible Manufacturing
paragraphs: 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.
subsections: section_title: Surge Capacity
paragraphs: 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.
section_title: Core Services
paragraphs: 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.
section_title: Workforce Training
paragraphs: 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.
section_title: HHS’s Flexible Manufacturing Activities Are Designed to Support the Development and Production of CBRN Medical Countermeasures, but It Is Too Early to Determine Their Effectiveness
paragraphs: 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.
subsections: section_title: Core Services Are Designed to Support the Development of Certain CBRN Medical Countermeasures
paragraphs: 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.
section_title: As Core Services Have Not Yet Been Provided, It Is Too Early to Tell How Helpful They Will Be to Countermeasure Developers
paragraphs: 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.
section_title: Agency Comments and Our Evaluation
paragraphs: 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.
section_title: Appendix I: The Department of Health and Human Services’ Priorities for Chemical, Biological, Radiological, and Nuclear Medical
section_title: Appendix II: Centers for Innovation in Advanced Development and Manufacturing Core Services
paragraphs: Developing the appropriate requirements for  growing cells upstream (media) and preparing  ingredients for downstream purification (buffers)
subsections: section_title: Core Service
section_title: Appendix III: Comments from the Department of Health and Human Services
section_title: Appendix IV: GAO Contact and Staff Acknowledgments
subsections: section_title: GAO Contact
section_title: Staff Acknowledgments
paragraphs: 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.
section_title: Related GAO Products
paragraphs: 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.