Biomedical Advanced Research and Development Authority

The Biomedical Advanced Research and Development Authority (BARDA) is a U.S. Department of Health and Human Services office responsible for procurement and development of countermeasures principally against bioterrorism, but also including chemical, nuclear and radiological threats as well as pandemic influenza and emerging diseases.[1]:140 BARDA reports to the Office of the Assistant Secretary for Preparedness and Response and manages Project BioShield.[1]:140 BARDA also procures materials, such as vaccines, for the Strategic National Stockpile, and more broadly is an established interface between the U.S. Government and the biomedical industry.[1]:267 BARDA also manages the governmental inter-agency Public Health Emergency Medical Countermeasures Enterprise, providing coordination across the government in development and deployment of such countermeasures.[1]:267

The Project BioShield Act of 2004 created a way to fund the research, development and stockpiling of vaccines and treatments that the government could use during public health emergencies such as a chemical, biological, radiological, or nuclear attacks. The agency gives funds to pharmaceutical companies to develop these countermeasures. Between 2007 and 2017, BARDA procured and stockpiled 21 products to be used in potential public health emergencies.[2]

The office was established in 2006 through the Pandemic and All-Hazards Preparedness Act.[1]:267

Requirements setting

BARDA sets for requirements for medical countermeasures in order to reduce the threats of public health emergencies such as pandemic influenza, CBRN threats, and emerging diseases. The requirements tell private industry what is required in order to produce medical countermeasures acceptable for BARDA.

Stakeholders across the federal government and the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) create the requirements. After the requirements are established, they drive BARDA advanced research and development and acquisition. The requirements are created consistent with the planning and prioritization expressed in the HHS PHEMCE Implementation Plan for CBRN Threats.[3]

Pandemic Influenza requirements are defined by strategic objectives established in the "National Strategy for Pandemic Influenza",[4] and the "HHS Pandemic Influenza Plan".[5]

Major initiatives

  • Research and development
    • Medical countermeasures
      • Vaccines
      • Antimicrobial drugs
      • Therapeutic products
      • Diagnostics
      • Non-pharmaceutical medical supplies
  • Stockpiling programs (see below)
  • Manufacturing infrastructure

Advanced research and development

From its inception, BARDA has been committed to creating a robust and dynamic pipeline of medical countermeasures through advanced development of new and improved medical countermeasures. The goal of medical countermeasure development is to provide multiple product candidates in each program to both account for attrition in medical countermeasure development and to establish multi-product/multi-manufacturer portfolios for sustainability and redundancy.

BARDA medical countermeasures include vaccines, antimicrobial drugs, therapeutic products, diagnostics and non-pharmaceutical medical supplies and devices for public health medical emergencies including chemical, biological, radiological, and nuclear threats, pandemic influenza and emerging infectious diseases. BARDA currently has three programs dedicated to overseeing the advanced development of these medical countermeasures: Chemical, Biological, Radiological, and Nuclear (CBRN); pandemic influenza; and emerging infectious diseases. BARDA’s Influenza and Emerging Diseases Division is in the planning phase for its Emerging Infectious disease program. This program will, when stood up, support the advanced development of vaccine, therapeutic and diagnostic medical countermeasures that address emerging disease threats.

Nerve agents and other chemical weapons are a top priority for fighting CBRN threats. VX gas, which was the nerve agent that reportedly killed the half-brother of North Korean leader Kim Jong-un, is an example. BARDA Is preparing to stockpile an anti-seizure medication called midazolam, developed by Meridian Medical Technologies (a subsidiary of Pfizer), which will be made available in an autoinjector that could treat the effects of nerve agents on the neurological system.[2]

In October 2017 BARDA entered a nine-month $12-million contract with the San Francisco-based biopharmaceutical company Achaogen, sponsoring late-stage development of C-scape, an antibiotic used against resistant bacteria and a potential treatment against bioterrorism chemical agents.[6][7][8]

Integrated National Biodefense Medical Countermeasures Portfolio

Integrated National Biodefense Medical Countermeasure Portfolio “One-Portfolio Approach.” The Department of Defense (DoD) and HHS each identify medical countermeasure requirements to address their different missions and focus. DoD’s focus is on protecting the armed forces prior to exposure, whereas HHS’s focus is on response to threats to the civilian population after exposure in a CBRN event. However, there are areas of common requirements or interest where medical countermeasure candidates, resources and information can be appropriately shared to maximize opportunities for success in the development of medical countermeasures for the highest priority threats. BARDA, in partnership with other HHS and DoD partners, is leading an Integrated National Biodefense Medical Countermeasure Portfolio to leverage resources and programs across the agencies that develop and acquire CBRN medical countermeasures to more effectively address the broad range of common threats and requirements. Members of this Integrated Portfolio include BARDA, biodefense programs in NIAID and other Institutes of NIH, and multiple elements of the DoD Chemical and Biological Defense Program

Stockpiling programs

The Pandemic and All Hazards Preparedness Act (PAHPA) established BARDA as the focal point within HHS for the advanced development and acquisition of medical countermeasures to protect the American civilian population against Chemical, Biological, Radiological, and Nuclear (CBRN) and naturally occurring threats to public health.

BARDA’s stockpiling efforts are focused on building reserves of critical countermeasures as they emerge from Advanced Development. Stockpiling contributes to preparedness in two ways:

  1. Stockpiled medical countermeasures directly support readiness, as the stockpiled products can help to mitigate the effects of an event or outbreak.
  2. Establishment of the stockpile helps to ready suppliers to meet the increased demands that an event will bring about, becoming practiced in the production and delivery of products.

BARDA’s acquisitions for the stockpile are not one-time events, complete upon the approval/licensure of a product. Rather, programs are structured to include incremental milestone acquisitions during late stage development, to make available products still in development that may increase preparedness in an event, pending Emergency Use Authorization. Furthermore, we aim to establish stockpiling milestones to address long term commitments post-licensure.

CBRN stockpiling programs

In FY 2004, Congress appropriated $5.6 billion to the Project BioShield Special Reserve Fund (SRF) to support the Project BioShield goal of acquiring CBRN medical countermeasures over a 10-year period. BARDA has used these funds to support major acquisition programs leading to procurement of medical countermeasures against top priority threats.

Pandemic influenza stockpiling programs

Using funds from the Pandemic Influenza Emergency Supplemental Fund, BARDA is leading the nation toward the vaccine and antiviral stockpile goals for preparedness for pandemic influenza.

Strategic National Stockpile

The Public Health Security and Bioterrorism Preparedness Act of 2002 directed the Secretary of Health and Human Services to develop and maintain a Strategic National Stockpile (SNS). The mission of the SNS is to provide for the emergency health security of the United States in the event of a terrorist attack or any other public health emergency.[9]

The SNS is the nation’s largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a small outbreak to a large-scale, multiple-threat emergency. When state, local, tribal, and/or territorial responders request federal assistance to support their response efforts, the stockpile is supposed to ensure that supplies are available when and where needed.[10] The stockpile contains enough vaccines, antimicrobial drugs, therapeutic products, and non-pharmaceutical medical supplies to save thousands of lives in the wake of any type of public health emergency including terrorist attacks whether chemical, biological, radiological, and/or nuclear, as well as pandemic influenza and emerging infectious diseases.[11]

Emergent BioSolutions is a Maryland-based pharmaceutical company that manufactures vaccines and related products for use against common diseases and biological weapons. Emergent manufactures the only FDA licensed vaccine against anthrax disease, called BioThrax, which is recommended by the CDC as a post-exposure prophylactic for anthrax infection.[12]

As part of a $450 million contract with BARDA for the SNS, Emergent also developed the only FDA-licensed botulinum antitoxin, BAT [Botulism Antitoxin Heptavalent] for treating naturally occurring botulism.[v] Canada has also approved BAT.[13]

The federal government improved its plan against chemical, biological, radiological and nuclear threats after the 2001 anthrax letters attack, which killed five Americans. It was the worst biological attack in United States history.[2]

The agency also invested in the late stage development of a product called NuThrax developed by Emergent Biosolutions, which makes the other anthrax vaccine, BioThrax. According to Homeland Preparedness News, NuThrax will be able to provide immunity to anthrax after two doses, versus the three doses under the currently stockpiled vaccine (BioThrax).[2]

Medical countermeasure products

Threat Product Development stage
Smallpox In process Future development
Botulism Botulism therapeutic product Procured
Anthrax Nuthrax (Emergent Biosolutions) Late stage development and procurement
Anthrax BioThrax (Emergent Biosolutions) Stockpiled
Ebola virus Ebola therapeutic and Ebola vaccine Late stage development
Nerve agents

(such as VX)

 Midazolam in an autoinjector (Pfizer subsidiary Meridian Medical Technologies) In process of preparing to stockpile
Mustard gas In process Future development
Chlorine gas In process Future development
Improvised nuclear device or dirty bomb Cytokine products Procured
Burn injuries Silverlon, a metallic silver-based antimicrobial wound dressing (Argentum Medical) Stockpiled

Table source:[2]

Manufacturing and infrastructure building

Ensuring the availability of medical countermeasures for public health emergencies is central to BARDA’s mission. This includes ensuring that manufacturing infrastructure is sufficient to support the production of required products, in a manner that is timely, reliable and cost effective.

BARDA is taking several approaches to bringing online the necessary infrastructure for medical countermeasure manufacturing. We are supporting the construction of new facilities as well as retrofitting existing facilities for maximal capacity and flexibility. We are also exploring the use of multiproduct manufacturing facilities to provide flexibility and surge capacity. So that we are able to rapidly provide countermeasures in the dosage forms required for use in the field, we are establishing a network of formulation/fill-finish manufacturers for emergency production and distribution. BARDA is also exploring the creation of centers of excellence for the development and production of non-commercial products, with assistance from industry partners.

Advancing innovation

The Pandemic and All Hazards Preparedness Act (PAHPA) charges BARDA to support innovation to reduce the time and cost of medical countermeasures and product advanced research and development. This is to be accomplished through development of technologies that assist the advanced development of countermeasures, investment in research tools and technologies, and research to promote strategic initiatives including rapid diagnostics, broad spectrum antimicrobials, and vaccine manufacturing technologies.

BARDA sees this innovation mandate as an opportunity to work with their partners (including NIH, DoD, CDC, industry, and academia) to create new ways to “make medical countermeasure better.” Examples of this approach to innovation could include the development of animal models to support efficacy testing, immune modulation and other broad-spectrum approaches, immunity assessment, and analytical (potency) assays.

An example of innovation from the Pandemic Influenza program is BARDA’s Mix and Match study, assessing various combinations of antigens and adjuvants to obtain a more robust immune response.[14] BARDA plans to support similar initiatives, leveraging technology platforms and products from multiple companies. PAHPA provided an important “antitrust” authority that is used to facilitate cooperation among companies for whom such cooperation would otherwise be difficult to accomplish.

Fujifilm Corporation announced in April 2017 that it would invest $130 million to increase production capacity for its BioCDMO division. The division “focuses on contract development & manufacturing for biologics.”[15] Fujifilm Diosynth Biotechnologies, with help from a BARDA grant, has invested around $93 million to build a production facility in Texas. The facility will include “mammalian cell culture bioreactors” and is planned to open operations at the start of 2018.[15]

In April 2017, Switzerland-based Basilea Pharmaceutica and the Food and Drug Administration reached an agreement regarding two phase 3 clinical studies of an antibiotic developed by Basilea called ceftobiprole. The two clinical studies will examine ceftobiprole for the treatment of “Staphylococcus aureus bacteremia (bloodstream infections) and acute bacterial skin and skin structure infections.”[16] Basilea has a contract with BARDA, which it entered into in 2016 for the clinical phase 3 development of the antibiotic. BARDA provided initial funding of $20 million but could provide up to $100 million over a period of 4-5 years.[16]

In 2017, BARDA signed a three-year $8.1 million contract with InBios International, Inc. of Seattle, Washington to develop a “point-of-care diagnostic test that may be able to determine within 15 minutes whether a patient has been infected with the bacterium that causes anthrax.”[17]

In September 2017, BARDA awarded Velico Medical $15.5 million for development of a technology that uses spray drying of human plasma for transfusions. The current industry standard is to freeze plasma. Frozen plasma can take 40 or more minutes to defrost and deliver.[18] According to Fierce Biotech, “Velico has Spray Dried Plasma technology (SpDPTM) that enables the storage of blood as dry powder, rather than the typical freezing, for subsequent rehydration. It's expected to be useful in hospital emergency rooms, operating suites and intensive care units--as well as in a military or field hospital setting.”[19]

In July 2005, at the hearings before the Committee on Health, Education, Labor, and Pensions, the first CEO and Director of the center, Tara O'Toole, MD, MPH, has pointed to center's role as the "BioDARPA" (i.e. "biomedical DARPA").[20][21]

See also

References

  1. 1 2 3 4 5 Kraft, Michael; Marks, Edward (2016). U.S. Government Counterterrorism: A Guide to Who Does What. Boca Raton, Florida: CRC Press. ISBN 9781439851470. OCLC 635488871 – via Google Books.
  2. 1 2 3 4 5 "With some biological threats mitigated, BARDA shifts focus to combat highly pathogenic viruses, chemical agents". Homeland Preparedness News. 2017-03-06. Retrieved 2017-03-14.
  3. ↑ "HHS PHEMCE Strategy and Implementation Plan". MedicalCountermeasures.gov. U.S. Department of Health & Human Services. Archived from the original on 15 October 2011.
  4. ↑ Homeland Security Council (November 2005). "National Strategy for Pandemic Influenza" (PDF). Flu.gov. U.S. Department of Health & Human Services. Retrieved 1 October 2016.
  5. ↑ "HHS Pandemic Influenza Plan". HHS.gov. U.S. Department of Health & Human Services. Archived from the original on 2 March 2012.
  6. ↑ Editors, BioPharm International. "HHS Sponsors Development of Antibiotic-Resistant, Anti-Biowarfare Antibiotic". www.biopharminternational.com. Retrieved 2017-12-20.
  7. ↑ "News Release - PHE". www.phe.gov. Retrieved 2017-12-20.
  8. ↑ "BARDA, Achaogen partner to develop antibiotic to combat infections from drug resistant bacteria". Homeland Preparedness News. 2017-10-12. Retrieved 2017-12-20.
  9. ↑ Policy, Board on Health Sciences; Division, Health and Medicine; National Academies of Sciences, Engineering (2016-10-24). The Strategic National Stockpile: Origin, Policy Foundations, and Federal Context. National Academies Press (US).
  10. ↑ "Strategic National Stockpile | PHPR". www.cdc.gov. Retrieved 2017-01-19.
  11. ↑ "Inside A Secret Government Warehouse Prepped For Health Catastrophes". NPR.org. Retrieved 2017-01-19.
  12. ↑ "1 And HPA Announce Botulinum Vaccine Collaboration". www.biospace.com. Retrieved 2017-01-19.
  13. ↑ "Health Canada approves Emergent BioSolutions' botulism antitoxin". Homeland Preparedness News. 2016-12-13. Retrieved 2017-01-19.
  14. ↑ World Health Organization. (2010). Proceedings of the ninth global vaccine research forum and parallel satellite symposia: Bamako, Mali 6-9 December 2009.
  15. 1 2 "Fujifilm expands biopharma facilities in US & UK with $ 130 mn investment". Business Standard India. 2017-04-24. Retrieved 2017-04-25.
  16. 1 2 "Basilea announces agreement with FDA on Special Protocol Assessments for antibiotic ceftobiprole phase 3 clinical studies in bloodstream and skin infections". Yahoo Finance. 2017-04-21. Retrieved 2017-04-25.
  17. ↑ "Anthrax: HHS advances point-of-care diagnostic test - Outbreak News Today". Outbreak News Today. 2017-09-26. Retrieved 2017-10-01.
  18. ↑ "Velico Medical Announces a Further $18.9m BARDA Funding for Spray Dried Alternative to Frozen Plasma". PRWeb. Retrieved 2017-10-01.
  19. ↑ "Startup Velico nabs another $15.5M from BARDA for dried plasma tech | FierceBiotech". www.fiercebiotech.com. Retrieved 2017-10-01.
  20. ↑ Hearing before the Committee On Health, Education, Labor, And Pensions United States Senate, One Hundred Ninth Congress (July 14, 2005). U.S. Government Printing Office, Washington : 2007
  21. ↑ Klabukov, Ilya (2017). "The BioDARPA Concept". SSRN Electronic Journal.
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