Global & Disaster Medicine

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Project BioShield over 15 years of progress

ASPR

Project BioShield Evolution: Fifteen Years of Bridging the ‘Valley of Death’ in the Medical Countermeasures Pipeline

Author: By Dr. Robert Kadlec, Assistant Secretary for Preparedness and Response
Published Date: 7/17/2019 12:15:00 PM
Category: Innovations; Medical Countermeasures; National Health Security;

Saving lives in a public health emergency requires cutting-edge medical countermeasures: medications, vaccines, diagnostics, and more. In some types of emergencies, like an act of bioterrorism, some of those medical products have no commercial market. People don’t use an anthrax antitoxin every day – thank goodness. Yet that lack of commercial market also means pharmaceutical or biotech companies had only one possible buyer for their products: the federal government for stockpiling.

In 2004, Congress passed the Project BioShield Act to create a market for products necessary for disaster response but with limited or no commercial market. The Act provides HHS with a multi-year special reserve fund to support late-stage development and manufacturing, and the financial resources to buy these life-saving medical products for the American people to use in public health emergencies. In this way, Project BioShield is a critical part of the U.S. strategy for biodefense and our commitment to the American people.

Last month, Congress took action to further strengthen Project BioShield as part of the Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019 (PAHPAIA). PAHPAIA increases the budget authorization and provides ten-year funding for product development. We know next-generation medical countermeasures aren’t developed overnight – in fact, getting a product across the finish line takes many years. Multi-year funding helps BARDA continue building the strong public-private partnerships needed to spur innovation and provide the private sector with the stability needed to produce potentially lifesaving medical countermeasures.

For example, smallpox is one of the most consequential infectious diseases in human history, responsible for nearly 300 million deaths in the 20th century alone. It is also a high-priority threat requiring federal agencies to develop strategies and countermeasures against this threat. Thanks to our partners at NIAID and DoD and the support of Project BioShield, last year our industry partner was issued an FDA approval for a treatment for smallpox via the animal rule. At present, there are now over 2 million treatment courses in ASPR’s Strategic National Stockpile to protect Americans in the event of a smallpox national security emergency.

However, we have found over the past 15 years the most practical and cost-effective approach is, whenever possible, to look at products that not only can be used for emergencies, but also have uses in daily medical care, such as burn care, the radiation effects cancer patients encounter, or seizures.

In some cases, we’ve worked with companies to expand indications for existing products. For example, three medical countermeasures are now FDA-approved to treat patients suffering bone marrow and blood cell damage from acute radiation syndrome. All three of these products were already licensed drugs used to treat patients undergoing radiation therapy for cancer. Project BioShield funding was used to conduct the critical studies needed to expand the indications for these products so they could also be used to treat the damage caused by acute radiation syndrome in a radiation emergency. Using such drugs is helpful in emergencies because healthcare facilities already stock the drugs, and clinicians are already familiar with using them.

We are using Project BioShield to support other new products with commercial market potential. For example, we supported a large study of a seizure treatment because seizures are one of the potentially deadly effects of nerve agents. The product is used commonly in preparing patients for surgery and for epileptic seizures; thanks to Project BioShield, the product is now approved as an antiseizure medication for status epilepticus and has been added to the Strategic National Stockpile for use in a chemical emergency response.

For 15 years, BARDA has been proud to partner with industry to develop cutting-edge medical countermeasures. Our country is better prepared to respond to health security threats because of Project BioShield. We look forward continued collaboration as we work to develop and produce medical countermeasures that can be used to save lives in the event of an emergency.


Can Sydney, Australia manage a smallpox attack? It depends.

MacIntyre CR, Costantino V, Kunasekaran MP (2019) Health system capacity in Sydney, Australia in the event of a biological attack with smallpox. PLoSONE 14(6): e0217704.https://doi. org/10.1371/journal.pone.0217704

“……We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios.

If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced.

At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions…..”

 


Ready or Not: Protecting the Public’s Health from Diseases, Disasters and Bioterrorism, 2019

Trust For America’s Health

One lesson from recent events is that emergencies happen. And happen often. From disease outbreaks to natural disasters to man-made crises, the stakes are high: Americans face serious health risks and even death with increasing regularity. Therefore, as a nation, it’s critical to ask, “Are we prepared?”

Executive Summary

The public health emergencies of the past year—an unusually severe flu season, confounding cases of acute flaccid myelitis, two major hurricanes, and the deadliest fire season in California’s history reinforce the need for every jurisdiction to be vigilant about preparing for emergencies in order to safeguard the public’s health.

A fundamental role of the public health community is to protect communities from disasters and disease outbreaks. To this end, the nation’s health security infrastructure has made tremendous strides since 2001 by building modern laboratories, maintaining a pipeline of medical countermeasures, and recruiting and retaining a workforce trained in emergency operations. Yet, unstable and insufficient funding puts this progress at risk, and a familiar pattern takes shape: underfunding, followed by a disaster or outbreak, then an infusion of onetime supplemental funds, and finally a retrenchment of money once attention wanes. What’s more, states are uneven in their levels of preparedness. Some—often those that most frequently face emergencies—have the personnel, systems, and resources needed to protect the public. But others are less prepared and less experienced, elevating the likelihood of preventable harms. This unstable funding and uneven preparation undermines America’s health security.

The Ready or Not: Protecting the Public’s Health from Diseases, Disasters and Bioterrorism series, produced by Trust for America’s Health (TFAH), has tracked public health emergency preparedness in the United States since 2003. The series has documented significant progress in the nation’s level of preparedness as well as those areas still in need of improvement.

Ready or Not examines the country’s level of public health emergency preparedness on a state-by-state basis using 10 priority indicators. (See Table 1.) Taken together, the indicators are a checklist of priority aspects of states’ readiness for public health emergencies. However, these indicators do not necessarily reflect the effectiveness of states’ public health departments. Improvement in these priority areas often requires action from other agencies, elected officials or the private sector.

The 2019 report finds that states have made progress in key areas, including public health funding and participation in provider compacts and coalitions. However, performance in other areas—such as flu vaccination, hospital patient safety, and paid time off for workers—has stalled or lost ground.

Table 1: Top-Priority Indicators of State Public Health Preparedness

Indicators
1 Incident Management: Adoption of the Nurse Licensure Compact. 6 Water Security: Percentage of the population who used a community water system that failed to meet all applicable health-based standards.
2 Cross-Sector Community Collaboration: Percentage of hospitals participating in healthcare coalitions. 7 Workforce Resiliency and Infection Control: Percentage of employed population with paid time off.
3 Institutional Quality: Accreditation by the Public Health Accreditation Board. 8 Countermeasure Utilization: Percentage of people ages 6 months or older who received a seasonal flu vaccination.
4 Institutional Quality: Accreditation by the Emergency Management Accreditation Program. 9 Patient Safety: Percentage of hospitals with a top-quality ranking (Grade A) on the Leapfrog Hospital Safety Grade.
5 Institutional Quality: Size of the state public health budget, compared with the past year. 10 Health Security Surveillance: The public health laboratory has a plan for a six- to eight-week surge in testing capacity.

Notes: The National Council of State Boards of Nursing organizes the Nurse Licensure Compact. The federal Hospital Preparedness Program of the U.S. Office of the Assistant Secretary for Preparedness and Response supports healthcare coalitions. The U.S. Environmental Protection Agency assesses community water systems. Paid time off includes sick leave, vacation time, or holidays, among other types of leave. The Leapfrog Group is an independent nonprofit organization. Every indicator, and some categorical descriptions, were drawn from the NHSPI, with one exception: public health funding. See “Appendix A: Methodology” for a description of TFAH’s funding data-collection process, including its definition.

Source: National Health Security Preparedness Index.

For the first time, Ready or Not groups states and the District of Columbia into one of three tiers based on their performance across the 10 indicators. This year, 17 states scored in the top tier, 20 and the District of Columbia placed in the middle tier, and 13 were in the bottom tier. (See Table 2).

By gathering together timely data on all 50 states and the District of Columbia, the report assists states in benchmarking their performance against comparable jurisdictions. To help states track their own progress, TFAH will strive to maintain continuity among the indicators tracked in this edition of the report for the next several years.

Table 2: State Public Health Emergency Preparedness

State performance, by scoring tier, 2018

 Performance Tier States Number of States
Top Tier AL, CO, CT, FL, ID, KS, MA, MD, MO, MS, NC, NE, NJ, RI, VA, WA, WI 17 states
Middle Tier CA, DC, GA, HI, IA, IL, LA, ME, MI, MN, MT, ND, NH, NM, NV, OK, OR, SC, TX, VT, WV 20 states and DC
Bottom Tier AK, AR, AZ, DE, IN, KY, NY, OH, PA, SD, TN, UT, WY 13 states

Report Findings

A majority of states have made preparations to expand capabilities in an emergency, often through collaboration. In 2018, 31 states participated in the Nurse Licensure Compact, which allows registered nurses and licensed practical or vocational nurses to practice in multiple jurisdictions with a single license. In an emergency, this enables health officials to quickly increase their staffing levels. For example, nurses may cross state lines to lend their support at evacuation sites or other healthcare facilities. The number of states participating in the compact is up by five from 26 in 2017.

In addition, hospitals in most states have a high degree of participation in healthcare coalitions. On average, 89 percent of hospitals were in a coalition and 18 states had universal coalition participation, meaning every hospital in the state was part of a coalition. Such coalitions bring hospitals and other healthcare facilities together with emergency management and public health officials to plan for, and respond to, events requiring extraordinary action. This increases the likelihood that patients are served in a coordinated and efficient manner during an emergency.

Finally, 44 states and the District of Columbia had a plan to surge public health laboratory capacity for six to eight weeks as necessary during overlapping emergencies or large outbreaks.

Most residents who got their household water through a community water system had access to safe water.  On average, just 6 percent of state residents used a community water system in 2017 that did not meet all applicable health-based standards. Water systems with such violations increase the chances of water-based emergencies in which contaminated water supplies place the public at risk.

Most states are accredited in the areas of public health, emergency management, or both. In 2018, the Public Health Accreditation Board or the Emergency Management Accreditation Program accredited 42 states and the District of Columbia; 26 states were accredited by both groups. Eight states (Alaska, Hawaii, Indiana, New Hampshire, South Dakota, Texas, West Virginia, and Wyoming) were accredited by neither. Both programs help ensure that necessary emergency prevention and response systems are in place and staffed by qualified personnel.

Seasonal flu vaccination rate, already too low, fell further. The seasonal flu vaccination rate among Americans ages 6 months or older dropped from 47 percent in the 2016–2017 season to 42 percent in the 2017–2018 season. This drop-in coverage may have exacerbated the severity of the 2017-2018 influenza season and the high number of illnesses, hospitalizations and deaths due to flu. Healthy People 2020, a set of federal 10-year objectives and benchmarks for improving the health of all Americans by 2020, set a seasonal influenza vaccination-rate target of 70 percent annually.

In 2018, only 55 percent of employed state residents, on average, had access to paid time off. Those without such leave are more likely to work when they are sick and risk spreading infection. In the past, some infectious disease outbreaks have been linked to or exacerbated by the absence of paid sick leave.

Only 28 percent of hospitals, on average, earned a top-quality patient safety grade. Hospital safety scores measure performance on such issues as healthcare-associated infection rates, intensive-care capacity, nursing staff volume, and an overall culture of error prevention. In the absence of diligent actions to protect patient safety, deadly infectious diseases can take hold or strengthen.

Climate Change Increases Likelihood of Extreme Weather

According to the Center for Climate and Energy Solutions, a nonprofit advocacy group, climate change is expected to increase the frequency, intensity, and consequences of some types of extreme weather events, including:

  • Drought, which can contribute to food insecurity and exacerbate wildfires.
  • Extreme heat, which in a typical year already kills more people in the United States than hurricanes, lightning, tornadoes, earthquakes, and floods combined. Extreme heat is especially dangerous for medically vulnerable people. It also worsens droughts and increases the risk of wildfires.
  • Heavy rains, which cause catastrophic flooding, landslides, and contaminated waterways.
  • Hurricanes, which sometimes have more destructive wind speeds, precipitation, and storm surges.
  • Wildfires, which can now burn more land and are more difficult to extinguish.

In 2017 alone, at least 15 extreme weather events across the globe were made more likely by climate change, according to studies published by the American Meteorological Society.

On top of possible federal action, states and localities can act to mitigate these threats, particularly the dangers they pose to people with health ailments or in poor living conditions. For example, land-use planning can reduce loss of life and property from wildfires. Zoning rules that limit building in flood-prone areas reduces the dangers from floods, and replacing nonpermeable surfaces with “green infrastructure,” such as rain gardens and bioswales, reduces stormwater runoff and subsequent flooding. In drought-prone areas, green infrastructure can retain stormwater for later use. Cooling centers can keep vulnerable populations safe during heat waves, and green roofs can reduce the urban heat island effect. Finally, preserving coastal wetlands, dunes, and reefs can help absorb storm surges from hurricanes.

Report Recommendations

There are a host of concrete actions to further protect the public’s health that TFAH recommends be taken by federal, state, and local officials; the healthcare system; academia; and the private or nongovernmental sectors.

Those that are of highest priority include:

  • Providing stable, dedicated, and sufficient funding for preparedness activities and a significant funding increase for core public health capabilities.
  • Establishing a complementary emergency response fund to accelerate crisis responses.
  • Maintaining a long-term investment in the Global Health Security Agenda framework and global preparedness and response programs to help prevent infectious disease threats from becoming global crises.
  • Fully implementing the National Biodefense Strategy including with transparent goals, implementation plans, and budgets for all relevant agencies.
  • Monitoring and addressing any potential challenges caused by the transition of the Strategic National Stockpile and significantly strengthening the “last mile” of distribution and dispensing.
  • Developing a multiyear strategic vision, and fully funding surveillance infrastructure, for fast, accurate outbreak detection at all levels of government.
  • Bolstering the Hospital Preparedness Program and multisector healthcare collaboration as well as adopting state policies to improve healthcare delivery during disasters.
  • Adopting comprehensive climate change adaptation plans, including a public health assessment and response.
  • Increasing public and private investments in efforts to combat antimicrobial resistance, including through diagnostic, stewardship, detection, and treatment methods.
  • Supporting vaccine infrastructure and first-dollar coverage of recommended vaccines.
  • Promoting health equity in emergency preparedness planning, response, and recovery, including through the appointment of a chief equity or resilience officer.

Taken together, action on TFAH’s recommendations would make the United States safer for all its residents.


An enhanced-delivery anthrax vaccine formulation

Weir GM, MacDonald LD, Rajagopalan R, et al. Single dose of DPX-rPA,
an enhanced-delivery anthrax vaccine formulation, protects against a
lethal _Bacillus anthracis_ spore inhalation challenge. npj Vaccines,
Abstract
——–
Anthrax is a serious biological threat caused by pulmonary exposure to
aerosolized spores of _Bacillus anthracis_. Biothrax® (anthrax
vaccine adsorbed (AVA)) is the only Food and Drug
Administration-licensed vaccine and requires 5 administrations over 12
months with annual boosting to maintain pre-exposure prophylaxis. Here
we report the evaluation of a single intramuscular injection of
recombinant _B. anthracis_-protective antigen (rPA) formulated in the
DPX delivery platform. Immune responses were compared to an alum-based
formulation in mice and rabbits. Serological analysis of anti-rPA
immunoglobulin G and toxin neutralization activity demonstrated higher
responses induced by DPX-rPA when compared to rPA in alum. DPX-rPA was
compared to AVA in rabbits and non-human primates (NHPs). In both
species, DPX-rPA generated responses after a single immunization,
whereas AVA required two immunizations. In rabbits, single injection
of DPX-rPA or two injections of AVA conferred 100% protection from
anthrax challenge. In NHPs, single-dose DPX-rPA was 100% protective
against challenge, whereas one animal in the 2-dose AVA group and all
saline administered animals succumbed to infection. DPX-rPA was
minimally reactogenic in all species tested. These data indicate that
DPX-rPA may offer improvement over AVA by reducing the doses needed
for protective immune responses and is a promising candidate as a
new-generation anthrax vaccine.

North Korea: “advanced, underestimated and highly lethal” bioweapons program.

NYT

“…..But today, analysts say, the gene revolution could be making germ weapons more attractive. They see the possibility of designer pathogens that spread faster, infect more people, resist treatment, and offer better targeting and containment. If so, North Korea may be in the forefront.

South Korean military white papers have identified at least ten facilities in the North that could be involved in the research and production of more than a dozen biological agents, including those that cause the plague and hemorrhagic fevers…..”

North Korea Biological Weapons Program


Emergent BioSolutions Inc. announced that Health Canada has approved the company’s New Drug Submission (NDS) for its anthrax vaccine, BioThrax® (Anthrax Vaccine Adsorbed).

Emergent BioSolutions

  • BioThrax is indicated for active immunization for the prevention of disease caused by Bacillus anthracis, in individuals 18 through 65 years of age, whose occupation or other activities place them at risk of exposure, regardless of the route of exposure.
  • BioThrax is administered in a three-dose primary schedule (0, 1 and 6 months) with boosters at three-year intervals recommended thereafter.

 


Summary of Process for Emergency Use Authorization (EUA) Issuance

The flow chart below provides a summary of the process for Emergency Use Authorization (EUA) issuance.

Flow chart providing a summary of the process for Emergency Use Authorization (EUA)

 

Description of chart:

Issuance of an EUA by the FDA Commissioner requires several steps under section 564 of the FD&C Act. First, one of the four following determinations must be in place:

  1. The Department of Defense (DoD) Secretary issues a determination of military emergency or significant potential for military emergency
  2. The Department of Homeland Security (DHS) Secretary issues a determination of domestic emergency or significant potential for domestic emergency.
  3. The Department of Health and Human Services (HHS) Secretary issues a determination of public health emergency or significant potential for public health emergency
  4. The DHS Secretary issues a material threat determination

After one of the above four determinations is in place, the HHS Secretary can issue a declaration that circumstances exist to justify issuing the EUA.  This declaration is specific to EUAs and is not linked to other types of emergency declarations.

The FDA Commissioner, in consultation with the HHS Assistant Secretary for Preparedness and Response (ASPR), Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH), can then issue the EUA, if criteria for issuance under the statute are met.  FDA publishes public notice of each EUA that is issued in the Federal Register.

The last step in the process is termination of declaration and EUA, if appropriate and needed.


Current Emergency Use Authorizations

Emergency Use Authorization, with Emergency sign

FDA

The Emergency Use Authorization (EUA) authority allows FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of MCMs needed during public health emergencies.

Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives.

Section 564 of the FD&C Act was amended by the Project Bioshield Act of 2004 and the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), which was enacted in March 2013

Current EUAs

The tables below provide information on current EUAs:


An alleged ricin terror plot in Cologne, Germany

Ricin

 

The CTC Sentinel

The June 2018 Cologne Ricin Plot: A New Threshold in Jihadi Bio Terror

August 2018, Volume 11, Issue 7
Authors:  Florian Flade
  • “…..German intelligence had learned that Sief Allah H. had bought various materials via the internet, including more than a thousand castor beans and an electronic coffee grinder.
  • During the police raid, a powdery substance was found, which subsequently tested positive for ricin……
  • Investigators found 84.3 milligrams of already-produced ricin and 3,150 castor beans……..”

See the source image


Synthetic Bioterrorism: New genetic tools are making it easier and cheaper to engineer viruses and bacteria in the lab and potentially making them more contagious and lethal.

NPR

Biodefense in the Age of Synthetic Biology:  http://nap.edu/24890

ISBN 978-0-309-46518-2 | DOI 10.17226/24890
Committee on Strategies for Identifying and Addressing Potential Biodefense
Vulnerabilities Posed by Synthetic Biology; Board on Chemical Sciences and
Technology; Board on Life Sciences; Division on Earth and Life Studies;
National Academies of Sciences, Engineering, and Medicine

One danger is making existing bacteria or viruses more dangerous by giving them antibiotic resistance or altering them so that they produce toxins or evade vaccines.

“…..in a table-top exercise conducted last month by the Johns Hopkins Center for Health Security…..experts in pandemic response and national security grappled with a fictional virus called “Clade X” that was created by a terrorist group that inserted genetic elements of deadly Nipah virus into a normally-mild human parainfluenza virus.

The terrorist group in this scenario wanted to depopulate the Earth, and deliberately released the contagious virus at multiple spots around the globe. The resulting pandemic killed 150 million people within a year as officials struggled to contain the social and economic chaos until a vaccine could be made…….”


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