|Year : 2018 | Volume
| Issue : 1 | Page : 1-3
Global health security: Radiation countermeasures for acute radiation syndrome
L Andrew Huff, Ayodele O Olabisi, Vijay K Singh
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
|Date of Web Publication||22-Jan-2018|
Dr. L Andrew Huff
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Huff L A, Olabisi AO, Singh VK. Global health security: Radiation countermeasures for acute radiation syndrome. J Radiat Cancer Res 2018;9:1-3
|How to cite this URL:|
Huff L A, Olabisi AO, Singh VK. Global health security: Radiation countermeasures for acute radiation syndrome. J Radiat Cancer Res [serial online] 2018 [cited 2022 Jun 25];9:1-3. Available from: https://www.journalrcr.org/text.asp?2018/9/1/1/223745
In response to increased international disease threats and global terrorism in an increasingly connected world, 194 countries across the globe agreed to implement the International Health Regulations (2005) (IHR). This international law was enacted on June 15, 2007. The stated purpose and scope of the IHR, “to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade,” requires states to strengthen core surveillance and response capacities at the primary, intermediate, and national level. An important component of IHR implementation is the national monitoring and evaluation of each country's capacity to detect, assess, and report potential public health emergencies of global concern. The US has recognized that assessments of preparedness and response capacities using the Joint External Evaluation Tool (JEE) and subsequent development of the JEE national action plans are critical priorities for countries to enhance their national health security. The US Government has prioritized the finalization and public release of the JEE National Action Plan as part of this commitment.
The JEE of the United States, conducted in 2016, identified strengths and gaps in US capacities to prevent, detect, and respond to public health emergencies. The “National Action Plan to Strengthen Implementation of the IHR (2005) in the USA based on the 2016 JEE” was developed to strengthen IHR (2005) implementation in the US by addressing the gaps identified  and the recommendations presented by a panel of external subject matter experts.
Increasing global risks of nuclear and radiological accidents or terrorism continue to challenge national capacities to simultaneously maintain a global nonproliferation stance while maintaining global security. This has driven renewed research interest in developing radiation countermeasures for clinically significant ionizing radiation exposure. The availability of safe and effective countermeasures against these threats currently represents an important unmet medical need. To expedite chemical, biological, radiological, and nuclear (CBRN) countermeasure development, the US Food and Drug Administration (FDA) has implemented the “Animal Rule” which applies to the development and testing of drugs and biologics to reduce or prevent life-threatening conditions caused by exposure to lethal or permanently disabling CBRN agents when human efficacy trials are not feasible or ethical., Several drugs for CB indications and two agents for acute radiation syndrome (ARS), Neupogen and Neulasta, have been approved by the US FDA following the Animal Rule. In addition, many radiation countermeasures for different types of exposures are under development, and a few of these countermeasure agents are progressing well.,,
Big corporations with several successful drugs in clinical use or under development are not interested in developing drugs for rare diseases that may not lead to high revenues, particularly when there is a significant risk of failure to reach Proof of Concept. The FDA provides orphan drug designation to drugs intended for the treatment of rare diseases that either (a) affect fewer than 200,000 people in the US (or <5/10,000 people in a community) or (b) affect more than 200,000 people but still may not be economically viable (i.e., the drug sponsor is not expected to recover the costs of developing and marketing the drug). Assignment of orphan drug status provides the sponsor tax concessions and the exclusive rights to the treatment for a specific indication for 7 years postapproval. It attracts corporations to enter a market where the high costs of development are less likely to be recovered but provide a means to gain a fast approval in an orphan indication that can then be quickly extended into a variety of extra and more valuable indications. Due to the key advantages to developing orphan drugs, radiation countermeasures developed for ARS and delayed effects of acute radiation exposure (DEARE) are assigned US FDA orphan drug status.
The FDA usually considers radiation countermeasures under a “fast track” approval process. The FDA's fast track programs are in place to facilitate the development and approval of new drugs that are intended to treat life-threatening conditions and those that demonstrate the potential to address unmet medical needs. The objective is to get promising new drugs approved earlier to benefit patients/victims. Most radiation countermeasures at an advanced stage of development have received FDA fast-track status.
Repurposing is vital for making drugs available to combat CBRN threats. Drugs are commonly repurposed for new indications not originally envisioned. Four out of five drugs that enter clinical trials are never approved for their intended indication. Such a high level of failure means there are several partially developed agents with identified pharmacological properties. Finding new uses for existing experimental/approved drugs or biologics builds on previous research and development so that candidate therapies can be advanced for new uses faster than starting from scratch. By repurposing a drug, one can make it available through the FDA approval pathway much faster, but this process also involves intellectual property issues as corporations are hesitant to risk exposing their blockbuster drugs to additional scientific scrutiny with possible loss of approval and consequent financial loss. Federal funding initiatives in the US started to encourage that preclinical and/or early-stage agents be repurposed to further develop existing experimental drugs or biologics investigated to a significant level in addition to drugs already in clinical use for another indication. As stated above, both radiation countermeasures approved for hematopoietic ARS following the Animal Rule (Neupogen and Neulasta) are repurposed agents., Currently, many agents (Promacta, Pentoxifylline, Lova-, Sim-, Atorvastatin, Oprelvekin, Celecoxib, Mozobil™, Neumega, Epogen, Palifermin, Anakinra, Forteo, Cozaar, Increlex, Surfaxin, Neurontin, Metformin, etc.) previously approved for other indications are being evaluated as radiation countermeasures for ARS and DEARE. Some of these agents are progressing well for FDA approval.
The emergency use authorization (EUA) is a legal means for the FDA to approve new drugs or new indications for previously approved drugs for use during a declared emergency and is an acceptable option to expedite drug development., The EUA authority allows the FDA to strengthen the nation's public health protections against CBRN threats by facilitating the availability and use of countermeasures needed during public health emergencies. The Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 improved the current EUA authority to better serve rapid response needs to public health emergencies. There are highly effective and essential medical countermeasures that carry only investigational new drug status. The EUA requires a reasonable database in clinical and animal models. Neupogen and Neulasta were recommended for EUA status before their FDA approval for ARS due to their convincing safety and efficacy data in clinical and preclinical studies. These two drugs were procured for vendor-managed inventory much earlier than their FDA approval for the treatment of hematopoietic ARS.
In summary, we need to make concerted efforts in global health security through the development of radiation countermeasures.
The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Armed Forces Radiobiology Research Institute, the Uniformed Services University of the Health Sciences, or the Department of Defense. Mention of specific therapeutic agents does not constitute endorsement by the US Department of Defense, and trade names are used only for the purpose of clarification. We apologize to those having contributed substantially to the topics discussed herein that we were unable to cite because of space constraints.
| References|| |
Baker MG, Forsyth AM. The new international health regulations: A revolutionary change in global health security. N
Z Med J 2007;120:U2872.
Strom JS. Health impacts from acute radiation exposure. Office of Security Affairs US Department of Energy under Contract DE-AC06-76RLO 1830. Richland, Washington: Pacific Northwest National Laboratory; 2003.
Snoy PJ. Establishing efficacy of human products using animals: The US Food and Drug Administration's “Animal Rule”. Vet Pathol 2010;47:774-8.
Singh VK, Seed TM. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures. Int J Radiat Biol 2017;93:851-69.
Singh VK, Garcia M, Seed TM. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status. Int J Radiat Biol 2017;93:870-84.
Singh VK, Hanlon BK, Santiago PT, Seed TM. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part III. Countermeasures under early stages of development along with 'standard of care' medicinal and procedures not requiring regulatory approval for use. Int J Radiat Biol 2017;93:885-906.
Shulman SR, Manocchia M. The US orphan drug programme 1983-1995. Pharmacoeconomics 1997;12:312-26.
Cole P. Accelerating drug development and approval. Drug News Perspect 2010;23:37-47.
Austin BA, Gadhia AD. New therapeutic uses for existing drugs. Adv Exp Med Biol 2017;1031:233-47.
Farese AM, MacVittie TJ. Filgrastim for the treatment of hematopoietic acute radiation syndrome. Drugs Today (Barc) 2015;51:537-48.
Kels CG. Dispensing medical countermeasures: Emergency use authorities and liability protections. Health Secur 2015;13:139-51.
Nightingale SL, Prasher JM, Simonson S. Emergency use authorization (EUA) to enable use of needed products in civilian and military emergencies, United States. Emerg Infect Dis 2007;13:1046-51.