LANCET

BBC

FDA

First medical product cleared in U.S. for use on certain injuries caused by sulfur mustard

The U.S. government reached a milestone in its long-standing efforts to defend the country against potential use of chemical weapons:  the first U.S. Food and Drug Administration (FDA) clearance of a product to manage certain blister injuries caused by sulfur mustard, commonly known as mustard gas.

“Our top priority is saving lives during national emergencies. To do so, we must make safe and effective medical products for all the illnesses and injuries stemming from the serious health security threats confronting our nation,” said Robert Kadlec, M.D., Assistant Secretary for Preparedness and Response (ASPR) at U.S. Department of Health and Human Services. “This product clearance is the latest step in delivering on that promise to the American people.”

The ASPR’s Biomedical Advanced Research and Development Authority (BARDA) provided technical expertise and funding to support the studies necessary to show that the product, Silverlon, is appropriate for use on first- and second-degree skin burns caused by exposure to sulfur mustard.

“Chemical weapons like sulfur mustard cause horrific, painful, and life-altering injuries, yet in the 100-year history of sulfur mustard use, no medical countermeasures existed – until now,” added BARDA Director Rick Bright, Ph.D. “At BARDA, we are excited to have supported the first cleared product for use on skin injuries caused by sulfur mustard. This clearance exemplifies BARDA’s ongoing commitment to our partners and the nation as we seek out promising technologies and products to improve our nation’s health security and protect Americans.”

Argentum Medical, LLC, has received FDA clearances for multiple indications for Silverlon since 2003 and in that time the wound dressing has been used extensively by the U.S. military to treat burn and blast wounds. Silverlon dressings also are used widely by the healthcare and first responder communities.

“The FDA plays an important role in preparing our nation for a range of threats, including chemical, biological, radiological, and nuclear threats, providing guidance and support for the development of medical countermeasures that can be used safely, effectively and reliably during public health emergencies,” said Acting FDA Commissioner Ned Sharpless, M.D. “The expanded indication for this first-of-its-kind wound contact dressing to include management of certain injuries caused by sulfur mustard vapor exposure demonstrates our commitment to working closely with our federal partners, including BARDA, to expedite the availability of medical countermeasures essential for managing responses to chemical weapons attacks in both civilian and battlefield settings.”

BARDA’s support for this additional indication began in 2013 as part of the federal government’s effort to repurpose approved drugs and medical products to save lives and reduce injury in an attack on the United States.

This multi-purpose approach has proven to be cost-effective in preparing mass casualty emergencies from chemical, biological, and radiological agents. Repurposing products in widespread use additionally ensures first responders have a familiar product to use in a time of crisis.

Beginning in 2015, BARDA used Project BioShield authorities and the Project BioShield Special Reserve Fund to purchase Silverlon for the Strategy National Stockpile as part of BARDA’s burn countermeasure program. BARDA continues to work with Argentum on studies necessary for FDA clearance of Silverlon for use on radiation burns.

Silverlon is a silver-plated nylon dressing available commercially and used widely to aid in the management of acute skin wounds and first- and second-degree thermal burns. The silver plating helps kill bacteria within the dressing, and one dressing can be used for up to seven days. This allows for fewer dressing changes, which reduces the burden on caregivers and minimizes the pain and damage that would occur if the wound was disturbed.

Sulfur mustard was first used as a chemical weapon in World War I and can be released into the air, food or water. More recently the chemical was used in the Iran-Iraq war and in the Syrian Civil War.

CHEMM

Fourth Generation Agents
(Information as of January 18, 2019)

After the incidents in the United Kingdom (U.K.) in 2018 involving a fourth generation agent, the White House National Security Council convened a federal interagency working group to identify and develop resources to help the emergency response community prepare for and respond to a fourth generation agent incident if one ever occurs in the U.S., as well as support the development of specific guidance and training to enhance overall preparedness efforts. These resources meet the needs of U.S. emergency response professionals who sought to learn more about the agent used in the U.K. and how to protect themselves and respond if such incidents ever occur in their communities.

Fourth generation agents, also known as Novichoks or A-series nerve agents, belong to a category of chemical warfare agents that are unique organophosphorus compounds. They are more persistent than other nerve agents and are at least as toxic as VX. While fourth generation agents share similar characteristics with other nerve agents, fourth generation agents also pose several unique challenges in terms of toxicity, detection, persistence, and potential for delayed onset of symptoms. The following resources were developed to address these characteristics and challenges and provide tailored guidance to various segments of the emergency response community.

• Safety Awareness for First On-Scene Responders Bulletin – Designed to educate and prepare first responders for situations when law enforcement, fire, and emergency medical services (EMS) personnel are first to arrive on scene and initially may be unaware that a fourth generation agent is present. This bulletin will assist departments and agencies develop specific guidance and training to enhance overall preparedness efforts. (PDF – 791 KB)

• Reference Guide – Designed to educate and prepare hazardous materials (HAZMAT) response teams, the guide includes chemical and physical properties of fourth generation agents, as well as detection, firefighting, personal protective equipment, and decontamination recommendations for situations when responding to a known or suspected fourth generation agent incident. This guide will assist HAZMAT response teams develop specific guidance and training to enhance overall preparedness efforts. (PDF – 789 KB)

• Medical Management Guidelines – Designed to educate and prepare fire, EMS, and hospital staff and guide the medical management of patients exposed or potentially exposed to a fourth generation agent. (PDF – 858 KB) (Note: This is one PDF document that is divided into two Web pages, one for pre-hospital care and one for in-hospital care.)
  • Pre-hospital Medical Management Guidelines
  • Hospital Medical Management Guidelines

These resources were developed by a federal interagency working group comprising experts in medicine, science, public health, law enforcement, fire, EMS, HAZMAT, and occupational safety and health from the Department of Defense, Department of Health and Human Services (Office of the Assistant Secretary for Preparedness and Response, Centers for Disease Control and Prevention, and National Institute for Occupational Safety and Health), Department of Transportation (Pipeline and Hazardous Materials Safety Administration and National Highway Traffic Safety Administration’s Office of Emergency Medical Services), Department of Homeland Security, Federal Bureau of Investigation, Occupational Safety and Health Administration, and Environmental Protection Agency.

These resources are based on the interpretation of available data on fourth generation agents by U.S. government experts and previously developed federal guidance related to nerve agents. Moreover, the guidance was developed through a collaborative process which included extensive stakeholder review in the form of listening sessions and consultations with representatives from the various disciplines across the emergency response community.

Information as of January 18, 2019, was used to inform the development of these resources. They will be updated as new data becomes available that can further support any response to a potential fourth generation agent incident and help protect responders if such an incident ever occurs in the U.S.

Please refer comments and questions on these fourth generation agent resources to askasprtracie@hhs.gov.

The Hill

TaskandPurpose

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

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.

NYT

“……Investigators released a cache of evidence in the case, including security camera images that captured the progress of two husky men [Alexander Petrov and Ruslan Boshirov] from an Aeroflot flight to the scene of the crime, near the victim’s home, and from there back to Moscow.

They also released photographs of the delicate perfume bottle that was used to carry Novichok……..two swabs taken from the suspects’ hotel were found to contain traces of the nerve agent...……“The same two men are now the prime suspects in the case of Dawn Sturgess and Charlie Rowley,” Mrs. May said, adding that the same poison was used in both cases and that the two were “victims of the reckless disposal of this agent.”…….Russia imprisoned Mr. Skripal in 2004 for selling secrets to Britain, and released him in 2010 as part of a spy swap with Western countries. He settled in Salisbury but quietly continued working in intelligence, offering insights into Russian espionage practices...…..”

https://nyti.ms/2CoRPdb

https://nyti.ms/2MOY3rE

NY Times

“……In attacks on Jan. 13, Jan. 22 and Feb. 1, the draft said, government forces fired chemical agents, “most probably chlorine,” into a residential part of eastern Ghouta’s Douma neighborhood, near a sports stadium, roughly 800 yards from the front lines, between 5 a.m. and 6:30 a.m.

Some witnesses described a “slow-acting agent” that smelled like chlorine, the draft said, and they had sufficient time “to rouse the victims, obtain wet cloths to serve as makeshift face masks, and evacuate the affected areas.”……..Thirty-one people, including 11 children, were sickened in the first three attacks, but none died. Two other episodes of possible chlorine use, on Feb. 25 and March 7, caused more extensive casualties, killing two children, including an infant, and injuring 18 civilians...…..”

BBC

“…..Dr Stephen Jukes, an intensive care consultant at the hospital, said: “When we first were aware this was a nerve agent, we were expecting them not to survive.

“We would try all our therapies. We would ensure the best clinical care. But all the evidence was there that they would not survive.”

Both Skripals were heavily sedated which allowed them to tolerate the intrusive medical equipment they were connected to, but also helped to protect them from brain damage, a possible consequence of nerve agent poisoning.

Over time, the sedation was reduced and the ventilation switched from the mouth to the trachea, as shown by the vivid scar seen on Yulia Skripal’s neck in the TV statement she gave after she was released.

Once the patients became more conscious, staff had to carefully consider what they could tell them without prejudicing the police investigation, and decide on the right moment to allow questioning by detectives.

Medical director Dr Christine Blanshard explained: “Those are very difficult decisions, because on the one hand you want to provide reassurance to the patients that they are safe and they are being looked after, and on the other hand you don’t want to give them information that might cause difficulties with subsequent police interviews.”

It was the doctors and nurses that, out of concern for their patients, insisted that international inspectors obtain a court order before they would be allowed to take blood samples from the Skripals.

Dr Jukes explained: “These are vulnerable patients, they needed some form of advocate and without a court order we could not allow things to happen to them without their consent.”

Once the Skripals were stable and able to speak, the key concern for medical staff was how their production of the key enzyme acetylcholinesterase – needed to re-establish their normal body functions – could be stimulated.

The body will do this naturally after nerve agent poisoning, but the process can take many months.

In trying combinations of drugs, Dr Murray says the hospital received input from “international experts”, some of them from Porton Down.

The laboratory, internationally known for its chemical weapons expertise, processed tests and offered advice on the best therapies.

New approaches to well-known treatments were tried. Dr Jukes said that the speed of the Skripals’ recovery came as a very pleasant surprise that he cannot entirely explain……”

NY Times

‘……….“One thing, perhaps, which is important to note is that the nerve agent seems to be very persistent,” he said. “It’s not affected by weather conditions. That explains, actually, that they were able to identify it after a considerable time lapse. We understand it was also of high purity.”