The U.S. Army has received the go-ahead from the FDA to move forward with plans to develop a new type of plasma that will be easier to use on the battlefield.
A dependable, portable emergency blood supply is key to ensuring the military’s ability to treat battlefield injuries immediately.
With that in mind, the U.S. Food and Drug Administration (FDA) has broadened military access to freeze-dried plasma (FDP).
Last month, the FDA
Currently, the Army uses a substance officially known as Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma. It’s manufactured in France by the Centre de Transfusion Sanguine des Armées (Blood Transfusion Center of the Armies).
“Through our collaborative program with the DoD, they’ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma. Granting this authorization will support access to this important product in the event it’s needed,” Dr. Scott Gottlieb, the FDA’s commissioner, said in a press release.
The current French freeze-dried plasma product is stored in glass bottles.
Physicians and medical personnel reconstitute the plasma with a vacuum pressure system.
However, as an article on the Army website notes, the bottles are heavy and damage-prone if not handled correctly.
In addition, the vacuum system requires a spiking process that, if not performed precisely, can cause problems.
The new U.S. version will use lighter, state-of-the-art plastic bags that use a standard fluid transfer set to mix the product with sterile water for injection.
Meanwhile, the U.S. Army Medical Materiel Development Activity (USAMMDA) at Fort Detrick, Maryland, is developing its own FDP.
Why is this plasma needed?
“Availability, convenience, and rapid preparation are the main factors,” said Larry J. Dumont, MBA, PhD, director and senior investigator at the Blood Systems Research Institute in Denver and clinical professor of pathology at the University of Colorado School of Medicine.
“Standard plasma is frozen and requires thawing in special devices,” Dumont told Healthline. “That takes time and isn’t available at forward positions where injuries occur. The plasma must also be held in a freezer. FDP can be transported in a medic’s pack right to the forward point of injury, enabling rapid treatment of the injured.”
How does FDP work?
“FDP is plasma with the water removed by freeze-drying,” Dumont said. “This leaves plasma and clotting proteins in a dried and stable state and then it may be stored at room temperature. After rehydration, the product can be transfused. The primary effects are to correct coagulopathy [prolonged or excessive bleeding following injury or medical procedures] following trauma to help correct or prevent bleeding. There are other effects on the endothelium that lines the blood vessels, helping to maintain a good lining in the vessel and to fight inflammation. These latter effects are only just starting to be understood by medical investigators.”
Dumont added that “when FDP is available for civilian use, it will be used in a similar manner in ambulances and helicopters to push care closer to the point of injury. It will also be helpful in hospital emergency departments and in other situations where plasma is urgently needed.”
Dumont said FDP will provide the same crucial value in disaster relief.
“It can be deployed quickly to points of injury and added easily to the strategic emergency stockpile,” he said.
The Army, which began using the French plasma in 2012, is working with a medical device company to develop the improved FDP.
Andrew Atkinson, product manager for the Pharmaceutical Systems Project Management Office at USAMMDA, said his department has a Cooperative Research and Development Agreement to develop FDP with Vascular Solutions, Inc. (VSI), based in Minnesota.
“The U.S. FDP developed by VSI will eliminate the bottle container for both the FDP and the sterile water for injection, which will make it easier (less weight and less breakage) to transport in the field — all the way forward to the point of injury,” Atkinson told Healthline. “The new product will also have a greater manufacturing capacity, which will increase its availability. Lastly, the U.S. FDP product will be available commercially, which will help ensure sustainability of the product as it will not be dependent only on the military.”
The Army’s minimum temperature requirement for storing the new FDP product is 2 to 8°C (35 to 46°F), Atkinson said. The Army will be able to store FDP for an extended time at that temperature range and at room temperature for a slightly shorter period of time.
How can scientists ensure the safety of FDP stored in plastic bags?
“The plastic bag storage container that Vascular Solutions uses is made of polyvinyl chloride and has undergone extractables and leachable testing to ensure that the bag is biocompatible and safe,” Atkinson said. “The product will also be put on stability studies to detect any changes in the FDP over time.”
VSI will continue to ensure that the packaging is safe. It will also sponsor the license application with the FDA, and will be responsible for marketing and distribution after the license is approved, he said.
Clinical and safety studies are under way.
The phase I dose range-finding safety study has been completed, and the final clinical study report is currently pending, Atkinson said. The next clinical step, an efficacy study, is in the planning stages.
The Army’s target date — for approval and shipment to the troops — is early next year.
Use of freeze-dried plasma began during World War II.
“FDP was used as an alternative to fresh frozen plasma,” Atkinson said. “It required no refrigeration, was easy to reconstitute, and there were no known reports of lack of efficacy. However, the safety of this product wasn’t acceptable due to pathogen transmission.”
The product was found to transmit hepatitis B virus because it was manufactured from large plasma pools with hundreds of donors that were not pathogen-inactivated, Atkinson said.
The product was withdrawn from use. No supplies of FDP have been available since that time in the United States.
The military already has experienced success with French FDP. The Marine Corps received approval to use it in October 2016.
“We were the second component of U.S. Special Operations Command to receive permission to use it, just behind U.S. Army Special Operations Command,” Major Nicholas Mannweiler told Healthline.
He is communication strategy officer for the U.S. Marine Corps Forces, Special Operations Command (MARSOC).
“Our Special Amphibious Reconnaissance Corpsmen [SARC] began deploying with freeze-dried plasma in December 2016 and we began looking at ways to increase our familiarity with the product,” he said. “By October 2017, every SARC forward-deployed with MARSOC units had received training in and an appropriate supply of freeze-dried plasma.”
MARSOC maintains forward-deployed forces in the areas of operations for U.S. Indo-Pacific Command, Central Command, and Africa Command, he said.
The use of FDP helps military medical personnel to provide more effective battlefield care.
Freeze-dried plasma allows the treatment of blood-volume loss and coagulopathy from catastrophic injuries, Mannweiler said.
That applies to formal medical treatment settings as well as austere field environments, regardless of a unit’s mission or which force administers the treatment.
“What makes special operations unique are the challenges presented by their location, risk, and, frequently, the distances to more definitive healthcare,” Mannweiler said. “Special operations forces [SOF] operate globally, often far forward of conventional forces and associated support. This impacts medical care by frequently limiting SOF care providers in the amount of resources and supplies available to them during field treatment.”
“In some cases, it may be literally what they can carry in a medic’s aid bag along with their other mission-essential equipment and supplies,” he added. “Freeze-dried plasma alleviates a major logistical requirement for SOF care providers — refrigeration and transport of fresh whole blood or fresh frozen plasma.”
Mannweiler said MARSOC first used FDP in August 2017 in the Central Command area of operations from the Horn of Africa through the Arabian Gulf region.
A suicide bomber had attacked a partner-nation force unit — a security element of a host nation in which the U.S. operates. Two soldiers were injured critically.
“One of them sustained multiple shrapnel wounds in the attack,” Mannweiler said. “He received initial treatment at the point of injury before being moved to more definitive care in our layered trauma system.”
“The patient arrived at a U.S. SOF medical site in a state of severe shock,” Mannweiler added. “He was treated with packed red blood cells and freeze-dried plasma by MARSOC SOF independent-duty corpsmen, our top-tier SOF medics.
“His vitals showed near immediate improvement. The patient was resuscitated and survived his injuries,” Mannweiler explained. “This was the first MARSOC use of this product, which has been approved by the FDA as an investigational treatment for use by special operations medics. This successful first application showed that MARSOC’s freeze-dried plasma and fresh whole-blood transfusion protocols can directly enhance battlefield survivability of trauma patients.”
This capability has great potential to provide advanced resuscitation in the field and extends the “golden hour” in prolonged battlefield care, Mannweiler said.
In many parts of the world, the extra time gained helps to overcome the challenges of being moved to more definitive care over large distances, he added.