Freeze-dried plasma: the trail back to the battlefield

Defense AT&L, Sept-Oct, 2006 by Elizabeth Barrows

I would like to share with you my current view of the path traveled by a product with a long history within the U.S. armed forces: freeze-dried human plasma. I have joined this path in the recent history of the product, and I hope to be part of the team that once again brings freeze-dried plasma to the aid of wounded soldiers.

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Whole blood donations are divided into component products to allow more effective storage and more efficient use. Plasma, a clear yellow liquid that contains the clotting proteins needed to stop bleeding in the injured, is a component of blood; in modern hospitals, it is stored frozen at a temperature no higher than -18 degrees Celsius for up to one year before thawing and use. In civilian trauma centers, plasma is often available in the emergency room, but for our soldiers in remote areas, plasma is not available until they get to a combat-support hospital, potentially hours after the injury.

Early Issues with Freeze-dried Plasma

Ironically, freeze-dried plasma was one of the first blood components identified, separated, and stored for shipment into war zones. That was back in the 1940s, before physicians and scientists understood that within the life-saving fluid, there lurked deadly viruses. To efficiently freeze-dry large quantities of plasma, the individual units were poured into a large pool often containing the plasma from more than a thousand donors. If even a small fraction of these units contained active viruses, they could easily be transmitted to the entire pool, subsequently infecting hundreds of recipients. The distribution of pooled whole plasma in the United States was stopped in 1968.

When faced with a barrier, humans simply try to overcome it, which is what they did in the late 1980s, when a number of methods for inactivating the viruses in blood products were developed. In 1989, virally inactivated plasma products were brought to the European market; and in 1998, a product was approved for marketing by the U.S. Food and Drug Administration (FDA). The Army saw the opportunity to bring freeze-dried plasma safely back to the marketplace, and initiated a research program in 2000.

I was introduced to the Army's freeze-dried plasma research program when I joined the Army's Combat Casualty Care Research Program as a contracted project coordinator in 2004. At that time, researchers in the Department of Blood Research at Walter Reed Army Institute of Research had already freeze dried the American solvent/detergent-treated product, but that product was no longer in production. They were also working on stabilizing the proteins in single-donor, untreated units of plasma; however, there were significant manufacturing problems that would be difficult, if not impossible, to overcome. Though the researchers in the Department of Blood Research had expanded the science of freeze drying human proteins, there appeared to be no commercially viable way forward for American freeze-dried plasma.

Then suddenly, everything changed--with one e-mail.

New Developments

The major supplier of solvent/detergent-treated plasma in Europe, Octapharma, produces and sells their product as frozen bags, similar to the traditional product. However, the German Red Cross--Blood Service West, Octapharma's development partner, has maintained a license and production facility in Germany for both frozen and freeze-dried solvent/detergent-treated plasma since May 2004.

The medical director for the German Red Cross--Blood Service West contacted the Walter Reed Department of Blood Research by e-mail, describing manufacturing facility upgrades and offering either processing of American plasma or sale of German plasma. Discussions ensued, and in the spring of 2005, the Blood Research Department chief invited Dr. Albrecht Hoburg, the director of blood safety for the German Red Cross Blood Service West, to visit the Walter Reed Army Institute of Research, where he presented the German Red Cross' product, LyoPlas.

The Potential of LyoPlas

Over the following summer, there was much discussion within the Department of Blood Research over the desire to purchase some of the LyoPlas and test its properties in house. Unfortunately, the budgets had already been set, and there was no way to incorporate LyoPlas testing without cutting some portion of the existing research program. It looked as if that path was going to remain unexplored, until I read about the Foreign Technology and Science Assessment Support Program, a small program run by the U.S. Army Research, Development and Engineering Command with the goal of supporting foreign technology testing for transition into U.S. Army projects--exactly what we wanted to do with LyoPlas. With support from the Blood Research Department chief and the research area director for the Combat Casualty Care Research Program, I drafted the Foreign Technology and Science Assessment Support Program application package. After a number of reviews and a presentation by the department chief to the U.S. Army Research, Development and Engineering Command review board, we were awarded $75,000 to purchase and test LyoPlas.