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Lyophilization

Expanding the shelf-life of plasma

Technical file

Innovation leader: Josep Antoni Grífols i Lucas, Víctor Grífols i Lucas

Year: 1943

Period: Postwar period (1940-1959)

Type of innovation: Technical procedure

Scope: Bioengineering

Patent: Yes

Geographical reach: National

Economic impact:  1-High

Level of innovation:  3-Adaptive

Interdisciplinary connections: -

Related innovations: The lyophilizer

From 1935, brothers Josep Antoni and Víctor Grífols i Lucas pursued research into the newly discovered process of lyophilization and its application to human blood plasma. The technique is a way of extracting water from a material without affecting its basic structure or composition.

Essentially a sophisticated type of freeze-drying, lyophilization had first been used to conserve food for long periods of time. The Grífols i Lucas brothers' work built on earlier research by Flosdorf, who demonstrated that the technique could also be used on biomedical materials without changing their fundamental properties.

 

Exploring new techniques to improve processes

It's now widely used, but its origin as an industrial-scale process are in the mid-1930s, with a great deal of progress made as a result of the Second World War. The technique was in use in the UK, at the time, but it was the Grífols family who introduced lyophilization to Spain.

During the ten-year life of the Spanish patent, the next challenge was to build a freeze-dryer up to the task of lyophilization, with only the most basic equipment and materials. It was a task that would require Víctor Grífols i Lucas's unique ingenuity and expertise to accomplish.

Freeze drying process

An innovative technique for conserving plasma

Pioneers of a new technique, inventors of a new technology

 

Landmarks in plasma lyophilization

1935 Flosdorf presents the first work in which the method of lyophilization in different biological substances is established.
1936 Elliott proposes the idea of using plasma as a substitute for whole blood (in this case, liquid, not lyophilized, plasma).
1938 First successful tests of reinfusion of lyophilized plasma in animals and humans (Mahoney and Thompson et al.).
1940 Strumia presents his method to lyophilize plasma. Large-scale production begins by the United States and Great Britain to meet the needs of World War II.
1941 The Swedish Defense Department also works on dried plasma, in this case as a spray.
1941-1953 The massive spread of hepatitis means that the use of lyophilized plasma begins to be reduced, and is increasingly replaced by albumin.
1968 The method is practically abandoned in the United States.
1990 The German Red Cross begins to use lyophilized plasma again, this time with the appropriate safety measures. From then until the present day, it has been used by the Israeli army, French special forces and in South Africa.

 

Bibliography

  • Flosdorf, E.W., i Mudd, S. (1935). Procedure and apparatus for preservation in "Lyophile" form of serum and other biological substances. Journal of Immunology, 29, 389-425.
  • Mahoney, E.B. (1938). A study of experimental and clinical shock with special reference to its treatment by the intravenous injection of preserved plasma. Annals of Surgery, 108, 178-193.
  • Thompson, W.D., et. al. (1938). Use of lyophile plasma in correction of hypoproteinemia and prevention of wound disruption. The Archives of Surgery, 36, 509-518.
  • Strumia, M.M., et. al. (1940). The intravenous use of serum and plasma, fresh and preserved. Annals of Surgery, 111, 623-629.
  • Ellis, C., i Thompson, R. (1942, maig). Your Blood goes to war. Saturday Evening Post, 214(44), 26-49.
  • Grífols Roig, J.A. (1943). Un procedimiento para conservar vivos largo tiempo los fermentos lácticos. Patente de invención no. 155611. Madrid, España: Oficina Española de Patentes.
  • Robinson, G.C. (1946). American Red Cross blood donor service during World War II; its organization and operation. Washington (DC): American National Red Cross.
  • Navarro-Alfano, M. (1998). La liofilización de productos farmacéuticos. Sintefarma, 4(1).
  • Schneider, W.H. (2003). Blood transfusion between the wars. Journal of the History of Medicine and Allied Sciences, 58(2), 187-224.
  • Grífols-Lucas, V. (2009). Amb un suro i un cordill. Vivències d'un empresari de postguerra. Barcelona: Grífols Group, S.A.
  • Schmidt, P. J. (2012). The plasma wars: a history. Transfusion, 52, 2-4.
  • Avellà, R., & Miquel, B. (Eds.). (2015). Cuando un sueño se cumple. Crónica ilustrada de 75 años de Grifols . Barcelona: Grupo Grifols S.A.
  • Pusateri, A.E. et al (2016). Dried plasma: State of the science and recent developments. Transfusion, 56(2), 128-139.
  • Watson, J.J.J. et al (2016). Plasma transfusion: history, current realities and novel improvements. Shock: Injury, Inflammation and Sepsis: Laboratory and Clinical Approaches , 46(5), 468-479.