Lyophilization
Expanding the shelf-life of plasma
Technical file
Type of innovation: Procedure
Scope: Bioengineering
Innovation leader: Grifols i Lucas, Víctor; Grifols i Lucas, Josep Antoni
com.grifols.labels.cabinet.year: 1943
Period: 1909-1971
Geographical scope: Spain
Economic impact: High
Level of innovation: Adaptive
Patent: Yes
Interdisciplinary connections: -
From 1935, brothers Josep Antoni and Víctor Grifols i Lucas pursued research into the newly discovered process of lyophilization and its application to human blood plasma. This offered a means 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 Grifols i Lucas brothers' work built on earlier research by Flosdorf, who demonstrated that the technique could also be used on biomedical material without changing its fundamental properties.
“Lyophilization has its origins as an industrial-scale process in the mid-1930s and it was the Grifols family who introduced it to Spain.”
Exploring new techniques to improve processes
This procedure is now widely used, but it has its origins as an industrial-scale process in the mid-1930s, with a great deal of progress made as a result of the Second World War. The procedure was in use in the UK at the time, but it was the Grifols family who introduced lyophilization to Spain.
During the ten-year life of the Spanish patent, the next challenge was to build a freeze-dryer that would be up to the task of lyophilization, with the equipment and materials available. Víctor Grifols i Lucas led the efforts to innovate.
Chronology
| 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 demand during World War Two. |
| 1941 | The Swedish Defense Department also works on dried plasma, in this case, as a spray. |
| 1945-1953 | The massive spread of hepatitis means that the use of lyophilized plasma is 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., & 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. & Ravdin, I.S. & Rhoads, J.E., & Frank, I.L. (1938). Use of lyophile plasma in correction of hypoproteinemia and prevention of wound disruption. The Archives of Surgery, 36, 509-518.
Strumia, M.M., & Wagner, J.A., & Monaghan, J.F. (1940). The intravenous use of serum and plasma, fresh and preserved. Annals of Surgery, 111(4), 623-629.
Ellis, C., & Thompson, R. (1942, May). Your Blood goes to war. Saturday Evening Post, 214(44), 26-49.
Laboratorios Grifols, S.A. (1941). Procedimiento para conservar vivos largo tiempo los fermentos lácticos. Patente española de invención, no. 155.611. Madrid: Oficina Española de Patentes.
Grifols-Roig, J.A. (1943). Un procedimiento para desecar plasmas, sueros, líquidos biológicos en general y organismos inferiores conservando al máximo sus propiedades originales. Patente española de introducción, no. 161.700. Madrid: Oficina Española de Patentes.
Robinson, G.C. (1946). American Red Cross blood donor service during World War II; its organization and operation. Washington: 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.
Grifols-Lucas, V. (2009). Amb un suro i un cordill. Vivències d'un empresari de postguerra. Barcelona: Grupo Grifols, 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.
Related innovations
DEVICE
The lyophilizer