Scientific problems in the regulation of red blood cell products

BACKGROUND: For the past 30 years, red blood cell (RBC) storage systems have been licensed in the United States based on the demonstration that 24-hour in vivo recovery was greater than 75% and hemolysis was less than 1%. Now additional requirements for storage system licensure have being added. The meaning and value of these new requirements have been questioned. STUDY DESIGN AND METHODS: The literature regarding the performance of present and suggested new tests for RBC licensure was reviewed. RESULTS: 51Cr 24-hr in vivo recovery has an intrinsic 4% error of measurement whereas the error in measures of hemolysis is less than 0.1%. Both measures have large donor-dependent end-of-storage variability; nevertheless, they have successfully guided RBC storage system development for six decades. Adenosine 5'-triphosphate and 2,3-diphosphoglycerate are difficult to measure accurately and international shared-sample studies suggest 6 and 11% coefficients of variation across laboratories. There is no readily available way to measure the oxygen equilibrium curve accurately. The new failure criteria provide no useful information and randomly fail good products. CONCLUSIONS: Attempts to expand the useful regulatory requirements for RBC storage system licensure are limited by poor understanding of the storage lesion and its effect of RBC performance. Measures of 51Cr 24-hour in vivo recovery remain critical and resources for this measure are limiting. The interaction between limited testing resources and large donor variability remains a major limit on RBC storage system development. It is important that new required tests contribute meaningful information and not make development and licensure of better products more difficult.