International biological standards for coagulation factors and inhibitors.

The use of international biological standards during the last 30 years has proved extremely successful in promoting global harmonization of estimates between laboratories and methods. Experience has led to the identification of physical criteria essential for standards to be suitable for long-term use. High precision of liquid filling coupled with low residual moisture and oxygen and the use of sealed glass ampoules have been found consistent with homogeneous and stable International Standards (ISs). Most plasma coagulation factors and inhibitors are calibrated in International Units (IU), which are defined as the amount of analyte in 1 mL of normal pooled plasma. Adoption of the IU has provided clarity in the definition of normal and abnormal states and has facilitated dose calculation for replacement therapy. The assay of like-versus-like materials (e.g., concentrate versus concentrate) has been found to improve interlaboratory agreement and there are now both plasma and concentrate ISs available for many coagulation factors and inhibitors. Studies into the assay of recombinant factor VIII have indicated that additional measures, such as modifications to assay methodology, are necessary to reduce interlaboratory variability. This experience may prove valuable in the future, when we have to deal increasingly with the challenges to standardization associated with the products of bioengineering.