Plasma derived therapies are drug products derived from human plasma using fractionation processes where target proteins in plasma are purified to homogeneity. Plasma derived therapies are used to treat a wide variety of rare diseases from bleeding disorders (Hemophilia) and inhibitor deficiencies (Antithrombin Ill Deficiency) to primary (Autoimmune lymphoproliferative syndrome or ALPS) and secondary immunodeficiencies (AIDS). Coagulation factors remaining in plasma derived from these preparations can result in thrombotic/thrombolytic events, and in some cases death.
These contaminants are very often present in very low levels which still carry significant risk to the patient. Quantitative measurement of these trace contaminants can result considerable challenges for analytical method development. Manufacturers of these products are required to investigate the ability of their production process to remove procoagulant activities making them safe for release into the clinic. Here we will explore a quantitative analytical method that measures Factor Xla like activity as a function of thrombin generation. This method is a powerful release assay that ensures patient safety by quantitation of a process contaminant that poses a risk to normal hemostasis.