Biological standards for potency assignment to fibrinolytic agents used in thrombolytic therapy.

Thrombolytic drugs are used for the treatment of thrombotic disorders such as acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Biological standards are used for potency assignment to the range of fibrinolytic proteins used in thrombolytic therapy. The World Health Organization (WHO) International Standards are primary reference materials, calibrated in arbitrary units (international unit), assigned by collaborative study using the range of assay methods available at the time. Provided the standard and test material are equivalent, adhering to the principle of measuring like versus like, the exact nature of the assay method is unimportant. This approach has been applied successfully for several decades since the advent of fibrinolytic treatment, ensuring consistency for potency labeling and the correct dosing of patients. The emergence of generic biosimilar products and new recombinant variants poses a challenge to this system, where functional differences impact on the relative biological activity in different assay systems. A more demanding system of standardization may therefore be required on the basis of international reference materials with associated reference methods. WHO recognizes this, and where possible and practical is seeking to incorporate concepts of traceability, uncertainty, and commutability to International Standards. However, some caution is needed because limitations on the characterization of many complex biologicals remain real, and a flexible approach is required on the basis of real-world needs.