Assignment of quantities to biological medicines: an old problem re-discovered.

A distinction exists between 'chemical' and 'biological' medicines. While, from antiquity, both organic and inorganic substances had been used in therapy, developing chemical sciences were inapplicable to materials extracted from natural sources, and the active principles could be neither identified nor characterized. The distinction between biological medicines or 'biologicals' grew out of this realization. Such 'biologicals' in clinical use were, however, variable in efficacy and in safety, and controlling the strength or quality was necessary. Without information on what biological medicines are, it was necessary to quantify what they do, and such medicines were quantified using systems based on biological responses (bioassays) in animals, organs or cells. Bioassays are defined in terms of an external standard rather than in absolute terms, and depend on a number of key assumptions: the need to assay 'like against like', the desirability of making the assay principle relevant to the intended clinical effect in man, and the importance of appropriate statistical models of design and analysis. The science of 'biological standardization' has kept pace with developments in medicine and continues to allow the use of biological medicines in man to be controlled on the basis of common measurement systems.