Chromatographic removal of viruses from plasma derivatives.

Progress in protein separation technology has led to the development of a new generation of plasma derivatives, generally prepared by procedures involving one or several chromatographic steps. In addition to providing two to three log purification factors of several therapeutic products, with regard to some protein contaminants, chromatography has been shown to improve the potential safety of new plasma derivatives by contributing to the removal of plasma-borne viruses. Indeed, validation studies have demonstrated that each immuno-affinity, ion-exchange, and heparin affinity chromatography step can eliminate 1 to 5 log of HIV-1, or of several model viruses, enveloped or non-enveloped, such as sindbis virus, pseudorabies virus, vesicular stomatitis virus, reovirus 3, or simian virus 40. Several parameters can be considered as influencing the chromatographic behaviour of viruses, including the size, shape, symmetry, and membrane structure. In addition, buffer conditions that may induce aggregation and change their apparent size and surface properties, as well as chromatography flow-rate and packing material characteristics, are, among others, important parameters potentially influencing the binding of viruses on chromatographic resins. Due to the complexity of the phenomena potentially influencing the chromatographic behaviour of viruses, and because these are not well understood, it is important to design chromatographic production processes of plasma derivatives and to perform their validation studies following a rigorous scientific approach.