Quality of plasma and its fractionation

Abstract

Human plasma (plasma for fractionation) is used as a source material for the manufacture of a large range of therapeutic products that are essential for the treatment of life‐threatening injuries as well as bleeding and immunological diseases. The industrial multistep process carried out to isolate the various therapeutic plasma proteins is known as ‘fractionation’. Typical plasma fractionation batches have a volume of 2000–4000 l obtained by pooling the individual donations from thousands of donors. The provision of safe plasma products relies upon the quality of the starting plasma and on a correct implementation of the fractionation processes, both under conditions meeting Good Manufacturing Practices (GMP) standards. The preparation of plasma for fractionation according to GMP is one key element in the quality and safety of medicinal plasma products. The quality specifications of plasma for fractionation should be precisely defined by the plasma fractionators and approved by the relevant regulatory authorities. Aspects of particular relevance for the control of infectious risks include (i) the selection criteria of blood/plasma donors, (ii) the methods used for the testing of blood/plasma donations, (iii) the epidemiological surveillance of the donor population, (iv) the adherence to GMP principles by blood establishments, and (v) the existence of a postdonation information system. Other quality aspects that may impact the range, quality, or recovery of fractionated products include the operational parameters used for plasma separation, rate of freezing and storage temperature. The industrial plasma fractionation process should be carried out under highly hygienic conditions in licenced facilities (plasma fractionation plants) operated in compliance with GMP. Manufacturing steps used to isolate the various fractions are implemented in a sequential and integrated manner. Crude fractions obtained by cryoprecipitation and cold ethanol precipitation steps are purified into individual therapeutic products most often by chromatographic methods. Validated dedicated treatments are implemented within the manufacturing process of each product to inactivate and/or remove enveloped and non‐enveloped viruses potentially present in the starting plasma pool. Recent experimental spiking studies also demonstrate that, several fractionation steps contribute to prion removal. When using current production technologies and under strict regulatory oversight, plasma products have reached a high level of quality and safety.