Fractionation, Blood, Plasma Fractionation

Abstract

Blood plasma fractionation is a biopharmaceutical manufacturing operation in which high quality, proteinaceous products are prepared for clinical use from human plasma. Products prepared in this manner include albumin, eg, human serum albumin, and plasma protein fraction, for volume and protein replacement in surgery and for the treatment of injury and disease; coagulation factors, eg, Factor VIII and Factor IX Complex, for the prevention and treatment of bleeding disorders; and immunoglobulins, eg, immune serum globulin and immune globulin intravenous, for the prevention and treatment of infectious diseases and immune disorders. A number of highly integrated bioseparation processes are employed to fractionate human plasma into its different constituents. These range from established cold‐ethanol precipitation technology, devised in the 1940s, to more recently developed solid‐phase adsorption/desorption techniques. The principal developments since 1980 have been immunoglobulin products for intravenous use, and highly effective technologies for the inactivation of viral contaminants, such as hepatitis viruses and Human Immunodeficiency Virus (HIV), which were associated with earlier coagulation factor preparations.

Protein composition and activation markers in plasma collected by three apheresis procedures

“…Although modest quality requirements have historically been set for plasma used for albumin fractionation, 43 quality criteria have increased as new fractionated components were developed and new purification and viral‐reduction technology implemented, making fractionation a sophisticated procedure 44,45 . In addition, for economic reasons and because of plasma shortage, good protein recovery at the collection and fractionation stages is essential.…”

“…Although modest quality requirements have historically been set for plasma used for albumin fractionation, 43 quality criteria have increased as new fractionated components were developed and new purification and viralreduction technology implemented, making fractionation a sophisticated procedure. 44,45 In addition, for economic reasons and because of plasma shortage, good protein recovery at the collection and fractionation stages is essential. Optimal coagulation factors content and absence of proteases 46 in starting plasma helps counterbalance yield losses due to fractionation steps 43,46 and limits risks of side effects in the final components, including FIX and IVIG, due to activated factors such as FVIIa, FXIa, plasmin, or prekallicrein activator.…”

Studies on the Removal of Abnormal Prion Protein by Processes Used in the Manufacture of Human Plasma Products

“…A number of blood products are prepared for medical use from pooled donations of human plasma including normal and specific immunoglobulins, coagulation factor concentrates and solutions of albumin [11]. A total volume of 2E10 7 litres of plasma per annum is processed in Europe and the USA for this purpose [12] with about 7 E10 5 litres per annum being available from the UK blood transfusion services.…”

Assessment of the potential of plasma fractionation processes to remove causative agents of transmissible spongiform encephalopathy

“…The preparation of each product involves extensive processing via a carefully designed, closely controlled series of operations ( Fig. 1) ( Foster, 1994). Each process includes a number of steps in which macromolecular constituents are preferentially removed; these steps are summarized below on a product‐by‐product basis.…”

“…As abnormal prion proteins are strongly membrane bound ( Stahl et al ., 1990 ), possess hydrophobic and hydrophilic domains ( Bolton et al ., 1987 ) and tend to adhere to surfaces, it is probable that they will interact with chromatographic ( Foster, 1994; Burnouf, 1995) and filtration ( Meltzer, 1987) media used in plasma fractionation. In these circumstances, a high degree of separation from abnormal prion protein may be possible where a plasma protein does not adsorb to a given matrix.…”