Recombinant blood factor preparations

Despite the undoubted advantages of recombinant production, it remains the case that many protein-based products extracted directly from native source material remain on the market. In certain circumstances, direct extraction of native source material can prove equally/more attractive than recombinant production. This may be for an economic reason if, for example, the protein is produced in very large quantities by the native source and is easy to extract/purify, e.g. human serum albumin (HSA Chapter 12). Also, some blood factor preparations purified from donor blood actually contain several different blood factors and, hence, can be used to treat several haemophilia patient types. Recombinant blood factor preparations, on the other hand, contain but a single blood factor and, hence, can be used to treat only one haemophilia type (Chapter 12). 

C. Negrier, J. Astermark, 1. Pabinger, ). Di Paola et al. Surgical Evaluation of rAHF-PFM, an Advanced Category Recombinant Antihemophilic Factor Prepared Using a Plasma/Al-bumin-Free Method. Blood 2003 102(ll) Ab-stract 2944. 

Better methods for preparing clotting factors from blood and the development of recombinant clotting factors provided the solutions. Methods of detecting, inactivating, and removing viruses were improved, and none of the hemophilia replacement products— conventional or recombinant—has transmitted either HIV or hepatitis since 1987. As an alternative, recombinant clotting factors 8 and 9, produced in animal cells, were approved in 1992 and 1997, without the risk associated with human blood products. 

A (very rare) genetic deficiency in the production of factor XIII also results in impaired clotting efficacy in affected persons. In this case, covalent links that normally characterize transformation of a soft clot into a hard clot are not formed. Factor XIII preparations, partially purified from human blood, are used to treat individuals with this condition to date, no recombinant version of the product has been commercialized. 

Walsh (2003) defined biopharmaceuticals as therapeutic protein or nucleic acid preparations made by techniques involving recombinant deoxyribonucleic acid (DNA) technology. Therapeutic proteins include blood clotting factors and plasminogen activators, hemopoietic factors, hormones, interferons and interleukins, and monoclonal antibodies (LeVine, 2006). Over time, the term biopharmaceutical has broadened, and, in addition to proteins and nucleic acids, now includes bacteriophages, viral and bacterial vaccines, vectors for gene therapy, and cells for cell therapy (Primrose and Twyman, 2004). Attention here focuses on proteins, since the majority of approved biopharmaceuticals are proteins. 

Genetically, determined clotting diseases include classical haemophilia, which is due to lack of factor VIII, and there is another form of haemophilia due to deficiency of factor IX (Christmas factor). These are treated by giving fresh donor blood or plasma, preparations of factor VIII or factor IX, or increasingly as one of the recombinant versions which are becoming available. 

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