Human source materials

Evidence of adverse health effects resulting from PFAA exposure has yet to be clearly established. Despite the lack of evidence, interest in the determination of PFAAs in human source materials (e.g., whole blood. 

Chan et al. [198] present evidence to show that many current and past methods for the determination of PFAAs may have inherent biases when applied to human source materials. Two classes of interferences are identified that share common fragmentation pathways (mj/z 399- 80 and m/z 399—>99) with the PFAAs TDCA isomers (previously identified by Benskin et al. [172]) and steroid sulfates (specifically, pregnandiol sulfate and isopregnanalone sulfate). Chan et al. recommend improvements for the chromatographic separation and the use of an alternative mass transition m/z 399—>119. The alternative mass transition resolves the interference but provides less-sensitive response to PFHxS. 

Proteins such as antibodies, enzymes, hormones and vaccine antigens can be used to prevent, diagnose and treat a range of diseases. Such molecules are therefore of paramount importance in health and medicine. Historically, many of these proteins have been isolated from human or animal sources. However, the low quantities present in such source material coupled with safety risks and high purification costs have limited the availability of protein therapeutics and vaccines for many types of disease. 

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). 

Figure 9.17. Overview of the manufacture of Ceprotin. As the active ingredient is derived directly from pooled human plasma, particular emphasis is placed upon ensuring that the finished product is pathogen-free. Precautions entail the incorporation of two independent viral inactivation steps and high-resolution chromatographic purification. Additionally, extensive screening of plasma pool source material for blood-borne pathogens is undertaken. Viral screening is undertaken using a combination of immunoassay and PCR analysis for the presence of viral nucleic acid...

Moller B. 1979. Reactions of human dental pulp to silver amalgam restorations. A study with emphasis on source material characteristics. Swedish Dent [Suppl] 2 1-37. 

The inescapable variability of the source material and potential threat to safety due to unrecognized infectious agents [transmission ofAIDS by blood products and the undefined potential for either human or bovine source materials to spread Creutzfeld-Jakob disease (CJD)/ transmissible or bovine spongiform encephalopathy (TSE, BSE)]... 

The ability to obtain cell clones that respond to cytokines and serve as source material for bioassays has aided the development of bioassays. The cell lines, obtained mainly from human or murine cancers, often depend on a cytokine for their growth and tend to be immortal, thus providing a unique homogeneous cell source, which may be distributed among laboratories (Mire-Sluis and Thorpe, 1998). The advent of recombinant DNA technology has enabled the cloning of specific cytokine receptors and their expression in any cell line (Canosi et al., 1996). In this way, a cell line can be created that responds specifically to almost any cytokine, and avoids the necessity to isolate a cell line with an endogenous receptor. 

For example, Council Directive 89/107/EEC of 21 December 1988 on the approximation of the laws of the Member States concerning food additives authorised for use in foodstuffs intended for human consumption. OJ L40, 11.21989, p. 27, Council Directive 88/388/EC of 22 June 1988 on the approximation of the laws of the Member States relating to flavourings for use in foodstuffs and to source materials for their production of L 184 of 15.07.1988. 

The starting source materials used for the production of therapeutic proteins were heterogeneous mixtures obtained from several humans or animals, requiring the pooling of somce material from a large number of individuals to eliminate individual and batch to batch variation of post-translational modifications in the final product. Thus, starting plasma lots used in fractionation are made from pools of plasma derived from 10,000 to 12,000 individuals (Snape, 1991). 

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