Biomedical Engineering Reference
In-Depth Information
Product analysis
7.1 Int roduc t ion
All pharmaceutical fi nished products undergo rigorous QC testing in order to confi rm their con-
formance to predetermined specifi cations. Potency testing is of obvious importance, ensuring that
the drug will be effi cacious when administered to the patient. A prominent aspect of safety testing
entails analysis of product for the presence of various potential contaminants.
The range and complexity of analytical testing undertaken for recombinant biopharmaceu-
ticals far outweighs that undertaken with regard to 'traditional' pharmaceuticals manufactured
by organic synthesis. Not only are proteins (or additional biopharmaceuticals such as nucleic
acids; Chapter 14) much larger and more structurally complex than traditional low molecular
mass drugs, their production in biological systems renders the range of potential contaminants
far broader (Table 7.1). Recent advances in analytical techniques render practical the routine
analysis of complex biopharmaceutical products. An overview of the range of fi nished-product
tests of recombinant protein biopharmaceuticals is outlined below. Explanation of the theoretical
basis underpinning these analytical methodologies is not undertaken, as this would considerably
broaden the scope of the text. Appropriate references are provided at the end of the chapter for the
interested reader.
7.2 Protein-based contaminants
Most of the chromatographic steps undertaken during downstream processing are specifi cally
included to separate the protein of interest from additional contaminant proteins. This task is not
an insubstantial one, particularly if the recombinant protein is expressed intracellularly.
In addition to protein impurities emanating directly from the source material, other proteins
may be introduced during upstream or downstream processing. For example, animal cell culture
media are typically supplemented with bovine serum/foetal calf serum (2-25 per cent), or with a
defi ned cocktail of various regulatory proteins required to maintain and stimulate growth of these
cells. Downstream processing of intracellular microbial proteins often requires the addition of
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