Monoclonal antibodies (mAbs) were firstly described by Köhler and
Milstein in 1975, and their potential as powerful therapeutic agents recognized in the
following years. Currently, the US Food and Drug Administration (FDA) has already
approved 56 monoclonal antibodies for the treatment of several diseases, including
cancer (e.g. breast cancer, leukemia and prostate cancer), auto-immune disorders
(rheumatoid arthritis and Crohn’s disease), asthma, and cardiovascular and infectious
diseases. Despite their advantages and therapeutic potential, the cost of manufacturing
these biopharmaceuticals with high quality and purity level is still extremely high due
to the absence of current cost-effective extraction/purification methods, and which has
also impaired their widespread application as recurrent therapeutic agents. The
upstream processing of mAbs has gone through several improvements in recent years,
by using alternative expression systems or by optimizing the medium formulations and
feeding strategies. On the contrary, the downstream processing is considered the
bottleneck in the manufacturing of mAbs for therapeutic purposes at reliable costs,
representing up to 80% of their total production costs – which is a frontier in clinical
drug research. In the past years, several chromatographic and non-chromatographic
alternatives have been explored for this purpose, resulting in the development of
efficient platforms for the purification of mAbs, that are overviewed and discussed in
this chapter. In summary, this chapter provides a vision on the current state of the art of
the biopharmaceuticals market, on the production and use of mAbs as valuable
therapeutic agents, including their use for the treatment of infectious diseases, while
summarizing the mAbs-based products already approved by regulatory agencies. New
insights concerning the development of new and alternative platforms or the extraction and purification of mAbs are also discussed, while envisaging the adoption of the most
relevant techniques by the pharmaceutical industry to allow the widespread use of
biopharmaceuticals in the near future.
Keywords: Affinity precipitation, Aqueous two-phase systems, Biopharmaceuticals,
Biopharmaceutical market, Cancer, Chromatographic methods,
Downstream processing, High performance tangential flow filtration, Infectious
diseases, Ionic exchange chromatography, IVIG, Magnetic separation,
Monoclonal antibodies, Multimodal chromatography, Non-chromatographic
methods, Passive immunity, Pharmaceutical industry, Preparative electrophoresis,
Purification, Therapeutic agents, Upstream processing.
