Introduction to Biopharmaceuticals

J.G. Wagner, Introduction to biopharmaceutics, Chapter 1, in Biopharmaceutics and Relevant Pharmacokinetics, J.G. Wagner, ed., Drug Intelligence Publications, pp. 1-5, 1971. 

SMITH, D.A. (1997) Pharmacokinetics and pharmacodynamics in toxicology. Xenobiotica 27, 513. YANG, R.S.H. and ANDERSEN, M.E. (1994) Pharmacokinetics. In Introduction to Biochemical Toxicology, edited by E.Hodgson and P.E.Levi, 2nd edition (Connecticut Appleton-Lange). ZBINDEN, G. (1988) Biopharmaceutical studies, a key to better toxicology. Xenobiotica, 18, Suppl. 1,9. 

This short overview provides an introduction to the more generally applied analytical schemes associated with QC. However, in the following section more specific aspects relating to modern biopharmaceuticals will be highhghted in greater detail. 

Samanen J. (2013) Similarities and differences in the discovery and use of biopharmaceuticals and small molecule chemo-therapeutics. In Ganellin CR, Roy Jefferis R, Roberts S, editors. Introduction to biological and small molecule drug research and development. Elsevier, p 161-200. 

Many of the initial biopharmaceuticals approved were simple replacement proteins (e.g. blood factors and human insulin). The ability to alter the amino acid sequence of a protein logically coupled to an increased understanding of the relationship between protein structure and function (Chapters 2 and 3) has facilitated the more recent introduction of several engineered therapeutic proteins (Table 1.3). Thus far, the vast majority of approved recombinant proteins have been produced in the bacterium E. coli, the yeast S. cerevisiae or in animal cell lines (most notably Chinese hamster ovary (CHO) cells or baby hamster kidney (BHK) cells. These production systems are discussed in Chapter 5. 

Since the commercial introduction of the P-CAC in 1999, several industrial applications have been shown to be transferable to the system. Moreover, users in the biopharmaceutical and foodstuff industry have seen their productivity increasing dramatically as a result of using the P-CAC technology. Furthermore, a P-CAC has been shown capable of continuously separating stereoisomers when using chiral stationary phases even when there is more than one chiral center in the desired molecule. Below some of the applications are described in more details. Others are proprietary and hence cannot be disclosed. 

The protein microarray represents an emerging technology. While we have described its potential utility, several key problems remain to be overcome before this tool is fully adopted by the research and biopharmaceutical commxmities. The most likely first embodiment will be an antibody "protein-detecting" microarray. This is understandable based upon the availability and suitability of antibody libraries originally developed for ELISA. We have discussed many demonstrahons of antibody arrays in this chapter but commercial introductions (Pierce, Beckman Coulter) have been limited. 

Many of the initial biopharmaceuticals approved were simple replacement proteins (e.g. blood factors and human insulin). The ability to logically alter the amino acid sequence of a protein, coupled to an increased understanding of the relationship between protein structure and function has facilitated the more recent introduction of several engineered therapeutic... 

In 1996, about 10 years after the introduction of the first recombinant DNA product for human use, the FDA modified and streamlined the approval process for biotechnology products considered to be well characterized. These modifications, in essence, established the direction of how biologic macromolecules are researched and developed today in biotechnology-based and traditional pharmaceutical companies [2]. Well-characterized biotechnology products include (1) synthetic peptides consisting of fewer than 20 amino acids, (2) monoclonal antibodies and derivatives, and (3) recombinant DNA-derived products. Anticipating future developments, the FDA is also prepared to consider DNA plasmid products as well-characterized when the first medicinal in this class is submitted for approval. CBER now approves well-characterized biopharmaceuticals under the BLA process [3]. 

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