Biopharmaceutical sources

FIGURE 45.5 New molecular entities and biopharmaceuticals. Source EFPIA. 

The three main sources of competitive advantage in the manufacture of high value protein products are first to market, high product quaUty, and low cost (3). The first company to market a new protein biopharmaceutical, and the first to gain patent protection, enjoys a substantial advantage. The second company to enter the market may find itself enjoying only one-tenth of the sales. In the absence of patent protection, product differentiation becomes very important. Differentiation reflects a product that is purer, more active, or has a greater lot-to-lot consistency. 

Table 1.5 Approximate annual market values of some leading approved biopharmaceutical products. Data gathered from various sources, including company home pages, annual reports and industry reports...

This chapter aims to overview the manufacturing process of therapeutic proteins. It concerns itself with two major themes (1) sources of biopharmaceuticals and (2) upstream processing. The additional elements of biopharmaceutical manufacturing, i.e. downstream processing and product analysis, are discussed in Chapters 6 and 7 respectively. 

Biopharmaceutical products are also subjected to screening for the presence of viral particles prior to final product release. Although viruses could be introduced, for example, via infected personnel during downstream processing, proper implementation of GMP minimizes such risk. Any viral particles found in the finished product are most likely derived from raw material sources. Examples could include HIV or hepatitis viruses present in blood used in the manufacture of blood products. Such raw materials must be screened before processing for the presence of likely viral contaminants. 

Figure 1.2 R D investments by research-based US pharmaceutical companies. Source. The Pharmaceutical Research and Manufacturers of America (PhRMA). Pharmaceutical Industry Profile 2006. http //www.phrma.org/files/2006%20Indusry%20 Profile.pdf, and http //www.phrma.org/news room/press releases/r%26d spending by u.s. biopharmaceutical companies reaches a record %2455.2 billion in 2006/ [accessed July 7, 2007].

Source Walsh G. Biopharmaceutical benchmarks—2006, Nature Biotechnology 24 769-776 (2006). 

Figure 4.3 Production of polyclonal antibodies from horse antisera. Source Walsh G. Biopharmaceuticals Biochemistry and Biotechnology, Wiley, Hoboken NJ, 1998.)...

Insulin was originally (since the 1930s) obtained from porcine and bovine extracts. Bovine insulin differs from human insulin by three amino acids, and it can elicit an antibody response that reduces its effectiveness. Porcine insulin, however, differs in only one amino acid. An enzymatic process can yield insulin identical to the human form. Currently, insulin is produced via the rDNA process it was the first recombinant biopharmaceutical approved by the FDA in 1982. The recombinant insulin removes the reliance on animal sources of insulin and ensures that reliable and consistent insulin is manufactured under controlled manufacturing processes. A description of diabetes meUitus and insulin is presented in Exhibit 4.13. 

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