Macromolecules biotechnology products

BIOTECHNOLOGY PRODUCTS OF MACROMOLECULES AND CHEMICAL PRODUCTS CURRENT TRENDS IN DRUG DEVELOPMENT... 

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]. 

Farnley and colleagues [96] have recently reviewed the complexity of intellectual property around biotechnology and biotechnology products. The authors note that the IP issues for small molecules and macromolecules, with a few exceptions, may be more similar than commonly assumed. The most important difference relevant to this overview is that each step in the discovery process may potentially be subject to different intellectual property considerations, which the authors note as unusual. The major differences between small-molecule and macromolecule patenting are shown in Table 1.3-11. 

The economic feasibility of a bioreaction process clearly depends on the characteristics of the associated bioseparation process, especially in the usual case when the product is present at low concentration in a complex mixture. For example, the existence of an extremely efficient and low-cost separation process for a particular compound could significantly lower the final concentration of that compound required in the bioreactor to achieve a satisfactory overall process. After noting that special approaches and processes are needed for efficient recovery of small molecules (ethanol, amino acids, antibiotics, etc.) from the dilute aqueous product streams of current bioreactors, I shall discuss further only separations of proteins. These are the primary products of the new biotechnology industry, and their purification hinges on the special properties of these biological macromolecules. 

The stability of biotechnology-produced products, proteins (macromolecules), and peptides is unique when compared with conventional pharmaceuticals (small molecules). Protein degradation by both chemical and physical processes leads to the loss of biological activity, whereas peptides decompose only through chemical instability with loss of efficacy and produce undesirable biological effects. 

Aqueous two-phase systems are generated by mixing aqueous solutions of two water-soluble polymers, or a polymer and a salt. These systems offer extremely mild conditions for separation of cells, organelles, proteins and other biomolecules, in biochemical processes. Considerable attention has been directed towards the use of the two-phase systems in several areas of biotechnology. The present paper summarizes the state of the art concerning extractive bioconversions for production of small as well as macromolecules, and protein purification using aqueous two-phase system. 

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