Insulin biotechnological production

The bulk production of sterile drug products such as antibiotics, corticosteroids, insulin, and certain biotechnology products requires that a number of processes be carried out under aseptic conditions. These processes can be evaluated in a manner adapted from those employed for aseptic filling processes. A joint PDA/PhRMA task force has developed the definitive guidance document on this subject. ... 

Insulin is an early and classic example of a biotechnology product. It illustrates some of the general problems that are associated with peptide drugs and how modem technology leads to improved therapy. Prior to the production of human insulin by cell-based fermentation processes, treatment was with pancreatic extracts of porcine or bovine origin. Many patients developed insulin resistance, and... 

Recombinant insulin was the first biotechnology product, which emerged in 1982. Today, biopharmaceutical products have diverged to encompass not only recombinant forms of natural proteins and biologicals derived from natural sources, including recombinant plant-derived pharmaceutical proteins, but also monoclonal antibody (mAb)-based therapeutics. All these products require special consideration from a regulatory point of view. 

With all the above in mind, the general impression in 1971 was that gene transfer, controlled gene expression, and stable inheritance, particularly across species barriers, would not be likely or would lead to transient-crippled unstable hybrids with poor expression that would certainly not be suitable as a source for biotechnology products. The mainstream of the classical pharmaceutical industry management was of this opinion, right up to the announcement that Genentech s recombinant insulin had been approved for clinical use in 1984. 

At present the unique performance of biotechnological products is the main driver of this technology, especially in the pharma and cosmetic markets. API s, active pharma ingredients, are often protein based, like antibodies. These are one of the backbones of red biotechnology. But also other API s and nutrition ingredients, which can only be synthesized in a complex series of chemical steps are nowadays synthesized in microbes. Examples are insulin or vitamins, examples of White Biotechnology. Many of these are described in the beginning of this chapter. 

Despite the enormous success of biotechnology products to date, much effort continues to be focused on the development of more convenient and noninvasive routes of administration for those products that require frequent and prolonged dosing. Here we present an overview of the technologies, both developed and emerging, which are applicable to protein dehvery. In addition, chapters 11 through 13 detail case studies on physical methods for delivery of insulin and growth hormone. 

Biotechnology era beginning First recombinant DNA products Human insulin Human growth hormone Interferons, etc. Monoclonal antibodies Nucleotide blockage Growth in use of natural products and neutraceuticals... 

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

Biotechnology-derived products have led to renewed interest in establishing reference standards based on the same bulk of material. Thus a single formulation, assay, and reference standard may be the fact worldwide. This situation can become complex such as with insulin where both biotechnology-derived insulin and animal-source insulin are in the marketplace at the same time. 

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