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INTRODUCTION TO BIOTECHNOLOGY

Biotechnology simply means the technology of life or the industrial use of life forms. The definition of pharmaceutical biotechnology include all materials made or derived from natural materials that can be used as drugs for human or animal medicine. Accordingly, it defines 1. Use of biological systems to produce drug substances 2. Exploitation of modern technologies to produce drug substances from biological systems More than a decade later, the word biotechnology has changed meaning in a very subtle way and now encompasses the use of material manipulation using DNA in living cells. If we add Pharmaceutical to the key word we can suggest that the subject is about the development of drug substances, in particular those large protein and polypeptide molecules involved in some way or another in the disease states humans (and animals) suffer from. The inference now is that DNA in cells is manipulated so that the cells will produce a required molecule, usually proteinaceous, that has desirable properties in terms of the treatment of disease. Although it might be assumed that biologic refers to any pharmaceutical product produced by biotechnological endeavour, its definition is more limited. In pharmaceutical circles, biologic generally refers to medicinal products derived from blood, as well as vaccines, toxins and allergen products. Biotechnology has a much broader and long-established meaning. Essentially, it refers to the use of biological systems (e.g. cells or tissues) or biological molecules (e.g. enzymes or antibodies) for/in the manufacture of commercial products. Areas of interest in biotechnology: Journey from biotechnology to pharmaceutical biotechnology More than 150 approved biotech drugs or vaccines are on the market and 70% were approved in the last six years (Fig. 1). A recent survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) found 369 drugs in the pipeline meeting the criteria as biotechnological drugs and medicines. These drugs target 200 potential diseases and provide new therapies for autoimmune diseases, asthma, Alzheimer, multiple sclerosis, and cancer including immunization and different infectious diseases (AIDS, Malaria). Biotechnology-produced pharmaceuticals currently account for 5% of the worldwide pharmaceutical market and are expected to reach approximately 15% by the year 2050. At the same time, the explosive growth of genetic diagnostic techniques will allow personalized genetic profiling of each individual in one hour and for less than US$100. Not only drugs but also new medical diagnostic tests will be produced and distributed by pharmaceutical biotech industry. Hundreds of tests will be available to increase the safety of blood products. Also, costs for clinical analysis will be reduced. One example is the testing of Low Density Lipoproteins (LDL), cholesterol, and other parameters in one test design. In comparison to conventional tests, cholesterol, total triglycerides, and LDL were determined separately at high costs. In the future, biotechnology-derived tests will be more accurate and quicker than previous tests and will allow earlier diagnosis of the disease.

Immunological and Biological Products -RATHEESH

Proteomics may increase sensitivity and may discover today unknown molecular markers that indicate incipient diseases before symptoms appear, helping to prevent diseases and conduct therapies much earlier Xenotransplantation from transgenic animals is a future field in pharmaceutical industry. In general, organ transplantation is an effective and cost-efficient treatment for severe and life-threatening diseases of organs, mostly heart, liver, and kidney. Genetically modified organs and cells from other organisms like pigs called as xenotransplantation are promising sources of donor organs that can be used to overcome the lack of a sufficient number of human organs. But, the spread of infectious pathogens by transplantation of nonhuman organs and the induction of oncogenes is a potential risk and needs close attention. Tissue engineering, in relation to xenotransplantation, is another attractive field in pharmaceutical biotechnology. Tissue engineering combines advances in cell biology and biomaterial science. Tissues consist of scaffolding material (e.g. collagen, biodegradable polymers),which eventually degrades after forming organs or cell implants. Skin tissues and cartilages were the first tissues successfully engineered and tested in vivo; recently, biohybrid systems to maintain patients liver or kidney function were also successfully tested. Stem cells are considered today as a new avenue in therapy to cure most deadly and debilitating diseases such as Parkinson, Alzheimer, leukemia, and genetic disorders like adenosine deaminase (ADA) deficiency and cystic fibrosis (CF). The potential of embryonic and adult stem cells are intensively discussed, but no major breakthrough can be expected in the next 10 years to turn these cells and techniques into industrial applications. It should also be clear that therapeutic cloning, which is related to stem cell research, will bring ethical questions Discussions of ethical and social implications are important today to convince the public of potential benefits and to explain the future risks of applied techniques. Significant impediments of diagnostics and therapeutics exist, and deep concerns must be respected before any genetic therapy like somatic gene therapy, stem cell, or cloning will ever be accepted.

The role of pharmaceutical biotechnology in drug discovery and development The most frequent trends for the pharmaceutical industry in biotechnology are surely new technologies and innovations, especially genomics, and also influences of government regulations, health care legislation affecting own product pricing, changes in demographics, and an aging population . With special emphasis, more topics with minor influence relate to patent protection, ebusiness, multinational scope of industry, requirements for new drugs, and changes in information technology to address some of them. In the first decade of this century, the biotech industry is likely to show even more explosive growth as progress in computer modeling, automated lab techniques, and knowledge of human genes and proteins continues. As a result, more life-saving therapies will reach the people who most need them. Today, pharma industry seems to be in good shape to work on these challenges, as indicated by some impressive statistics that emphasize the industrys growth:
Immunological and Biological Products -RATHEESH

During the 1980s, the biotech industry turned out 18 new drugs and vaccines. By comparison, 33 biotech medicines were approved in both 1998 and 1999, and 25 more were approved in the first half of 2000. Most of the 19981999 approvals were for new products, though a few were for expanding the application of drugs or vaccines to more diseases. The number of patents granted to biotech companies has tripled from nearly 3000 per year in the early 1990s to more than 9000 in 1998. After a decade of slow, steady growth, biotechnology patent awards began a steep ascent in 1995, when nearly 4000 patents were granted. Since then, the number of patents has skyrocketed at a rate of 25% or more each year. Pharmaceutical companies, which traditionally have focused on chemical approaches to treating disease, have become increasingly supportive of biotech R&D in their ownlabs, in partnerships with biotech firms, and through acquisitions of biotech firms. Alliances in the biotech industry doubled to nearly 250 between 1998 and 2000. Between 1998 and 1999, industry-wide sales and revenues increased by 13% to $16.1 billion and $22.3 billion respectively. For the future, the biotechnology and genomic way is technology-driven and formed by the integration of highthroughput technologies, genomics, and bioinformatics. Even the genetics wave is data-driven and is an applied new life science field to identify genes that make individuals as their carriers susceptible to particular diseases and allows personalized medicines based on pharmacogenetic facts. So, what is the impact of pharmaceutical biotechnology and genomics on the economics of R&D? Reducing Costs in R&D: Before biotechnology had been intensively introduced to industrial research, developing costs of each drug had cost companies on average US$880 million and had taken 15 years from start to market authorization. About 75% of these costs were spent on failures. Using genomic technologies, there is a realistic chance of reducing companies costs to US$500 million, largely as a result of efficacy gains.Significant savings not only of money but also of time by 15% are possible . Increase in Productivity: From trial-and-error approaches and complex biochemical in vitro assays, biotechnology allows industrialized target detection and validation. By the use of micro array technologies and bioinformatics, thousands of genes in diseased and healthy tissues will be analyzed by a single DNA chip. By the use of bioinformatics, results from different assays can be analyzed and linked to an integrated follow-up of information in databases. In total, the potential savings per drug by intelligent information retrieval systems and genetic analytics are estimated at about US$140 million per drug and less than one year of time to market. Accelerating the Drug Development Process: There is not only an effect on the preclinical development of a drug by biotechnology and genomics but pharmaceutical biotechnology will also help predict drug properties and pharmacokinetic parameters (ADME) to accelerate the industrial drug development process. Companies will be in the position to pull certain preclinical activities into the chemistry and drug validation part of the value chain. Potential savings are in the order of US$20 million and 0.3 years per drug

Immunological and Biological Products -RATHEESH

Maintaining High Standards in Quality Assurance: Biotechnological drugs have the same high standard in quality and safety as conventional drugs. Of high interest is the question of costs of quality control for recombinant drugs. Boston Consulting Group expects an increase of US$200 million and more than one year per drug. The main reason for this is explained by the extra time needed for unknown chemical and physical properties of recombinant proteins and oligonucleotides. Another time- and cost-consuming aspect is the importance of developing new drugspecific appropriate test assays for drug validation, standardization, activity determination (e.g. biological units), toxicity, and bioanalytical methods. Future Outlook Integrating biotechnology and genomics in the whole drug development process gives companies the opportunity to save up to US$300 million per drug about one-third of the costs today and the prospect of bringing the drug two years earlier on the market . Each day lost before market entry will lead to a loss of US$1.5 million per day, indicating the value of recombinant drugs and the need for making manufacturing processes operational and effective.

Immunological and Biological Products -RATHEESH

Immunological and Biological Products -RATHEESH