Journal of Pharmacy Practice

Modern biotechnology has advanced rapidly in the past few decades, driven largely by scientific advances which have led to the development of techniques such as recombinant DNA and hybridoma technology. The United States is a leader in the growing biotechnology field. Biotechnology has wide potential application in diverse areas including health care, chemicals, food, and waste treatment. Health care represents the largest sector in the biotechnology industry with hundreds of products in development including therapeutics, vaccines, diagnostics, devices and drug delivery systems. Unique legal, regulatory, and societal issues associated with biotechnology-derived products are being addressed as the field continues to evolve.

Growth and change are the hallmarks of the developing biotechnology industry. Since the first approval of a biological product in 1982, over 40 biologicals, many of them medical breakthroughs, have been brought to market. The majority of biotechnology companies focus on developing human therapeutic agents, but about 25 percent of biotechnology companies focus on the diagnostic area, using monoclonal antibody technology, polymerase chain reaction (PCR) technology, and genetics to provide advances in diagnosis and disease monitoring. Structurally, few biotechnology firms are fully integrated companies with full capabilities in research, development, manufacturing, and sales and marketing. Many pursue strategic alliances with other companies to enhance their capabilities in research, development, and sales and marketing. Research alliances between companies and universities are also frequently used to enhance research capabilities. As the industry has matured, consolidation has occurred, with major pharmaceutical companies purchasing biotechnology companies and biotechnology companies merging to expand their capabilities. Research investment, as a percentage of gross sales, continues to be very high for biotechnology companies compared with traditional pharmaceutical companies. The cost of drug development is high, but the probability of approval appears to be somewhat better in the biotechnology field compared with traditional pharmaceuticals. Today, the biotechnology product pipeline is rich, with between 400 to 700 products in various stages of clinical development. Technology developments beyond recombinant DNA technology and monoclonal antibodies, such as antisense, genomics, and combinatorial chemistry, will lead to additional therapeutic and diagnostic breakthroughs.

The quest to understand how genetic information is passed from one generation to the next reached a major milestone in the 1950s with the discovery of the complementary double-helix structure of DNA by Watson and Crick and the demonstration by Kornberg that DNA was capable of self-replication. These breakthroughs provided the stimulus for a flurry of research that culminated in a basic understanding of the genetic code and a statement of the central dogma of molecular biology: DNA goes to RNA goes to protein. In expressing a gene, RNA is formed from the DNA template in a process called transcription. The process of RNA forming protein is known as translation. During translation, amino acids are linked to form protein. The primary structure of proteins is thus determined by the sequence of amino acids. Using x-ray crystallography and computer imaging, it has been possible to determine the three-dimensional structure of many proteins and to design small molecule peptides which can either mimic or block the function of the protein and thus be useful therapeutic agents.

Since the discovery of the structure and function of DNA over 40 years ago, the established knowledge of molecular biology has increased dramatically, and many new tools have been discovered and utilized by scientists to develop new therapeutic agents. Important tools that are used in recombinant DNA technology include restriction endonucleases (cleave DNA), DNA ligase (link DNA molecules together), and cloning vectors (place foreign DNA into an organism such as bacterial or yeast cells in order to mass produce the protein encoded by that foreign DNA). The development of hybridoma technology provided a method to produce virtually unlimited quantities of pure antibody with a single specificity. These immuno-globulins are known as monoclonal antibodies, and have provided both therapeutic and diagnostic agents. Antisense molecules are oligonucleotides which bind to the messenger RNA (mRNA) of a target gene and selectively inhibit the production of specific proteins. Potential applications for these molecules include cancer and viral and inflammatory diseases. The more recent development of the polymerase chain reaction (PCR) has provided a tool that has revolutionized diagnostic testing in diverse areas such as infectious diseases, genetic abnormalities, and cancer.

Providing biotechnology pharmaceutical care poses unique challenges for pharmacists. Biotechnology products often have special requirements for storage, dispensing, and administration which have traditionally limited their distribution to hospitals and clinics. The growing number of biotechnology products and the increasing use of these products in outpatient settings will provide opportunities for pharmacists who are prepared to deal with the special needs of these products. Biotechnology products are often expensive which has led to close scrutiny of their use. A careful analysis of these products, however, should consider both the cost of the products and the benefit to patients. Pharmacoeconomics provides the pharmacist with rigorous methods for determining the value of biologic products by carefully balancing the cost with the patient outcomes achieved. Providing biotechnology pharmaceutical care services requires substantial commitment on the part of pharmacists, but provides an opportunity to fill a need and develop a rewarding practice.

The unique nature of biotechnology products requires specific additional education and training for pharmacists. To understand how these products were developed and their mechanism of action, expanded knowledge in molecular biology, immunology, genetics, and the techniques of biotechnology is essential. Since these products are often used for disease states that were not previously treated with drug therapy, a basic understanding of the pathophysiology of the disease being treated is essential. Many biotechnology products are administered parenterally, and pharmacists must be familiar with these methods of administration to provide proper equipment, guidance, and counseling for patients. Stability and compatibility issues frequently arise with biotechnology products as many require refrigeration, special diluents, and are susceptible to compatibility problems. Because these products are often used in chronic disease settings and because patients may be expected to self-administer using a parenteral route, drug therapy monitoring and patient education needs are often substantial. The patient education role, in particular, may be the most important responsibility for pharmacists providing care to patients undergoing treatment with biotechnology products.

Biotechnology has contributed to important advances in the healthcare field. Products include various hormones, enzymes, cytokines, vaccines, and monoclonal antibodies, with use in diverse therapeutic areas. The majority of approved biotechnology-derived therapeutic products are recombinant proteins. Many have orphan drug status and, therefore, are used in relatively small patient populations. Newer generation biotechnology products are likely to include small molecules, gene therapy products, and increased numbers of vaccines and monoclonal antibody products. Biotechnology provides the means to develop diverse, innovative, and effective approaches to the prevention, treatment, and cure of human disease.

We report a case of a 25-year-old, female Jehovah'S Witness (JW) with severe anemia secondary to emergent salpingectomy who was treated with high dose human recombinant erythropoietin (rHu-EPO). Post-operative laboratory values were significant for a Hgb of 3.4 g/dl and a Hct 9.6%. The patient received rHu-EPO 150 u/kg IV q 12 hrs x 10 days, iron dextran, folic acid, cyanocobalamin, and fluid replacement. The patients Hgb and Hct were 6.0 g/dl and 18.9% upon discharge, increased from a nadir of 2.4 g/dl and 6.7%, respectively. The immediate administration of high dose rHu-EPO to severely anemic JW patients may decrease the period of severe anemia by accelerating erythropoiesis.