Pharmaceutical Career Field Structure
In the pharmaceutical industry, the process of discovering and developing a new product is particularly complicated and painstaking for several reasons. First, the human body itself is so complex, and the makers of drugs have to understand a great deal about the body’s functions and malfunctions before they begin. Second, a drug not only must work against illness, it must do so without killing a person, and its curative effects have to outweigh any adverse side effects. For instance, chemotherapy has toxic side effects on the human body, with symptoms such as vomiting and hair loss, because it destroys healthy cells along with cancerous tissues. The risk of such side effects is worth it to a patient whose life can be saved through chemotherapy treatments. Third, because of the potential risks of drugs to human lives, drugs must go through a long and rigorous testing process.
Most modern drug research begins by studying how the body functions and malfunctions. Because a disease usually progresses in a typical sequence of events, scientists try to interrupt this sequence in the lab and break it down into separate parts. They study each part to figure out what goes wrong at the cellular and molecular levels. Then they select a specific part on which to focus their development of a new drug, with the aim of correcting the cellular or molecular malfunction and interrupting, changing, or halting the course of the disease.
Scientists and researchers may test hundreds or thousands of compounds before finding one that is promising. They work with receptors (molecules on the surface of cells to which other active molecules may bind) and with enzymes that they suspect of playing a role in the disease. The cost of this research is high, but today it is aided considerably by computers. For example, a drug researcher can look at a three-dimensional model of a molecule on a computer screen with a technique called molecular modeling—this helps target specific disease sites for drug development.
Another huge breakthrough in drug research is the application of biotechnology, or genetic engineering, which involves manipulating human genes and proteins to create drugs and develop diagnostic tests. The first biotechnology drug, recombinant human insulin, was approved for use against diabetes in the early 1980s; since then more than 50 new biological therapeutics and vaccines, including interferon and certain hormones, have been approved for use against such ailments as hepatitis, anemia, dwarfism in children, and heart attacks.
After scientists working in a pharmaceutical lab, federal government lab, or university lab have come up with a drug that looks promising, the drug must undergo extensive testing in specific stages for an average period of 10 to 15 years before being approved for use by the FDA. The first stage is called preclinical testing, in which the chemical compound is tested on animals and in the lab to determine if it’s biologically active and safe. This stage takes an average of three and a half years.
The company sponsoring the drug then files an Investigational New Drug Application (IND) with the FDA, explaining the results of the preclinical testing and how the drug is made. If the IND is not rejected within 60 days, human clinical testing—a three-phase period that takes an average of six years—may commence. Phase I consists of studies on 20 to 80 healthy volunteers to determine the safe dose of the drug, how much is too much, how the drug works chemically on the human body and how the body in turn processes it, and how long its effects last. This one-year phase is followed by Phase II, a two-year period of testing the drug on a few dozen to 300 volunteer patients suffering from the specific disease the drug is meant to attack. Further animal tests conducted at the same time help biomedical scientists determine whether the drug is effective against the condition and whether it is safe for these patients to take. Finally, Phase III, usually a three-year period, tests that the drug is highly effective against the disease in several hundred to 3,000 volunteer patients in clinics and hospitals, and that its side effects are tolerable.
Individuals in some groups may never be used for drug testing. For example, testing drugs on pregnant women is considered an unethical research practice; therefore many drugs have not been proven safe for these women. Pregnant women have to avoid most drugs because it may risk harming the fetus, and there are few research methods that will sufficiently test for fetal drug safety. Animal studies may help, but they also may be inconclusive, as well as controversial.
Finally, the sponsoring company or agency files a New Drug Application, a lengthy document summarizing all the data collected in the clinical trials. In the early 1990s, the FDA took an average of two and a half years to review a drug at this stage. The FDA Modernization Act of 1997 intended to reduce this time, however; pharmaceutical companies are contributing funds to allow the FDA to hire more reviewers, as well as to make other improvements.
Out of all the chemical compounds that initially look promising, only one in 5,000 survives this screening process and eventually reaches the shelves as a new drug. The drug must not only prove to be sufficiently safe for the affected population to use, it also must prove to be reasonably effective for the population it is meant to treat. Being harmless is not enough to get a drug passed by the FDA.
The pharmaceutical industry is highly technical and sophisticated. The process described above requires teams of experts that include traditional organic chemists, physiologists, statisticians, biochemists, molecular biologists, toxicologists, pharmacologists, computer scientists, and physician investigators. The initial teams in the early stages of drug development usually include chemists and biologists who are experts in synthesizing and testing compounds and setting day-to-day goals. Much of this basic research takes place in a university setting or in a National Institutes of Health lab, while much of the applied research is more likely to be the responsibility of the pharmaceutical industry. The initial teams of scientists are joined by experts in drug metabolism, pharmaceutical development, and clinical development. Toxicologists, statisticians, and physician reviewers are called upon to evaluate the drug’s safety. Other types of specialists work in a variety of disciplines as molecular modelers, protein chemists, and X-ray crystallographers.
A research laboratory may cost several hundred million dollars, plus millions more for the libraries and computer facilities needed to complement it. And the equipment, some of which either becomes outdated quickly or has a working life of only five to seven years, includes such items as fluorescence-activated cell sorters that cost $1 million each, nuclear magnetic resonance spectrometers that cost $1 million each, and robotic screening operations that cost as much as $3 million. In light of these costs, the time needed for testing, plus the salary costs of highly trained professionals, it’s a little easier to understand the Pharmaceutical Research and Manufacturers of America’s (PhRMA) estimate that it costs an average of $800 million to discover and develop just one new medicine. In 2005, research and development expenditures by research-based pharmaceutical companies were about $51.3 billion.
Pharmaceutical companies, in addition to the human market, produce drug preparations for the veterinary market. Most leading drug companies have specific animal health divisions.
An emerging subfield of pharmaceuticals is the medicinals and botanicals industry. These firms oversee the complex process of producing extracts of natural substances and the organic and inorganic chemicals used in a majority of modern medicines. Specific formulas for the preparation of these substances can be found in the official U.S. pharmacopeia or in the National Formulary. If a substance has never been produced on an industrial scale or is entirely new, its manufacturer must produce a document listing the acceptable legal standards of purity and potency. Finished active ingredients, known as batches, are then shipped to the preparation firm awaiting them. These batches must meet the approval of the FDA and the customer company, as well as match a master batch in regard to purity and strength. The FDA uses Good Manufacturing Practices and frequent inspection to insure that optimum standards are observed.
Another emerging field of the pharmaceutical industry is ethnobotany. Nearly 25 percent of commercially available prescription drugs contain plant-derived compounds. As a result, many major companies have begun to invest time and money in the search for potentially lucrative medications. Discoveries include vinblastine, for treating Hodgkin’s disease; taxol, a Pacific yew derivative used to treat ovarian and breast cancer; and scopolamine for treating motion sickness.
There are numerous complicated laws regarding the development and marketing of drugs in the United States. Marketing is the largest segment of the industry today both in terms of number of employees and money spent. In 1997, certain restrictions were lifted on the advertising of pharmaceuticals to consumers, which led to drug companies allocating large percentages of their budgets to advertising and marketing. Fierce competition among drug manufacturers also has created jobs in law (for example, a new specialty in biotechnology patents) and government, particularly in lobbying.