Introduction
The U.S. system for developing and approving drugs is rigorous, complex and expensive. On the average, it takes ten to 15 years for a company to get one new medicine from the laboratory to patients, costing $1 billion or more. This significant investment of time and money is attributable to the multiple steps involved in drug development.
Target Identification and Testing
The starting point in drug research is the identification of a potential target presumably involved in the disease condition of interest. Once a relevant target has been identified and validated in biological studies, compounds are tested to identify those that may interfere with the target. In most cases thousands of different compounds, originating from natural sources such as plants, microorganisms or from the synthetic efforts of laboratory chemists, are evaluated for activity. A "hit" is a compound that exhibits the desired activity, usually requiring massive screening efforts to identify.
Preclinical Testing
A company will evaluate a "hit" in several studies to ensure that it has the appropriate properties to advance into further development. This involves testing the compound in cell and tissue cultures and animals in order to determine its activity, selectivity and its potential toxicity. The manufacturing process for the compound must also be explored to ensure that a quality synthesis can be developed to produce large quantities. These various steps are called preclinical evaluation. A number of different scientists with a variety of skills are required for preclinical testing.
Investigational New Drug Application (IND)
After completing preclinical testing, a company files an IND with the U.S. Food and Drug Administration (FDA) to begin to test the drug in people. The IND becomes effective if the FDA does not disapprove it within 30 days.
Clinical Testing
Following the IND, the drug candidate is administered to humans in properly conducted clinical trials. There are three types of clinical studies.
Phase 1 studies are conducted in normal volunteers in good health, usually in the range of 50 to 100 persons, and are designed to determine the safety and behavior of the drug candidate in people.
Phase 2 studies are conducted in patients, usually numbering in the hundreds, and are designed to determine whether the drug candidate has the expected activity in the targeted disease condition. Phase 2 studies also determine the appropriate dose.
Phase 3 studies usually involve several hundreds to tens of thousands of patients and are designed to evaluate the potential drug's activity and safety under normal or near-normal conditions. Physicians monitor patients closely to confirm efficacy and identify adverse events.
New Drug Application (NDA) and Approval
Following completion of all three phases of clinical trials, a company will analyze the data and, if satisfied with the results, file an NDA with the FDA. The NDA contains all the scientific information the company has gathered on the drug candidate. The FDA reviews this information and either approves the new drug or not. This review process averages over 12 months for each NDA. Once approval is obtained, the company manufactures and distributes the new medicine, making it available for physicians to prescribe.
References
- Tufts Center for the Study of Drug Development; Post-Approval R&D Raises Total Drug Development Costs to $897 Million; K. E. Kaitin; June, 2003
