Each year many new drugs, including existing drugs used for new purposes, become available for people with cancer. How do these drugs go from being an idea in the laboratory to a labeled vial in the doctor's office? The drug development and approval process is lengthy and expensive. Typically, this process takes many years and costs hundreds of millions of dollars. However, depending on the drug, the actual amount of time and money required varies. This two-part series [1] describes the basic steps involved in the drug development and approval process in the United States.

The FDA

One of the primary roles of the U.S. Food and Drug Administration (FDA) is to make sure that drugs and biological products (called “biologics,” such as vaccines and products that come from blood and tissues) available in the United States are safe and effective for treating or preventing the conditions for which they are prescribed. All drugs and biologics sold in the United States, whether prescription or over-the-counter (nonprescription), must first be approved as safe and effective by the FDA. Within the FDA, the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER) is responsible for reviewing research conducted on investigational drugs and biologics and using this information to decide whether a drug or biologic should be approved for use.

Drug developers and sponsors

The FDA does not develop or test drugs. Pharmaceutical companies and other organizations, such as university medical centers and some government agencies (for example, the National Cancer Institute [NCI]), do the actual work of discovering and testing new drugs. The organization that develops a drug is called the sponsor. The sponsor conducts the research needed to provide CDER or CBER with the necessary information to make decisions regarding drug approval.

Preclinical research: Drug discovery and preliminary testing

The discovery of new cancer drugs happens in a variety of ways.

Accidental discovery. In the early 1940s, an explosion exposed sailors to poisonous mustard gas. After observing low white blood cell counts in these sailors, doctors began using nitrogen mustard (mechlorethamine [Mustargen]) to treat Hodgkin lymphoma, a cancer of the lymph system involving the white blood cells. Mechlorethamine is still used for treating cancer today. Accidental discoveries are rare, however.

Testing plants, fungi, and animals. Paclitaxel (Taxol), used to treat several types of cancer, was originally identified in the bark of the Pacific Yew tree. More recently, the drug eribulin was developed from a primitive animal called a sea sponge. The NCI has samples from about thousands of plants, marine organisms, bacteria, and fungi collected from around the world.

Studying the biology of cancer cells. Researchers who are developing drugs to treat cancer start by comparing the cellular and genetic processes that occur in healthy cells to those in cancerous cells. This information is used to identify important steps in the cancer process that could potentially be altered by a drug. For example, researchers learned that nearly a quarter of all breast cancers have a specialized protein called HER2 that controls the growth and spread of breast cancer. Two drugs, trastuzumab (Herceptin) and lapatinib (Tykerb), that specifically target HER2 were developed. Now, a person diagnosed with breast cancer has her tumor tested to check for HER2 to find out if one or both of these drugs can be used to treat the cancer. Learn more about these types of treatments [2].

Understanding the chemical structure of a drug target. Scientists may use computers to simulate the interaction of a potential drug and its target, similar to fitting two puzzle pieces together. Using information from the computer models, researchers can then design chemical compounds that interact with the specific drug target.

Once potential drugs are identified, they are usually tested in human tumor cell lines in the laboratory to see if the new agent stops the growth of cancer cells. Next, the potential drug is tested in animals to see if it still stops cancer cell growth. Typically, researchers test the drug in two or more different animal species. Testing in animals also helps researchers learn how the new drug is used by the body, what side effects the drug may cause, and what dose of the drug should be used in human research trials.

Clinical research: Testing in humans

Before beginning human research, the sponsor of a potential drug must submit an Investigational New Drug (IND) application to the FDA. The IND contains the results of the preclinical (laboratory and animal) studies, plans for clinical (human) trials, and details about how the new drug is made. The FDA approves potential drugs for human testing if the preclinical research indicates that the drug is likely to be safe and effective, if the proposed clinical trials are designed correctly, and if the drug can be made repeatedly the same way each time.

Clinical trials are research studies in humans that are designed to evaluate whether a new drug is safe to use and able to treat cancer. There are usually three (sometimes four) consecutive phases of a clinical trial. Each successive phase involves a larger number of patients and provides more detail about the new drug's safety and effectiveness. Clinical trials frequently take years to complete and may involve thousands of patients. Clinical trials follow a risk-based approach. Earlier phases focus on safety, dosing, and how the body processes the drug. Meanwhile, later phases focus on how well the drug works. Later phases include a larger group of clinical trial participants. Read more about clinical trials [3].

Clinical review and FDA approval

If the clinical trials are successful, the drug sponsor submits a New Drug Application (NDA) to the FDA requesting approval of the drug for public use. The NDA contains results from the preclinical and clinical studies, details on how the drug will be manufactured, and proposed labeling, which includes how the drug will be given (injection or pill, for example) and the potential side effects and known interactions with food and other medications. The FDA may approve the drug if the evidence shows that it is substantially effective and safe for use as proposed in the labeling. The FDA balances the risks and benefits of the drug when making approval decisions. No drug is completely safe or free from side effects, but a drug is considered safe if the benefits from taking it outweigh the possible risks.

Post-approval research and post-marketing surveillance

Once a drug receives FDA approval, it can be marketed and made available to doctors and patients. However, the FDA may require that the sponsor conduct additional clinical trials (phase IV trials) to look for other potential side effects; to study the drug in new populations, such as children or older adults; or to evaluate the drug's long-term effects. Some drug manufacturers may conduct their own phase IV trials or perform new research aimed at securing future FDA approval to use the drug in a new way or in a different population.

The FDA also conducts ongoing safety monitoring of drugs currently on the market, and drug manufacturers are responsible for reporting any new or serious side effects to the FDA. The FDA may withdraw a drug from the market if new evidence from ongoing use indicates that it is not an effective treatment or that it is not safe.

More Information

Drug Development and Approval, Part II [1]

ASCO Expert Corner: Informed Consent [4]

Last Updated: August 02, 2010