The Food and Drug Administration (FDA) decides whether a sponsor may market a new drug in the United States after evaluating animal and human evidence, including trial design, the severity of side effects, and the conditions under which the drug is manufactured. The path from a laboratory to a medicine cabinet is usually long, and every drug takes a unique route, according to the FDA. A sponsor asks for that decision by filing a new drug application, and the agency then reviews the application.
Who may test a drug in people
A sponsor is a company, a research institution, or another organization that takes on the work of developing a drug. The pharmaceutical industry sometimes seeks advice from the FDA before filing an investigational new drug application, known as an IND. A sponsor must show the FDA the results of preclinical testing in laboratory animals and what it proposes to do for testing in people.
The FDA then decides whether it is reasonably safe for the company to move forward with testing the drug in humans. Most drugs that undergo preclinical testing never make it to human testing and review by the FDA. Studies in people can begin only after an IND is reviewed by the FDA and a local institutional review board.
An institutional review board, or IRB, is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research. The board approves the clinical trial protocols. Those protocols describe the type of people who may participate, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study’s objectives, and other details. The board makes sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.
What each phase of testing examines
Phase 1 studies are usually conducted in healthy volunteers. The goal is to determine the drug’s most frequent side effects and, often, how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80, according to the FDA.
Phase 2 studies begin if Phase 1 studies do not reveal unacceptable toxicity. The emphasis in Phase 1 is on safety, and the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition.
For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment, usually an inactive substance called a placebo, or a different drug. Safety continues to be evaluated, and short-term side effects are studied. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300.
At the end of Phase 2, the FDA and sponsors try to come to an agreement on how large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points before a new drug application is submitted. The other most common time is the pre-NDA meeting, right before a new drug application is submitted.
Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people.
How a marketing application is filed and reviewed
A new drug application, or NDA, is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for marketing in the United States. An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured.
When an NDA comes in, the FDA has 60 days to decide whether to file it so that it can be reviewed. The FDA can refuse to file an application that is incomplete. Some required studies may be missing, for example.
In accordance with the Prescription Drug User Fee Act, known as PDUFA, the FDA’s Center for Drug Evaluation and Research, or CDER, expects to review and act on at least 90 percent of NDAs for standard drugs no later than 10 months after the applications are received. The review goal is six months for priority drugs. Clinical trials usually take several years, and the emphasis on speed for the FDA mostly relates to review time and to timelines for meeting with sponsors during a drug’s development, according to the FDA.
What may be studied after approval
Postmarket requirement and commitment studies are required of or agreed to by a sponsor and are conducted after the FDA has approved a product for marketing. The FDA uses those studies to gather additional information about a product’s safety, efficacy, or optimal use.
Often, a drug is developed to treat a specific disease. An important use of a drug may also be discovered by accident. According to the FDA, Retrovir, the drug zidovudine also known as AZT, was first studied as an anti-cancer drug in the 1960s with disappointing results. Twenty years later, researchers discovered the drug could treat AIDS, and the FDA approved the drug, manufactured by GlaxoSmithKline, for that purpose in 1987.