How the FDA Drug Approval Process Works

The FDA Drug Approval Process

The FDA Center for Drug Evaluation and Research (CDER) is the watchdog for potential medications seeking approval for use in the United States. In order for CDER to begin evaluating a drug, pharmaceutical companies must first do extensive testing and document the results.

Those results are sent in to the CDER, who assigns a team of doctors, chemists, pharmacologists, and other scientists to review the evidence. From initial formulating to FDA approval, most drugs take around 10 years to make it to the market. This may seem unnecessarily long, but the result is that only the safest drugs make it to the pharmacy.

Phases of Drug Development

picture of clear test tubesPhase I: Discovery & Development

Discovery involves researchers finding new possibilities for medication through testing molecular compounds, noting unexpected effects from existing treatments, or the creation of new technology that allows novel ways of targeting medical products to sites in the body. Drug development occurs after researchers identify potential compounds for experiments.

Studies are conducted on appropriate dosage; methods for administration; side effects and how they may vary within different demographic groups; how the drug is absorbed, metabolized, and excreted; drug interactions, and how effective it is compared with similar compounds.

Phase II: Preclinical Research

Once researchers have examined the possibilities a new drug may contain, they must do preliminary research to determine its potential for harm (toxicity). This is categorized as preclinical research and can be one of two types: in vitro or in vivo.

In vitro refers to experimenting within a controlled environment outside of a living organism, while in vivo means the experiment occurs in a living organism. Both kinds of preclinical research must follow regulated laboratory practices, known as Good Laboratory Practices (GLP), which outline basic requirements for researchers, facilities, equipment, etc.

Preclinical studies are smaller than most clinical trials, but they must provide detailed evidence about appropriate dosing and toxicity levels. If researchers review the findings and determine it is safe to test in humans, drug development moves on to Phase III.

Phase III: Clinical Research

After the safety of a drug is determined, researchers must examine the ways in which drugs interact with the human body. Clinical research involves trials of the drug on people, and it is one of the most involved stages in the drug development and approval process. Clinical trials must answer specific questions and follow a protocol determined by the drug researcher or manufacturer. To design a study, researchers must determine its length and scope, as well as who can participate and how the data will be collected and analyzed.

There are four sub-phases of clinical trials:

  • Phase 1 involves 20 – 100 study participants and lasts several months. This phase is used to determine the safety and dosage of the drug, and about 70% of these drugs move on to the next clinical research phase.
  • Phase 2 involves up to several hundred people, who must have the disease or condition the drug supposes to treat. This phase can last from a few months to two years, and its purpose is to monitor the efficacy of the drug, as well as note side effects that may occur. Only around 30% of these drugs move on to the next clinical research phase.
  • Phase 3 involves 300 – 3000 volunteers and can last up to four years. It is used to continue monitoring the efficacy of the drug, as well as exploring any longer-term adverse reactions. About 25% to 30% of these drugs move on to the last phase of clinical research.
  • Phase 4 involves several thousands of volunteers who have the disease or condition and continues to monitor safety and efficacy. If a drug passes this phase, it goes on to FDA review.

Pills flowing out of a tipped blue plastic bottlePhase IV: FDA Review

Once the pharmaceutical company can prove (through preclinical research and clinical trials) that a drug is safe and is effective in treating a condition, they can file an application to allow marketing of the drug. The application contains clinical results, labeling information, safety information, drug abuse potential, patient information, and directions for use.

The FDA review team ensures that each application is complete, and then takes the next 6 – 10 months to make a decision. The application is reviewed, as well as the clinical study sites. Often, there are issues that must be resolved before approval; the review team may request further data before they make a final decision. If the FDA review team greenlights the drug, they work with the applicant to develop prescribing information and then move on to the next phase.

Phase V: FDA Post-Market Safety Monitoring

Although researchers and applicants must work for many months to determine the safety of a potential drug, there are still issues that may arise only after the drug is on the market.

The last phase of drug approval is an ongoing one while the drug is on the marketplace. If a developer wants to change anything about the drug formulation or approve it for a new use, they must apply with the FDA. The FDA also frequently reviews the drug’s advertising and its manufacturing facility to make sure everything involved in its creation and marketing is in compliance with regulations.

New drugs are protected by patents when they are approved for marketing, and generic drugs can only be manufactured once the patent expires. Generics must contain the same dosage form, strength, safety, quality, and intended use.

Will It Always Take This Long?

The FDA approval process can be long, tenuous, and frustrating, especially for patients waiting on new or generic drugs to hit the market. Although the intention of the process is to ensure patient safety and drug effectiveness, there are some elements that may prove unnecessary and can be expedited under critical circumstances. The FDA has developed four methods to speed up the approval process for drugs designated as such.

  • Fast Track: this process is designed to speed up development and expedite the review of drugs that treat serious conditions and “fill an unmet medical need”.
  • Breakthrough Therapy: this process expedites drugs that are found to be substantially more effective for a certain condition than others on the market.
  • Accelerated Approval: this process is for drugs that fill an unmet medical need and have evidence of potential clinical benefit (although they don’t yet prove clinical benefit).
  • Priority Review: this designation means the FDA has a goal of making a decision on a drug application within six months.

For more information:

U.S. Food & Drug Administration Drug Approval Process

Drugs, Devices, and the FDA: An Overview of Approval Processes for Drugs

Development and Approval Process (Drugs)


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