The FDA Drug Approval Process

The Food and Drug Administration (FDA), a division of the United States Department of Health and Human Services, bears responsibility for overseeing the testing and approval process of all new drugs. This includes prescription medication and some dietary supplements, herbal products, and medicines sold without a prescription. However, these non-prescription products are not subject to the same level of scrutiny by the U.S. Food and Drug Administration.  The FDA oversees work performed by Center for Drug Evaluation and Research (CDER).

New drugs must meet the FDA’s definition of drug for the FDA to consider approving it. The FDA describes drugs in this manner:

  • Substance recognized as a formulary or official pharmacopoeia
  • Substance used as a component of medicine but not an accessory, device, independent component, or part
  • Substance used to cure, diagnose, mitigate, prevent, or treat a disease
  • Substance used to affect how the structure of a bodily function performs

What Are the Responsibilities of the CDER?

The drug approval process by the CDER involves testing the safety of the new drug to ensure that both brand names and generic equivalents work as intended. Another goal of the CDER is to only approve new drugs when the health benefits of taking them outweighs any side effects. An independent team of scientists and clinicians evaluate the labeling, efficacy, and safety of the new drug. The FDA then gives final approval and continues to regularly monitor the new drug once it’s on the market.

According to the Tufts Center for the Development of Drug Research, drug manufacturers spend an average of 2.6 billion dollars and 12 to 15 years moving a new drug from the laboratory into the hands of healthcare consumers. This includes several years of laboratory testing before the drug manufacturer can submit a New Drug Application (NDA) to the FDA. Approximately one of every 1,000 new drug compounds tested in a laboratory advances to human clinical trials. Below is a full outline of the drug approval process.

Drug Manufacturer Files an Investigational New Drug (IND) Application

During pre-clinical research, the manufacturer tests the new drug on animals to determine any issues with toxicity before proceeding to clinical trials with humans. The IND application provides specific information about details of the new drug such as the manufacturing process, its chemistry, and future plans for clinical trials. After the Food and Drug Administration receives the IND, it reviews it to ensure the safety of upcoming human clinical trials.

Phases of Clinical Trials for FDA Approval

Upon approval from the FDA to proceed, the drug manufacturer completes three phases of clinical trials. During Phase I, between 20 and 80 healthy adult volunteers take the new drug to test its safety and profile. Phase I takes around one year to complete. Drug manufacturers and the FDA are especially concerned with how the new drug metabolizes in the human body and how the Phase I clinical trial participants excrete it.

Approximately 100 to 300 people participate in Phase II of clinical trials. The volunteer participants have a specific disease or medical condition that the new drug aims to treat. Phase II runs for about two years. Some participants receive the actual drug going through the FDA approval process while others receive a placebo to test the effectiveness of the new drug. The research team also reviews potential side effects and other safety concerns.

For Phase III, several thousand people receive careful medical monitoring at a clinic or hospital to further determine the drug’s side effects and overall effectiveness. The staff in charge of clinical trials selects volunteers to represent a wide range of ages and other demographic factors. The drug company may experiment with different dosing scenarios and combine the new drug with other treatments to determine if that makes a difference in patient outcome. Phase III of clinical trials takes approximately three years to complete.

New Drug Application (NDA) Process

The typical NDA contains several thousand pages and acts as the official request by the drug company for the FDA to approve the new drug. Here is some of the detailed data that the typical NDA contains:

  • Animal testing and human clinical trial data
  • Dosing
  • Effectiveness
  • Manufacturing specifics of the new drug, including drug development
  • Pharmacokinetics report, which details how the new drug moves and metabolizes within the body
  • Side Effects

The FDA review occurs within 60 days of receipt of the NDA. Upon review, the Food and Drug Administration announces whether it will file the NDA for further review. In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA) that allows a drug company to pay for an expedited FDA review. Also known as the accelerated approval process, the purpose of PDUFA is to allow new drugs that treat severe or life-threatening illnesses to gain FDA approval faster.

The accelerated approval process relies on a reasonable prediction of the benefits of the new drug. Even so, the drug company must complete post-marketing clinical trials to prove the drug can treat serious conditions and that the benefits outweigh the potential risks. If the drug company fails to confirm safety information and effectiveness during post-marketing clinical trials, the Food and Drug Administration can withdraw its approval. New drugs that pass through the accelerated approval process fall into one of these three categories:

  • Breakthrough therapy: Results of clinical research indicate that patients with a serious condition could benefit from a substantial improvement in their health because the new drug is much more effective than the patient’s current drug.
  • Fast Track: New drugs that treat serious conditions and fill a current unmet need can receive fast track status. As part of the FDA approval process for a fast track drug, the drug company must provide clinical trial reports that prove the positive impact of the new drug on human and animal subjects.
  • Priority review: A priority review happens within six months compared to the 10 months it normally takes for a standard review. A new drug becomes eligible for priority review if it offers significant improvement in the diagnosis, treatment, and prevention of serious conditions.

Meeting of FDA Advisory Board

The FDA Advisory board is an independent group of doctors, pharmacists, statisticians, pharmacologists, chemists, and occasionally patient representatives. The board meets with FDA reviewers and the drug manufacturer. At the conclusion of the two-day meeting, the FDA Advisory Board makes a recommendation on FDA drug approval or denial.

Although the Food and Drug Administration often follows the advice of the FDA Advisory Board, it isn’t legally obligated to do so. This is the final approval stage. The FDA will continue to monitor the new drug’s performance and requires the drug company to report any adverse events brought to its attention.

Have You Been Harmed by a Prescription Drug?

Although the FDA approval process is long and detailed, dangerous drugs still receive approval. If you developed cancer or experienced another adverse event after taking a drug for its intended use, there is help available.