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FDA Drug Approval Process

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Apr 13, 2020.

Steps from Test Tube to New Drug Application Review

FDA approval process

FDA Approval Process

The U.S. Food and Drug Administration's (FDA's) Center for Drug Evaluation and Research (CDER) is a science-led organization in charge of overseeing the drug approval process before a drug is marketed. CDER ensures that both brand and generic drugs work correctly and that the health benefits outweigh the known risks. They review each drug closely using an independent team of clinicians and scientists who evaluate safety, efficacy and labeling of the drug product. After approval, FDA follow-up continues to make sure new drugs continue to be safe and effective.

It takes over $2.6 billion for a manufacturer to get a new drug from the laboratory onto the pharmacy shelf, according to the Tufts Center for the Study of Drug Development. The full research, development and approval process can last from 12 to 15 years. What happens during this time period to be sure that the drug you pick up at the pharmacy is safe and effective?

Investigational New Drug (IND) Application

In the manufacturer's early phases of drug discovery (preclinical research) they are synthesizing and screening a drug candidate for toxicity in animals before the medicine moves on to human trials. The sponsor files an Investigational New Drug (IND) Application that details specifics such as chemistry, manufacturing and the initial plans for human testing.

The IND is reviewed by the FDA to ensure that clinical trials will be safe for humans and that adequate informed consent is included to protect humans subjects.

Once a company develops a drug, it undergoes several years of laboratory testing before a New Drug Application (NDA) is made to the FDA to begin testing the drug in humans. Only one in 1000 of the compounds that enter laboratory testing will ever make it to human testing.

Phases of Human Testing for Investigational Drugs

If the FDA gives the green light, the investigational drug will then enter three phases of clinical trials:

  • Phase 1: About 20 to 80 healthy volunteers to establish a drug's safety and profile, and takes about 1 year. Safety, metabolism and excretion of the drug are also emphasized.
  • Phase 2: Roughly 100 to 300 patient volunteers to assess the drug's effectiveness in those with a specific condition or disease. This phase runs about 2 years. Groups of similar patients may receive the actual drug compared to a placebo (inactive pill) or other active drug to determine if the drug has an effect. Safety and side effects are reviewed. 
  • Phase 3: Typically, several thousand patients are monitored in clinics and hospitals to carefully determine effectiveness and identify further side effects. Different types and age ranges of patients are evaluated. The manufacturer may look at different doses as well as the experimental drug in combination with other treatments. This phase runs about about 3 years on average.

New Drug Application (NDA)

For an NDA, the company writes and submits an application which includes thousands of pages to the FDA for review and approval. The NDA is the official request for US approval of a drug. The NDA includes all animal and human data, plus side effects, dosing, and effectiveness. Other information, such as pharmacokinetics (how the drug moves through the body), and specifics of manufacturing are also addressed. The FDA team has 60 days to review the NDA and determine if it will be filed for further review.

Once an NDA is filed, the FDA review the product label (package insert) to be sure the clinical information needed to safely use this drug is outlined. The FDA also takes action to inspect manufacturing plants where the drug will be made.

  • PDUFA: Some companies will pay for an expedited review with the FDA through a process known as an PDUFA (Prescription Drug User Fee Act), enacted in 1992. PDUFA allows the FDA to access more resources to quicken the drug approval process. Many important drugs have been approved through PDUFA, including medicines for cancer, AIDS and heart disease.
  • Accelerated Approval: The Accelerated approval process began in 1992 to allow promising therapies for serious or life-threatening conditions to come to market more quickly. This method uses a "surrogate endpoint"  that predicts a reasonable clinical benefit of the drug. However, standard endpoints must still be proven after a drug is approved under post-marketing clinical trials to prove it's benefit. If further post-marketing studies fail to verify the predicted clinical outcome, FDA may withdraw approval.

Drugs that may be the first available treatment for an illness or with a significant benefit over existing drugs may receive a special designation:

  • Fast Track: Drugs that treat serious medical condition and fill unmet medical needs may receive fast-track designation based on positive human or animal data. This FDA process, requested by the manufacturer, can get new drugs to patients who need them more quickly.
  • Breakthrough Therapy: Preliminary clinical research demonstrates that a drug candidate for a serious condition may provide substantial improvement over available therapy. A drug designated for Breakthrough Therapy is also eligible for the Fast Track process. The sponsor must request this designation from the FDA.
  • Priority Review: During Priority Review, the FDA takes action on a new drug application within six months, compared to 10 months under standard review. These drugs receive higher priority because they can significantly improve the treatment, diagnosis, or prevention of serious conditions.

FDA Advisory Board

A group of independent physicians and other clinicians, called an FDA Advisory Board, meets to discuss the NDA with the FDA reviewers and manufacturer of the product. These meetings often take one or two days. After the meeting, the Advisory Board will make a recommendation for approval, or not, to the FDA, usually through a vote. The FDA often follows the advice of the Board, but is not obligated to do so. This advisory team includes physicians, pharmacists, chemists, pharmacologists, statisticians, and even patient representatives.

Final Drug Approval

After final approval, the drug becomes available for physicians to prescribe. However, drugs may not come to the market immediately because of patents disputes, manufacturing issues, or controlled substance designation from the DEA. Pricing is usually revealed after approval, but the FDA does not consider drug pricing or economics as part of the FDA approval process. This is in contrast to many other countries that do consider the economic impact of new drugs in their society.

MedWatch: At this stage, the drug company will continue to report cases of adverse reactions and other clinical data to the FDA. Patients and healthcare providers can also report side effects or other concerns through the MedWatch Program run by the FDA. When a new risk of a drug is identified, the FDA will update the product label to inform everyone. MedWatch can be access online or at 1-800-FDA-1088. See up-to-date FDA MedWatch Alerts here.

Phase 4 post-marketing studies may take place in groups of patients who are using the drug in a real-world setting. These studies may identify additional uses, long-term effectiveness, and previously undetected side effects. Rare side effects that occur in fewer than 1 in 5,000 patients are unlikely to be seen in Phase 1 to 3 studies before approval, but groups of patients this large are not usually studied. These rare side effects are more likely to be found when large numbers of patients use a drug after it has been approved and marketed.

Related: See New FDA Drug Approvals and New Indications

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.