What is the FDA Drug Approval Process?

The U.S. Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) reviews data from drug companies to ensure they are safe and effective before the company can sell them. The process involves a preclinical phase, clinical trials, New Drug Application (NDA) review, and post-marketing surveillance.

Alexis Bryan MPH, is a recent graduate of Columbia’s Mailman School of Public Health. She is passionate about increasing access to care to improve health outcomes. Outside of work, she loves to travel, read, and pay too much attention to her plants.

FDA Drug Approval Process

A drug has a long journey from development to a store shelf. The FDA drug approval process is a rigorous evaluation that looks at everything from clinical study design to the risk of side effects of new drugs. The main purposes of the FDA drug approval process are

1. To ensure drugs, both brand-name and generic, are effective
2. Their health benefits outweigh their known risks (are safe)
3. Provide doctors and patients the information they need to use medicines wisely

The review team consists of physicians, statisticians, pharmacologists, and scientists. The CDER does not test drugs, but it does conduct drug quality, safety, and effectiveness research.

Drug Review Steps

1. Preclinical (animal) testing
2. Investigational new drug application (IND) submission
3. Clinical trials (Phase 1, Phase 2, Phase 3 studies)
4. New drug application (NDA) submission
5. An FDA review team evaluates the sponsor's research on the drug's safety and effectiveness, drug labeling, and inspects the facilities where the drug will be manufactured
6. FDA reviewers will approve the application or issue a complete response letter

Pre-Clinical Phase

Once a new drug compound is developed, the sponsor (usually the company or research institution) seeks to have it approved by the FDA for sale in the U.S. The drug is tested on animals to gather data on the safety and effectiveness of the compound.

Then, the sponsor submits an Investigational New Drug (IND) application to the FDA, which includes the results of preclinical testing in laboratory animals, details on the drug manufacturing and composition, and a plan for testing the drug on humans. Most drugs that undergo preclinical (animal) testing never make it to human testing or FDA review.

The FDA looks at the IND to make sure:

1. The clinical trials will not put participants at unreasonable risk or cause them harm
2. There are informed consent procedures
3. There is adequate human subject protection

If the FDA approves the IND, the company can enroll participants in clinical trials.

Clinical Trials

There are three main phases of clinical trials. The first two evaluate if the new drug is safe and effective, while the third is to see if the new drug is better than existing treatments. Once a phase is completed without any red flags, the next phase can begin. Clinical trials can take several years to conduct.

Clinical Trial Phases

• See how the drug is metabolized and excreted
• Test for toxicity | 20-80 | | Phase 2: Effectiveness | - Obtain preliminary data on whether the drug works
• Safety continues to be evaluated | Anywhere from a few dozen to about 300, usually in the hundreds | | Phase 3 | - Gather more information about safety and effectiveness
• Study different populations and different dosages
• Observe drug interactions | From several hundred to about 3,000 people, usually 1000+ |

Clinical trials of drugs provide information about:

• Whether the drug has the effect it is supposed to have
• How much of the drug to give to a patient and how often
• What side effects are associated with the drug and how they can best be managed
• How a drug is broken down in the body, and how long it stays in the body
• Which foods, drinks, or other drugs can be used at the same time or should be avoided
• Clinical trial results allow the FDA to make decisions about whether or not a drug should be approved for marketing

New Drug Application (NDA) Review

An NDA is the main review of the drug approval process. It asks the FDA to allow a drug to be sold in the U.S. and includes all animal and human testing data, documentation of how the drug works, and manufacturing.

The FDA has 60 days to decide to file the application for review. The review team then looks at the research and the drug labeling (information on how to use the drug) to ensure all the appropriate information is communicated to physicians and consumers. Lastly, the FDA inspects the manufacturing facility.

Post-Marketing

After approving the drug for sale in the U.S., monitoring of safety issues continues. The FDA has a system to detect and act on unexpected adverse events if necessary. The sponsor is required to submit periodic updates to the FDA.

FDA Drug Approval Process Frequently Asked Questions (FAQs)

The FDA drug approval process is an intricate framework to protect consumer health.

What products are reviewed by the FDA?

As defined by the FDA, “A drug is any product that is intended for use in the diagnosis, cure mitigation, treatment, or prevention of disease.” In addition to medications, the FDA reviews fluoride toothpaste, antiperspirants (not deodorant), dandruff shampoos, and sunscreens.

Is there an expedited approval process?

Accelerated approval is given to new drugs that treat serious and life-threatening illnesses or for conditions that don’t have existing treatments. This process allows drug sponsors to submit parts of an application as the information becomes available instead of waiting to present it all together. Most drugs to treat HIV have been approved under the accelerated approval program.

How do I report an adverse side effect of a drug?

MedWatch is the FDA’s safety monitoring system. Physicians and consumers can use it to report adverse events. Usually, when important new risks are uncovered, the risks are added to the drug's labeling, and in rare cases, the drug is withdrawn from the market.

Bottom Line

The FDA approval process is a meticulous evaluation process for new drugs to go from a laboratory to a store shelf. This process ensures consumer safety and encourages the development of lifesaving therapies.