US Food and Drug Administration's Drug Approval Process

What is a Drug, as Defined by the FDA?

A drug is any product that is intended for the use in the diagnosis, cure, mitigation, treatment
or prevention of disease and is intended to affect the structure or any function of the body.


Drug Sponsor’s Discovery and Screening Phase:

Drug sponsor develops a new drug compound and seeks to have it approved by FDA for sale in the United States.

  • Animals Tested: Sponsor must test new drug on animals for toxicity. Multiple species are used to gather basic information on the safety and efficacy of the compound being investigated/researched.
  • IND Application: The sponsor submits an Investigational New Drug application to FDA based on the results from initial testing. This application includes the drug’s composition and manufacturing specifications and offers a plan for testing the drug on humans.

IND Review: FDA reviews the IND to ensure that the proposed studies, generally referred to as clinical trials, do not place human subjects at unreasonable risk of harm. FDA also verifies that there are adequate informed consent and human subject protections.


Drug Sponsor’s Clinical Trials/Studies:

  • Phase 1 (20-80 healthy volunteers): The typical number of healthy volunteers used in Phase 1; this phase emphasizes safety. The goal in this phase is to determine what the drug’s most frequent side effects are and, often, how the drug is metabolized and excreted.
  • Phase 2 (100s of patients): The typical number of patients used in Phase 2; this phase emphasizes effectiveness. The goal is 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 a placebo or a different drug. Safety continues to be evaluated, and short-term side effects are studied.At the end of Phase 2, FDA and sponsors discuss how large-scale studies in Phase 3 will be conducted.
  • Phase 3 (1000s of patients): The typical number of patients used in Phase 3. These studies gather more information about safety and effectiveness, study different populations and different dosages, and use the drug in combination with other drugs.

FDA’s requirement for the number of patients needed to conduct a study/trial does change based on the size of the patient population being studied. For bleeding disorder studies/trials, counts are significantly reduced and sometimes can be fewer than 10 patients for Phase I trials. By Phase III, trials may include more than 100 people. 
The objective: Have a statistically relevant sample size from which to draw conclusions.
For example, 200 trial participants in a hemophilia study is 1% of the U.S. hemophilia population, whereas 1% of the U.S. diabetic population in a diabetes study trial would equal 291,000 participants.

NDA Review

FDA’s New Drug Application Review:

  • Review Meeting: FDA meets with a drug sponsor prior to submission of a new drug application.
  • NDA Application: The drug sponsor formally asks FDA to approve a drug for marketing in the United States by submitting an NDA. 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.
  • Application Reviewed: After an NDA is received, FDA has 60 days to decide whether to file it so it can be reviewed. If FDA files the NDA, an FDA review team is assigned to evaluate the sponsor’s research on the drug’s safety and effectiveness.
  • Drug Labeling: FDA reviews the drug’s professional labeling and ensures appropriate information is communicated to health care professionals and consumers.
  • Facility Inspection: FDA inspects the facilities where the drug will be manufactured.
  • Drug Approval: FDA reviewers will approve the application or issue a complete response letter, which will describe the specific deficiencies that the agency has identified in an application.


FDA’s Post-Approval Risk Assessment Systems:

  • Phase 4: Because it’s not possible to predict all of a drug’s effects during clinical trials, monitoring safety issues after drugs get on the market is critical. The role of FDA’s post-marketing safety system is meant to detect serious unexpected adverse events and take definitive action when needed.Once FDA approves a drug, the post-marketing monitoring stage begins. The sponsor (typically the manufacturer) is required to submit periodic safety updates to FDA.FDA’s MedWatch voluntary system makes it easier for physicians and consumers to report adverse events. Usually, when important new risks are uncovered, the risks are added to the drug’s labeling and the public is informed of the new information through letters, public health advisories and other educational means. In some cases, the use of the drug might be substantially limited. And in rare cases, the drug might need to be withdrawn from the market.