Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on May 28, 2022.
How do you get a drug to market in the U.S?
What is the 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.
The four phases of a drug approval process includes:
- Pre-clinical, INDA
- Clinical
- New Drug Application (NDA) Review
- Post-marketing risk assessments
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?
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.
Human drug studies can begin only after the IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research.
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 1 in 1000 of the compounds that enter laboratory testing will ever make it to human testing.
Once a drug is approved and on the market, Phase 4, which is post-marketing review, takes place to be sure the new medicine remains safe now that it is for public use. Pediatric studies, or special safety studies may be completed during this time frame. Phase 4 post-marketing studies and a public safety program called Medwatch helps to monitor side effects after drug approval.
What are the 4 phases of drug approval?
If the FDA gives the green light, the investigational drug will enter several phases of clinical trials and post-marketing approval:
- Phase 1: Phase 1 focuses on safety. 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: Phase 2 focuses on effectiveness. 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: Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. Typically, several hundred to 3,000 patients are monitored in clinics and hospitals to carefully determine effectiveness and identify further side effects. Very rare diseases may have fewer study patients. 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.
- Phase 4: Phase 4 studies gather additional information about a product's safety, efficacy, or optimal use after approval. 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.
What is a New Drug Application (NDA)?
The New Drug Application (NDA) is the formal step the manufacturer takes to ask that the FDA to approve their drug for US marketing.
For an NDA, the company writes and submits an application which includes thousands of pages to the FDA for review and approval. 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.
CDER expects to review and act on at least 90% of NDAs for standard drugs no later than 10 months after the applications are received. The review goal is six months for priority drugs.
Once an NDA is filed, the FDA reviews 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), originally 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.
Drugs that may be the first available treatment for an illness or with a significant benefit over existing drugs may receive one or more special designations:
- Orphan drug program: Gives financial incentives to sponsors for manufacturing drugs that treat rare (orphan) diseases. In the US, an orphan disease is defined as one that affects fewer than 200,000 individuals. One example is Rubraca (rucaparib), designated an orphan drug in 2016 for treatment for ovarian cancer. Learn more: What is an orphan drug?
- 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, the FDA may withdraw accelerated approval of the new use or drug. One example of a drug that received accelerated approval is Gleevec (imatinib mesylate), an oral treatment for patients with a life-threatening form of cancer called chronic myeloid leukemia (CML).
- 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. For example, Xywav (calcium, magnesium, potassium, and sodium oxybates) received Fast Track designation by the FDA in September 2020 for treatment of idiopathic hypersomnia. In August 2021, it was fully approved for this use.
- 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. For example, in Feb. 2018 Pfizer received Breakthrough Therapy designation for Cibinqo (abrocitinib), a Janus kinase (JAK) 1 inhibitor for the treatment of patients with moderate-to-severe atopic dermatitis (AD). In Jan. 2022, the FDA fully approved Cibinqo for atopic dermatitis in adults.
- 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. An one example, in Feb 2017, the FDA granted Priority Review to AbbVie for Mavyret (glecaprevir / pibrentasvir) for the treatment of chronic hepatitis C in all major genotypes. It was also granted Breakthrough Therapy designation. In August 2017, Mavyret received final FDA approval for this use.
Who is on an 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. This advisory team includes physicians, pharmacists, chemists, pharmacologists, statisticians, and even patient representatives. These meetings often take one or two days.
After the meeting, the Advisory Board will make a recommendation for new drug 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.
How much does it cost to get a drug to market?
It can take billions of dollars for a manufacturer to get a new drug from the laboratory onto the pharmacy shelf. In a study from the London School of Economics, the median cost was determined to be $985 million. But other studies have estimated up to $2.6 billion. For example, differences can occur due to therapeutic class; for example, cancer and immunomodulators have a median cost up to $2.7 billion.
What happens after 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 with many other countries that do consider the economic impact of new drugs in their society.
What is the Medwatch safety program?
Once on the market, the drug company will continue to report cases of adverse reactions (side effects) 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.
Related: See New FDA Drug Approvals and New Indications
Sources
- NDA and BLA Approvals. US Food and Drug Administration (FDA). Accessed May 28, 2022 at https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/nda-and-bla-approvals
- Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020 Mar 3;323(9):844-853. doi: 10.1001/jama.2020.1166.
- Suvarna V. Phase IV of Drug Development. Perspect Clin Res. 2010;1(2):57–60. PMID: 21829783.
- Development & Approval Process - Drugs. US Food and Drug Administration (FDA). Accessed May 28, 2022 at https://www.fda.gov/drugs/development-approval-process-drugs
- The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective. US Food and Drug Administration (FDA). Accessed May 28, 2022 at https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-ensuring-drugs-are-safe-and-effective
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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FAQs
What is the FDA process for approving a drug? ›
FDA Drug-Approval Process. A pharmaceutical company seeking FDA approval to sell a new prescription drug must complete a five-step process: discovery/concept, preclinical research, clinical research, FDA review and FDA post-market safety monitoring.
What are the 4 phases of FDA approval? ›- Step 1: Discovery and Development.
- Step 2: Preclinical Research.
- Step 3: Clinical Research.
- Step 4: FDA Drug Review.
- Step 5: FDA Post-Market Drug Safety Monitoring.
The FDA will then take 6-10 months to review all of the data submitted and either accept or deny the NDA. Once a medication is approved, the FDA requires the manufacturer to continue to monitor safety of its drug.
How do I check my FDA approval status? ›- Drugs@FDA lists most prescription and over-the-counter (OTC) drug products approved since 1939. ...
- The FDA "Orange Book" contains drugs approved by FDA under New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs).
There are three phases to complete in the clinical trial process before a sponsor can submit their treatments* to the FDA for consideration to be sold on the market. Each stage of a clinical trial has its own purpose in ensuring that a treatment is safe and effective for use by the public.
How long does it take for FDA to approve fast track? ›FDA is required by the statute to decide within 60 days of receipt of the request whether the conditions for fast track designation have been met.
What are the 5 steps for FDA approval? ›- Step 1: Discovery and Development.
- Step 2: Preclinical Research.
- Step 3: Clinical Research.
- Step 4: FDA Drug Review.
- Step 5: FDA Post-Market Drug Safety Monitoring.
The FDA approval process can take between one week and eight months, depending on whether you self-register, submit a 510(k) application or submit a Premarket Approval (PMA) application.
How long does it take from Phase 2 to FDA approval? ›They found that, on average, it took 10.5 years for a drug to get from Phase I to regulatory approval. Looking at individual stages of the process, the averages were 2.3 years for Phase I, 3.6 years for Phase II, 3.3 years for Phase III, and 1.3 years between Phase III and regulatory approval.
What is the quickest FDA approval? ›Fast Track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and make a decision within sixty days based on whether the drug fills an unmet medical need in a serious condition.
Why does FDA drug Approval take so long? ›
New medicines are constantly under development. However, the Food and Drug Administration (FDA) has strict safety protocols on the steps new drugs must go through before people can use them.
What is the success rate of FDA approval? ›Overall success rates from Phase I to FDA approval is nearly 9%. This number is comprised of lead and secondary indications. When separated, lead indications have close to a one in seven rate of approval and secondary indications have a rate of one in 30.
What does the FDA approval process look like? ›The name-brand approval process consists of five steps — discovery/concept, preclinical research, clinical research, FDA review, and FDA post-market safety monitoring. The company must test the product on animals before humans to ensure safety. After the product is tested, the company submits a New Drug Application.
What time of day do FDA approvals come out? ›Notes: Before the market open for announcements released before 9:30 ET of the FDA announcement dates; during market hours for those announced from 9:30 to 16:00 ET; after the market close for FDA notifications occurred after 16:00 ET of the announcement dates or a couple of days after the FDA announcement dates.
What is difference between FDA cleared and approved? ›Clearance: What does "FDA cleared" mean? When a medical device is cleared, this means it has undergone a 510(k) submission, which FDA has reviewed and provided clearance. Approval: For Class III medical devices to be legally marketed they must undergo a rigorous review and approval process.
How long does Phase 3 of FDA approval last? ›According to the FDA, 33 percent of medications move on to phase 3. Phase 3: Phase 3 of a clinical trial usually involves a few thousand participants that have the condition the medication is meant to treat. This phase usually lasts for several years.
How long do FDA Phase 3 trials take? ›How Long Does a Phase 3 Clinical Trial Take? The length of study for phase 3 clinical trials is usually 1 to 4 years. This phase involves 300 to 3,000 patients, with tests designed to determine the drug's longer-term effects.
What is phase 3 of FDA approval? ›Phase III trials
The experimental study drug or treatment is given to large groups of people. Researchers confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.
There is no typical length of time it takes for a drug to be tested and approved. It might take 10 to 15 years or more to complete all 3 phases of clinical trials before the licensing stage. But this time span varies a lot. There are many factors that affect how long it takes for a drug to be licensed.
How long does FDA priority review take? ›A Priority Review designation means FDA's goal is to take action on an application within 6 months (compared to 10 months under standard review).
How often does the FDA deny approval? ›
So in reality, the FDA approval rate is more like 96%. Eliminating BioMedTracker's counting of multiple uses for the same drug means FDA approved 23 drugs and rejected 1, Merck 's anesthesia antidote, Bridion. Again, that means 19 of 20 new drug applications were approved.
What are the 4 phases of drug development? ›Drug development can be divided into four phases: discovery, preclinical studies, clinical development and market approval. The image below provides an overview of the process, including an estimated timeline for each step.
What is FDA process validation? ›Process Validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.
How many drugs fail FDA approval? ›Despite this validated effort, the overall success rate of clinical drug development remains low at 10%–15%5, 6, 7. Such persistent high failure rate raises several questions: Why 90% of clinical drug development fails despite implementation of many successful strategies in the past several decades?
How much does it cost to get FDA approval? ›The overall cost to get FDA approval for a 510(K) notification ranges between $30,000 and $44,000 USD. This includes the preparation of the submission and all associated FDA costs.
Can a drug be approved after Phase 2? ›A confirmatory phase II trial, which need not be randomized if an active control is not available, can provide sufficient evidence to convince regulatory authorities to grant accelerated approval, and the process can be completed in three years or less.
What is the difference between FDA Phase 2a and 2b? ›Phase 2a are the proof of concept studies and Phase 2b are the definite dose-finding studies. Phase II's main goal is to test effectiveness (how well the drug works) and to further evaluate safety in a larger group of subjects.
What is the difference between Phase 2 and 3 clinical trials? ›Phase II trials test if one type of cancer responds to the new treatment. Phase III trials test if a new treatment is better than a standard treatment. Phase IV trials find more information about long-term benefits and side effects.
What is the FDA accelerated process? ›The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint.
What Covid shot is closest to FDA approval? ›- Pfizer-BioNTech COVID-19 Vaccines.
- Moderna COVID-19 Vaccines.
- Janssen COVID-19 Vaccine.
- Novavax COVID-19 Vaccine, Adjuvanted.
Are there different levels of FDA approval? ›
Devices are placed into three classes, with Class I being the lowest risk, and Class III being the highest. Before a new device can be marketed, companies must submit appropriate applications to the FDA. Depending on the device class, they may be marketed as “FDA-registered,” “FDA-cleared,” or “FDA-approved” devices.
Can a drug lose FDA approval? ›A drug is usually taken off the market because of safety issues with the drug that cannot be corrected, such as when it is discovered that the drug can cause serious side effects that were not known at the time of approval.” The FDA also takes into account the number of people taking a drug being considered for removal ...
How many drugs pass Phase 1? ›A Phase I trial takes several months to complete. About 70 percent of experimental drugs pass this initial phase of testing.
What phase do most clinical trials fail? ›Phase II clinical studies represent a critical point in determining drug costs, and phase II is a poor predictor of drug success: >30% of drugs entering phase II studies fail to progress, and >58% of drugs go on to fail in phase III.
How many drugs pass Phase 3? ›Around 70% of drugs progress to the second phase, which is designed to measure safety in a larger group of volunteers (typically several hundred), while also measuring the effectiveness of the treatment on the participants. Phase 3: About 33% of drugs will make it past the second phase and go on to Phase 3.
What is Pdufa approval? ›The Prescription Drug User Fee Act (PDUFA) was created by Congress in 1992 and authorizes FDA to collect user fees from persons that submit certain human drug applications for review or that are named in approved applications as the sponsor of certain prescription drug products.
How often does the FDA approve a drug before Pdufa date? ›The PDUFA date is 10 months after the drug application has been accepted by the FDA or 6 months, if the drug is given a priority review designation. As each PDFUA date approaches, CheckRare will be covering the FDA meetings and outcomes.
What is an FDA 30 day notice? ›The Act states that changes in manufacturing procedures or method of manufacturing that affect safety or effectiveness require a 30-day notice. Where FDA finds such notice inadequate, FDA will inform the applicant that a 135-day PMA supplement or 75-day HDE supplement must be submitted.
Does FDA approved mean it works? ›The FDA approves new human drugs and biological products.
If the FDA grants an approval, it means the agency has determined that the benefits of the product outweigh the risks for the intended use.
FDA Cleared: When used correctly, this term refers to FDA allowing a device to market through the 510(k) process based on substantial equivalence to a legally marketed predicate device. It doesn't sound as glamorous as “FDA approved,” but “clearance” is a critical step on the path to market for many devices.
Why does FDA Drug Approval take so long? ›
New medicines are constantly under development. However, the Food and Drug Administration (FDA) has strict safety protocols on the steps new drugs must go through before people can use them.
How FDA approves drugs and regulates their safety? ›FDA seeks to ensure product integrity through product and facility registration; inspections; chain-of-custody documentation; and technologies to protect against counterfeit, diverted, subpotent, adulterated, misbranded, and expired drugs.
What is the approval process for generic drugs? ›Generic drug companies must perform studies that show that the same amount of drug gets to the bloodstream and that it gets there at about the same time. FDA scientists analyze the results to be sure the generic will produce the same result as the brand-name drug.
How can I speed up my FDA approval? ›Fast Track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and make a decision within sixty days based on whether the drug fills an unmet medical need in a serious condition.
Who approves drugs for FDA approval? ›CDER ensures that drugs, both brand-name and generic, are effective and their health benefits outweigh their known risks. FDA's Center for Drug Evaluation and Research (CDER) evaluates new drugs before they can be sold.
What are regulatory requirements for drug approval? ›New Drug Application (NDA) is an application submitted to the individual regulatory authority for authorization to market a new drug i.e. innovative product. To gain this permission a sponsor submits preclinical and clinical test data for analyzing the drug information, description of manufacturing trials.
When FDA approves a medicine What does this tell consumers? ›If the FDA grants an approval, it means the agency has determined that the benefits of the product outweigh the risks for the intended use.
How long does it take the FDA to approve a generic drug? ›Some generics of priority drugs – drugs that FDA's CDER has determined are important to public health -- have been approved in six months or less. Other times, it may take several revisions to the application and several cycles of review before an application meets our rigorous approval standards.
Do generic medications require prior authorization? ›What types of prescriptions require prior authorizations? Insurance companies will most likely require prior authorizations for the following drugs: Brand-name drugs that have a generic available. Drugs that are intended for certain age groups or conditions only.