Out of every 10,000-15,000 new compounds identified during discovery only Five are considered as safe for testing in human volunteers and only one of those compounds are typically approved as a marketed drugs
Typically, researchers discover new drugs through:
At this stage in the process, thousands of compounds may be potential candidates for development as a medical treatment. After early testing, however, only a small number of compounds look promising and call for further study.
Once researchers identify a promising compound for development, they conduct experiments to gather information on:
Before testing a drug in people, researchers must find out whether it has the potential to cause serious harm, also called toxicity. The two types of preclinical research are:
FDA requires researchers to use good laboratory practices (GLP), defined in medical product development regulations, for preclinical laboratory studies. These regulations set the minimum basic requirements for:
Usually, preclinical studies are not very large. However, these studies must provide detailed information on dosing and toxicity levels. After preclinical testing, researchers review their findings and decide whether the drug should be tested in people.
STEP 3: CLINICAL RESEARCH
While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body. “Clinical research” refers to studies, or trials, that are done in people. As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins.
Designing Clinical TRials
Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol, that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide:
The Investigational New Drug Process
Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.
In the IND application, developers must include:
Asking for FDA Assistance
Drug developers are free to ask for help from FDA at any point in the drug development process, including:
Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. As long as clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.
FDA IND Review Team
The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials. FDA responds to IND applications in one of two ways:
A clinical hold is rare; instead, FDA often provides comments intended to improve the quality of a clinical trial. In most cases, if FDA is satisfied that the trial meets Federal standards, the applicant is allowed to proceed with the proposed study.
The developer is responsible for informing the review team about new protocols, as well as serious side effects seen during the trial. This information ensures that the team can monitor the trials carefully for signs of any problems. After the trial ends, researchers must submit study reports.
This process continues until the developer decides to end clinical trials or files a marketing application. Before filing a marketing application, a developer must have adequate data from two large, controlled clinical trials.
STEP 4: FDA REVIEW
If a drug developer has evidence from its early tests and preclinical and clinical research that a drug is safe and effective for its intended use, the company can file an application to market the drug. The FDA review team thoroughly examines all submitted data on the drug and makes a decision to approve or not to approve it.
New Drug Application
A New Drug Application (NDA) tells the full story of a drug. Its purpo
A drug developer must include everything about a drug—from preclinical data to Phase 3 trial data—in an NDA. Developers must include reports on all studies, data, and analyses. Along with clinical results, developers must include:
Once FDA receives an NDA, the review team decides if it is complete. If it is not complete, the review team can refuse to file the NDA. If it is complete, the review team has 6 to 10 months to make a decision on whether to approve the drug. The process includes the following:
In cases where FDA determines that a drug has been shown to be safe and effective for its intended use, it is then necessary to work with the applicant to develop and refine prescribing information. This is referred to as “labeling.” Labeling accurately and objectively describes the basis for approval and how best to use the drug.
Often, though, remaining issues need to be resolved before the drug can be approved for marketing. Sometimes FDA requires the developer to address questions based on existing data. In other cases, FDA requires additional studies. At this point, the developer can decide whether or not to continue further development. If a developer disagrees with an FDA decision, there are mechanisms for formal appeal.
FDA Advisory Committees
Often, the NDA contains sufficient data for FDA to determine the safety and effectiveness of a drug. Sometimes, though, questions arise that require additional consideration. In these cases, FDA may organize a meeting of one of its Advisory Committees to get independent, expert advice and to permit the public to make comments. These Advisory Committees include a Patient Representative that provides input from the patient perspective. Learn more about FDA Advisory Committees.
STEP 5: FDA POST-MARKET STRATEGY MONITORING
Even though clinical trials provide important information on a drug’s efficacy and safety, it is impossible to have complete information about the safety of a drug at the time of approval. Despite the rigorous steps in the process of drug development, limitations exist. Therefore, the true picture of a product’s safety actually evolves over the months and even years that make up a product’s lifetime in the marketplace. FDA reviews reports of problems with prescription and over-the-counter drugs, and can decide to add cautions to the dosage or usage information, as well as other measures for more serious issues.
Developers must file a supplemental application if they wish to make any significant changes from the original NDA. Generally, any changes in formulation, labeling, or dosage strength must be approved by FDA before they can be made.
INDs for Marketed Drugs
If sponsors want to further develop an approved drug for a new use, dosage strength, new form, or different form (such as an injectable or oral liquid, as opposed to tablet form), or if they want to conduct other clinical research or a post-market safety study, they would do so under an IND.
FDA officials conduct routine inspections of drug manufacturing facilities across the United States, and abroad if approved products are manufactured overseas. Manufacturers may be informed of inspections in advance, or the inspections may be unannounced. Inspections may be routine or caused by a particular problem or concern. The purpose of these inspections is to make sure that developers are following good manufacturer practice. FDA can shut down a facility if minimum standards are not met.
FDA regulates prescription drug advertisements and promotional labeling. By law, a developer is prohibited from advertising unapproved uses of their product.
All advertisements, such as product claims or reminder ads, cannot be false or misleading. They must contain truthful information about a drug’s effectiveness, side effects, and prescribing information. These advertisements can be found in medical journals, newspapers, and magazines, and on the Internet, television, or radio.
Promotional labeling differs from drug advertisements in the way it is distributed. Pharmaceutical companies give out brochures or other promotional materials to physicians or consumers. The drug’s prescribing information must accompany promotional labeling.
New drugs are patent protected when they are approved for marketing. This means that only the sponsor has the right to market the drug exclusively. Once the patent expires, other drug manufacturers can develop the drug, which will be known as a generic version of the drug. Generic drugs are comparable to brand name drugs and must have the same:
Because generic drugs are comparable to drugs already on the market, generic drug manufacturers do not have to conduct clinical trials to demonstrate that their product is safe and effective. Instead, they conduct bio-equivalence studies and file an Abbreviated New Drug Application.
FDA has several programs that allow manufacturers, health professionals, and consumers to report problems associated with approved drugs.
Under the Sentinel Initiative, FDA is developing a new national system to more quickly spot possible safety issues. The system will use very large existing electronic health databases—like electronic health records systems, administrative and insurance claims databases, and registries—to keep an eye on the safety of approved medical products in real time. This tool will add to, but not replace, FDA's existing postmarket safety assessment tools.