Table of Contents:
- What are the stages of drug development?
- 1: Discovery and Development
- 2: Preclinical Research
- 3: Clinical Research
- 4: FDA Drug Review
- 5: FDA Post-Market Drug Safety Monitoring
Typically, researchers discover new drugs through:
- Existing treatments have unforeseen side effects.
- New insights into a disease process allow researchers to create a product that must include the prescribed information for the medicine.
- Many molecular compound experiments may find more information to discover potential positive effects against a wide range of ailments.
- New technologies, such as those that allow medicinal items to be targeted to particular areas inside the body or enable genetic material to be manipulated
At this point in the process, hundreds of molecules may be prospective candidates for development as a medicinal therapy. However, based on preliminary testing, only a few chemicals appear promising and warrant additional investigation.
Once researchers have identified a potential molecule for development, they run trials to acquire information on:
- The best dosage
- The best way to give the drug
- Its potential benefits and mechanisms of action.
- Its effectiveness as compared with similar drugs.
- How it interacts with other drugs and treatments
- How it affects different groups of people differently
- How it is absorbed, distributed, metabolized, and excreted
- Side effects or adverse events can often be referred to as toxicity
Before testing medicine on humans, researchers must determine if it can cause substantial harm, a term known as toxicity. There are two categories of preclinical research:
- In Vitro
- In Vivo
For preclinical laboratory investigations, the FDA requires researchers to follow good laboratory practices (GLP), as established in medical product development rules. 21 CFR Part 58.1: Good Laboratory Practice for Nonclinical Laboratory Studies contains the GLP rules. These regulations provide the fundamental minimum standards for:
- study conduct
- study reports
- written protocols
- operating procedures
- and a quality assurance monitoring structure for each trial to ensure the safety of FDA-regulated products
Preclinical investigations are often minor in size. These studies, however, must offer thorough information on dose and toxicity levels. Following preclinical testing, researchers evaluate their data to determine if they should try the medicine in humans.
While preclinical research provides answers to fundamental issues regarding a medicine’s safety, it is not a replacement for how the medication will interact with the human body. The term “clinical research” refers to human investigations or trials. As the developers construct the clinical trial, they will assess what they aim to achieve for each clinical research phase and begin the Investigational New Drug Process (IND), which must complete before clinical research can commence.
This page contains information on:
- FDA IND Review Team
- Designing Clinical Trials
- Asking for FDA Assistance
- Clinical Research Phase Studies
- The Investigational New Drug Process
Designing Clinical Trials
Researchers design clinical trials to solve particular research questions about a medical product. These trials adhere to a defined study strategy, known as a protocol, devised by the researcher or manufacturer. Researchers analyze prior knowledge regarding medicine to generate study questions and objectives existing to the start of a clinical trial. Then they make a decision:
- How long the study will last
- Who qualifies to participate
- How many people will be part of the study
- How the data will be reviewed and analyzed
- How the drug will be given to patients and at what dosage
- What assessments will be conducted, when, and what will collect data
- Whether there will be a control group and other ways to limit research bias
Clinical trials typically go from early-stage, small-scale Phase 1 studies through late-stage, large-scale Phase 3 studies.
Clinical Research Phase Studies
The Investigational New Drug Process
Before initiating clinical research, drug developers or sponsors must file an Investigational New Drug (IND) application to the FDA.
In the IND application, developers must include:
- Manufacturing information
- Information about the investigator
- Data from any prior human research
- Animal study data and toxicity data
- Clinical protocols for studies to be conducted
Suppose a drug developer has proof from early testing, preclinical and clinical studies that a medicine is safe and effective for its intended use. In that case, the business can apply to commercialize the drug. The FDA review committee meticulously reviews all provided data on the medication before deciding whether or not to approve it.
New Drug Application
A New Medicine Application (NDA) describes the whole life cycle of a drug. Its goal is to show that a medicine is safe and effective for the intended usage in the population being researched.
An NDA must include all information on medicine, from preclinical research to Phase 3 trial results. Developers must consist of reports on all investigations, data, and analysis. In addition to clinical outcomes, developers must include:
- Safety updates
- Proposed labelling
- Patent information
- Directions for use
- Drug abuse information
- Institutional review board compliance information
- Any data derived from investigations done outside of the United States
When the FDA receives an NDA, the review team determines if it is complete. The review team may refuse to file the NDA if it is not complete. If it is done, the review team has 6 to 10 months to decide whether or not to approve the medicine. The following steps are included in the procedure:
Each member of the review team completes a thorough examination of his or her area of the application. For example, the medical officer and statistician evaluate clinical data, but a pharmacologist evaluates data from animal trials. There is also a supervisory review for each technical field represented on the team.
FDA inspectors visit clinical trial sites to perform routine inspections. The Agency searches for evidence of data falsification, manipulation, or withholding.
All individual evaluations and other papers, such as the inspection report, are compiled into an “action package” by the project manager. This document serves as the official record for FDA review. The review team makes a recommendation, and a senior FDA official makes a decision.
When the FDA determines that a medicine has been proven safe and effective for its intended use, it must then collaborate with the applicant to establish and modify prescription information. Referred to as “labelling.” Labelling correctly and objectively conveys the grounds for approval and the best way to utilize the medicine.
However, many times one must address unresolved concerns before the medicine may be licensed for commercialization. The FDA may occasionally request the developer to respond to inquiries based on current data. In other circumstances, the FDA demands further research. At this stage, the developer can choose whether or not to continue working on the project. If a developer disagrees with an FDA decision, he or she has the option of filing a formal appeal.
FDA Advisory Committees
Frequently, the NDA offers enough information for the FDA to assess a drug’s safety and efficacy. But, now and again, an issue arises that necessitates further thought. In some instances, the FDA may convene a meeting of one of its Advisory Committees to get independent, expert counsel and allow the public to comment. These Advisory Committees include a Patient Representative who gives feedback from the patient’s point of view. Learn more about FDA Advisory Committees.
Even though clinical trials give vital information about a drug’s efficacy and safety, it is challenging to have comprehensive knowledge on a drug’s safety at the time of approval. Despite the rigorous procedures in the medication development process, there are limits. When the FDA receives complaints of difficulties with prescription and over-the-counter pharmaceuticals, it may opt to add cautions to the dose or usage instructions and take further steps in the case of more significant challenges.
On this page, you will find information on:
- Generic Drugs
- Drug Advertising
- Reporting Problems
- Active Surveillance
- INDs for Marketed Drugs
- Manufacturer Inspections
- Supplemental Applications
If developers want to make significant changes from the initial NDA, they must submit a supplemental application. In general, any modifications to formulation, labelling, or dose strength must be authorized by the FDA before implementation.
INDs for Marketed Drugs
Sponsors might utilize an IND further to develop an authorized medicine for a new purpose, dosage strength, new form, or different form (such as an injectable or oral liquid instead of tablet form) or perform further clinical research a post-market safety study.
FDA inspectors undertake routine inspections of drug manufacturing sites in the United States and internationally if authorized drugs are made elsewhere. May notify manufacturers in advance of reviews, or the assessments may be unannounced. Checks might be routine or prompted by a specific problem or concern. The goal of these inspections is to ensure that developers are adhering to best manufacturing practices. If minimal criteria are not reached, the FDA has the authority to close a facility.
The FDA is in charge of regulating prescription medicine ads and promotional labels. In addition, a developer is barred by law from advertising unauthorized applications for their product.
All marketing, such as product claims or reminder advertising, must be valid and not deceptive. In addition, they must provide accurate information regarding a drug’s efficacy, adverse effects, and prescribing instructions. May see these ads in medical journals, newspapers, magazines, and the Internet, television, and radio.
How promotional labelling is delivered distinguishes it from medication ads. Pharmaceutical businesses distribute pamphlets and other promotional materials to doctors and patients. Must include the prescribed information for the medicine with the promotional labelling. May find more details at Prescription Drug Advertising.
When a new medicine is authorized for commercialization, it is patent protected. It implies that only the sponsor has the sole right to market the drug. When the patent expires, other medication producers will make the medicine known as a generic version. Generic medications are equivalent to brand-name medications and must have the following characteristics:
- Dosage form
- Intended use
- Performance characteristics
Because generic pharmaceuticals are interchangeable with existing drugs, generic medication producers must not undergo clinical trials to verify that their product is safe and effective. Instead, they undertake bioequivalence studies and submit an Abbreviated New Drug Application (ANDA). May find more information at Generic Drugs: Questions & Answers.
The FDA has several mechanisms that allow producers, health professionals, and consumers to report concerns with authorized pharmaceuticals.
- MedWatch is a website where you can report medical items (drugs and equipment) and learn about updated safety information. In addition, you may sign up for MedWatch safety alerts regularly.
- The Medical Product Safety Network (MedSun) keeps track of the safety and efficacy of medical products. The FDA hires 350 healthcare practitioners around the country to report any medical device concerns that cause significant damage or death. The FDA issues the MedSun newsletter once a month. The newsletter provides vital information on medical device safety to customers.
The FDA is building a new nationwide system to detect potential safety hazards faster as part of the Sentinel Initiative. The system will monitor the safety of licensed medicinal items in real-time by utilizing massive current electronic health datasets, such as electronic health records systems, administrative and insurance claims databases, and registries. This tool will supplement, rather than replace, the FDA’s existing postmarket safety assessment tools. Discover more about the Sentinel Initiative and its main initiatives.