By An Nguyen
The United States Food and Drug Administration (FDA) is responsible for protecting public health and ensuring human drugs, vaccines, and other biological products are safe and effective for patients to use. According to the agency’s April 2023 statistics from the Office of the Commissioner, there are currently “over 20,000 prescription drug products approved for marketing.”
In one of the most prominent industries in the world, it is important to understand the drug development process and how an idea in the lab can turn into a product on the market. The drug development process involves multiple disciplines, with different teams working on areas such as drug discovery, pharmacology, safety testing, manufacturing, clinical trials, and marketing. This timeline can span ten years and cost pharmaceutical developers upwards of $2 billion.
The following is an overview of the five main stages that get a prescription drug on the market for patients to use according to the FDA.
Stage 1: Discovery and Development
The drug development process begins with the discovery of phenomena that inspire researchers to begin developing new drugs. This encompasses diseases, effects of molecular compounds, existing treatments with unanticipated effects, and new technologies that become the reason why these drugs are created. Similar to the first step of the scientific process, the discovery stage deals with the research question and identifying a problem to justify the proceeding research. Thousands of compounds may be potential candidates for drug development, but only a small number make it to further experimentation after early tests.
Once a compound becomes of interest to a developer, researchers begin to conduct experiments to determine the essential characteristics of that molecule. This includes how it is absorbed and distributed, its benefits and mechanism of action, proper dosage, route of administration, possible side effects, drug interactions, and efficacy. All of this information is elementary at this stage in the process and only serves as background for future studies.
Stage 2: Preclinical Research
The first phase of research a drug goes through is preclinical, meaning before human subjects are used to test the compound. These studies are regulated by the FDA with a series of good laboratory practices to ensure standard protocol across all drug research. The FDA requires extensive data and testing before the compound can be approved for testing on humans. This especially includes “detailed information on dosing and toxicity levels.”
Preclinical research is divided into two classifications, in vivo and in vitro. In vivo research tests the safety and efficacy of the drug using non-human models such as mice and rats. In vitro research experiments on human or non-human cells outside of their normal biological environment in a controlled setting. Both types are vital in producing the necessary data to advance to the next stage of the drug development process.
Stage 3: Clinical Research
Once a developing drug goes through substantial research in a laboratory setting, studies can begin to be performed on humans to determine the drug of interest’s interactions with the body. To begin clinical research, drug developers must submit an Investigational New Drug (IND) application to the FDA for approval. The application must include animal study and toxicity data, manufacturing information, clinical protocols, and investigator information. After 30 days, the FDA can either approve the IND and the commencement of clinical trials, or place a temporary hold on the application pending more information, or stop the investigation. Once given the green light, the drug undergoes clinical research, which is further separated into four phases.
Phase 1 is used to determine the safety and proper dosage of the drug. Researchers gather information on how the drug interacts with the body, including adjusting dosages based on any side effects. This phase can span several months and usually involves 20 to 100 healthy volunteers or people with the disease or condition being treated. About 70% of drugs move on to the next phase.
Phase 2 is used to determine the efficacy of the drug and any possible side effects. This is done to provide researchers with additional safety data. This phase can take several months to two years and tests up to several hundred people with the disease or condition being treated. About 33% of drugs move on to the next phase.
Phase 3 is used to monitor adverse reactions and further determines the efficacy of the drug. Studies in this phase are specifically designed to determine the drug’s treatment benefits to a specific population and provide the majority of the safety data. This phase can take one to four years and tests 300 to 3,000 volunteers who have the disease or condition. With a longer clinical phase, researchers are also able to discover more long-term or rarer side effects. Only 25-30% of these drugs move on to the next phase.
Phase 4, the final phase, is carried out once the drug has already been approved by the FDA. Clinical research on drugs is ongoing, even once they hit the market. This is so that observations can continue to be made in case anything was possibly overlooked in the first three phases.
Stage 4: FDA Drug Review
Once a drug developer has compiled thorough and substantial evidence from early discovery tests, preclinical research, and clinical trials that the drug is safe and effective for its intended use, the pharmaceutical company files a New Drug Application (NDA) to market the drug. The NDA must include data from the preclinical stage to the Phase 3 clinical trial as well as proposed labeling, safety updates, drug abuse information, and directions for use.
The FDA review team first has to determine whether or not the NDA is complete with all the required information. This review team consists of members from various disciplines who review components of the drug research that corresponds with their specialty. If deemed satisfactory, the review team has six to ten months to either approve or reject the drug.
Once the FDA approves the drug, the agency works with the drug developer to refine prescribing information and iron out any remaining details. There are instances, however, where the FDA requires the developer to perform additional studies and further research.
Stage 5: Post-Market Monitoring
The final stage of the drug development process, post-market monitoring is when the true extent of the drug’s efficacy and limitations is seen with patients. The FDA continuously reviews reports of issues with drugs once they reach the market and adds cautions as time progresses. The FDA also regulates drug advertising and promotional labeling such as commercial ads and pharmaceutical company product brochures.
To remain vigilant in preserving the safety of drugs on the market, the FDA has multiple resources to facilitate reporting adverse events. The following are public tools to report and monitor problems with FDA-regulated medical products:
An Nguyen is a Decency LLC Summer 2023 intern. He is a Pharm.D. candidate at Rutgers University's Ernest Mario School of Pharmacy.