Exploring the five phases of drug development

Phase One: Discovery and development

Long before any drug development and manufacturing work can be done, researchers must identify or “discover” a specific molecule — typically a DNA sequence, RNA molecule, protein, or metabolite — that plays a crucial role in a disease state and can be targeted by a drug to produce beneficial and therapeutic effects. After that discovery, researchers can then search for a compound or compounds that interact with the target molecule and have the potential to become drug candidates. A variety of compounds are usually identified as potential candidates, so researchers must conduct a series of experiments on each one to gauge their performance and viability as the final, most effective drug substance. Typically, they assess factors such as absorption, administration, side effects, and potential interactions. After those experiments are finalized, and the most promising compounds are isolated, the preclinical research phase can begin.

“The purpose of preclinical research is largely to assess whether a compound has the potential to cause serious harm.”

Phase Two: Preclinical research

Before any compound can be tested in humans, researchers must conduct preclinical research either in vitro (i.e., in a test tube) or in vivo (i.e., in an animal). The purpose of preclinical research is largely to assess whether a compound has the potential to cause serious harm. Additionally, candidates undergo testing for pharmacodynamics and pharmacokinetics, examining what the drug does to the body and what the body does to the drug. Preclinical research also plays a crucial role in determining pharmaceutical formulation development, including such factors as stability, bioavailability, and administration method. All preclinical research must comply with the FDA’s good laboratory practice (GLP) regulations, which set the standard for data quality, integrity, and reliability. After a drug successfully navigates through preclinical research, it’s ready to be tested in humans.

Phase Three: Clinical research

Clinical research via clinical trials is the next step in drug development, and it serves to test the safety and efficacy of compounds in humans. Clinical research is typically divided into four phases: phase I, phase II, phase III, and phase IV. According to the FDA, phase I involves 20 to 100 healthy volunteers or individuals with the disease or condition, phase II involves up to several hundred people with the disease or condition, phase III involves 300 to 3,000 people with the disease or condition, and phase IV involves several thousand people with the disease or condition. If a drug compound successfully demonstrates safety and efficacy during clinical trials, it can advance to FDA review. As previously stated, it’s important to note that only a small percentage of new drugs that enter clinical trials eventually receive FDA approval. Factors such as lack of efficacy and safety issues often contribute to this low success rate.

“If the drug is deemed safe and effective for its intended use, the FDA grants approval to manufacture, market, and distribute the drug in the United States.”