Drug Development Process
The drug development process is time consuming and expensive. It is estimated that of the 5, 000 new molecular entities (NME) developed; only 5 make it to clinical testing and only 1 of the 5 actually receive FDA approval.
The goal is to find better ways to prevent, detect, and treat diseases. Once a new molecular entity (NME) is tested in vitro and proved to be a hopeful compound, the compound is then tested in animal models to determine the pharmacologic and toxicology effects in specific animal models. The key focus of animal testing is to understand the absorption, distribution, metabolism and excretion (ADME). The goal of preclinical development is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development.
- Drug Development Timeline
- FDA: How Drugs are Developed and Approved
- FDA: Information for Consumers (Drugs)
- Understanding Clinical Trials
- FDA: Types of Applications
Investigational New Drug (IND):
The IND is an application that sponsors must submit to the FDA to receive an exemption to transport or distribute drugs across state lines. The IND must state the purpose to test the agent in human subjects and supply pre-clinical data and justification to warrant clinical studies. The application must be submitted prior to the start of any human subject research studies. The research study cannot begin participant recruitment until 30 days after FDA receipt or after all FDA requests have been fulfilled. INDs require annual updates to reflect protocol changes, new information, or serious adverse events.
- HRPP Policy on Research Involving Investigational Drugs
- IND Information
- FDA 21 CFR 312
- FDA IND Forms and Instructions
Phases of Clinical Trials
PHASE I TRIALS
Phase I clinical trials are conducted to determine the safety and tolerance of study agents in normal healthy participants, with the exception of serious and life threatening conditions such as cancer or HIV. These studies are often known as the “first in man” studies because they are the first introduction of an investigational new drug to humans. Understanding how the drug is metabolized and excreted is usually the scientific focus of these studies. Pharmacology, pharmacokinetics, physiological side effects, bioavailability, bioequivalence and establishing the maximum tolerated dose (MTD) are common data elements collected and analyzed. Phase I trials are usually short term studies that include less than one hundred participants.
PHASE II TRIALS
Phase II clinical trials are conducted to determine the safety and efficacy of a drug within a particular disease or specific patient population. These trials are often referred to as Pilot (determine efficacy) or Pivotal (determine efficacy and safety to include in the New Drug Application [NDA]). Efficacy, safety, pharmacokinetics, drug-drug interactions, drug-disease interactions, bioavailability and physiological side effects are common data elements collected for these studies. Phase II trials usually include hundreds of participants.
PHASE III TRIALS
Phase III clinical trials are conducted to confirm or expand the data collected on the efficacy, safety, risk-benefit ratio, long term effects, tolerance and adverse events. The primary objective of a phase III trial is to demonstrate or confirm therapeutic benefit to support the marketing approval of the drug for a specified patient population. Phase III trials usually include hundreds to thousands of participants and include long term data collection. The trials commonly include multiple treatment groups, with control groups such as standard of care comparative drugs or placebo.
Phase IV trials are post market trials. These trials generally are conducted to determine pharmacoeconomic, epidemiologic, adverse event and quality of life data. Phase IV trials usually include thousands of participants in the marketed populations.
- OSU ORRP Guidelines for Writing a Research Protocol
- Good Clinical Practices GCP ICH E 6
- ICH E 10: Choice of Control Group and Other Related Issues in Clinical Trials
- Cancer Therapy Evaluation Program (CTEP) Protocol Templates and Guidelines
New Drug Application (NDA)
The New Drug Application (NDA) is the formal request of a sponsor for FDA review and approval of a new drug for commercial sale and marketing in the United States. This application encompasses all data gathered during pre-clinical and clinical research. The goal is to show that the drug is safe and effective for the proposed indication and patient population. Details regarding potential side effects, absorption, metabolism, risks, benefits, drug composition, manufacturing details and packaging are all included in this application.