Investigational New Drugs (INDs) are medications or biological products not yet approved for widespread public use by regulatory bodies like the U.S. Food and Drug Administration (FDA). These drugs undergo rigorous scientific testing in human subjects, known as clinical trials, to determine their safety and effectiveness. The development of INDs is a multi-step process, advancing medical science and bringing new treatments to patients.
Early Development and IND Application
Before a drug can be tested in humans, it undergoes extensive preclinical research. This phase involves laboratory studies using cell cultures and animal models to evaluate the drug’s initial safety profile and potential therapeutic effects. Researchers gather data on how the drug is absorbed, distributed, metabolized, and excreted by the body, alongside any signs of toxicity.
If preclinical studies demonstrate a promising safety profile and potential efficacy, the drug’s sponsor submits an Investigational New Drug (IND) application to the FDA. This application seeks authorization to administer the investigational drug to human subjects. The IND application includes comprehensive information, such as results from animal studies, detailed manufacturing processes, and proposed plans for future clinical trials.
The FDA reviews the IND application to ensure that the proposed human trials are reasonably safe and ethically sound. A sponsor must wait 30 calendar days after submission before beginning any clinical trials, allowing the FDA time to review the contents and raise any concerns. This initial review helps determine if the drug has enough preliminary data to justify human testing.
Clinical Trial Phases
Once an IND application is authorized, the investigational drug moves into human clinical trials, typically conducted in three sequential phases before potential approval. Each phase has distinct objectives and involves an increasing number of participants. Ethical oversight from an Institutional Review Board (IRB) is a constant throughout these trials to protect the rights and well-being of volunteers.
Phase 1 trials are the first step in human testing, involving a small group of healthy volunteers. The primary objective is to assess the drug’s safety, determine a safe dosage range, and identify any initial side effects. Researchers also study how the drug is processed by the human body during this phase, lasting several months.
Following successful Phase 1 completion, Phase 2 trials begin, enrolling a larger group of participants who have the specific condition the drug aims to treat. The focus shifts to evaluating the drug’s effectiveness for its intended purpose while continuing to monitor safety and side effects. These trials help establish the optimal dosage for larger-scale studies and can last from several months to two years.
Phase 3 trials involve an even larger patient population. The main goal is to confirm the drug’s effectiveness, monitor adverse reactions, and compare it against existing standard treatments or a placebo. This phase generates extensive data on the drug’s overall benefit-risk profile, taking one to four years to complete.
Accessing Investigational Treatments
Patients can primarily gain access to investigational treatments by participating in clinical trials. These trials are carefully designed studies where eligible individuals volunteer to receive the investigational drug under strict medical supervision. Participation offers the potential to receive a new treatment for a condition when other options may be limited.
For patients with serious or immediately life-threatening conditions who are unable to participate in a clinical trial and have no comparable or satisfactory alternative treatments, other pathways exist, such as expanded access programs, also known as “compassionate use.” These programs allow for the use of investigational drugs outside of clinical trials.
Expanded access can be granted for individual patients. Criteria for these programs include the patient having a serious or life-threatening illness, having exhausted other options, and not being eligible for ongoing trials. The FDA must determine that the potential benefits outweigh the risks.
Pathway to Drug Approval
After the completion of all clinical trial phases, if the investigational drug demonstrates sufficient evidence of safety and effectiveness, the drug sponsor will compile all collected data and submit a New Drug Application (NDA) to the FDA. This comprehensive application formally requests marketing approval for the drug.
The FDA then undertakes a thorough review of the NDA, scrutinizing all aspects of the drug’s development. This review process can take several months to over a year. The FDA evaluates whether the drug’s benefits outweigh its risks for the proposed use.
Upon completion of the review, the FDA can make one of several decisions: approve the drug for marketing, issue a complete response letter requesting additional information or studies, or reject the application. If approved, the drug becomes available for prescription to the general public for its specified indication. If rejected, the sponsor may need to conduct further research or address the FDA’s concerns before resubmitting the application.