Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. However, a manufacturer will need to ship the investigational drug to clinical investigators throughout the county, in order to do so they must seek an exemption. The investigational new drug (IND) application is the means through which a manufacturer obtains the exemption from the FDA.
The Federal Food, Drug and Cosmetic Act which required new drugs to be tested for safety before marketing, imbued the FDA with the authority to regulate the drug approval process and manufacturer actions.1
The Food, Drug and Cosmetic Act is intended to assure consumers that drugs and devices are safe and effective for their intended uses. The IND application removes a potential contradiction due to access to an unapproved therapy being a crucial step in development.
During a new drug's early preclinical development, the sponsor's primary goal 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. The FDA's role in the development of a new drug begins when a manufacturer wants to test its diagnostic or therapeutic potential in humans. At that point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system.2
There are three types2 of IND applications:
An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.
An Emergency Use IND which allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND. It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist.
Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.
The IND application must contain information on animal pharmacology and toxicology Studies and manufacturing information (i.e. composition, manufacturer, stability, and controls). The IND application must also include detailed clinical protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. As well as information on the qualifications of clinical investigators to assess whether they are qualified to fulfill their clinical trial duties. The final IND application requirement pertains to an investigator's commitment to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board, and to adhere to the IND regulations. Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.2
FDA's Center for Drug Evaluation and Research (CDER) receives about 1500 initial IND applications per year.3
The FDA’s CDER has a pre-IND application consultation program that fosters early communications between sponsors and new drug review divisions to provide guidance on the data necessary to warrant IND submission. The review divisions are organized generally along therapeutic classes.2
Holbein ME. Understanding FDA regulatory requirements for investigational new drug applications for sponsor-investigators. J Investig Med. 2009;57(6):688-694. doi:10.2310/JIM.0b013e3181afdb26
Investigational New Drug (IND) Application. U.S. Food and Drug Administration. https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application. Published 2021. Accessed September 10, 2021.
Lapteva L, Pariser AR. Investigational New Drug applications: a 1-year pilot study on rates and reasons for clinical hold. J Investig Med. 2016;64(2):376-382. doi:10.1136/jim-2015-000010