Investigational New Drug Application

Before starting clinical trials, the clinical investigators must submit an Investigational New Drug (IND) application to the FDA. It is a critical early step in clinical trial development. The IND files refer to three major required information, including manufacturing information, animal pharmacology and toxicology studies, and clinical protocols and investigator information. In the United States, the FDA is the agency responsible for ensuring the safety, efficacy, and security of human as well as veterinary drugs in addition to other areas of regulatory authority. Once an IND application is approved, the study may begin 30 days after the FDA acknowledges receipt and assigns an IND. The clinical investigator must also continue to meet a set of regulations for monitoring the study and reporting to the FDA when the IND is active.

Fig.1 Contents of an Investigational New Drug (IND) application (Oner, 2021)

What are INDs?

The IND is the launching point for clinical investigations and the primary purpose of an initial IND submission is to ensure the safety and rights of clinical trial participants. In addition, the IND also performs an additional legal function, which provides a legal framework that allows sponsors to transport their investigational products to clinical investigators in different states. There are two IND categories, including commercial and research IND. Commercial INDs are the most common IND type that allows for the development of a drug or biologic to ultimately submit a marketing application. Research IND is studied for research purposes, such as publishing articles or evaluating a potential mechanism. In addition, emergency IND is used for quick authorization of a drug in an emergency where no alternative treatment is available, such as the COVID-19 pandemic. All IND applications must include information about the nonclinical safety and quality of the new drug as well as the proposed clinical protocol and investigator.

Pre-IND Meeting

The Pre-IND meeting is a formal meeting between the FDA and sponsors to discuss the development and review of an IND application for drugs. The purpose of the pre-IND meeting is intended to address the specific questions that could affect the IND application. Typically, the meeting includes a discussion of the nonclinical program, manufacturing and product quality for the investigational product, and regulatory considerations. Once a meeting request is submitted, the FDA typically responds within 21 days of receiving the request, and meetings are usually scheduled within 60 days of the request.

General Principles

The goal of IND is to provide FDA information to allow a review that assures the safety of participants. Generally, the scheme for an IND must contain information in three broad areas. Firstly, clinical researchers need to submit the preclinical data of animal pharmacology and toxicology studies to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Secondly, the manufacturing Information about the drug composition, manufacturer, stability, and controls are also essential for drug development to ensure that the company can adequately produce and supply consistent batches of the drug. Finally, detailed clinical protocols are important to assess whether the initial-phase trials will expose subjects to unnecessary risks. Also, the clinical investigators must be professionals and need to provide information on their qualifications to assess whether they are qualified to fulfill their clinical trial duties.

Submitting an IND

For sponsor-investigator, questions about the IND submission process can be known on the FDA website. It listed extensive information for sponsors and provided the completion of the forms and clerical requirements. The contact information for both CDER and CBER officials is also available on the FDA website. Clinical researchers can be directly contacted by phone or email to the appropriate office or department. Once the IND is submitted, it will be routed to the appropriate division for review. The sponsors must wait 30 days before initiating any clinical trials and the FDA has an opportunity to review the IND for safety during this time. If the FDA does not notify the investigator otherwise, they can start the studies after the 30-day interval.

Reference

1. Oner, E., Labra, S. and Fehr, S., 2021. FDA Drug Regulation: Investigational New Drug Applications. Academic Entrepreneurship for Medical and Health Sciences.