In a major development on the regulatory landscape for clinical trials, the US  Food and Drug Administration (FDA) has now issued a guidance which is intended to assist clinical investigators, sponsors, sponsor-investigators and institutional review boards (IRBs). The norms are to determine whether research studies involving human subjects need to be conducted under an investigational new drug application (IND).

The title 21 of the Code of Federal Regulations, part 312 (21 CFR part 312)  states that when an IND is required, there are specific situations in which it  is also not required. Now the regulatory authority has viewed these range of issues as a source of confusion or misperceptions about the application of the IND regulations.

The new guidance addresses only whether an IND is needed. If a study also involves the use of a device, then the clinical research organisation (CRO) should determine whether its  application is subject to 21 CFR part 812.

The regulatory authority has stated that it has two primary objectives in reviewing an IND. Firstly it is to assure the safety and rights of subjects in all phases of an investigation. Secondly it is for phases II and III of the human studies to help assure that the quality of the scientific evaluation of the drug is adequate to permit an evaluation its effectiveness and safety.

FDA receives frequent inquiries from the academic community, clinical investigators, IRBs  and the pharmaceutical industry about whether an IND should be submitted for various types of clinical research. Inquiries have related to a range of issues concerning application of the IND requirements in part 312. These include clinical investigations using marketed drugs,  bioequivalence/bioavailability studies  using radio-labeled or cold isotopes, dietary supplements or foods, endogenous compounds, pathogenesis assessments  using modified organisms, wild-type organisms in challenge models and studies that do not have a commercial purpose.

With a large number of inquiries and wide range of issues, FDA has  determined that it would be helpful to provide to potential sponsors, clinical investigators and sponsor-investigators an overview of the IND requirements and related issues.

With certain exceptions, clinical investigations in which a drug is administered to human subjects must be conducted under an IND as required in Part 312. Sections III, IV, and V of the guidance elaborates on the criteria for when a study must be conducted under an IND. It would depend on  the types of studies that involve drugs and those  exempt from the IND requirements. Studies involving radioactive drugs that are generally recognized as safe and effective the IND requirements do not apply.

FDA’s has also used its enforcement discretion with certain studies using cold isotopes conducted without an IND. Section VI discusses specific issues that frequently arise concerning application of the IND regulations. The section VII contains frequently asked questions and section VIII describes the process for seeking advice from FDA concerning the application of the IND regulations to a planned clinical investigation.