In a new draft guidance published for comment in the April 14 Federal Register, the Food and Drug Administration (FDA) clarifies submission requirements for early phase I exploratory studies under an investigational new drug (IND) application.

FDA says such applications often contain more data than required by regulations. According to the new draft guidance, "Exploratory IND Studies," depending on the study, the preclinical testing programs for exploratory INDs "can be less detailed and more flexible than for traditional INDs."

FDA developed the exploratory IND guidance document with input from NCI through the Interagency Oncology Task Force (IOTF), which fosters closer cooperation between the agencies. "We were looking for ways to streamline the early drug development process," notes Dr. Michaele Christian, associate director of NCI's Cancer Therapy Evaluation Program and IOTF member. The goal is to allow researchers to conduct early proof-of-principle evaluations of compounds and target effects to identify promising candidates for more extensive testing, she adds.

Dr. Joseph Tomaszewski, chief of NCI's Toxicology and Pharmacology Branch and acting associate director of the Developmental Therapeutics Program concurs, saying, "It will be especially beneficial when you have a series of analogs and you cannot or do not want to make a decision about which one agent to move forward with. This guidance will allow investigators to test each one in a limited clinical trial that will provide sufficient human data to help inform the decision."

FDA is seeking input on the draft guidance, and NCI is especially encouraging comment from the cancer research community during the 90-day comment period. The document can be viewed and downloaded at http://www.fda.gov/cder/guidance/6384dft.pdf.

Although FDA's regulations are flexible, many researchers and drug sponsors "have not taken full advantage of that flexibility and limited, early phase I studies - such as those described in this guidance - are often supported by a more extensive preclinical database than is needed for those studies," FDA contends.

The draft guidance defines an exploratory IND study as a clinical trial that occurs very early in phase 1, involves very limited human exposure to a product (e.g., maximum 7 days), and has no therapeutic intent. Such tests are useful, for example, to "select the most promising lead product from a group of candidates designed to interact with a particular therapeutic target in humans," FDA notes. Exploratory testing usually occurs prior to the more extensive "traditional dose escalation, safety, and tolerance studies" conducted later in phase 1 development of drugs and biological products.