Draft Guidance for Industry on Exploratory Investigational New Drugs Studies; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Exploratory IND Studies.” This draft guidance clarifies what preclinical and clinical issues (including chemistry, manufacturing, and controls issues) should be considered when planning exploratory studies in humans, including studies of closely related drugs or biologics, under an investigational new drug (IND) application. This draft guidance emphasizes the concept that limited investigations in humans can be initiated with more limited preclinical support because such studies present fewer potential risks than do traditional phase 1 studies that look for dose-limiting toxicities.

DATES:

Submit written or electronic comments on the draft guidance by July 13, 2005. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the draft guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments . See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

David Jacobson-Kram, Center for Drug Evaluation and Research (HFD-24), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-5346.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Exploratory IND Studies.” In its March 2004 Critical Path Report, the agency explained that to reduce the time and resources expended during early drug development on candidates that are unlikely to succeed, tools are needed to allow developers to distinguish earlier in the process those candidates that hold promise from those that do not. This guidance describes some exploratory approaches that will protect human subjects while providing early information about candidate performance in humans.

Exploratory IND studies have a number of different goals. In some cases, an exploratory study can help developers gain an understanding of the relationship between a specific mechanism of action and the treatment of a disease. In other cases, a study can provide important information on pharmacokinetics, including, for example, biodistribution of a candidate drug. Whatever the goal of the study, exploratory IND studies can help sponsors identify, early in the process, promising candidates for continued development.

Existing regulations allow a great deal of flexibility in terms of the amount of data that need to be submitted in an IND application, depending on the goals of an investigation, the specific human testing being proposed, and the expected risks. Nevertheless, sponsors have not always taken advantage of that flexibility and limited, early phase 1 studies, such as those described in this document, are often supported by a more extensive preclinical database than is needed. In many cases, a more extensive workup is done because sponsors intend to move immediately into a more traditional phase 1 trial if the screening results are favorable. Because exploratory studies will typically involve administering either subtherapeutic doses of a product, or doses expected to produce a pharmacological, but not a toxic effect, the potential risk to human subjects is less than for a traditional phase 1 study that, for example, seeks to establish a maximally tolerated dose.

This guidance applies to exploratory studies (i.e., early phase 1 clinical studies), involving investigational new drug and biological products, that assess feasibility for further development of a drug or biological product. For the purposes of this guidance the phrase “exploratory study” is intended to describe clinical trials that occur very early in phase 1, involve very limited human exposure, and often have no therapeutic intent.

Typically, these exploratory studies are conducted prior to the traditional dose evaluation, safety, and tolerance studies that ordinarily initiate a clinical drug development program. Thus, FDA believes that, typically, the duration of dosing would be limited (e.g., 7 days). The agency is, however, interested in soliciting comment from the public on the appropriate duration of dosing for such exploratory studies.

The amount and type of preclinical information necessary to support an exploratory study will depend on the planned nature and extent of human exposure relative to the toxicity (or lack thereof) at the planned dose. Thus, this guidance emphasizes the concept that limited investigations in humans can be initiated with more limited preclinical support because such studies present fewer potential risks than do traditional phase 1 studies that look for dose-limiting toxicities. The studies discussed here ordinarily do not have therapeutic intent. They are designed to evaluate whether a particular candidate should be entered into a drug development program.

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency's current thinking on exploratory IND studies. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

This draft guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collection of information in this guidance has been approved under OMB control number 0910-0014 and expires on January 31, 2006.

III. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments on the draft guidance. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The draft guidance and received comments are available for public examination in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

IV. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm .