Regulatory Blog Post #1 - Exploratory IND Studies

Laura Salomon
September 9, 2010

Name of Guidance:
Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies

Status of Guidance/Release Date:
The final version of this guidance was released by the Center for Drug Evaluation and Research (CDER) in January, 2006.

Link to the Guidance:
The guidance on Exploratory IND Studies can be found at the following location: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078933.pdf

Target Audience:
Exploratory IND Studies is targeted to sponsors performing preliminary studies in support of Initial New Drug (IND) Applications. The Agency believes that this guidance’s suggestion of exploratory approaches will allow sponsors to more efficiently develop potential drug candidates. Particularly, these approaches are meant for pharmacology/toxicology scientists and researchers who would be involved in the clinical drug development program prior to traditional dose escalation, safety, and tolerance studies.

Laws and Regulations Referenced:
Code of Federal Regulations
21 CFR 312.23(a)(8) IND Content and Format (pharmacology/toxicology data)
21 CFR 312.23(a)(7)(i) IND Content and Format (chemistry, manufacturing, and controls information)
21 CFR 330.1 describes GRAS concept (excipients that are generally recognized as safe)
21 CFR 58 describes processes for ensuring consistency with Good Laboratory Practices
21 CFR 314, Subpart H Accelerated Approval of New Drugs for Serious of Life Threatening Illnesses

Food and Drug Administration Guidances for Industry
Fast Track Drug Development Programs – Designation, Development, and Application Review
Nonclinical Studies for Development of Pharmaceutical Excipients
INDs for Phase 2 and Phase 3 Studies, Chemistry, Manufacturing, and Controls (CMC) Information

International Conference on Harmonisation Guidances for Industry
M3 Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals
S7A Safety Pharmacology Studies for Human Pharmaceuticals
S2A Guidance of Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals
S2B Genotoxicity: A Standard Battery for Genotoxicity Testing for Pharmaceuticals

Summary:
The FDA asserts that existing regulations allow for a great deal of flexibility in the amount of data sponsors are required to submit with an IND application, depending on the proposed investigational plan and the specific human testing proposed and expected risks involved. Sponsors have not generally taken advantage of this flexibility and often submit more than what is required; this approach is inefficient and often lengthens the amount of time and resources expended on candidate products that are not likely to succeed. The early phase I approaches described in this guidance are consistent with regulatory requirements and maintain human subject protection, but involve fewer resources, thus enabling sponsors to more quickly distinguish drug candidates that are promising from those that are not.

Exploratory IND studies involve limited human exposure and have no therapeutic or diagnostic intent. This guidance proposes that such studies can help sponsors make early distinctions among potential drug candidates in several ways:

• Gathering information on the mechanism of action defined in experimental systems (e.g. binding property or enzyme inhibition) that may or may not be observed in humans
• Selecting a promising lead product for a particular therapeutic human target based on pharmacokinetic (PK) or pharmacodynamic (PD) properties
• Exploring a product’s biodistribution characteristics using imaging technologies

The guidance continues to provide sponsors with instruction on how to utilize exploratory IND studies in an overall Initial New Drug Application, including information on constructing an appropriate clinical development plan, CMC information, pharmacology and toxicology sections, and previous human experience (if any). Depending on the study, the preclinical testing programs that utilize exploratory IND studies can be less extensive than those for traditional IND studies because they involve sub-pharmacologic doses of candidate programs and therefore present fewer potential risks to humans.

Rationale:
This guidance references the FDA’s March, 2004 report, Innovation or Stagnation, Challenge and Opportunity on the Critical Path to New Medical Products, as its rationale. As part of its effort to reduce the time spent in early drug development on products that are unlikely to succeed, the Agency recommends sponsors take advantage of exploratory approaches, which are consistent with regulatory requirements but allow for a more efficient separation of potential drug candidates from hundreds or thousands of new molecular entities that a sponsor may develop.

Resulting Recommendations:
The Agency recommends that sponsors take advantage of the flexibility in IND data required, which varies according to the goals of a proposed investigation, specific human testing proposed, and expected risks. This flexibility allows for exploratory IND research techniques that may reduce the time and resources needed for sponsors to indentify promising potential drug candidates.

Impact:
As part of the FDA’s continuous effort to reduce unnecessary time and resources in drug development programs, the impact of this guidance is widespread in industry. Sponsors focused on exploratory studies may be able to more efficiently identify a potential drug candidate and therefore make better use of time and resources. Reducing costs and time involved in drug development results in huge gains for the sponsor: they spend less on drug development and have the potential to bring therapeutic products to market more quickly. The Agency benefits as well – receiving more focused IND applications based on exploratory studies without extraneous data allows for a more efficient review process and may enable sponsors to move forward with later phase clinical trials more quickly.