Drug Applications

Investigational New Drug (IND) Application Process

Introduction

Current Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND is the means through which the sponsor technically obtains this exemption from the FDA.

During a new drug's early preclinical development, the sponsor's primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development. When a product is identified as a viable candidate for further development, the sponsor then focuses on collecting the data and information necessary to establish that the product will not expose humans to unreasonable risks when used in limited, early-stage clinical studies.

FDA's role in the development of a new drug begins when the drug's sponsor (usually the manufacturer or potential marketer) having screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans.  At that point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system. 

There are three IND types:

• An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.  A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.

• Emergency Use IND allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with  21CFR , Sec. 312.23 or Sec. 312.34.  It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist.

• Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

There are two IND categories:

• Commercial

• Research (non-commercial)

The IND application must contain information in three broad areas:

• Animal Pharmacology and Toxicology Studies - Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans.  Also included are any previous experience with the drug in humans (often foreign use).

• Manufacturing Information -  Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.  This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.

• Clinical Protocols and Investigator Information - Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks.  Also, information on the qualifications of clinical investigators--professionals (generally physicians) who oversee the administration of the experimental compound--to assess whether they are qualified to fulfill their clinical trial duties.  Finally, commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.

Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials.  During this time, FDA  has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.

This interactive chart summarizes the IND process, including how CDER determines if the product is suitable for use in clinical trials.

This web site is designed for individuals from pharmaceutical companies, government agencies, academic institutions, private organizations, or other organizations interested in bringing a new drug to market.  Each of the sections below contains information from CDER to assist you in the IND application process.  For specific information, click on a link to go directly to a section or webpage.

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Resources for IND Applications

The following resources have been gathered to provide you with the legal requirements of an IND application, assistance from CDER to help you meet those requirements, and internal IND review principles, policies and procedures.

Pre-IND Consultation Program: CDER offers a Pre-Investigational New Drug Application (IND) Consultation Program to foster early communications between sponsors and new drug review divisions in order to provide guidance on the data necessary to warrant IND submission. The review divisions are organized generally along therapeutic class and can each be contacted using the designated Pre-IND Consultation List. (12/5/2006)

Guidance Documents for INDs

Guidance documents represent the Agency's current thinking on a particular subject. These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products.   They also establish policies intended to achieve consistency in the Agency's regulatory approach and establish inspection and enforcement procedures.  Because guidances are not regulations or laws, they are not enforceable, either through administrative actions or through the courts.  An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. For information on a specific guidance document, please contact the originating office.

For the complete list of CDER guidances, please see the Guidance Index.  Most of these documents are in Adobe Acrobat format , also know as PDF.   The free upgrade to Adobe Acrobat 3.0 or higher is recommended, especially if you have difficulty opening any of the documents below. For information on a specific guidance document, please contact the originating office.

Guidance documents to help prepare INDs include:

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Laws, Regulations, Policies and Procedures

The mission of  FDA is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook.  The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments it is the most extensive law of its kind in the world.  The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.

Code of Federal Regulations (CFR)

Code Of Federal Regulations (CFR).  The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR.  The CFR is divided into 50 titles that represent broad areas subject to Federal regulations.  The FDA's portion of the CFR interprets the Federal Food, Drug and Cosmetic Act and related statutes.  Section 21 of the CFR contains most regulations pertaining to food and drugs.   The regulations document all actions of all drug sponsors that are required under Federal law. 

• The following regulations apply to the IND application process:

21CFR Part 312	Investigational New Drug Application
21CFR Part 314	INDA and NDA Applications for FDA Approval to Market a New Drug (New Drug Approval)
21CFR Part 316	Orphan Drugs
21CFR Part 58	Good Lab Practice for Nonclinical Laboratory [Animal] Studies
21CFR Part 50	Protection of Human Subjects
21CFR Part 56	Institutional Review Boards
21CFR Part 201	Drug Labeling
21CFR Part 54	Financial Disclosure by Clinical Investigators

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Manual of Policies and Procedues (MaPPs)

CDER's Manual of Policies and Procedures (MaPPs). MaPPS are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities. MaPPs define external activities as well.  All MAPPs are available for the public to review to get a better understanding of office policies, definitions, staff responsibilities  and procedures. MaPPs of particular interest to IND sponsors include:

IND Forms and Instructions

Forms for use in submitting INDs include:

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Emergency use of an Investigational Drug or Biologic

• FDA proposes rules overhaul to expand the availability of experimental drugs. The Agency also clarifies permissible charges to patients. FDA News (12/11/2006)

• The Guidance for Institutional Review Boards and Clinical Investigators contains information on: Obtaining an Emergency IND, Emergency Exemption from Prospective IRB, Approval Exception from Informed Consent, and Requirement Planned Emergency Research, Informed Consent Exception.

• For assistance in obtaining unapproved cancer drugs, please see Access to Unapproved Drugs.

• Federal Register notice for Emergency Use of an Investigational New Drug; Technical Amendment

• Directions to Sponsors of Emergency Investigational New Drug (EIND) Application. From the Office of Antimicrobial Products, Division of Antiviral Products (11/29/2005)

Emergency use requests:

• For investigational biological products regulated by CBER, call 301-827-2000.

• For all other investigational drugs, call 301-827-4570.

• After working hours, call FDA’s Office of Emergency Operations at 301-443-1240.

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FDA/Center for Drug Evaluation and Research
Last Updated: Decmeber 28, 2007
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