<
 
 
 
 
>
hide
You are viewing a Web site, archived on 10:02:06 Nov 01, 2004. It is now a Federal record managed by the National Archives and Records Administration.
External links, forms, and search boxes may not function within this collection.

U.S. Food and Drug Administration Center for Drug Evaluation and Research

CDER - Center for Drug Evaluation and Research Logo

Drug Applications

CDER Home Site Information Comments and Feedback What's New CDER Navigation Bar
 

CDER ArchivesSpecific AudiencesCDER CalendarRegulatory InformationDrug InformationAbout CDERSide Navigational Buttons

botside1.gif (9072 bytes)

apptop.jpg (7106 bytes)

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 Adobe Acrobat Symbol 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.

Back to Top


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. Adobe Acrobat Symbol 7/14/2004

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 Adobe Acrobat Symbol, 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:

Back to Top

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

Back to Top

MaPPs

CDER's Manual of Policies and Procedures (MaPPs).   These documents 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:

  • 4200.1 Adobe Acrobat Symbol Consulting the Controlled Substance Staff on INDs and Protocols That Use Schedule I Controlled Substances and Drugs (Issued 5/8/2003)
  • 5240.4 Submission of an IND Application to the Office of Generic Drugs (OGD). Adobe Acrobat Symbol OGD policy and procedures regarding submissions on INDs for bioequivalence studies.  These INDs are called Bio-INDs to distinguish them from clinical INDs submitted to CDER's new drug reviewing divisions.
  • 6030.1  IND Process and Review Procedures (Including Clinical Holds). Adobe Acrobat Symbol  Includes general IND review principles, policies and procedures for issuing clinical holds of INDs, and processing and responding to sponsors' complete responses to clinical holds.
  • 6030.2 Adobe Acrobat Symbol INDs: Review of Informed Consent Documents (Issued 11/13/2002)
  • 6030.4 INDs: Screening INDs. Adobe Acrobat Symbol (Issued 5/9/2001, Posted 5/14/2001).  This MsPP describes procedures for the review of multiple active moieties or formulations under the single investigative new drug application (IND) called a screening IND.
  • 6030.8 Adobe Acrobat Symbol INDs: Exception from Informed Consent Requirements for Emergency Research. (Issued 2/4/2003)

IND Forms and Instructions

Forms for use in submitting INDs include:

  • FDA 1571 PDF documentInvestigational New Drug Application
  • FDA 1572  PDF document   Statement of Investigator
  • Instructions for completing FDA forms 1571 and 1572
  • FDA Form Distributions Page PDF document includes links to:
    Certification: Financial Interest and Arrangements of Clinical Investigators
    Disclosure: Financial Interest and Arrangements of Clinical Investigators
    MedWatch: FDA Medical Product Reporting Program - Voluntary
    MedWatch: FDA Medical Products Reporting Program - Mandatory
  • For electronic form submissions, see ERSR

Back to Top

Emergency use of an Investigational Drug or Biologic

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 FDAs Office of Emergency Operations at 301-443-1240.

Targeted Product Information (TPI) Project

After a 12-month collaborative effort between FDA and the Pharmaceutical Research Manufacturers Association (PhRMA), FDA’s Office of Drug Evaluation IV (ODE IV) started a pilot test of a tool that may improve the drug development process.   This tool is the Targeted Product Information (TPI) Document.  The sponsor writes the TPI to guide the design, conduct, and analysis of clinical trials so that at the end of the development program, the sponsor will have gathered the necessary data to support the sponsor’s desired outcome -- the approval and appropriate labeling, or package insert, of the drug under development.

  • TPI Program Overview.   Includes background information, intent of the TPI document, what the TPI document is and is not, plus a summary.
  • TPI Template.   The template provides a recommended outline for a TPI with a description of suggested information for each section.

Back to Top

Related Topics

ToTop  Back to Top        Back Back to Drug Applications       


FDA/Center for Drug Evaluation and Research
Last Updated: October 26, 2004
Originator: OTCOM/DML
HTML by  SJW