Investigational New Drug (IND) Submissions for Sponsor-Investigators

IND Development Process

IND Development Process

Confused about the need to file an IND? Think your study may be exempt? Not sure where to start? You are not alone. The HUB provides information, templates and resources to guide you through the IND process.

An academic researcher may be required to submit an IND application to the FDA in order to study a marketed medical product in a new (i.e. unapproved) clinical indication.  An investigator is always required to hold an IND to study an unmarketed (i.e. unapproved) medical product.  In both cases, the products are considered "investigational" by FDA.  The vast majority of INDs on file with the FDA are for noncommercial research. 

This toolkit (adapted from The Institute of Translational Health Sciences) helps you navigate each step of the IND process by providing guidance and templates relevant to each step. The information provided focuses on INDs for studies of marketed medical products for new indications.

For additional information on submitting INDs for unmarketed medical products and/or review of your IND submission, please contact CTSI Consultation Services. Please review the latest FDA guidance for determining the need for an IND.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 17 Oct 2013

The Pre-IND Process

The Pre-IND Process

Review the five requirements below to determine if your study qualifies for exemption from an IND (21 CFR 312.2).

Still not sure? Start with the IND Decision Tool. Pay particular attention to requirement #3. The FDA Draft Guidance Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted without an IND provides more detail on a range of issues, including the process for consulting with FDA.

If you think a pre-IND meeting is warranted please contact the HUB for assistance.  Templates for a meeting request letter and pre-IND briefing packet are provided below.  In addition, please consult with your IRB to determine whether a formal letter from FDA is required to document the waiver.

Exemptions - A drug that is lawfully marketed in the United States is exempt from the requirements for an IND if all of the following apply:

  • The investigation is not intended to be reported to the FDA in support of a new indication for use or any other significant change in the labeling for the drug.
  • The investigation is not intended to support a significant change in the advertising for a prescription drug product.
  • The investigation does not involve a change in route of administration, dosage level, or patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with use of the drug product.
  • The investigation is conducted in compliance with the requirements for IRB review (21 CFR 56) and informed consent (21 CFR 50).
  • The drug may not be represented as safe or effective for the purposes for which it is under investigation, nor may it be commercially distributed or sold.

For additional information about whether or not an IND is required for a cancer therapy drug you must contact the NCI Regulatory Affairs Branch.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 6 Jun 2012

The IND Study Protocol

The IND Study Protocol

A fully developed clinical protocol is the basis for both the IRB Application and the initial IND submission

Review the IND Protocol Template for required content. A completed protocol must be included in the IND application.

Start with a protocol synopsis (page 7 and 8 of the protocol template). The protocol synopsis will be valuable if you are planning a pre-IND meeting. Compile a reference list - include all published articles and unpublished reports or manuscripts cited.

Collect a copy of each article or report listed. For approved medications, print and read the Prescribing Information.

Product information should be integrated into the protocol. In addition, your safety plan should acknowledge known safety risks from the prescribing information and incorporate relevant safety monitoring into the protocol - or show why it is not relevant to the disease under study.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 6 Jun 2012

Prepare the Initial IND Submission

Prepare the Initial IND Submission

The IND Sponsor-Investigator compiles information in three broad areas:

  • Animal Pharmacology and Toxicology Studies: Preclinical data used to assess whether the product is reasonably safe for studies in humans. For studies of marketed drugs in new indications, this section might contain data from animal models supporting the utility of the drug in the new indication.
  • Manufacturing Information: The composition, stability, and controls used for manufacturing the drug substance and the drug product. For marketed drugs, the FDA already has this information on file in the manufacturer’s Drug Master File (DMF). An Investigator-Sponsor can request a Letter of Authorization (LOA) from the manufacturer to refer to the information, although it is not required. For legally marketed drugs, the information in the product label or package insert might suffice for the manufacturing information.
  • Clinical Protocols and Investigator Brochures: A detailed clinical study protocol, and Investigator Brochure are required sections of an IND application. The Investigator Brochure is primarily needed for multi-center studies and is a summary of information needed by participating investigators to assess the safety of the investigational product. For approved medications, a copy of the Prescribing Information may be used in place of an Investigator Brochure.

The IND Sponsor-Investigator writes the IND in the format of IND Application Template. The initial IND submission should be accompanied by a cover letter, an IND Application Form - FDA 1571 (see instructions) and a Certification of Compliance - FDA 3674.

The IND Sponsor-Investigator must also submit a Statement of Investigator - FDA Form FDA 1572 (see instructions). This form is a formal contract with FDA to adhere to Informed Consent, IRB review, and general IND regulations.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 15 Aug 2013

Maintain the IND

Maintain the IND

To maintain an IND, the Sponsor-Investigator has three reporting responsibilities.  Each type of report is time-sensitive and has a specific structure.  The first two, Protocol Amendments and Safety Reports, are submitted when needed to report updated or unforeseen circumstances. The third type, the Annual Report, is submitted every year, even when no studies are in progress under the IND.  Send all submissions to the address provided in the IND Acknowledgement letter received in response to the initial submission.

IND Protocol Amendments
Once an IND is in effect, the IND Sponsor-Investigator is responsible to amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application.  An IND Protocol Amendment a cover letter and is a submission to an existing IND notifying the FDA of one or more of the following:

  • A new study protocol
  • A change in an existing study protocol
  • A new investigator

IND Annual Reports
An IND Annual Report requires a cover letter and is a brief report of the progress of studies conducted under an IND, due annually to the FDA within 60 days of the anniversary of the date that the IND went into effect.

IND Safety Reports
An IND Safety Report is expedited, written notification to the FDA of an adverse experience associated with the use of a study drug that is both serious and unexpected. “Associated with the use of the drug” is a Code of Federal Regulations term meaning “There is a reasonable possibility that the experience may have been caused by the drug.”  An  IND Safety Report  consists of a MedWatch Form and a cover letter.  It is due to the FDA within 15 calendar days of initial receipt of the SAE Report.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 26 Jun 2012

IND Templates, Education & Useful Links

IND Templates, Education & Useful Links

IND Submissions

IND Amendments

Annual Reporting

Safety Reporting

Useful Links

IND Education Resources
(courtesy of Duke Translational Medicine Institute)

IND Webcasts
This is a series of recorded segments on topics relevant to IND Best Practices for Initial Submission and Maintenance.

Is My Study IND Exempt?
This is a recorded lecture on determining when a clinical study is exempt from the IND regulations.

Drug Studies-Points to Consider for IRB Reviewers
This short lecture describes what IRB reviewers should consider when evaluating drug studies

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

Last updated 4 Dec 2014

 
File the Initial IND

File the Initial IND

All forms completed during  Initial IND Submission Preparation must be assembled into one submission packet. The forms are submitted in triplicate (the original and two photocopies) as well as one PDF of the original documents.

For an initial submission, the IND Sponsor-Investigator sends the original and two photocopies to the appropriate address via overnight courier.  Keep one copy of the submission packet as well as a photocopy of the courier airbill.

For a Drug:
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Rd.
Beltsville, Md. 20705-1266
 
For a Therapeutic Biological Product:
Food and Drug Administration
Center for Drug Evaluation and Research
Therapeutic Biological Products Document Room
5901-B Ammendale Road
Beltsville, MD 20705-1266
 

On the delivery date, track the shipment on the courier website for confirmation of delivery.  Print the delivery confirmation (select Adobe from the print menu) and file it with the PDF and third copy of the submission packet, which is kept in an IND Binder.

The FDA responds to the initial submission of a new IND with a letter, acknowledging receipt of the submission and assigning the IND number. 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. If there are no issues, the IND generally goes into effect 30 days after the Date of Receipt shown in this letter. It is advised that you obtain written confirmation (email or fax) that the FDA review has been completed and that the Study May Proceed. Please upload FDA Study May Proceed confirmation in iRIS under other study documents.

The IND Acknowledgement letter also provides the mailing address for all subsequent submissions to the IND.

Need assistance or have regulatory questions? Please contact CTSI Consultation Services

 

Last updated 11 Aug 2014