Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore

Tools

Investigational New Drug (IND) Submissions for Sponsor-Investigators

IND Development Process

Do you have questions about the need to file an IND? Do you think your study may be exempt? Not sure where to start? You are not alone. The OCT IND Toolkit (adapted from The Institute of Translational Health Sciences) 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 or unapproved clinical indication. An investigator is always required to hold an IND to study an un-marketed or 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.

The Pre-IND Process

Review the requirements below to determine if your study qualifies for exemption from an IND.

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 appropriate office listed below:

For DRUG PRODUCTS contact:
Drug Information Branch (HFD-210)
Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane Rockville, Maryland 20857
301-827-4573

For a BIOLOGICAL BLOOD product, contact:
Office of Blood Research and Review (HFM-300)
Center for Biologics Evaluation and Research
Food and Drug Administration
1401 Rockville Pike Rockville, Maryland 20852
301-827-3518

For a BIOLOGICAL VACCINE product, contact:
Office of Vaccines Research and Review (HFM-400)
Food and Drug Administration
8800 Rockville Pike Bethesda, Maryland 20892-0001
301-827-0648

For a BIOLOGICAL THERAPEUTIC product, contact:
Office of Therapeutics Research and Review (HFM-500)
Food and Drug Administration
1451 Rockville Pike Rockville, Maryland 20852-1420
301-594-2860

For a MEDICAL DEVICE product, contact:
Program Operations Staff (HFZ-403) Office of Device Evaluation
Center for Devices and Radiological Health
Food and Drug Administration
9200 Corporate Blvd. Rockville, Maryland 20850
301-594-1190

If you still feel uncertain about whether your study requires an IND, start with the IND Determination Checklist. Pay particular attention to requirement #3. The FDA 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 (FDA Guidance Determination.)

If you've determined that a pre-IND meeting is needed, templates for a meeting request letter and pre-IND briefing packet are provided below. In addition, please consult with the IRB to determine whether a formal letter from FDA is required to document the waiver.

The IND Study Protocol

A comprehensive clinical protocol is an essential part of the initial IND submission

Review theTemplate Drug Protocol for required content. A complete drug protocol must be included in the IND application.

Start with a protocol synopsis. 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.

Preparing 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 The Template IND Application. The initial IND submission should be accompanied by an Initial IND Submission Cover Letter, a Form1571 (1571 Instructions), and a Certification Form 3674.

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

Filing the Initial IND

All forms completed during the initial IND submission 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 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.

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

Maintaining 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. A Template Protocol Amendment and a Template Cover Letter Protocol Amendment for New InvestigatorsTemplate Change in Protocol Cover Letter,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

Template IND Annual Report requires a Template IND Annual Report Cover 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

Template 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." AnIND Safety Report consists of a Medwatch FDA Form and a Template IND Safety Report Cover Letter. It is due to the FDA within 15 calendar days of initial receipt of the Serious Adverse Event Report.

 


Merge CTMS

The Office of Clinical Trials (OCT) uses Merge CTMS, a clinical trials internet based management system used to track and account the work of trials that are administered.

This allows our office the ability to:

  • Record study information
  • Store and organize electronic documents
  • Schedule and track patient appointments
  • Build budgets
  • Manage financials
  • Manage Invoicing and collections
  • Reconcile charges and payments
  • Customize reports

Study coordinators will use the software to help manage their trials. Minimal patient information will be used to monitor visit completions and study accruals.

 


 

 

Greenphire ClinCard

OCT has arranged for payments due to study subjects for travel, meals, and their study participation to be handled on the day of their visit, with a technology solution that enables the subject to be compensated at the time of his/her visit.

The ClinCard System is a web-based technology designed to comply with all applicable regulations. It allows PIs to deliver subject payments (stipends, travel reimbursements, and other ad-hoc payments) in a controlled and automated manner in compliance with industry regulation and in accordance with the specific requirements of each study. This automated system similar to a debit card, enables prompt patient compensation for his/her study visit.

This system should:

  • Reduce paperwork and processing of dispensed funds
  • Increase subject retention & compliance
  • Improve patient satisfaction
 
 
 

Resource

Walk-In Biostatistics Consultation service available on both campuses: East campus and West campus 
 
 
 

Brochures and Guides

 
We have a number of brochures and guides available for your use.
 
 
 
 
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