This Slide explains US-FDA requirements for IND. It will answer; What is an IND ?What are the IND Phases ?What is the IND Content?When FDA Terminates an IND ?Are cGMP Required for IND ?What Studies are exempt from IND?

1. FDA REQUIREMENTS FOR IND IN USA
Dr. Suzan Davis
February 2020

2. What is an IND ?
Investigational New Drug (IND) is an application that is
submitted to US FDA by a pharmaceutical company to
obtain permission from the Agency to start human clinical
trials and ship an experimental drug across different states in
United States of America.

3. What are the Types of INDs ?
 Commercial IND is submitted by a sponsor that is usually a corporation,
with the intend to commercialize the product at a later date.
 Research IND is submitted by an Individual Investigator or research
organization that conducts the investigation for research purpose.
 Expended Access IND is submitted to allow patients to use the
investigational drug for the treatment of serious or life-threatening
conditions with no comparable alternative treatment, outside the formal
clinical trial.

4. What are the IND Phases ?
 An IND may be submitted for one or
more phases of an investigation.
 The clinical investigation of a
previously untested drug is generally
divided into the following three
phases:
 Phase 1: safety, proof of concept,
and exploratory.
 Phase 2: safety, efficacy, and
dose ranging.
 Phase 3: efficacy confirmatory,
dose ranging, and safety.

5. What is the IND Content?
 The IND needs to be
submitted in electronically
and in eCTD format.
 The IND needs to include
Module 1, Module
2,Module 3, Module 4 and
Module 5.

6. What is the IND Content?
CTD Modules Description
Module 1 –Regional Admin
 Cover letter
 Table of contents
 FDA 1571 (cover sheet), FDA 3674 (clinical trials Certification)
 Clinical supply Labels
 General Investigational Plan
 Investigator Brochure
Module 2- Summaries
 Summary of CMC
 Summary of toxicology studies
 Summary of pharmacology , Pharmacokinetic studies
 Summary of clinical studies if available
Module 3- CMC
 CMC on Drug Substance
 CMC on Drug Product
Module 4- Nonclinical Reports
 Pharmacology Toxicology Information
 Nonclinical Reports
Module 5- Clinical Studies
 Protocol
 FDA Form 1572
 Investigator CV
 Clinical reports of Previous human studies if available

7. FDA Timelines for IND Review?
 Upon receipt of an IND application, FDA will notify the sponsor of the
date it receives the application through an IND acknowledgment
letter.
 An IND application may go into effect:
 30 days after FDA receives the application, unless FDA notifies the
sponsor that the investigations described in the application are
subject to a Clinical Hold; or
 on earlier notification by FDA that the clinical investigations in the
IND may begin.

8. When FDA puts Clinical Hold on IND?
FDA can put a clinical hold on IND when:
 No CMC information is submitted in the IND
 No CMC information is incorporated by reference within
submission
 IND contains insufficient information as required under 21 CFR
312.23 to assess the risks to subjects of the proposed studies.

9. When FDA Terminates an IND ?
FDA can terminate an IND under 21 CFR 312.44 in the following
conditions:
 Lack of the requisite CMC information.
 The process of manufacturing/processing is inadequate to maintain
standards and ensure subject safety.
Note : In general FDA will not terminate an IND until after first attempting to resolve
the issues.

10. What Studies are exempt from IND?
1. Clinical studies conducted with a marketed drug are exempt from IND
requirements if they meet all the following criteria:
 The drug product is lawfully marketed in the United States.
 The investigation is not intended to support a new indication or significant change
in the labeling or in the advertising for the drug.
 The investigation does not involve a route of administration, dose, patient
population, or other factor that significantly increases the risk (or decreases the
acceptability of the risk) associated with the use of the drug product.
 The investigation is conducted in compliance with the requirements for review by
an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR
part 50).

11. What Studies are exempt from IND?
2. Bioavailability or Bioequivalence Studies in Humans if they meet all
the following criteria:
 The drug product does not contain a new chemical entity, is not
radioactively labeled, and is not cytotoxic.
 The dose (single dose or total daily dose) does not exceed the dose
specified in the labeling of the approved version of the drug product.
 The investigation is conducted in compliance with the requirements for
review by an IRB and with the requirements for informed consent
 The sponsor meets the requirements for retention of test article samples
and safety reporting .

12. Are cGMP Required for IND ?
In July 2008 the FDA issued a guidance which details the cGMP
expectations for the early stages of drug development
 Investigational drugs used in Phase 1 studies are exempt from the
cGMP requirements.
 Investigational drug used in Phase 2 or Phase 3 studies must
comply with cGMP.

13. References
 https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/exploratory-ind-studies
 https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/content-and-format-investigational-new-drug-
applications-inds-phase-1-studies-drugs-including-well
 https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/inds-phase-2-and-phase-3-studies-chemistry-
manufacturing-and-controls-information

14. Thank you
For additional information please contact us at:
Global Regulatory Partners, Inc.
400 Fifth Avenue, Suite 115, Waltham, Massachusetts, 02451, USA
Phone 781-672-4200
Email: info@globalregulatorypartners.com