This document provides information about Investigational New Drug (IND) applications submitted to the FDA to request permission to study an unapproved drug in clinical trials. It discusses the types of INDs (investigational use, emergency use, treatment use), contents required in an IND submission, and circumstances where an IND is or is not required. The key purposes of an IND are to provide safety data from animal studies to begin human trials and to describe the initial proposed clinical study for FDA review before starting research.

1. INVESTIGATIONAL
NEW DRUG
APPLICATION
Venugopal N

2. IND Application
• Investigational New Drug Application.
• It is a submission to FDA requesting permission to initiate the study
of New drug product in humans.
• It is the result of successful preclinical development program.
• IND is a vehicle through which a sponsor advances to the next stage
of drug development known as Clinical Trials ( Human trials).
Three IND types:
1. Investigational use
2. Emergency Use
3. Treatment use
Two IND categories:
• Commercial
• Research (non-commercial)

3. • The IND allows you to legally ship an unapproved drug or
import the new drug from a foreign country.
• In reality the IND is much more than a legal tool allowing a
company to ship a drug.
• The IND application allows a company to initiate and conduct
clinical studies of their new drug product.
• The IND application provides the FDA with the data necessary
to decide whether the new drug and the proposed clinical trial
pose a reasonable risk to the human subjects participating in
the study.

4. Purpose
• Notifies regulators of intent to begin clinical studies in US.
• Provides preclinical data indicating that the drug is reasonably
safe to adminster to humans.
• Provides information about manufacturing process and
chemistry background
• Describes the initial clinical study being proposed
• Provides assurance that an Institutional Review Board will
approve the study before it begins

5. The investigators must sign commitments to
• Conduct the clinical study in accordance with the IRB approved
protocol
• Personally conduct or supervise the conduct of the
investigation
• Inform potential subjects that the drugs are being used for
investigational purpose only.
• Report to the sponsor adverse events that occur in the course of
the investigation.

6. IND required if
To answer if an IND is needed, one needs to ask following three
questions;
• Is it a drug?
• Is it being used in a clinical investigation?
• Does it meet the IND exemption criteria?
– Marketed under NDA/BLA, approved indication, no
significant change in advertising, no new route of
administration, new patient population

7. IND applicable for
• An IND is required any time you want to conduct a clinical trial
of an unapproved drug in the U.S.
• An IND would be required to conduct a clinical trial if the drug
is:
– A new chemical entity
– Not approved for the indication under investigation
– In a new dosage form
– Being administered at a new dosage level
– In combination with another drug and the combination is
not approved

8. IND not applicable for
An IND is not required to conduct a study if the drug:
• Is not intended for human subjects, but is intended for in vitro testing or
laboratory research animals (nonclinical studies)
• Is an approved drug and the study is within its approved indication for use.
The regulations also exempt studies of approved drugs if all of the following
criteria are satisfied:
• The study will not be reported to the FDA in support of a new indication or
other change in labeling or advertising for the product.
• The study will not utilize a route of administration, dose level, or patient
population that increases the risks associated with the use of the drug.
• The studies are to be conducted in compliance with IRB and informed
consent regulations.
• The studies will not be used to promote unapproved indications.

9. Terminologies
 IND Amendment: A submission to the IND file that adds new
or revised information to the file.
 IND Safety Report: An expedited report to the FDA and all
participating investigators of a serious and unexpected adverse
experience associated with use of the drug or findings from
nonclinical studies that suggest a risk to human subjects.
 IND Annual Report: A brief report to the FDA of the progress
of the clinical investigations. It is submitted each year within 60
days of the anniversary date that the IND went into effect.

10. Terminologies
• Institutional Review Board (IRB): a board or committee
formally designated by an institution to review and approve the
initiation of biomedical research involving human subjects. The
primary purpose of the IRB is to protect the rights and welfare
of human subjects.
• CMC: Stands for chemistry, manufacturing, and controls,
describing the chemical structure and chemical properties of
the compound, the composition, manufacturing process and
control of the raw materials, drug substance, and drug product
that ensure the identity, quality, purity, and potency of the drug
product.

11. 1. Investigational use
This is submitted by the physician responsible for initiating
and investigating. The same physician will manage the
administration and/or dispensing of the investigational drug.
This type of application is typically requested for the study of
an unapproved drug, or an approved drug for use of the drug
in an unlicensed indication, or a different patient population.

12. 312.23 IND Content & Format
1. Cover Sheet (FORM FDA 1571).
2. Table of Contents.
3. Introductory Statement & General Investigational Plan.
4. Reserved
5. Investigator’s Brochure.
6. Clinical Protocols.
7. Chemistry, Manufacturing and Control Information.
8. Pharmacology and Toxicology information.
9. Previous human experience with investigational drug.
10. Other relevant information like no. of IND submissions, No. of
copies to be submitted (1+2).
11. Protocol amendments, any changes in the protocol.

13. Pre-IND Meeting
• A written request by sponsor to FDA
• Resolve questions and issues raised during preparation of IND.
• FDA aid in providing solution for scientific problems.
• Like design of animal studies, scope and design of initial study
in humans.
• Meeting may be face-to-face or telephonic.

14. 1. Cover Sheet
• FORM 1571
• For initial IND, IND amendment, IND safety report, IND annual
report.
• Basic information about the submission: name of the sponsor,
IND number, name of the drug, type of submission, serial
number, and the contents of the application.
• When signing the 1571, the sponsor is also making three
important commitments to the FDA. These are significant
commitments and the sponsor should be aware that signing the
1571 is more than a formality and that making a willfully false
statement on the 1571 is a criminal offense.

15. • The sponsor is committing not to initiate the clinical study until
30 days after the FDA receives the IND, unless otherwise
notified by the FDA, and not to begin or continue clinical studies
covered by the IND if they are placed on clinical hold.
• The sponsor is committing to ensure that an IRB will be
responsible for initial and continuing review and approval of
each study in the proposed clinical investigation.
• The sponsor is committing to conduct the investigation in
accordance with all other applicable regulatory requirements.

16. 2. TOC
• This should be a comprehensive listing of the contents of the
IND broken down by volume and page number.
• The TOC should include all required sections, appendices,
attachments, reports, and other reference material.

17. 3. Introductory Statement and General
Investigational Plan
• Brief, three- to four-page overview of the investigational drug
and the sponsor’s investigational plan for the following year.
• Name of drug, all active ingredients, drug pharmacological class,
structure, formulation to be used, dosage, duration and
objective of study.
• Previous human experience with the drug
• Investigational plan – rationale for research, indication,
evaluation, types of study design, no. of subjects, risks and
benefits, toxicology data in animals or prior human study.

18. 5. Investigator’s Brochure
• Brief description of Drug Substance and Formulation
• Summary of pharmacological and toxicological effects
• PK and biological disposition of drug
• Safety and effectiveness data in humans, if any
• Possible risks and side effects,

19. 6. Protocols
• A statement of the objectives and purpose of the study.
• The name and address and a statement of the qualifications of each
investigator, the name and address of the research facilities to be used; and
the name and address of each reviewing Institutional Review Board.
• Inclusion and exclusion criteria for subjects.
• A description of the design of the study, and a description of methods to be
used to minimize bias on the part of subjects, investigators, and analysts.
• Method for determining the dose(s) to be administered, planned maximum
dosage, and the duration of individual patient exposure to the drug.
• Observations and measurements, made to fulfill the objectives of the study.
• Clinical procedures, laboratory tests, taken to monitor the effects of the drug
in human subjects and to minimize risk.

20. 7. CMC Information
• Composition, manufacture, and control of the drug substance
and the drug product.
• An initial phase 1 submission should generally be placed on the
identification and control of the raw materials and the new
drug substance.
• Final specifications for the drug substance and drug product are
not expected until the end of the investigational process.
• The amount of information to be submitted depends upon the
scope of the proposed clinical investigation.

21. Drug substance.
• A description of the drug substance, including its physical,
chemical, or biological characteristics;
• The name and address of its manufacturer;
• The general method of preparation of the drug substance; the
acceptable limits and analytical methods used to assure the
identity, strength, quality, and purity of the drug substance; and
• Information sufficient to support stability of the drug substance
during the toxicological studies and the planned clinical studies.
 A brief general description of the composition, manufacture,
and control of any placebo used in a controlled clinical trial.
 Labeling.
 Environmental analysis requirements.

22. Drug product.
• A list of all components, which may include reasonable
alternatives for inactive compounds, used in the manufacture of
the investigational drug product,
• The quantitative composition of the investigational drug
product,
• The name and address of the drug product manufacturer;
• A brief general description of the manufacturing and packaging
procedure as appropriate for the product;
• The acceptable limits and analytical methods used to assure the
identity, strength, quality, and purity of the drug product; and
• Information sufficient to assure the product's stability during
the planned clinical studies.

23. 8. Pharmacology and Toxicology
• Adequate information about pharmacological and toxicological
studies of the drug involving laboratory animals or in vitro, on
the basis of which the sponsor has concluded that it is
reasonably safe to conduct the proposed clinical investigations.
• Pharmacology and drug disposition: A section describing the
pharmacological effects and mechanism(s) of action of the drug
in animals, and information on the ADME of the drug, if known.
• Toxicological test results of acute, sub-acute, and chronic
toxicity tests; tests of the drug's effects on reproduction and the
developing fetus;

24. 9. Previous Human Experience
Previous human experience with the investigational drug: A
summary of previous human experience known to the applicant, if
any, with the investigational drug.
10. Additional information.
• Drug dependence and abuse potential.
• Radioactive drugs
• Pediatric studies
• Other information; that would aid the proposed clinical
investigation

25. 11. Relevant Information
• Information previously submitted; may incorporate the
information by reference. A reference to information submitted
previously.
• Material in a foreign language: The sponsor shall submit an
accurate and complete English translation of each part of the
IND that is not in English.
• Number of copies: The sponsor shall submit an original and
two copies of all submissions to the IND file, including the
original submission and all amendments and reports.
• Numbering of IND submissions.
• Identification of exception from informed consent.

27. FORMS
• FORM 1571
• https://www.fda.gov/media/116608/download
• FORM 1572
• https://www.fda.gov/media/71816/download

28. • A commercial IND is one for which the sponsor (usually a
corporate entity) intends to commercialize the product by
eventually submitting a marketing application. In this case, the
sponsor should select “Commercial IND” on FDA Form 1571
Field 6B. FDA may also designate an IND as commercial if it is
clear that the sponsor intends for the product to be
commercialized at a later date.
• In comparison, a research IND (also called a non-commercial
IND) is one for which the sponsor (generally an individual
investigator, academic institution or non-profit entity) does not
intend to later commercialize the product. These studies are
strictly for research, are usually shorter in duration and may
result in publications in peer-reviewed journals.

30. 2. Emergency use
An emergency use IND enables the regulator (FDA) to authorize the use of
an investigational drug in an urgent situation, without the obligation to
submit and IND.
This type of application is used for patients who do not meet existing
clinical study criteria, or in situations where an approved clinical protocol
doesn’t actually exist.
• When a physician would like to submit an Investigational New Drug
application (IND) to obtain an unapproved drug for an individual patient,
he or she should first ensure that the manufacturer of the unapproved
drug is willing to provide the drug.
• If the manufacturer agrees to provide the drug, the physician should
submit an IND to the appropriate review division.
• In an emergency situation, the request to use the drug may be made via
telephone or other rapid means of communication, and authorization to
ship and use the drug may be given by the FDA official over the
telephone.

31. 3. Treatment Use
 The purpose of this section is to facilitate the availability of
promising new drugs to desperately ill patients as early in the
drug development process as possible, before general
marketing begins.
 In the case of an immediately life-threatening disease, a drug
may be made available for treatment use, when no other
alterative treatment is available, under this section earlier than
Phase 3, but ordinarily not earlier than Phase 2.
 The “treatment use” of a drug includes the use of a drug for
diagnostic purpose.

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