Content and Format of an Investigational New Drug
(IND) Application
I. Background Information
A. Phases of a Clinical Investigation
1. Phase 1.
2. Phase 2.
3. Phase 3.
B. General Principles of the IND Submission
C. Reference to IND or Marketing Information Previously Submitted
D. FDA Administrative Actions
1. Effective date of FDA acceptance of an IND application.
2. Clinical holds and requests for modifications.
3. FDA termination of an IND.
4. Inactive status.
II. Initial IND Application: Content and Format
A. Form FDA 1571
B. Table of Contents
C. Introductory Statement and General Investigational Plan
D. Investigator’s Brochure
1. Investigator-sponsored IND.
2. University-sponsored IND.
E. Clinical Protocol(s)
1. General principles.
2. Protocol content and format.
F. Chemistry, Manufacturing and Control (CMC) Information
1. General principles.
2. CMC content and format.
3. cGMP compliance.
G. Labeling
1. IND submission requirements.
2. Investigational drug labeling requirements.
H. Pharmacology and Toxicology Information
1. General principles.
2. Content and format.
I. Previous Human Experience with the Investigational Drug
J. Additional Information
1. Drug dependence and abuse potential.
2. Radioactive drugs.
3. Pediatric studies.
4. Other information.
K. FDA-Requested Relevant Information
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I. Background Information
A. Phases of a Clinical Investigation1
An IND application is submitted for a specific drug substance and may
incorporate multiple clinical protocols corresponding the various phases of
the evaluation of its safety and effectiveness. The clinical investigation of
a previously untested drug is typically divided into three phases. Although
in general the phases are conducted sequentially, they may overlap. The
three phases of a clinical investigation are as follows:
1. Phase 1.
Phase 1 includes the initial introduction of the investigational new drug
into humans. Phase 1 studies are typically closely monitored and may
be conducted in normal volunteer subjects or patients. These studies
are designed to determine the metabolism and pharmacologic actions
of the drug in humans, the side effects associated with increasing
doses, and, if possible, to gain early evidence on effectiveness. During
Phase 1, sufficient information about the drug’s pharmacokinetics and
pharmacological effects should be obtained to permit the design of
well-controlled, scientifically valid, Phase 2 studies. The total number
of subjects and patients included in Phase 1 studies varies with the
investigational drug, but is generally in the range of 20-80.
Phase 1 studies also include studies of structure-activity relationships
and mechanism of action in humans, as well as studies in which
investigational drugs are used as research tools to explore biological
phenomena or disease processes.
2. Phase 2.
Phase 2 includes the controlled clinical studies conducted to determine
the common short-term side effects and risks associated with the
administration of the investigational drug to patients with the disease or
condition for which the drug is intended and to evaluate the
effectiveness of the investigational drug when administered to such
patients. Phase 2 studies are typically well controlled, closely
monitored, and conducted in a relatively small number of patients;
usually no more than several hundred subjects.
3. Phase 3.
Phase 3 studies are expanded controlled and uncontrolled trials. They
are performed after preliminary evidence suggesting effectiveness of
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21 CFR Sec. 312.21
2
the investigational drug has been obtained, and are intended to gather
the additional information about effectiveness and safety that is
needed to evaluate the overall benefit-to-risk relationship of the drug
and to provide an adequate basis for product labeling. Phase 3
studies usually include from several hundred to several thousand
subjects.
B. General Principles of the IND Submission2
FDA’s primary objectives in reviewing an IND are, in all phases of the
clinical investigation, to assure the safety and rights of subjects; and, in
Phase 2 and 3 investigations, to help assure that the quality of the
respective scientific evaluation is adequate to permit an evaluation of the
drug’s effectiveness and safety. Therefore, the FDA’s review of Phase 1
submissions will focus on assessing the safety of the respective
investigation(s); whereas the FDA’s review of Phase 2 and 3 submissions
will also include an assessment of the scientific quality of the respective
investigations and the likelihood that the investigations will yield data
capable of meeting statutory standards for granting marketing approval.
The amount of information on a particular investigational drug that must be
submitted in an IND application to assure the accomplishment of the
above objectives depends upon such factors as the novelty of the drug,
the extent to which it has been studied previously, the known or suspected
risks, and the developmental phase of the drug.
The central focus of the initial IND submission should be on the general
investigational plan and the protocols for specific human studies.
Subsequent amendments to the IND that contain new or revised protocols
should build logically on previous submissions/protocols and should be
supported by additional information, including the results of animal
toxicology studies or other human studies as appropriate. Annual reports
to the IND should serve as the focus for reporting the status of the clinical
investigations being conducted under the IND and should update the
general investigational plan for the coming year.
C. Reference to IND or Marketing Information Previously Submitted3
The sponsor of an IND application is not ordinarily required to resubmit
information that was previously submitted to the FDA, but may incorporate
the information by reference. A reference to information submitted
previously must identify the file by name, reference number, volume, and
page number where the information can be found. A reference to
information submitted to the agency by a person other than the sponsor is
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3
21 CFR Sec. 312.22
21 CFR Sec. 312.23(b)
3
required to contain a written statement that authorizes the reference and
that is signed by the person who submitted the information.
D. FDA Administrative Actions4
1. Effective date of FDA acceptance of an IND application. An IND goes
into effect (a) thirty (30) days after the FDA receives the IND, unless
the FDA notifies the sponsor that the clinical investigations described
in the IND are subject to a “clinical hold”; or (b) upon earlier notification
by FDA that the clinical investigation described in the IND may begin.

FDA will notify the sponsor in writing of the date it receives the IND.

An investigator may not administer an investigational drug to
human subjects until the IND goes into effect.
2. Clinical holds and requests for modifications.5
A “clinical hold” is an order issued by the FDA to the sponsor to delay a
proposed clinical investigation or to suspend an ongoing investigation.
The clinical hold order may apply to one or more of the clinical
investigations covered under the IND.
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5

When a proposed study is placed on clinical hold, subjects may not
be given the investigational drug.

When an ongoing study is placed on clinical hold, no new subjects
may be recruited to the study or given the investigational drug;
subjects already participating in the study should be taken off the
investigational drug unless specifically permitted by the FDA to
continue to receive the drug in the interest of the subjects’ safety.

Discussion of deficiencies: Whenever the FDA concludes that
deficiencies exist in a clinical investigation that may be grounds for
the imposition of a clinical hold, the FDA will (unless subjects are
exposed to immediate and serious risk) attempt to discuss and
satisfactorily resolve the deficiencies with the sponsor before
issuing the clinical hold order.

FDA’s imposition of a clinical hold: The clinical hold order may be
made by telephone or other means of rapid communication or in
writing.
21 CFR Part 312, Subpart C
21 CFR Sec. 312.42
4
o The clinical hold order will identify the clinical investigation(s)
under the IND to which the hold applies, and will briefly explain
the basis for the action.
o Within 30 days after imposition of the clinical hold, the director
of the FDA’s division with responsibility for review of the IND will
provide the sponsor with a written explanation of the basis for
the hold.

Resumption of studies placed on clinical hold: A study placed on
clinical hold by the FDA may not resume until such time that the
sponsor has been notified by the FDA that the clinical hold has
been lifted.
o Resumption of the affected clinical study (studies) will be
authorized by the FDA when the sponsor corrects the
deficiencies previously cited or otherwise satisfies the FDA that
the study (studies) can safely proceed.
o If the sponsor of the IND that has been placed on clinical hold
requests in writing that the hold be lifted and submits a complete
response to the deficiencies identified in the clinical hold order,
FDA shall respond in writing to the sponsor within 30 calender
days of its receipt of the request and complete response.


FDA’s response will either lift or maintain the clinical hold,
and will state the reasons for such determination.

Notwithstanding the 30 calendar day response time, a
sponsor may not proceed with a study on which a clinical
hold has been imposed until the sponsor has been notified
specifically by the FDA that the hold has been lifted.
Conversion of an IND on clinical hold to inactive status: If all
clinical studies covered by an IND remain on clinical hold for 1 year
or more, the IND may be placed on inactive status by the FDA.
3. FDA termination of an IND.6
FDA may terminate an IND based on deficiencies in the IND or in the
conduct of an investigation under the IND.

6
If an IND is terminated by the FDA, the sponsor shall end all clinical
studies being conducted under the IND and shall recall or otherwise
21CFR Sec. 312.44
5
provide for the disposition of all unused supplies of the
investigational drug.

Discussion of deficiencies: Unless the FDA concludes that
continuation of clinical studies under the IND presents an
immediate and substantial danger to the health of human subjects,
a termination order shall be preceded by a proposal to terminate
and an opportunity for the sponsor to respond. FDA will, in general,
only initiate a termination action after first attempting to resolve the
respective issues informally or, when appropriate, through the
clinical hold process.

FDA’s imposition of a termination order: If the FDA proposes to
terminate an IND, it will notify the sponsor in writing and invite
correction or explanation within a period of 30 calendar days.
o On such notification, the sponsor may provide a written
explanation or correction or may request a conference with the
FDA to provide the requested explanation or correction.

If the sponsor does not respond to such notification within
the 30 calendar day period, the IND shall be terminated by
the FDA.

If the sponsor responds to such notification, but the FDA
does not accept the explanation or correction submitted,
FDA shall inform the sponsor in writing of the reason for nonacceptance and provide the sponsor with an opportunity for
a regulatory hearing before the FDA. The sponsor’s request
for a regulatory hearing before the FDA must be made within
10 days of the sponsor’s receipt of the FDA’s notification of
non-acceptance; otherwise the IND will be terminated by the
FDA.
o Immediate termination of an IND: If at any time the FDA
concludes that the initiation or continuation of clinical studies
under the IND presents an immediate and substantial danger to
the health of human subjects, FDA shall immediately, by written
notice to the sponsor, terminate the IND.

An IND immediately terminated by the FDA due to a
dangerous health consideration is subject to reinstatement
only by the director of the FDA’s Division with responsibility
for review of the IND; i.e., based on additional submissions
to the IND that eliminate such danger.
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
If an IND is immediately terminated by the FDA due to a
dangerous health consideration, FDA will afford the sponsor
an opportunity for a regulatory hearing before the FDA.
4. Inactive status.

An IND may be placed on inactive status by either the FDA or the
sponsor if (1) no subjects are entered into clinical studies
conducted under the IND for a period or 2 years or more; or (2) the
IND remains on clinical hold for 1 year or more.
o If the FDA acts on its own to place an IND on inactive status,
FDA shall first notify the sponsor in writing of this proposed
action.

Upon receipt of such notification, the sponsor shall have 30
calendar days to respond to the FDA as to why the IND
should continue to remain active.

If an IND is placed on inactive status, all investigators shall be so
notified and all stocks of the investigational drug shall be returned
to the sponsor or otherwise disposed of at the request of the
sponsor. (See Sponsor Responsibilities)

Annual reports: A sponsor is not required to submit annual reports
to an IND on inactive status.

Resumption of an IND placed on inactive status: A sponsor who
intends to resume clinical studies under an IND placed on inactive
status shall submit a Protocol Amendment containing the proposed
general investigational plan for the coming year and the respective,
appropriate clinical protocol(s).
o If the Protocol Amendment relies on information previously
submitted under the IND, the investigational plan for the coming
year shall reference such information.
o Additional information supporting the proposed investigational
plan shall be submitted in an Informational Amendment.
o Clinical studies under an IND on inactive status may only
resume (1) 30 days after FDA receives the Protocol
Amendment, unless the FDA notifies the sponsor that the
clinical studies described in the amendment are subject to a
“clinical hold”; or (2) on earlier notification by the FDA that the
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clinical studies described in the Protocol Amendment may
begin.

FDA termination of an IND on inactive status: An IND that remains
on inactive status for 5 years or more may be terminated by the
FDA.
III. Initial IND Application: Content and Format
The content and format of the IND application set forth below has been
adopted from applicable FDA regulations and guidance documents and
should be followed by the sponsor in the interest of fostering an efficient FDA
review of the submission. It is recognized that certain redundancy exists with
regard to this content and format; however such is necessary to permit
adequate review of the application by multiple disciplines within the FDA (e.g.,
pharmacology/toxicology, clinical, chemistry, microbiology). Sponsors are
expected to exercise considerable discretion, however, regarding the content
of information submitted in each section; depending on the kind of drug being
studied and the nature of the available information. The IND content and
format requirements set forth below outline the information needed for an
sponsor-investigator IND for a new molecular entity. A sponsor-investigator
who desires to use, as a research tool, or evaluate an investigational new
drug that is already the subject of an industry-sponsored IND or a drug that is
currently approved for marketing should follow the same general format, but
ordinarily may, if authorized in writing by the drug’s sponsor/manufacturer,
refer to the sponsor’s IND or marketing application in providing certain
technical information supporting the sponsor’s proposed clinical investigation.
A sponsor-investigator who desires to use, as a research tool, or evaluate an
investigational drug that is not already the subject of an industry-sponsored
IND or currently approved for marketing is ordinarily required to submit all
technical information supporting the IND; unless such information may be
referenced from the scientific literature.
An IND application for initial submission to the FDA shall include, in the
following order:7
A. A completed FORM FDA 1571.
B. Table of Contents
C. Introductory Statement and General Investigational Plan
To include:
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21 CFR Sec. 312.23(a)
8
1. A brief introductory statement giving the name of the drug and all
active ingredients; the drug’s pharmacological class; the structural
formula of the drug (if known); the formulation of the dosage form(s) to
be used; the route of administration; and the broad objectives and
planned duration of the proposed clinical investigation(s).
2. A brief summary (if applicable) of previous human experience with the
drug, with reference to other IND’s if pertinent, and to investigational or
marketing experience in other countries that may be relevant to the
safety of the proposed clinical investigations(s).
3. If the drug has been withdrawn from investigation or marketing in any
country for any reason related to safety or effectiveness, identification
of the respective country (countries) and the reasons for withdrawal.
4. A brief description of the overall plan for investigating the drug product
for the following year. The plan should include the following:

the rationale for the drug or the research study;

the indication(s) to be studied;

the general approach to be followed in evaluating the drug;

the kinds of clinical trials to be conducted in the first year following
the submission (if plans are not developed for the entire year; the
sponsor should so indicate);

the estimated number of research subjects to be given the drug in
those clinical trials; and

any risks of particular severity or seriousness anticipated on the
basis of the toxicological data in animals or prior studies in humans
with the drug or related drugs.
D. Investigator’s Brochure
An Investigator’s Brochure is not, in general, required for sponsorinvestigator IND applications.8 However, if the University’s IND/IDE
Committee has granted approval for the conduct of a multi-center
(external site) clinical investigation under a University-based, sponsorinvestigator IND application, an Investigator’s Brochure should be
developed for dissemination to each of the involved study sites and should
address the following information:
8
21 CFR Sec. 312.55
9

A brief description of the active drug substance and the drug product
formulation, including the structural formula of the active drug
substance, if known.

A summary of the pharmacological and toxicological effects of the drug
in animals and, to the extent known, in humans.

A summary of the pharmacokinetics and biological distribution of the
drug in animals and, if known, in humans.

A summary of information relating to the safety and effectiveness of
the drug in humans obtained from prior clinical studies. (Reprints of
published articles describing such studies may be appended to the
Brochure if they are anticipated to be useful.)

A description of possible risks and side effects to be anticipated on the
basis of prior experience with the drug under investigation or related
drugs, and of precautions or special monitoring to be done as part of
the investigational use of the drug.
E. Clinical Protocol(s)
There should be a separate clinical protocol for each planned clinical
study of the investigational drug product. (Protocols for clinical studies of
the investigational drug product not incorporated into the initial submission
of the IND application should be submitted as a Protocol Amendment [see
IND Amendments: Requirements and Procedures].)
1. General principles.

Phase 1 clinical studies: In general, protocols for Phase 1 studies
may be less detailed and more flexible than protocols for Phase 2
and 3 studies. Phase 1 protocols should be directed primarily at
providing an outline of the clinical study (e.g., an estimate of the
number of patients to be involved; a description of the safety
exclusions; and a description of the dosing plan including duration,
dose, or method to be used in determining the dose) and should
specify in detail only those elements of the study that are critical to
safety; such as necessary monitoring of vital signs and blood
chemistries.

Phase 2 and 3 clinical studies: For Phase 2 and 3 studies, detailed
protocols describing all aspects of the study should be submitted.
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o A protocol for a Phase 2 or 3 clinical study should be designed
in such a way that, if the sponsor anticipates that some
deviation from the study design may become necessary as the
investigation progresses, alternatives or contingencies are built
into the protocol at the outset. (E.g., a protocol for a controlled
short-term study might include a plan for an early crossover of
non-responders to alternative therapy.)
2. Protocol content and format.
A protocol is required to contain the following sections; with the specific
elements and detail of the protocol sections reflecting the above
distinctions depending on the phase of study:

A statement of the objectives and purpose of the study.

The name and address and a statement of the qualifications
(curriculum vitae or other statement of qualifications) of each
investigator; the name of each sub-investigator (e.g., health care
professional or staff member, research fellow; research
coordinator) working under the supervision of the investigator; the
name and address of the research facilities to be used; and the
name and address of each reviewing institutional review board.

The criteria for research subject selection and for exclusion of
potential research subjects, and an estimate of the number of
research subjects to be studied.

A description of the design of the study, including the kind of control
group to be used, if any, and a description of the methods to be
used to minimize bias on the part of the research subjects,
investigators, and data analysts.

The method for determining the dose(s) to be administered, the
planned maximum dosage, and the duration of individual human
subject exposure to the drug.

A description of the observations and measurements to be made to
fulfill the objectives of the protocol.

A description of the clinical procedures, laboratory tests, or other
measures to be taken to monitor the effects of the drug in human
subjects and to minimize risk.
See also Good Clinical Practice (GCP) Guidelines – Clinical Study
Protocol and Protocol Amendments
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F. Chemistry, Manufacturing, and Control (CMC) Information
The CMC section of the IND application should include (i.e., as
appropriate for the particular clinical study (studies) covered by the IND)
information describing the composition, manufacture, and control of the
investigational drug substance and the investigational drug product.
1. General principles.

Although in each phase of the clinical investigation of an
investigational drug sufficient information is required to be
submitted to assure the proper identity, quality, purity, and strength
of the drug; the amount of information needed to make that
assurance will vary with the phase of the investigation, the
proposed duration of the investigation, the dosage form, and the
amount of information otherwise available.

FDA recognizes that modifications to the method of preparation of
the investigational drug substance and dosage form (i.e., the
investigational drug product) and changes in the dosage form itself
are likely to occur as the investigation progresses. Therefore, the
emphasis in a 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.

Note that the amount of information to be submitted depends also
on the scope of the proposed clinical investigation. (E.g., although
stability data are required in all phases of the IND to demonstrate
that the new drug substance and drug product are within
acceptable chemical and physical limits for the planned duration of
the proposed clinical study; if very short-term studies are proposed,
the supporting stability data can be correspondingly limited.)

As drug development proceeds and as the scale or production is
changed from the pilot-scale production appropriate for the limited,
initial (e.g., Phase 1 and 2) clinical studies to the larger-scale
production needed for expanded (i.e., Phase 3) clinical trials, the
sponsor should submit Information Amendments (see IND
Amendments: Requirements and Procedures) to supplement the
initial information submitted on the chemistry, manufacturing, and
control processes with information appropriate to the expanded
scope of the investigation.
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2. CMC content and format.
Reflecting the distinctions described above, and based on the phase(s)
of the clinical study (studies) incorporated in the IND application, the
CMC section of the application is required to address the following:

Drug substance: A description of the active drug substance,
including its physical, chemical, or biological characteristics; the
name and address of the 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 planned clinical studies.
o Note that reference to the current edition of the United States
Pharmacopeia-National Formulary (USP-NF), if applicable, may
satisfy relevant requirements.

Drug product: A list of all components, which may include
reasonable alternatives for inactive compounds, used in the
manufacture of the investigational drug product, including both
those components intended to appear in the drug product and
those which may not appear but which are used in the
manufacturing process; where applicable, the quantitative
composition of investigational drug product, including any
reasonable variations that may be expected during the
investigational stage; the name and address of the drug product
manufacturer; a brief general description of the manufacturing and
packaging procedure as appropriate for the drug 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 drug product’s stability during
the planned clinical studies.
o Note that reference to the current edition of the United States
Pharmacopeia-National Formulary (USP-NF) may satisfy
relevant requirements.

Placebo: A brief general description of the composition,
manufacture, and control of any placebo used in the proposed
clinical study (studies).
3. cGMP compliance.
Note that strict compliance with the FDA’s current Good Manufacturing
Practice (cGMP) regulations at 21 CFR Section 211 is not required for
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investigational drug products being used or evaluated in Phase 1
clinical studies. Rather, for Phase 1 clinical studies, the FDA will hold
the sponsor of the IND application accountable for manufacturing and
testing the investigational drug in accordance with the respective
procedures submitted in the IND application. The manufacture of
investigational drug products for use in Phase 2 and 3 clinical studies
is, however, subject to full compliance with the FDA’s cGMP
regulations at 21 CFR Part 211. A statement addressing whether or
not the investigational drug product is being manufactured in
compliance with the FDA’s cGMP regulations should be included in the
CMC section of the IND application.
G. Labeling
1. IND submission requirements.
The IND application shall include a copy of all labels that will be
assigned to the investigational drug product and, if applicable, all
labeling to be provided to each investigator.
2. Investigational drug labeling requirements.9

The immediate package of an investigational new drug intended for
human use shall be labeled with the statement “Caution: New Drug
– Limited by Federal (or United States) law to investigational use.”

The label or labeling of an investigational new drug shall not bear
any statement that is false or misleading and shall not represent
that the investigational new drug is safe or effective for the
purposes for which it is being investigated.
H. Pharmacology and Toxicology Information
This section of the IND application should include adequate information
about non-clinical (i.e., performed in laboratory animals or in vitro)
pharmacological and toxicological studies of the investigational drug; on
the basis of which the sponsor has concluded that it is reasonably safe to
conduct the proposed clinical study (studies) of the investigational drug
product.
1. General principles.

9
The kind, duration, and scope of animal and other tests required to
adequately support an IND application will vary with the duration
21 CFR Sec. 312.6
14
and nature of the proposed clinical studies(s). (Guidance
documents are available from the FDA [see FDA Guidance
Documents for Regulated Industry] that describe the ways in which
these requirements may be met for various drug products.)
o As drug development proceeds, the sponsor is required to
submit Informational Amendments (see IND Amendments:
Requirements and Procedures), as appropriate, with additional
non-clinical information pertinent to the safety of the
investigational drug product.
2. Content and format.

Qualifications of data reviewer(s): Include the identification and
qualifications of the individual(s) who evaluated the results of the
animal or in-vitro pharmacology/toxicology studies and concluded
that it is reasonably safe to begin the proposed clinical
investigation(s) of the investigational drug; and a statement of
where the respective records are available for inspection.

Pharmacology and drug disposition: Include a section describing
the pharmacological effects and mechanism(s) of action of the
investigational drug in animals, and information on the absorption,
distribution, metabolism, and excretion of the drug, if known.

Toxicology:
o Provide an integrated summary of the toxicological effects of the
investigational drug as observed in the animal studies and in
vitro. Depending on the nature of the drug and the phase of the
investigation, the summary is to include the results of acute,
subacute, and chronic toxicity tests; tests of the drug’s effects
on reproduction and the developing fetus; any special toxicity
test related to the drug’s particular mode of administration or
conditions of use (e.g., inhalation, dermal, or ocular toxicology);
and any in vitro studies intended to evaluate drug toxicity.
o For each non-clinical toxicology study that is intended primarily
to support the safety of the proposed clinical investigation,
provide a full tabulation of the respective data suitable for a
detailed review.
o For each non-clinical laboratory study subject to compliance
with the FDA’s Good Laboratory Practice (GLP) regulations (21
15
CFR Part 58)10, provide a statement indicating that the study
was conducted in compliance with these regulations.
Alternately, specify that the non-clinical study was not
conducted in compliance with the FDA’s GLP regulations and
describe, in detail, all differences between the practices actually
used and those required in the GLP regulations.
I. Previous Human Experience with the Investigational Drug
Include a summary of previous human experience with the investigational
drug, if any, known to the sponsor. This summary is required to include
the following information:
1. If the investigational drug has been investigated in humans or
marketed previously, either in the United States or other countries,
provide detailed information about such experience that is relevant to
the safety of the proposed clinical investigation(s) or the investigation’s
rationale. If the drug has been the subject of controlled clinical trials,
detailed information on such trials that is relevant to an assessment of
the drug’s effectiveness for the proposed investigational use(s) should
also be provided. Any published material that is relevant to the safety
of the proposed clinical investigation or to an assessment of the drug’s
effectiveness for its proposed investigational use should be provided in
full. Published material that is less directly relevant may be supplied
by a bibliography.
2. If the investigational drug product is a combination of drugs previously
investigated or marketed, the information required under this section
should be provided for each active drug component. However, if any
component in such combination is subject to an approved marketing
application or is otherwise lawfully marketed in the United States, the
sponsor is not required to submit published material concerning that
active drug component unless such material relates directly to the
proposed investigational use (including publications relevant to
component-component interactions).
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The FDA’s GLP regulations are applicable to non-clinical laboratory studies that support or are
intended to support applications for research (e.g., IND applications) or marketing permits for
products regulated by the FDA. Non-clinical laboratory studies are defined within these
regulations as:
“in vivo or in vitro experiments in which test articles are studied prospectively in test systems
under laboratory conditions to determine their safety. The term does not include studies
utilizing human subjects or clinical studies or field trials in animals. The term does not include
basic exploratory studies carried out to determine whether a test article has any potential
utility or to determine physical or chemical characteristics of a test article.”
16
3. If the drug has been marketed outside the United States, incorporate a
listing of the countries in which the drug has been marketed and, if
applicable, identify any of these countries in which the drug has been
withdrawn from marketing for reasons potentially related to safety or
effectiveness.
J. Additional Information
For certain IND applications, information related to special topics, as
described below, may be required. Such information, if applicable, should
be incorporated under this section of the IND.
1. Drug dependence and abuse potential. If the investigational drug is a
psychotropic substance or otherwise has abuse potential, describe
relevant clinical studies and experience and/or relevant studies in test
animals.
2. Radioactive drugs. If the investigational drug is a radioactive drug,
provide sufficient data from animal or human studies to allow a
reasonable calculation of radiation-absorbed dose estimates to the
whole body and critical organs of human subjects. Phase 1 studies of
radioactive drugs must include a clinical investigation directed at
obtaining sufficient human data for direct human radiation dosimetry
calculations.
3. Pediatric studies. Incorporate, if applicable, plans for assessing
pediatric safety and effectiveness of the investigational drug.
4. Other information. Include, if applicable, a brief statement addressing
any other information that would assist an evaluation of the proposed
clinical investigations of the investigational drug with respect to their
safety, or their design and respective potential as controlled clinical
trials to support marketing of the drug.
K. FDA-Requested Relevant Information
If requested by the FDA (e.g., FDA comments associated with a Pre-IND
meeting/assessment), include any other relevant information needed for
review of the IND application.
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