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IND Application - [Date]
[Sponsor-Investigator Name]
Investigational New Drug Application
Regulatory Sponsor:
Funding Sponsor:
Study Product:
Protocol Number:
Date:
Provide name of Sponsor-Investigator, department name,
address, and phone number during working hours
Provide name of primary funding institution, address, and
phone number during working hours
Provide study drug name - generic, followed by trade
name(s), if applicable
Provide COMIRB protocol number if available
Provide date submitted to FDA
Confidential
IND Application - [Date]
[Sponsor-Investigator Name]
SECTION 1.
-
FORM FDA 1571 & FORM FDA 3674
Insert the completed Form 1571 and Form 3674 as Section 1 after this page
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SECTION 2.
Section
TABLE OF CONTENTS
Page
SECTION 1.
FORM FDA 1571 & FORM FDA 3674.................................................................................. 2
SECTION 2.
TABLE OF CONTENTS ....................................................................................................... 3
SECTION 3.
INTRODUCTORY STATEMENT AND GENERAL INVESTIGATIONAL PLAN .............................. 4
3.1 INTRODUCTORY STATEMENT .........................................................................................................................4
3.2 GENERAL INVESTIGATIONAL PLAN ..................................................................................................................4
SECTION 4.
INVESTIGATOR’S BROCHURE (IB) ...................................................................................... 5
SECTION 5.
PROTOCOL ....................................................................................................................... 7
5.1 STUDY PROTOCOL .......................................................................................................................................8
5.1.1
Consent Form .........................................................................................................................10
5.2. INVESTIGATOR AND FACILITIES INFORMATION................................................................................................11
5.2.1 Principal Investigator ....................................................................................................................11
5.2.2 Form FDA 1572 .............................................................................................................................12
5.2.3 Principal Investigator Curriculum Vitae ........................................................................................13
5.2.4 Co-Investigator Credentials ..........................................................................................................14
5.3 COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD (COMIRB) INFORMATION ................................................15
SECTION 6.
CHEMISTRY, MANUFACTURING, AND CONTROL DATA ................................................... 16
6.1 LETTER OF AUTHORIZATION TO CROSS-REFERENCE ..........................................................................................17
6.2 RESPONSE TO GENE THERAPY LETTER ...........................................................................................................17
6.3 PRODUCT SUBSTANCE/COMPONENTS...........................................................................................................17
6.4 FINAL PRODUCT .......................................................................................................................................17
6.5. PLACEBO PRODUCT ..................................................................................................................................17
6.6. LABELING ...............................................................................................................................................17
6.7 ENVIRONMENTAL EXEMPTION CLAIM...........................................................................................................18
SECTION 7.
PHARMACOLOGY AND TOXICOLOGY DATA .................................................................... 19
7.1 PHARMACOLOGY ......................................................................................................................................19
7.2 SAFETY PHARMACOLOGY............................................................................................................................19
7.3 PHARMACOKINETICS .................................................................................................................................20
7.4 PHARMACOLOGY SUMMARY .......................................................................................................................20
7.5 PHARMACOLOGY CONCLUSIONS ..................................................................................................................20
SECTION 8.
PREVIOUS HUMAN EXPERIENCE ..................................................................................... 21
8.1 MARKETED EXPERIENCE .............................................................................................................................21
8.2 CLINICAL RESEARCH EXPERIENCE .................................................................................................................21
8.3 OFF-LABEL EXPERIENCE .............................................................................................................................21
SECTION 9.
ADDITIONAL INFORMATION ........................................................................................... 22
9.1 LETTER OF AUTHORIZATION TO CROSS-REFERENCE ..........................................................................................22
9.2 ADDITIONAL INFORMATION ........................................................................................................................23
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SECTION 3. INTRODUCTORY STATEMENT AND GENERAL
INVESTIGATIONAL PLAN
Instructions and Guidance:
- The information in this section should place the developmental plan for the investigational agent
into perspective and allow FDA to anticipate your needs.
- This section should average 2-3 pages.
- Sponsor-Investigators may provide information regarding the introductory statement and
investigational plan in the cover letter.
- Remember to delete all instructions and guidance from the submitted application.
3.1 Introductory Statement
Provide a brief summary of the objectives of the research plan(s) submitted in this IND application. This
should include a brief discussion of the disease state to be assessed.
[For studies referencing another IND and/or marketed products:]
Provide a brief statement that includes the name of the drug, and the name and address of the
manufacturer. The statement should contain a reference to the package insert or Letter of Authorization
to cross-reference another IND in order to address the requirements to identify the drug, its active
ingredients, structural formula and formulation.
Include a brief summary of the route of administration and planned exposure (e.g., duration of study drug
administration). If it applies, include a statement that the drug will be used in the same dose, duration,
route of administration as described in the labeling.
Note: Append the package insert in section 4 (Investigator’s Brochure) if applicable. Append the Letter of
Authorization to cross-reference in section 9 (Additional Information).
[For studies not using a cross-reference:]
Provide a brief introductory statement including the drug name, all active ingredients), pharmacological
class, structural formula (if known), formulation and dose, route of administration, and planned exposure
(e.g., duration of study drug administration).
Provide a high level summary of preclinical data to date including mechanism of action, efficacy and
safety. Content should be a brief synopsis of section 7 (Pharmacology and Toxicology Data).
Provide a high level summary of prior human experience with the investigational drug. Content should be a
brief synopsis of section 8 (Previous Human Experience). Include a statement about whether the drug has
been withdrawn from investigation or marketing in any country for reason related to safety or efficacy.
Cite the reason for the withdrawal.
3.2 General Investigational Plan
Discuss the rationale for the use of the drug and the specific study (ies).
Include the indication(s) to be studied, overall objectives, study design, estimated enrollment in the trial,
treatment plan, and anticipated risks based on preclinical and clinical experiences with the drug.
Note: Indicate whether research plans are developed for the entire year.
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INVESTIGATOR’S BROCHURE (IB)
SECTION 4.
Instructions and Guidance:
- Sponsor-Investigators are not required to submit an Investigator’s Brochure for a single center
study. An Investigator’s Brochure is required for multi-center studies.
A cross-reference letter or package insert may be submitted in lieu of required information for the
Investigator’s Brochure.
- The package insert may be found in the Physician’s Desk Reference, the FDA website, or the United
States Pharmacopoeia – National Formulary.
Remember to delete all instructions and guidance from the submitted application.
[For studies limited to UCD:]
Include a statement that the IND meets the requirements for a Sponsor-Investigator single center study,
and that under the provisions of 21 CFR 312.55, an Investigator’s Brochure is not required.
[For studies referencing another IND and/or marketed products:]
Provide a brief statement that references the package insert or Letter of Authorization to cross-reference
another IND in order to address the requirements of an Investigator’s Brochure.
Notes: Append a copy of the package insert behind this page. Append the Letter of Authorization to crossreference in section 9 (Additional Information).
[For multi-center studies not using a cross-reference:]
Provide an Investigator’s Brochure. The outline below embodies the elements of an Investigator’s Brochure
according to Good Clinical Practice. For detailed guidance related to content of the sub-sections, refer to
the ICH Guidance for Good Clinical Practice. (See http://www.ich.org - Efficacy Guidelines – E6.)
4.1
Title Page
4.2
Table of Contents
4.3
Summary
4.4
Introduction
4.5
Physical, Chemical, and Pharmaceutical Properties and Formulation
4.6
Nonclinical Studies
4.7
4.6.1
Non-Clinical Pharmacology
4.6.2
Pharmacokinetics and Product Metabolism in Animals
4.6.3
Toxicology
Effects in Humans
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4.7.1
Pharmacokinetics and Product Metabolism in Humans
4.7.2
Safety and efficacy
4.7.3
Marketing Experience
4.8
Summary of Data and Guidance for the Investigator
4.9
References
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SECTION 5.
PROTOCOL
Instructions and Guidance:
- A separate title page should be included for each section.
- The study protocol should use the standard UCD protocol format.
- Remember to delete all instructions and guidance from the submitted application.
Section
Page
5.1
Study Protocol
5.1.1 Consent Form
5.2
Investigator and Facilities Information
5.2.1
Principal Investigator
5.2.2
Form FDA 1572
5.2.3
Principal Investigator Curriculum Vitae
5.2.4
Co-investigator Credentials
5.3
Institutional Review Board Information
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Instructions and Guidance:
- List all protocols by title on this face sheet in the order they are attached.
- Include copies of all protocols to be conducted under this IND application.
- Remember to delete all instructions and guidance from the submitted application.
5.1 Study Protocol
Insert Protocol(s) on next page.
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Instructions and Guidance:
- Insert the study protocol(s) at this point.
- Phase 1 studies should provide an outline of the investigation including a statement of the
objectives and purpose of the investigation, an estimate of subjects to be studied, a description of
safety exclusions, a description of dosing plan (duration, dose, method used to determine dose),
measures to ensure and evaluate subject safety (e.g., performance of blood chemistries, and
toxicity-based stopping or dose adjustment rules).
- Phase 2 and 3 protocols should include alternative plans to address anticipated deviations (i.e. early
crossover of non-responders to alternative therapy).
- Remember to delete all instructions and guidance from the submitted application.
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[Sponsor-Investigator Name]
Instructions and Guidance:
- List protocol title(s) for which consent forms are attached. List in the order they are attached.
- Include copies of all consent forms for protocols noted in the protocol section.
- For gene therapy studies, the gene therapy component of the treatment and any associated risks to
the subject should be clearly identified in the consent form.
- Remember to delete all instructions and guidance from the submitted application.
5.1.1
Consent Form
Insert Protocol Consent Form(s) on next page.
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[Sponsor-Investigator Name]
Instructions and Guidance:
- Remember to delete all instructions and guidance from the submitted application.
5.2. Investigator and Facilities Information
5.2.1 Principal Investigator
The principal investigator for the protocol entitled “insert protocol name” is [name of PI].
His/Her office is located at:
University of Colorado Denver Anschutz Medical Campus
Department of supply correct department name
Street Address, Building and room #
Aurora, CO 80045
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Instructions and Guidance:
- The current version of this form may be downloaded from the FDA web site at:
http://www.fda.gov/opacom/morechoices/fdaforms/cder.html
- The names of each co-investigator, research fellow, resident, or other clinical staff working under
the supervision of the Sponsor-Investigator should be included in Item 6 of the Form 1572.
- The Sponsor-Investigator signs the Form 1572.
- Remember to delete all instructions and guidance from the submitted application.
5.2.2 Form FDA 1572
Insert Form 1572 on next page.
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Instructions and Guidance:
- The Principal Investigator should sign and date the CV in the upper right corner.
- Remember to delete all instructions and guidance from the submitted application.
5.2.3 Principal Investigator Curriculum Vitae
Insert CV on next page.
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Instructions and Guidance:
- Each co-investigator should sign and date the respective biosketch or CV in the upper right corner.
- Remember to delete all instructions and guidance from the submitted application.
5.2.4 Co-Investigator Credentials
Insert co-investigator credentials (i.e., biosketch or CV) on the next page.
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Instructions and Guidance:
- Indicate if COMIRB approval is pending.
- For multi-center studies (more than one IRB of record), indicate the IRB approval status for each
research institution and provide the name and address of the corresponding IRB.
- Remember to delete all instructions and guidance from the submitted application.
5.3 Colorado Multiple Institutional Review Board (COMIRB) Information
The protocol entitled “[insert protocol name]” select the appropriate text
has not been submitted to the local Institutional Review Board. The Certificate of Approval will be
forwarded to FDA upon receipt.
Or
has been submitted to the local Institutional Review Board. IRB approval is pending. The Certificate
of Approval will be forwarded to FDA upon receipt.
The protocol [select best response: will be or was] reviewed by:
Colorado Multiple Institutional Review Board
13007 E. 17th Place
Aurora, CO 80045
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[Sponsor-Investigator Name]
SECTION 6.
CHEMISTRY, MANUFACTURING, AND CONTROL DATA
Instructions and Guidance:
The information in this section should assure the proper identification, quality, purity, and strength
of the investigational drug and provide information to evaluate drug safety.
A cross-reference letter or package insert may be submitted in lieu of required information on
chemistry, manufacturing, and control data.
- The package insert may be found in the Physician’s Desk Reference, the FDA website, or the United
States Pharmacopoeia – National Formulary.
- If the proposed dose, route, frequency of dosing and duration of therapy do not exceed the
approved labeled dosing regimen, the investigator-sponsor may provide the product’s labeling
information and state in the non-clinical section of the application that they believe their IND
application may rely on the previous FDA’s acceptance of the CMC and/or Pharmacology and
Toxicology information related to the approved marketed drug intended for this investigation.
- Remember to delete all instructions and guidance from the submitted application.
- Delete any sub-section if not applicable.
Section
6.1
6.2
6.3
6.4
6.5
6.6
6.7
Page
Letter of Authorization to Cross-Reference (if applicable)
Response to Gene Therapy Letter (if applicable)
Product Substance/Components (if applicable)
Final Product (if applicable)
Placebo Product (if applicable)
Labeling (if applicable)
Environmental Exemption Claim
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Instructions and Guidance:
6.1 Letter of Authorization to Cross-Reference
[For studies referencing another IND and/or marketed products:]
Provide a brief statement that includes a reference to the package insert or Letter of Authorization to
cross-reference another IND in order to address the requirements for chemistry, manufacturing, and
control information.
If the proposed dose, route, frequency of dosing and duration of therapy do not exceed the approved
labeled dosing regimen, the investigator-sponsor may provide the product’s labeling information and state
in the non-clinical section of the application that they believe their IND application may rely on the
previous FDA’s acceptance of the CMC and/or Pharmacology and Toxicology information related to the
approved marketed drug intended for this investigation.
Note: Append the package insert in section 4 (Investigator’s Brochure). Append the Letter of Authorization
to cross-reference in section 9 (Additional Information).
6.2 Response to Gene Therapy Letter
[For gene therapy studies]
Information requested in the FDA’s March 6, 2000, Gene Therapy Letter should be provided as part of the
IND application. (See http://www.fda.gov/cber/ltr/gt030600.htm.)
Note: Responses to items 1-5 of the letter may be cross-referenced, if applicable. Responses to item 6 of
the letter may be addressed by the UCD Institutional Data and Safety Monitoring Plan included in section 9
of this IND application. Responses to item 7 of the letter may be included in the cover letter that
accompanies this IND application.
6.3 Product Substance/Components
[For studies not using a cross-reference]
6.4 Final Product
[For studies not using a cross-reference]
6.5. Placebo Product
[For studies not using a cross-reference]
6.6. Labeling
[For studies not using a cross-reference]
Describe the composition, manufacture, and control of the bulk substance and final product. Pertinent
information includes the name and address of the manufacturer, methods of manufacture,
container/closure system(s), analytical methods, and stability testing. Additional information may include
descriptions of any placebo used in the clinical trial, and labeling to be provided to investigators.
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The amount of supporting information varies with the investigational phase and product used in the
clinical trial. For detailed information on the content of this section, refer to the appropriate FDA guidance
document.
Phase 1: FDA Guidance for Industry: Content and Format of Investigational New Drug Applications (INDs)
for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products.
(See http://www.fda.gov/cder/guidance/phase1.pdf.)
Phase 2 and 3: FDA Guidance for Industry: INDs for Phase 2 and Phase 3 Studies: Chemistry,
Manufacturing, and Controls Information. (See http://www.fda.gov/cder/guidance/3619fnl.pdf.)
Gene Therapy: Draft Guidance for FDA Review Staff and Sponsors: Content and Review of Chemistry,
Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug
Applications (INDs). (See http://www.fda.gov/cber/gdlns/gtindcmc.htm.)
6.7 Environmental Exemption Claim
Most drugs qualify for a categorical exclusion from an environmental assessment. The categorical
exclusion claim is a statement that the investigational product meets the exclusion categories as
not having a significant effect on the quality of the human environment. The exclusion claim
should include statements that: the action qualifies for a categorical exclusion, with a citation to
the regulations for the specific categorical exemption claimed, and that to the applicant’s
knowledge, no circumstances exist that would warrant an environmental assessment.
[Sample text:]
In accordance with 21 CFR 25.30/25.31, [add Sponsor-Investigator name] requests a categorical
exclusion from the requirement for an environmental assessment for the manufacture and
formulation of [drug name] for use in human clinical trials. All waste from the investigational
drug(s) will be properly controlled. The amount of waste expected to enter the environment may
reasonably be expected to be nontoxic.
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SECTION 7.
PHARMACOLOGY AND TOXICOLOGY DATA
Instructions and Guidance:
A cross-reference letter or package insert may be submitted in lieu of required information on
pharmacology and toxicology data.
- The package insert may be found in the Physician’s Desk Reference, the FDA website, or the United
States Pharmacopoeia – National Formulary.
- If the proposed dose, route, frequency of dosing and duration of therapy do not exceed the
approved labeled dosing regimen, the investigator-sponsor may provide the product’s labeling
information and state in the non-clinical section of the application that they believe their IND
application may rely on the previous FDA’s acceptance of the CMC and/or Pharmacology and
Toxicology information related to the approved marketed drug intended for this investigation.
- Remember to delete all instructions and guidance from the submitted application.
[For studies referencing another IND and/or marketed products:]
Provide a brief statement that references the package insert or Letter of Authorization to cross-reference
another IND in order to address the requirements for available pharmacology and toxicology data.
Notes: Append a copy of the package insert in section 4 (Investigator’s Brochure). Append the Letter of
Authorization to cross-reference in section 9 (Additional Information).
[For gene therapy studies:]
Add the following statement where appropriate: Animal safety information provided to [add SponsorInvestigator name] has been submitted as described in 21 CFR 312.32-33.
[For studies not using a cross-reference:]
Describe the pharmacological effects and mechanism of action in animals, pharmacokinetics (absorption,
distribution, metabolism, excretion), and toxicological effects in animals and in vitro. The outline below
embodies the elements of pharmacology/toxicology reviews. For detailed guidance related to content of
the sections, refer to the FDA guidance for Pharmacology/Toxicology review Format. (See
http://www.fda.gov/cder/guidance//4120fnl.pdf).
[For PET IND studies:]
Make sure you include animal and/or clinical pharmacology‐toxicology information that supports safety of
study/trial, Summary of previous PET drug clinical experience and an estimate of radiation‐absorbed dose
to body and critical organs, with justification.
7.1 Pharmacology
7.2 Safety Pharmacology
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7.3 Pharmacokinetics
7.4 Pharmacology Summary
7.5 Pharmacology Conclusions
7.6 Toxicology
7.7 Genetic Toxicology
7.8 Carcinogenicity
7.9 Reproductive and Developmental Toxicology
7.10 Special Toxicity Studies
7.11 Toxicology Summary
7.12 Toxicology Conclusions
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SECTION 8.
PREVIOUS HUMAN EXPERIENCE
Instructions and Guidance:
A cross-reference letter or package insert may be submitted in lieu of required information on
previous human experience.
- The package insert may be found in the Physician’s Desk Reference, the FDA website, or the United
States Pharmacopoeia – National Formulary.
- Remember to delete all instructions and guidance from the submitted application.
- Delete any sub-section if not applicable.
[For studies referencing another IND and/or marketed products:]
Provide a brief statement that references the package insert or Letter of Authorization to cross-reference
another IND in order to address the requirements for information regarding previous human experience.
Notes: Append a copy of the package insert in section 4 (Investigator’s Brochure). Append the Letter of
Authorization to cross-reference in section 9 (Additional Information).
[For studies not using a cross-reference:]
Summarize any relevant clinical information available. The sub-sections below should be considered.
8.1 Marketed Experience
Provide marketed indications for the study drug either in the US or abroad. If the drug was withdrawn
from the market for any reason related to safety or effectiveness, identify the country (ies) where the
drug was withdrawn and the reasons for withdrawal.
8.2 Clinical Research Experience
Summarize results from any clinical trials using the investigational drug. Include published research
and any available unpublished research that relates to the safety and efficacy of the investigational
drug or the rationale of the proposed trial. Attach full reprints for highly relevant publications. Supply
a bibliography for lesser relevant publications.
8.3 Off-Label Experience
If available, indicate any published literature on the safety of the drug used in clinical care settings to
treat patients for indications that do not have FDA approval, published practice guidelines of the use
of the drug for standard-of-care, and any associated safety information.
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SECTION 9.
ADDITIONAL INFORMATION
Instructions and Guidance:
- Supply additional information if it is applicable to the investigational drug and/or study.
- Remember to delete all instructions and guidance from the submitted application.
- Delete any sub-section if not applicable.
9.1 Letter of Authorization to Cross-Reference
Attach the letter behind this page.
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9.2 Additional information
[Add any additional pertinent information not already included in other sections, such as labels and
labeling to be provided to investigators, drug dependence and abuse potential, radioactive drugs, pediatric
safety and efficacy studies, or other information that would aid in the evaluation of the safety or design of
the clinical investigation.]
Attach any additional pertinent information not already included in other sections
behind this page.
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