ICTR DDRS: IND Application Guidance and Template for Drug Products
Version 3.0
IND Application for an Investigational Drug:
Investigational New Drug Application Guidance and Template
for Drugs Products
ICTR Navigators
July 23, 2011
Version 3.0
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ICTR DDRS: IND Application Guidance and Template for Drug Products
1.0
Table of Contents
Section
1.0 Table of Contents
2.0 Abbreviations:
3.0 FDA Websites:
4.0 Introduction:
5.0 Guidance and Instructions:
5.1 Template Comments
5.2 Regulations and Guidance documents
5.3 Number of Copies to be submitted
5.4 Application Header and Footer
5.5 Binding
5.6 FDA, CDER Mailing Address
5.7 Website Address Hyperlinks
5.8 Questions and Additional Information Contact
6.0 Application Template Guidance:
2.0
IND
CFR
FDA
CDER
CBER
CDRH
CMC
GCP
GLP
GMP
BLA
NDA
PMA
IDE
3.0
Version 3.0
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3
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Abbreviations
Investigational New Drug
Code of Federal Regulations
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Center for Biologics Evaluation and Research
Center for Devices and Radiological Health
Chemistry, Manufacturing, and Controls
Good Clinical Practices
Good Laboratory Practices
Good Manufacturing Practices
Biologic License Application
New Drug Application
Pre-Market Application
Investigational Device Exemption
FDA Websites
A list of several FDA websites containing useful information for investigators using an investigational
drug product is provided below. It is strongly suggested that these websites be reviewed before
submitting an IND application to the FDA.
FDA Forms website:

http://www.fda.gov/aboutfda/reportsmanualsforms/forms/default.htm
FDA Title 21 Regulations Search Engine (e.g., IND regulations 21CRF312) website:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm
FDA Running Clinical Trials website:

http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm
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FDA – CDER Investigational New Drug (IND) Application website:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalAp
plications/InvestigationalNewDrugINDApplication/default.htm
FDA - Sponsor-Investigator IND website

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalAp
plications/InvestigationalNewDrugINDApplication/ucm071098.htm
FDA – CDER Drug Guidance documents:

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
FDA- Formal Meetings Between the FDA and Sponsors or Applicants (pre-IND, Phase 2, etc…):
 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
FDA - CDER PRE-IND Consultation Contacts

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/
ApprovalApplications/InvestigationalNewDrugINDApplication/Overview/UCM166356.pdf
4.0
Introduction
Introduction:
The enclosed information is intended to provide a general process overview and a template for an
Investigational New Drug (IND) application submission for drug products reviewed by the FDA Center
for Drug Evaluation Research (CDER). The document is written from the perspective that the person
submitting the IND application is a Sponsor-Investigator. A Sponsor-Investigator is someone who is
both 1) responsible for initiating the studies conducted with the investigational drug product and 2)
who conducts the studies.
The contents of this document are based on the FDA regulations governing investigational drugs,
21CFR312, FDA guidance documents, and personal experience. However, each drug product and
associated clinical trials may have unique features or circumstances that are not addressed by this
document or the reference guidance documents cited herein. In such cases, the Sponsor-Investigator
should consult with the ICTR-DDRS and are strongly encouraged to request a pre-IND meeting with
the FDA. A guidance and template for a pre-IND meeting request is available through the ICTRDDRS.
While there are numerous regulations, guidance documents and other references pertaining to IND
applications for drug products, those provided in this document are those most commonly used and/or
most widely applicable. The following references will give the Sponsor-Investigator a general
overview of the basic IND application content and format.
FDA Regulation - 21CRF312 Subpart B--Investigational New Drug Application (IND):

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=312&showFR=1&subp
artNode=21:5.0.1.1.3.2
FDA Guidance - Content and Format of Investigational New Drug Applications (INDs) for Phase
1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived
Products:
 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071597.pdf
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Version 3.0
Guidance and Instructions
5.1
Template Comments
The enclosed template guidance is a suggested format based on federal regulations, guidance
documents, and previous experience. Within each section of the application template are references
to applicable FDA regulations, web addresses to FDA guidance documents, comments/instructions,
web addresses to FDA forms, and suggested formatting and/or language. These instructions outline
what should be included or inserted into a particular section and may also address special
considerations. As this is a basic template and each IND is unique, best judgment should be used
concerning the information to be included in the submisison. The sponsor-investigator may use this
format or adapt it as appropriate for the particular investigational product being evaluated. Each
section of the application should begin on new page because as you see in the binding instructions,
you should use index tabs to mark each section of the application. Thus, each section in this
document starts on a new page. A blank template with just the cover letter, title page, and suggested
section headings and subheadings is available for download at the DDRS website.
5.2
Regulations and Guidance documents
Throughout this document are a number references to regulations and guidance documents. These
references have been included to provide the Sponsor-Investigator with direction and guidance when
completing an IND application. The references will not address every situation that may be
encountered. If the applicant has questions after reviewing the references provided, they should
contact the ICTR Research Navigators for assistance and/or request a pre-IND meeting with the FDA.
5.3
Number of Copies to be submitted
One original copy and two photocopies of the IND application must be sent with the initial submission.
Of note: Once the FDA receives the application and begins the review process, they may ask for
additional desk copies.
5.4
Application Header and Footer
The following is the suggested format of document headers and footers to be used with the initial IND
submission. Note: Headers and footers are not included in the template and must be inserted
manually and may be modified as appropriate.
Header:
[Left Hand Side]
IND Application Date: [INSERT DATE]
[INSERT Drug Product Name]
[Right Hand Side]
IND Number: pending
Serial Number: [1571 Serial #]
Footer:
[Left Hand Side]
John Hopkins University
[INSERT: Sponsor-Investigator Name]
Confidential and Proprietary
[Right Hand Side]
Page [##]
5.5
Binding
If a project manager has been assigned to the IND application being prepared for submission or if
contact information is available for a project manager within the Office/Division that will review the IND
application, it is suggested that the Sponsor-Investigator contact the project manager to review how
the IND materials should be bound.
If a project manager has not yet been assigned to the IND, general guidelines for binding a paper IND
application being submitted to CDER are provided below. The below binding guidance is the
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ICTR DDRS: IND Application Guidance and Template for Drug Products
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information posted at the FDA’s website entitled “FDA IND, NDA, ANDA, or Drug Master File Binders”
and located at following web address:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/DrugMasterFil
esDMFs/ucm073080.htm
IND submissions that are received loose or which are inadequately bound may be returned to
the Sponsor-Investigator for proper binding and resubmission which can significantly delay
the FDA review process. If the Sponsor-Investigator chooses to use a different type of binder than
suggested, the binders should be labeled as suggested below.
1. FDA CDER Guidance Recommendations:
a. Archive - Red POLYETHYLENE BINDER (or ACCO Executive Red Stock Number
25079 or Smead Red Stock Number 81752 or similar type*)
i. Front (flat size) - 248 x 292mm (9-3/4 x 11-1/2")
ii. Back (flat size) - 248 x 305mm (9-3/4 x 12") (size includes 13 mm (1/2") lip at
top)
1. Must be high impact linear plastic (matte finish or similar) - Must be able
to withstand temperatures up to 150 degrees - Material should have a
surface smooth enough to allow printing with a complete bonding of ink
to the surface after a minimum of one hour drying time - Should be free
from streaks, blisters, scratches and mottling . Binder weight MUST be
.023-.025 gauge - Ink color MUST be BLACK
b. Duplicate (or First Review Copy) - Green PAPER BINDER (or ACCO Green Stock
Number 25076 or similar type *)
i. Front (flat size) - 267 x 292mm (10-1/2 x 11-1/2")
ii. Back (flat size) - 267 x 305mm (10-1/2 x 12") (size includes 13mm (1/2") lip at
top)
1. Binder MUST be of 11-point plate rope stock of extra heavy weight - Ink
color MUST be BLACK
c. Second and additional review copies - Orange PAPER BINDER ( or ACCO Tangerine
Stock Number 25977 or Smead Orange Stock Number 81652 or similar type or any
color except Green or Red.* )
i. Same specifications as the Duplicate Copy
2. Identification of binders
a. Required on front folder in a clear, sharp, permanent-type print in BLACK ink Permanent adhesive labels may be used in a clear, sharp print - Printing must
withstand a "Scotch Tape Test" which consists of pressing a strip of "Scotch" tape
firmly on the printed area and removing - There should be NO transfer of the printed
area on the tape
b. Binders are identified with the following label:
VOLUME __________________
NOTICE OF CLAIMED INVESTIGATIONAL EXEMPTION FOR A NEW DRUG
IND. NO._____(For the initial submission of the new application leave
blank)_____
SPONSOR NAME
NAME OF DRUG
This submission: VOL._____OF______VOLS.
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3. Additional Information:
a. If submissions are received loose or are inadequately bound, they may be returned to
the sponsor or applicant for further handling and processing. If the submission is
returned, the submission will be date-stamped when resubmitted adequately bound.
b. If the application is sent in boxes, “Banker Boxes” should be used.
4. Information about ACCO Folders:
Note: The vendor information listed below is provided as an example of where these
items may be purchased and is not intended as an endorsement of the vendor or a
mandatory vendor to be used to purchase the folders.
a. Red (ACCO USA, Executive Red, #25079) – used for archive (original copy)
i. Example Vendor
1. Office Depot:
http://www.officedepot.com/a/products/193664/Acco-Presstex-60percentRecycled-Binder-Side/
b. Green (ACCO USA, Green, #25076) – used for 1st review copy
i. Example Vendor
1. Office Depot:
http://www.officedepot.com/a/products/193623/Acco-Presstex-60percentRecycled-Binder-Side/
c. Light Blue (ACCO USA, #25072) – used for 2nd review copy
NOTE: The FDA requests “Tangerine or Orange” binders, but these can be very
difficult to find. In the Navigators’ experience, the FDA will accept these light blue
binders in place of the tangerine/orange requested.
i. Example Vendor
1. Office Depot:
http://www.officedepot.com/a/products/102905/Acco-Presstex-60percentRecycled-Binder-Side/
5.6
FDA, CDER Mailing Address
Central Document Room
Center for Drug Evaluation and Research
Food and Drug Administration
5901-B Ammendale Rd.
Beltsville, MD 20705-1266
5.7
Website Address Hyperlinks
All hyperlinks to websites included in this document are operational as of the date of this version. If
any non-functional hyperlinks are identified in this document, please contact the ICTR Research
Navigators via the contact information below so that the links may be updated.
5.8
Questions and Additional Information Contact
For questions regarding any of the information presented or use of the template, please contact the
ICTR Research Navigators at ICTR_Navigators@jhmi.edu or via telephone at 410-955-8120 or 410614-5383.
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Application Template Guidance:
Application Section
Cover Letter
Cover Page
Section 1: Form FDA 1571
Section 2: Table of Contents
Section 3: Introductory Statement
Section 4: General Investigational Plan
Section 5: Investigator’s Brochure
Section 6: Protocol
Section 7: Chemistry, Manufacturing, and Controls
Section 8: Pharmacology and toxicology
Section 9: Previous human experience
Section 10: Additional Information
Section 11: Relevant Information
Section 12: Bibliography
Section 13: Appendices
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ICTR DDRS: IND Application Guidance and Template for Drug Products
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Cover Letter
[INSTRUCTIONS: The suggested format for the cover letter that accompanies the IND application
may be found below. If the Sponsor-Investigator has already had a pre-IND meeting with the FDA,
then the pre-IND number and meeting date should be referenced in the cover letter.]
[INSERT: Sponsor-Investigator letterhead or address]
[INSERT: DATE]
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Rd.
Beltsville, MD 20705-1266
RE: New IND Application Submission
Dear Reviewers,
Pursuant to 21 CFR 312, I am submitting an original, Sponsor-Investigator Investigational New Drug
(IND) application.
The IND is being submitted to [INSERT: Supply short description of experimental treatment/drug and
protocol]. [INSERT: If pre-IND meeting was held, then insert text referencing the pre-IND (PIND)
number and the date of meeting.]
[INSTRUCTIONS FOR ACCO BINDERS: Use the following text if submitting the application in ACCO
binders, per above guidance information. “Enclosed are the original application (red binders), first
copy of the application (green binders), and the second copy (light blue binders).”]
If you have any questions about the material included in this IND, please do not hesitate to contact me
at [INSERT: phone number of Sponsor-Investigator], by email at [INSERT: email address of
Sponsor-Investigator], or by fax at [INSERT: Sponsor-Investigator fax] any time during your review.
[COMMENT: If there is another person designated to interact with the FDA on behalf of the SponsorInvestigator, then state “{INSERT: name} is authorized to interact with the FDA on my behalf and
{INSERT: name‟s} contact information is {INSERT: phone, email, and fax}.”]
Thank you in advance for your consideration.
Sincerely,
[INSERT: Sponsor-Investigator Name]
[INSERT: Title]
[INSERT: Affiliation]
Enclosure:
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Cover Page
[COMMENTS: A suggested format for the title page to the IND application is provided below.]
Investigational New Drug Application
DATE
IND Application Title:
Drug Product:
Serial Number:
Sponsor-Investigator: Name and Contact Information
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ICTR DDRS: Sponsor-Investigator IND Guidance and Template for Drugs
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Section 1: Form FDA 1571
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[Regulatory Reference: 21CFR312.23(a)(1)- Cover sheet (Form FDA-1571) An FDA Form 1571 is a
required cover sheet for the application containing the following:
(i) The name, address, and telephone number of the sponsor, the date of the application, and the name of
the investigational new drug.
(ii) Identification of the phase or phases of the clinical investigation to be conducted.
(iii) A commitment not to begin clinical investigations until an IND covering the investigations is in effect.
(iv) A commitment that an Institutional Review Board (IRB) that complies with the requirements set forth in
part 56 will be responsible for the initial and continuing review and approval of each of the studies in the
proposed clinical investigation and that the investigator will report to the IRB proposed changes in the
research activity in accordance with the requirements of part 56.
(v) A commitment to conduct the investigation in accordance with all other applicable regulatory
requirements.
(vi)The name and title of the person responsible for monitoring the conduct and progress of the clinical
investigations.
(vii) The name(s) and title(s) of the person(s) responsible under 312.32 for review and evaluation of
information relevant to the safety of the drug.
(viii) If a sponsor [Sponsor-Investigator] has transferred any obligations for the conduct of any clinical study
to a contract research organization a statement containing the name and address of the contract research
organization, identification of the clinical study, and a listing of the obligations transferred. If all obligations
governing the conduct of the study have been transferred, a general statement of this transfer--in lieu of a
listing of the specific obligations transferred--may be submitted.
(ix) The signature of the sponsor [Sponsor-Investigator] or the sponsor's [Sponsor-Investigator‟s] authorized
representative. If the person signing the application does not reside or have a place of business within the
United States, the IND is required to contain the name and address of, and be countersigned by, an
attorney, agent, or other authorized official who resides or maintains a place of business within the United
States.
1. Form FDA 1571
[INSERT TEXT: “Please see the signed and dated Form FDA 1571 next.”]
[WEB ADDRESS TO FDA FORM AND FORM INSTRUCTIONS
 FDA form 1571:
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083533.pdf

Instructions for form 1571:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalAp
plications/InvestigationalNewDrugINDApplication/ucm071098.htm#form1571]
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Section 2: Table of Contents
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[Regulatory Reference: 21CFR312.23(a)(2)- Table of Contents.]
[INSTRUCTIONS: The IND Table of Contents must list all sections of the application broken down by
volume and section number. Additionally, the Table of Contents should include a list of tables,
figures, and attachments found within the application. The Table of Contents should be accurate and
easy to follow so that the FDA reviewers can find the sections they need to review quickly and easily.
Before submitting the IND application, double check to make certain that the Table of Contents
matches the content, title, page numbers, and volumes, of the final version of the IND application.]
[COMMENT: The Table of Contents below is provided as an example and is based on the
requirements set forth in 21CFR312.23 – IND content and format, found at:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=312.23.
Changes may be made to the Table of Contents provided based on the needs of individual IND
applications.]
2.0 Table of Application Contents
Volume 1
Section
1.0
FDA Form 1571
Title
2.0
Table of Contents
3.0
3.1
3.1.1
3.1.2
3.1.3
3.1.4
3.1.5
3.1.6
3.2
3.3
Introductory statement
Brief Introductory Statement
Drug Name
Pharmacological Class
Structural Formula
Formulation of Dosage Form
Route of Administration
Broad Objectives & Planned Duration of the Proposed Clinical Investigations
Brief Summary of Previous Human Experience
Withdrawn From Investigation or Marketing in any Country
4.0
4.1
4.1.1
General investigational plan
Rationale
Rationale for Drug
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4.1.2
4.2
4.3
4.4
4.5
4.6
Rationale for Study
Indications to be Studied the First Year
General Approach to be Followed in Evaluating the Drug
Clinical Trials to be Conducted First Year
Estimated Number of Subjects to be Given the Drug in First Year
Anticipated Risks of Particular Severity or Seriousness
5.0
Investigator’s brochure
6.0
6.1
6.2
Protocol
Objectives and Purpose of Study
Principal Investigator, Sub-investigators, Research Facilities, and
Institutional Review Boards.
Patient Selection and Estimated Number to be Studied
Description of Study Design
Drug Dosing – Method, Maximum Dose, and Duration of Exposure
Observations and Measurements Made to Fulfill Study Objectives
Procedures to Monitor Drug Effects in Human Subjects and Minimize Risks
Clinical Trial Registration
6.3
6.4
6.5
6.6
6.7
6.8
Volume 2
Section
Title
7.0
Chemistry, Manufacturing, and Controls
7.1
Introduction: Statement of Risk
7.2
Drug Substance
7.3
Drug Product
7.4
Placebo
7.5
Labeling
7.6
Claim for Categorical Exclusion for Environmental Assessment
8.0
8.1
8.2
Pharmacology and toxicology data
Pharmacology and drug disposition
Toxicology
9.0
Previous human experience
10.0
10.1
10.2
10.3
10.4
Additional information
Drug dependence and abuse potential
Radioactive drugs
Pediatric studies
Other information
11.0
Relevant Information
12.0
Bibliography
13.0
Appendices
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LIST OF TABLES
Volume #
Section
Title
Page
Title
Page
Table 1
Table 2
Table 3
Volume #
Section
Table 4
Table 6
Table 7
Table 8
Table 9
Table 10
LIST OF FIGURES
Volume #
Section
Title
Page
Title
Page
Title
Page
Title
Page
Figure 1
Figure 2
Figure 3
Volume #
Section
Figure 4
Figure 5
List of Attachments
Volume #
Section
Attachment 1
Attachment 2
Volume #
Section
Attachment 3
Attachment 4
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Section 3: Introductory Statement
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(3)(i-iii)
(3)Introductory statement and general investigational plan
(i) 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).
(ii) A brief summary 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 investigation(s).
(iii) If the drug has been withdrawn from investigation or marketing in any country for any reason related to
safety or effectiveness, identification of the country(ies) where the drug was withdrawn and the reasons for
the withdrawal.]
3.0
Introduction
3.1
Introductory Statement
[INSTRUCTIONS FOR 3.1 TO 3.1.6
A brief introductory statement including the name of the investigational 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)should be provided here. If a particular heading provided below
is not applicable or the information is not known/available at the time of the IND submission, then
state “not applicable” or provide an explanation stating that the information is not known or available.]
[NOTES:
 If submitting an Exploratory IND (eIND), a statement must be included in this section indicating
that the application is an eIND. See FDA eIND guidance for more information.
o FDA eIND Guidance:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078933.pdf

If a pre-IND meeting was already held with the FDA, the pre-IND number, meeting date, and
outcomes should be referenced here.]
3.1.1
Drug Name and all Active Ingredients
[ADDITIONAL INSTRUCTIONS: List all known names of the investigational drug including, but not
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limited to, the proprietary name, generic name, chemical name, and any other names of the drug.]
3.1.2
Pharmacological Class
[INSTRUCTIONS: Insert description of pharmacological class. If not known, explain why it is not
known.]
3.1.3
Structural and Chemical Formula
[INSTRUCTIONS: Insert both the chemical and structural formula of the final drug product. If not
known, explain why it is not known.]
3.1.4
Formulation of Dosage Form
[INSTRUCTIONS: Insert a succinct description of the formulation including dosage amounts of each
active ingredients of the drug product.]
3.1.5
Route of Administration
[INSTRUCTIONS: Insert a description of the route of administration.]
3.1.6
Broad Objectives and Planned Duration of the Proposed Clinical Investigation(s).
[INSTRUCTIONS: Provide description of the objectives of the clinical investigation(s) being proposed
as part of this application and how long you expect the investigation(s) (clinical trial) to last. If more
than one is being proposed, then insert appropriate subheading so the FDA can clearly distinguish
what information pertains to which trial.]
3.2
Brief Summary of Previous Human Experience
[INSTRUCTIONS: A brief summary 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 investigation(s) should be provided here. This should be
a high-level summary of the information provided in Section 9 – Previous Human Experience.]
3.3
Withdrawn From Investigation or Marketing in any Country
[INSTRUCTIONS: If the drug has been withdrawn from investigation or marketing in any country for
any reason related to safety or effectiveness, identification of the country(ies) where the drug was
withdrawn and the reasons for the withdrawal should be provided here.]
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Section 4: General Investigational Plan
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(3)(iv)A brief description of the overall plan for investigating the drug product for the following year should be provided
here. The plan should include the following:
(a) the rationale for the drug or the research study;
(b) the indication(s) to be studied;
(c) the general approach to be followed in evaluating the drug;
(d) 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);
(e) the estimated number of patients to be given the drug in those studies; and
(f) 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.]
4.0
General investigational plan
[INSTRUCTIONS: In this section, provide a brief overview of the investigational plan for the first year the drug is
being studied. Be sure to include/address the information requested in each of the subsections of section 4.]
4.1
Rationale for Drug and Study
[INSTRUCTIONS: In this section, state the rationale for using the investigational drug and/or
conducting the research study. Include background information on the science that supports the use
of the investigational drug and/or the research study. Note: This information can either be split into
two sections, as illustrated here (4.1.1. and 4.1.2., or included all together under 4.1). Use your best
judgment as to which style is more appropriate for your application.]
4.1.1
Rationale for Drug
[INSTRUCTIONS: See above instructions for 4.1.]
4.1.2
Rationale for Study
[INSTRUCTIONS: See above instructions for 4.1.]
4.2
Indications to be Studied the First Year
[INSTRUCTIONS: State the indication(s) to be studied during the first year of the IND here.]
4.3
General Approach to be Followed in Evaluating the Drug
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[INSTRUCTIONS: State the general approach to be followed in evaluating the drug here.]
4.4
Clinical Trials to be Conducted First Year
[INSTRUCTIONS: Provide an overview of the clinical trial(s) that are planned to be conducted during
the first year of the IND here. If the plans are not yet developed for the first year of the IND, indicate
this here.]
4.5
Estimated Number of Subjects to be Given the Drug in First Year
[INSTRUCTIONS: Provide an estimate of the number of total participants to be given the
investigational drug in the proposed clinical trial(s) to be conducted during the first year of the IND. If
the drug is to be given to multiple populations, i.e., healthy volunteers and patient populations, be sure
to provide an estimate for each individual population.]
4.6
Anticipated Risks of Particular Severity or Seriousness
[INSTRUCTIONS: Provide an overview of all risks of particular severity or seriousness anticipated on
the basis of the toxicological data in animals and/or prior studies with the investigational drug or
related drugs in humans here. Also include any study procedures that carry anticipated risks of
particular severity or seriousness in this section.]
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Section 5: Investigator’s Brochure
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(5) - Investigator's brochure. If required under
312.55, a copy of the investigator's brochure, containing the following information:
(i) A brief description of the drug substance and the formulation, including the structural formula, if known.
(ii) A summary of the pharmacological and toxicological effects of the drug in animals and, to the extent
known, in humans.
(iii) A summary of the pharmacokinetics and biological disposition of the drug in animals and, if known, in
humans.
(iv) A summary of information relating to safety and effectiveness in humans obtained from prior clinical
studies. (Reprints of published articles on such studies may be appended when useful.)
(v) A description of possible risks and side effects to be anticipated on the basis of prior experience with the
drug under investigation or with related drugs, and of precautions or special monitoring to be done as part of
the investigational use of the drug.]
Investigator’s brochure
5.0
[INSTRUCTIONS:

If an early phase trial is being conducted at a single center, then an investigator brochure (IB)
is not necessary. If no IB is included in the IND application, provide a brief explanation for
FDA reviewers as to why.

If studying an approved drug that has a package insert, change the section heading to
“Package Insert” and place the package insert information here. A number of package inserts
are available for download at http://dailymed.nlm.nih.gov/. The package insert needs to be
from the manufacturer of the drug that will be supplying the drug for the study.

If there is an IB, insert text after stating “Please see next the Investigator‟s Brochure” and then
insert the IB.]
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Section 6: Protocol
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(6)
(6)Protocols.
(i) A protocol for each planned study. (Protocols for studies not submitted initially in the IND should be
submitted in accordance with 312.30(a).) 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 investigation--an estimate of the number of patients to be involved, a description
of safety exclusions, and a description of the dosing plan including duration, dose, or method to be used in
determining 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. Modifications of the experimental design
of Phase 1 studies that do not affect critical safety assessments are required to be reported to FDA only in
the annual report.
(ii) In Phases 2 and 3, detailed protocols describing all aspects of the study should be submitted. A protocol
for a Phase 2 or 3 investigation 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 to provide for such deviation are built into the protocols at the outset. For example, a protocol
for a controlled short-term study might include a plan for an early crossover of non-responders to an
alternative therapy.
(iii) A protocol is required to contain the following, with the specific elements and detail of the protocol
reflecting the above distinctions depending on the phase of study:
(a) A statement of the objectives and purpose of the study.
(b) The name and address and a statement of the qualifications (curriculum vitae or other statement of
qualifications) of each investigator, and the name of each sub-investigator (e.g., research fellow,
resident) 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.
{NOTE: - FDA Form 1572 and CVs}
(c) The criteria for patient selection and for exclusion of patients and an estimate of the number of
patients to be studied.
(d) A description of the design of the study, including the kind of control group to be used, if any, and a
description of methods to be used to minimize bias on the part of subjects, investigators, and
analysts.
(e) The method for determining the dose(s) to be administered, the planned maximum dosage, and the
duration of individual patient exposure to the drug.
(f) A description of the observations and measurements to be made to fulfill the objectives of the study.
(g) A description of clinical procedures, laboratory tests, or other measures to be taken to monitor the
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effects of the drug in human subjects and to minimize risk.]
[COMMENTS: This section of the application may be written in a number of different formats.
Regardless of the format chosen, the information listed in the regulatory reference above and itemized
in the template to follow must be provided. If the Sponsor-Investigator is using the JHM IRB eFormA,
it is strongly suggested that the eIRB application in its entirety be submitted with in this section. This
is suggested because the eIRB application contains information that is not included in the eFormA
which should be submitted. If the eIRB application is submitted, the appropriate subheading in this
section or in the appendices should be added. Finally, if the protocol being submitted with the IND
application is already IRB approved, the Sponsor-Investigator should include the IRB approval letter
with the IND application and the appropriate subheading in this section or in the appendices should be
added.
[FORMATS:
 In the suggested format below, the applicant provides a high level summary of the requested
information and references the FDA reviewers to a full version of the documents (e.g., protocol,
eIRB application, consent, IRB approval letter) located in the appendices, including the page
number of document in which the information can be found. This format is suggested as it
provides the FDA reviewers an „easy to read‟ overview of the requested information as well as
specific references to full documents. Note: The instructions in the heading below also indicate the
information to be provided to the FDA regardless of the chosen format.

An alternate format starts with the „6.0 Protocol‟ heading, followed by subheadings „6.1 Protocol‟,
„6.2 Consent‟, „6.3 Investigator and Facilities Data‟, and „6.4 Clinical Trial Registration‟. The
Sponsor-Investigator should include additional subheading under each of the above as
appropriate to the documents being submitted.
The suggested format below illustrates
appropriate subheadings (e.g. “6.1.1. Protocol/eFormA”, “6.1.2 eIRB application”, “6.1.3 IRB
approval”, “6.3.1 Form FDA 1572”, “6.3.2. Sponsor-Investigator CV”, etc…) which may be used
with this alternate format. After each subheading, the applicant should insert the appropriate
document.]
[FDA GUIDANCE DOCUMENTS: Below are web addresses for a number of FDA guidance document
sites that may be useful with regard to choice of study design and drafting the protocol.
 FDA Guidance Documents on Clinical Pharmacology:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064982.htm

FDA Guidance Documents on Clinical / Medical:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064981.htm

FDA Guidance Documents on Biopharmaceutics:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064964.htm

FDA Guidance Documents on Drug Safety:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064993.htm

FDA Guidance Documents on International Conference on Harmonisation – Efficacy:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065004.htm]
6.0
Protocol(s)
[INSTRUCTIONS: If providing a high-level summary of the information listed below, it is suggested
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that the Sponsor-Investigator include the suggested text. Additionally, under each of the headings in
Section 6, the Sponsor-Investigator should cross-reference the appendix and page number where the
full version or actual document(s) can be found.]
[SUGGESTED TEXT: “Please see below a brief overview of the required information for this section
including cross references to the full versions of the documents in which this information can be
found.”
OR
“Please see next the protocol.”]
6.1
Objectives and Purpose of Study
[INSTRUCTIONS: Provide a brief statement of the objectives and purpose of the study here.]
6.2
Investigator and Facilities Data
[INSTRUCTIONS: Needed here are the name, address, and a statement of the qualifications
(curriculum vitae or other statement of qualifications) of each investigator as well as the name of each
sub-investigator (e.g., research fellow, resident) working under the supervision of the investigator.
Also needed are the name(s) and address(es) of the research facility(ies) to be used as well as the
name and address of each reviewing Institutional Review Board (IRB).
The information needed for this section is provided to the FDA on the FDA Form 1572 (see below for
additional guidance) along with copies of the Sponsor-Investigator‟s CV, medical license, and financial
disclosure forms (FDA Form 3454 and FDA Form 3455; see below for additional guidance). While not
required, the Sponsor-Investigator may also provide copies of the CVs, medical or other professional
licenses (if applicable), and financial disclosure forms (FDA Form 3454 and FDA Form 3455) for all
subinvestigators listed in Box 6 of the 1572. If the Sponsor-Investigator chooses not provide the
subinvestigators‟ information in the application, the applicant MUST maintain copies of this
documentation in their IND regulatory binder. Additional guidance on the completion of the FDA
forms for this section as well the website where fillable PDF forms can be found are provided below.
The FDA forms, CVs, and licenses may either 1) be placed after the appropriate subheading in this
section or 2) placed in the appendices.]
6.2.1
Form FDA 1572
[1572 INSTRUCTIONS and GUIDANCE: Please review the FDA 1572 FAQs guidance document
before completing the 1572. Both the FAQs and FDA Form 1572 may be downloaded from the
following websites:

Form FDA 1572:
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM074728.pdf

FDA Guidance on 1572 (FAQs):
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf]
[SUGGESTED TEXT: “Please see the signed and dated FDA Form 1572 on the next page.” OR
“Please see the signed and dated FDA Form 1572 in appendix ##.”]
6.2.2
Sponsor-Investigator
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[SUGGESTED TEXT: “The Sponsor-Investigator‟s CV and Medical License may be found on the next
page.” OR “Please see the Investigator‟s CV and Medical License in appendix ##.”]
6.2.3
Subinvestigator(s)
[SUGGESTED TEXT: “The CVs and medical licenses (if applicable) of the following subinvestigators
may be found on the next page.” OR “Please see the subinvestigators‟ CVs and medical licenses (if
applicable) in appendix ##.”]
[COMMENT: Provide a list of subinvestigators in the order that the CVs and licenses appear and
place the documents after this subheading or if you may place the documents in the appendices.]
[EXAMPLE TEXT (May be used here or in appendix):
“The CVs and licenses (if applicable) of the subinvestigators listed below may be found on the next
page.
John L Doe, MD, PhD
Lisa M. Name, PhD
Thomas Y. Doe, RN, MSN”]
6.2.3 Disclosure of Financial Interests
[Regulatory reference: 21CFR54
Sec. 54.1 Purpose.
(a) The Food and Drug Administration (FDA) evaluates clinical studies submitted in marketing applications, required by
law, for new human drugs and biological products and marketing applications and reclassification petitions for medical
devices.
(b) The agency reviews data generated in these clinical studies to determine whether the applications are approvable
under the statutory requirements. FDA may consider clinical studies inadequate and the data inadequate if, among other
things, appropriate steps have not been taken in the design, conduct, reporting, and analysis of the studies to minimize
bias. One potential source of bias in clinical studies is a financial interest of the clinical investigator in the outcome of the
study because of the way payment is arranged (e.g., a royalty) or because the investigator has a proprietary interest in
the product (e.g., a patent) or because the investigator has an equity interest in the sponsor of the covered study. This
section and conforming regulations require an applicant whose submission relies in part on clinical data to disclose
certain financial arrangements between sponsor(s) of the covered studies and the clinical investigators and certain
interests of the clinical investigators in the product under study or in the sponsor of the covered studies. FDA will use
this information, in conjunction with information about the design and purpose of the study, as well as information
obtained through on-site inspections, in the agency's assessment of the reliability of the data.
Sec. 54.2 Definitions.
For the purposes of this part:
(a)Compensation affected by the outcome of clinical studies means compensation that could be higher for a favorable
outcome than for an unfavorable outcome, such as compensation that is explicitly greater for a favorable result or
compensation to the investigator in the form of an equity interest in the sponsor of a covered study or in the form of
compensation tied to sales of the product, such as a royalty interest.
(b)Significant equity interest in the sponsor of a covered study means any ownership interest, stock options, or other
financial interest whose value cannot be readily determined through reference to public prices (generally, interests in a
nonpublicly traded corporation), or any equity interest in a publicly traded corporation that exceeds $50,000 during the
time the clinical investigator is carrying out the study and for 1 year following completion of the study.
(c)Proprietary interest in the tested product means property or other financial interest in the product including, but not
limited to, a patent, trademark, copyright or licensing agreement.
(d)Clinical investigator means only a listed or identified investigator or subinvestigator who is directly involved in the
treatment or evaluation of research subjects. The term also includes the spouse and each dependent child of the
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investigator.
(e)Covered clinical study means any study of a drug or device in humans submitted in a marketing application or
reclassification petition subject to this part that the applicant or FDA relies on to establish that the product is effective
(including studies that show equivalence to an effective product) or any study in which a single investigator makes a
significant contribution to the demonstration of safety. This would, in general, not include phase l tolerance studies or
pharmacokinetic studies, most clinical pharmacology studies (unless they are critical to an efficacy determination), large
open safety studies conducted at multiple sites, treatment protocols, and parallel track protocols. An applicant may
consult with FDA as to which clinical studies constitute "covered clinical studies" for purposes of complying with financial
disclosure requirements.
(f)Significant payments of other sorts means payments made by the sponsor of a covered study to the investigator or
the institution to support activities of the investigator that have a monetary value of more than $25,000, exclusive of the
costs of conducting the clinical study or other clinical studies, (e.g., a grant to fund ongoing research, compensation in
the form of equipment or retainers for ongoing consultation or honoraria) during the time the clinical investigator is
carrying out the study and for 1 year following the completion of the study.
(g)Applicant means the party who submits a marketing application to FDA for approval of a drug, device, or biologic
product. The applicant is responsible for submitting the appropriate certification and disclosure statements required in
this part.
(h)Sponsor of the covered clinical study means the party supporting a particular study at the time it was carried out.
Sec. 54.3 Scope.
The requirements in this part apply to any applicant who submits a marketing application for a human drug, biological
product, or device and who submits covered clinical studies. The applicant is responsible for making the appropriate
certification or disclosure statement where the applicant either contracted with one or more clinical investigators to
conduct the studies or submitted studies conducted by others not under contract to the applicant.
Sec. 54.4 Certification and disclosure requirements.
For purposes of this part, an applicant must submit a list of all clinical investigators who conducted covered clinical
studies to determine whether the applicant's product meets FDA's marketing requirements, identifying those clinical
investigators who are full-time or part-time employees of the sponsor of each covered study. The applicant must also
completely and accurately disclose or certify information concerning the financial interests of a clinical investigator who
is not a full-time or part-time employee of the sponsor for each covered clinical study. Clinical investigators subject to
investigational new drug or investigational device exemption regulations must provide the sponsor of the study with
sufficient accurate information needed to allow subsequent disclosure or certification. The applicant is required to submit
for each clinical investigator who participates in a covered study, either a certification that none of the financial
arrangements described in 54.2 exist, or disclose the nature of those arrangements to the agency. Where the applicant
acts with due diligence to obtain the information required in this section but is unable to do so, the applicant shall certify
that despite the applicant's due diligence in attempting to obtain the information, the applicant was unable to obtain the
information and shall include the reason.
(a) The applicant (of an application submitted under sections 505, 506, 510(k), 513, or 515 of the Federal Food, Drug,
and Cosmetic Act, or section 351 of the Public Health Service Act) that relies in whole or in part on clinical studies shall
submit, for each clinical investigator who participated in a covered clinical study, either a certification described in
paragraph (a)(1) of this section or a disclosure statement described in paragraph (a)(3) of this section.
(1) Certification: The applicant covered by this section shall submit for all clinical investigators (as defined in 54.2(d)), to
whom the certification applies, a completed Form FDA 3454 attesting to the absence of financial interests and
arrangements described in paragraph (a)(3) of this section. The form shall be dated and signed by the chief financial
officer or other responsible corporate official or representative.
(2) If the certification covers less than all covered clinical data in the application, the applicant shall include in the
certification a list of the studies covered by this certification.
(3) Disclosure Statement: For any clinical investigator defined in 54.2(d) for whom the applicant does not submit the
certification described in paragraph (a)(1) of this section, the applicant shall submit a completed Form FDA 3455
disclosing completely and accurately the following:
(i) Any financial arrangement entered into between the sponsor of the covered study and the clinical investigator
involved in the conduct of a covered clinical trial, whereby the value of the compensation to the clinical investigator for
conducting the study could be influenced by the outcome of the study;
(ii) Any significant payments of other sorts from the sponsor of the covered study, such as a grant to fund ongoing
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research, compensation in the form of equipment, retainer for ongoing consultation, or honoraria;
(iii) Any proprietary interest in the tested product held by any clinical investigator involved in a study;
(iv) Any significant equity interest in the sponsor of the covered study held by any clinical investigator involved in any
clinical study; and
(v) Any steps taken to minimize the potential for bias resulting from any of the disclosed arrangements, interests, or
payments.
(b) The clinical investigator shall provide to the sponsor of the covered study sufficient accurate financial information to
allow the sponsor to submit complete and accurate certification or disclosure statements as required in paragraph (a) of
this section. The investigator shall promptly update this information if any relevant changes occur in the course of the
investigation or for 1 year following completion of the study.
(c) Refusal to file application. FDA may refuse to file any marketing application described in paragraph (a) of this section
that does not contain the information required by this section or a certification by the applicant that the applicant has
acted with due diligence to obtain the information but was unable to do so and stating the reason.
Sec. 54.5 Agency evaluation of financial interests.
(a)Evaluation of disclosure statement. FDA will evaluate the information disclosed under 54.4(a)(2) about each covered
clinical study in an application to determine the impact of any disclosed financial interests on the reliability of the study.
FDA may consider both the size and nature of a disclosed financial interest (including the potential increase in the value
of the interest if the product is approved) and steps that have been taken to minimize the potential for bias.
(b)Effect of study design. In assessing the potential of an investigator's financial interests to bias a study, FDA will take
into account the design and purpose of the study. Study designs that utilize such approaches as multiple investigators
(most of whom do not have a disclosable interest), blinding, objective endpoints, or measurement of endpoints by
someone other than the investigator may adequately protect against any bias created by a disclosable financial interest.
(c)Agency actions to ensure reliability of data. If FDA determines that the financial interests of any clinical investigator
raise a serious question about the integrity of the data, FDA will take any action it deems necessary to ensure the
reliability of the data including:
(1) Initiating agency audits of the data derived from the clinical investigator in question;
(2) Requesting that the applicant submit further analyses of data, e.g., to evaluate the effect of the clinical investigator's
data on overall study outcome;
(3) Requesting that the applicant conduct additional independent studies to confirm the results of the questioned study;
and
(4) Refusing to treat the covered clinical study as providing data that can be the basis for an agency action.
Sec. 54.6 Recordkeeping and record retention.
(a)Financial records of clinical investigators to be retained. An applicant who has submitted a marketing application
containing covered clinical studies shall keep on file certain information pertaining to the financial interests of clinical
investigators who conducted studies on which the application relies and who are not full or part-time employees of the
applicant, as follows:
(1) Complete records showing any financial interest or arrangement as described in 54.4(a)(3)(i) paid to such clinical
investigators by the sponsor of the covered study.
(2) Complete records showing significant payments of other sorts, as described in 54.4(a)(3)(ii), made by the sponsor of
the covered clinical study to the clinical investigator.
(3) Complete records showing any financial interests held by clinical investigators as set forth in 54.4(a)(3)(iii) and
(a)(3)(iv).
(b)Requirements for maintenance of clinical investigators' financial records. (1) For any application submitted for a
covered product, an applicant shall retain records as described in paragraph (a) of this section for 2 years after the date
of approval of the application.
(2) The person maintaining these records shall, upon request from any properly authorized officer or employee of FDA,
at reasonable times, permit such officer or employee to have access to and copy and verify these records.
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[COMMENT: The Sponsor-Investigator must have documentation on file for each investigator and
subinvestigator who is involved in the clinical trial(s) under this IND which states whether or not the
individual has any type of financial interest which could be perceived as potentially influencing the
outcome. This documentation must be maintained in the IND regulatory files and updated as
needed.]
[GUIDANCE DOCUMENTS: The FDA, NIH, and JHU have guidance documents concerning financial
conflicts of interest which should be reviewed in order to verify that the Sponsor-Investigator and
project team are in compliance. Web addresses for these guidance document websites are listed
below.
Guidance Documents:
 FDA Guidances:
o Current Guidance dated 2001
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126832.htm
o
Draft Guidance Dated May 2011
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM256525.pdf

HHS-OHRP Guidance:
http://www.hhs.gov/ohrp/policy/fguid.pdf

JHM IRB Guidance:
http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/organization_policies/10
3_11.html

JHU Conflict of Interest Policy:
http://jhuresearch.jhu.edu/Policy_onConflict_of_Interest.pdf

JHU Research Administration – Conflict of Interest website:
http://jhuresearch.jhu.edu/compliance-conflict.htm
6.2.3.1 Form FDA 3454
[FORM FDA 3454 INSTRUCTIONS/COMMENTS: The Form FDA 3454 provides documentation to
the FDA that the Sponsor-Investigator, other clinical investigator(s), and/or subinvestigator(s) DO
NOT have any financial interests that may influence the outcome of the study.

Form FDA 3454:
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM048304.pdf]
[SUGGESTED TEXT: “The completed Form FDA 3454 may be found on the next page.” OR “Please
see the completed Form FDA 3454 in appendix ##.”]
6.2.3.2 Form FDA 3455
[COMMENT:
Reportable Disclosures:
If the Sponsor-Investigator, other clinical investigator(s), and/or
subinvestigator(s) have any financial conflict of interest(s) that is/are being managed per JHU policies,
each conflicted individual must complete and submit a Form FDA 3455 with attached copy of the
conflict management plan with the IND application. If this is not applicable, then delete this section
and delete from table of contents.
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No Reportable Disclosures: The DDRS has been informed that during FDA inspections/audits, the
FDA has cited investigators for not having a completed Form FDA 3455 as part of the IND‟s
regulatory documentation. Therefore, even if there are no reportable disclosures, any time a Form
FDA 3454 is being submitted a Form FDA 3455 should also be submitted. When completing the
Form FDA 3455, all sections of the form should be completed except you do not check off any of the
boxes describing reportable financial disclosures.]
[Form FDA 3455:

http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM048310.pdf]
[SUGGESTED TEXT: “The Sponsor-Investigator has completed Form FDA 3455 which may be found
on the next page.” OR “Please see the Form FDA 3455 for the Sponsor-Investigator in appendix ##.”]
6.3 Patient Selection and Estimated Number to be Studied
[INSTRUCTIONS: Provide a brief description of the criteria for patient selection and for exclusion of
patients as well as an estimate of the number of patients to be studied for the entire proposed trial
here.]
6.4 Description of Study Design
[INSTRUCTIONS: Provide a brief description of the design of the proposed study, including the type
of control group to be used, if any, and a description of methods to be used to minimize bias on the
part of subjects, investigators, and analysts here.]
6.5 Drug Dosing – Method, Maximum Dose, and Duration of Exposure:
[INSTRUCTIONS: Provide a brief description of the method for determining the dose(s) of
investigational drug to be administered, the planned maximum dosage, and the duration of individual
patient exposure to the investigational drug here].
6.6 Observations and Measurements Made to Fulfill Study Objectives
[INSTRUCTIONS: Provide a brief description of the observations and measurements to be made to
fulfill the objectives of the study here.]
6.7 Procedures to Monitor Drug Effects in Human Subjects and Minimize Risks
[INSTRUCTIONS: Provide a brief description of the clinical procedures, laboratory tests, or other
measures to be taken to monitor the effects of the investigational drug in human subjects and to
minimize risk here.]
[COMMENT: This is the data safety monitoring plan.]
6.8 Clinical Trial Registration
[COMMENTS: Per Title VIII of the Food and Drug Administration Amendments Act of 2007 or FDAAA
(U.S. Public Law 110-85) clinical trial registration and reporting requirements, all applicable trials must
be registered at clinicaltrials.gov, and results reported as required. As part of this requirement, the
FDA created the Form FDA 3674 to certify compliance with registration of trials. Below are a number
of resources that provide additional guidance and information concerning this requirement. If the
Sponsor-Investigator needs additional guidance, please contact the ICTR Research Navigators. Even
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if the protocol being submitted is not required to be registered at ClinicalTrials.gov, the SponsorInvestigator must check the appropriate box in section 9 of the form and submit the Form FDA 3674,
entitled „Certification of Compliance, under 42 U.S.C § 282(j)(5)(B), with Requirements of
ClinicalTrials.gov Data Bank (42 U.S.C § 282(j))‟, with the IND application.]
[GUIDANCE/INFORMATION RESOURCES FOR TRIAL REGISTRATION:

FDA Guidance Document on registering trials on ClinicalTrials.gov:
http://www.fda.gov/RegulatoryInformation/Guidances/ucm125335.htm

Clinicaltrials.gov Protocol Registration System Information Website
http://prsinfo.clinicaltrials.gov/fdaaa.html.

NIH Grantees Clinicaltrials.gov and FDAAA Policy Site
http://grants.nih.gov/ClinicalTrials_fdaaa/

JHM IRB Policy and Guideline
o Organizational
Policy
http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/organization_policies
/103_25.html
o
Guideline
http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/clinical_tri
als.html]
[FORM FDA 3674 website to download PDF fillable form:

http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM048364.pdf]
[Form FDA 3674 instructions website:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/Approva
lApplications/InvestigationalNewDrugINDApplication/ucm071098.htm#form3674]
6.8.1 Form FDA 3674
[SUGGESTED TEXT: “The signed and dated Form FDA 3674 can be found on the next page.” OR
“Please see the signed and dated Form FDA 3674 in appendix ##.”]
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Section 7: Chemistry, Manufacturing, and Controls (CMC)
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.
This section must be written by a person or organization familiar with the manufacture of drug
products.
If the drug product is a FDA approved product and not being adulterated for the proposed
clinical trials, then this section may not be needed. If you are not certain if this section is
needed, then you should consult with a Navigator or the FDA before submitting the IND
application.]
[REGULATORY REFERENCE: 21CFR312.23(a)(7):
(i) As appropriate for the particular investigations covered by the IND, a section describing the composition,
manufacture, and control of the drug substance and the drug product. Although in each phase of the
investigation sufficient information is required to be submitted to assure the proper identification, quality,
purity, and strength of the investigational 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 new drug substance and dosage form and changes in the dosage form itself are likely as
the investigation progresses. Therefore, the emphasis in 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.
(ii) It should be emphasized that the amount of information to be submitted depends upon the scope of the
proposed clinical investigation. For example, 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 investigation, if very short-term tests are proposed,
the supporting stability data can be correspondingly limited.
(iii) As drug development proceeds and as the scale or production is changed from the pilot-scale
production appropriate for the limited initial clinical investigations to the larger-scale production needed for
expanded clinical trials, the sponsor should submit information amendments to supplement the initial
information submitted on the chemistry, manufacturing, and control processes with information appropriate
to the expanded scope of the investigation.
(iv) Reflecting the distinctions described in this paragraph (a)(7), and based on the phase(s) to be studied,
the submission is required to contain the following:
(a) 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. Reference to the current
edition of the United States Pharmacopeia--National Formulary may satisfy relevant requirements in this
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paragraph.
(b) 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, and, where applicable, the quantitative composition of the
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 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. Reference to the current edition of the United States Pharmacopeia--National Formulary may
satisfy certain requirements in this paragraph.
(c) A brief general description of the composition, manufacture, and control of any placebo used
in a controlled clinical trial.
(d) Labeling. A copy of all labels and labeling to be provided to each investigator.
(e) Environmental analysis requirements. A claim for categorical exclusion under 25.30 or 25.31 or
an environmental assessment under 25.40.]
[GUIDANCE DOCUMENTS: Web addresses for various guidance documents concerning the CMC
are listed below.

FDA Guidance Document - Chemistry, Manufacturing, and Controls (CMC)
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064979.htm

FDA Guidance Documents - CMC - Microbiology (Chemistry, Manufacturing, and Controls)
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064983.htm

FDA Guidance Documents - Current Good Manufacturing Practices (CGMPs)/Compliance
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064971.htm

FDA Guidance Documents - International Conference on Harmonisation – Quality
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065005.htm

FDA Guidance Document - Exploratory IND Guidance Document
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078933.pd f
[ADDITIONAL REGULATIONS APPLICABLE TO CMC:

21CFR210 - CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING,
PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=210&showFR=1

21CFR211 - CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED
PHARMACEUTICALS
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=211&showFR=1

21CRF25 - ENVIRONMENTAL IMPACT CONSIDERATIONS
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=25]
[GENERAL COMMENTS:
For all phases of clinical trials (per 21CFR 312.23):
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1. Sufficient information must be submitted to assure proper identification, quality, purity, and
strength of the investigational drug.
2. Stability data is required at all phases of the trial. However, scope of data depends on the phase
of the investigation (i.e. limited data for very short-term studies)
3. When drug manufacturing shifts from smaller to larger scale production, any changes in the
manufacturing process must be submitted as information amendments to the IND.
4. If submitting a Phase 1 study, the following guidance should be reviewed:
 CGMP for Phase 1 Investigational Drugs:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070273.pdf]
7. Chemistry, Manufacturing, and Control Data
7.1 Introduction: Statement of Risk
[INSTRUCTIONS: A statement whether or not chemistry of either the investigational drug or drug
product or the manufacturing of either moiety presents any risk should be included here.
A description of any chemistry and/or manufacturing differences between the drug proposed for use in
proposed trial and that used in animal toxicology trials must be included here.
7.2 Drug Substance
[INSTRUCTIONS: Provide the following information for the Drug Substance Description:
a.
b.
c.
d.
Description including physical, chemical, and/or biological characteristics
Name and address of manufacturer
Description of manufacturing processes that should include flow diagram
Description Acceptable limits and analytical methods to demonstrate identity, strength, quality
and purity including copy of COA (Validation data and established specifications may only be
required for some well characterized biotechnology products)
e. Description stability data and test methods to obtain data during toxicologic studies and
proposed trial planned trial.
f. References to US Pharmacopeia-National Formulary may be made to supply requested
information]
7.3 Drug Product
[INSTRUCTIONS: Provide the following information for the Drug Product Description:
a. List of all components including reasonable substitutes for inactive compounds which do or do
not appear in final drug product
b. Quantitative composition of the drug product including any reasonable or anticipated variations
during the manufacture
c. Name and address of manufacturer
d. Written and diagrammatic descriptions of the manufacturing process including sterilization
processes where applicable and packaging procedures
e. Brief description of test methods used to show identity, strength, quality and purity, including
copy of COA for clinical batch (Assessment of bioactivity and preliminary specifications may
be required for some well characterized biotechnology products)
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Description of stability data and test methods to obtain data in the drug's final packaging
during toxicologic studies and proposed trial.]
7.4 Placebo
[INSTRUCTIONS: Provide a brief diagrammatic, tabular, and written description of the composition,
manufacture, and control of any placebo used in the proposed trial here.]
7.5 Labeling
[INSTRUCTIONS: Provide a copy of all investigational drug and/or placebo labels to be used here.]
7.6 Claim for Categorical Exclusion for Environmental Assessment
[INSTRUCTIONS: A statement regarding whether or not the investigational drug product qualifies for
a categorical exclusion from or the submission of an environmental assessment per
21CFR312.23(a)(7)(iv)(e) belongs here. Usually, for an IND, a claim for categorical exclusion is
requested under 21CFR25.30 or 21CFR25.31 or an environmental assessment under 21CFR25.40.
Below are the web address for all regulations for 21CFR25.30, 21CFR25.31, and 21CFR25.40.

21CFR25.30:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=25.30

21CRF25.31:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=25.31

21CFR25.40:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=25.40]
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Section 8: Pharmacology and toxicology
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(8) –
Pharmacology and toxicology information:- 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. The kind, duration, and scope of
animal and other tests required varies with the duration and nature of the proposed clinical investigations.
Guidance documents are available from FDA that describe ways in which these requirements may be met.
Such information is required to include the identification and qualifications of the individuals who evaluated
the results of such studies and concluded that it is reasonably safe to begin the proposed investigations and
a statement of where the investigations were conducted and where the records are available for inspection.
As drug development proceeds, the sponsor is required to submit informational amendments, as
appropriate, with additional information pertinent to safety.
(i) A section describing the pharmacological effects and mechanism(s) of action of the drug in animals, and
information on the absorption, distribution, metabolism, and excretion of the drug, if known.
(ii)(a) An integrated summary of the toxicological effects of the drug in animals and in vitro. Depending on
the nature of the drug and the phase of the investigation, the description 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.
(ii)(b) For each toxicology study that is intended primarily to support the safety of the proposed clinical
investigation, a full tabulation of data suitable for detailed review.
(iii) For each nonclinical laboratory study subject to the good laboratory practice regulations under part 58, a
statement that the study was conducted in compliance with the good laboratory practice regulations in part
58, or, if the study was not conducted in compliance with those regulations, a brief statement of the reason
for the noncompliance.
[INSTRUCTIONS: Under each of the following headings are listed the requirements for this section
as per the regulatory reference cited above. If this information is provided as a report from the vendor
who performed the nonclinical studies, it is suggested that a high level summary be provided below
and the vendor‟s reports placed in the appendix.
After each summary/description of nonclinical testing, be certain to indicate whether or not the testing
was performed in compliance with Good Laboratory Practices (GLP). If the testing was performed by
a vendor, please indicate whether or not a certificate of GLP compliance is being provided and crossreference the certificate‟s location in the IND application. If the testing was not performed in
compliance with GLP, provide a statement here describing why the testing was not performed in
compliance with GLP. The web address for FDA GLP regulations is provided below.
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Additionally, a list of web addresses for guidance documents that describe the various requirements
and options for nonclinical safety testing are also provided below.]
[GLP FDA REGULATIONS: For more information concerning Good Laboratory Practice, please see
the regulations at the following website:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=58&showFR=1]
[GUIDANCE DOCUMENTS: Below are web addresses for various guidance documents concerning
nonclinical safety testing:

FDA list of International Conference on Harmonisation – Safety Guidance Documents:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065007.htm

FDA Pharm / Tox Guidance Documents:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065014.htm

Exploratory IND Guidance Document:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078933.pdf

Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized,
Therapeutic, Biotechnology-Derived Products (Answers questions concerning Pharmacology and
Toxicology):
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078928.pdf
8. Pharmacology and toxicology information
8.1 Pharmacology and drug disposition
[INSTRUCTIONS: Describe 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) here.]
8.2 Toxicology
[INSTRUCTIONS: Provide an integrated summary of the toxicological effects of the investigational
drug in animals and in vitro. Depending on the nature of the investigational drug and the phase of the
investigation, the description should 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 testing 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 here.
For each toxicology study that is primarily intended to support the safety of the proposed clinical
investigation, a full tabulation of data suitable for detailed review should be included here.]
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Section 9: Previous human experience
[SECTION INTRODUCTION: The requirements for this section of the IND application are provided below.
NOTE: Some of the information included may not be applicable to all IND applications.
General instructions and comments on the format and content of this section of the IND application,
along with a list of guidance documents and additional regulation references, are provided. Within each
subheading of this section are additional instructions, comments, suggested text, web addresses for
forms, web addresses for specific guidance documents, and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(9) – Previous human experience with the investigational
drug. A summary of previous human experience known to the applicant, if any, with the investigational drug.
The information is required to include the following:
(i) If the investigational drug has been investigated or marketed previously, either in the United States or
other countries, detailed information about such experience that is relevant to the safety of the proposed
investigation or to the investigation's rationale. If the drug has been the subject of controlled 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 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.
(ii) If the drug is a combination of drugs previously investigated or marketed, the information required under
paragraph (a)(9)(i) of 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 interaction).
(iii) If the drug has been marketed outside the United States, a list of the countries in which the drug has
been marketed and a list of the countries in which the drug has been withdrawn from marketing for reasons
potentially related to safety or effectiveness.
9. Previous human experience with the investigational drug
[INSTRUCTIONS: Provide the information requested per the above regulatory requirements. Insert
subheadings as needed per the information provided. If there is no data on previous human
experience with the investigational drug, then insert text stating that there is no previous human
experience here.]
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Section 10: Additional Information
[SECTION INTRODUCTION: The requirements for this section of the IND application are
provided below. NOTE: Some of the information included may not be applicable to all IND
applications.
General instructions and comments on the format and content of this section of the IND
application, along with a list of guidance documents and additional regulation references, are
provided. Within each subheading of this section are additional instructions, comments,
suggested text, web addresses for forms, web addresses for specific guidance documents,
and/or regulations.]
[REGULATORY REFERENCE: 21CFR312.23(a)(10) - Additional information. In certain IND applications, as
described below, information about special topics may be needed. Such information should be submitted in this
section as follows:]
(i) Drug dependence and abuse potential. If the drug is a psychotropic substance or otherwise has abuse
potential, a section describing relevant clinical studies and experience and studies in test animals.]
(ii) Radioactive drugs. If the drug is a radioactive drug, sufficient data from animal or human studies to
allow a reasonable calculation of radiation-absorbed dose to the whole body and critical organs upon
administration to a human subject. Phase 1 studies of radioactive drugs must include studies which will
obtain sufficient data for dosimetry calculations.]
(iii) Pediatric studies. Plans for assessing pediatric safety and effectiveness.]
(iii) Other information. A brief statement of any other information that would aid evaluation of the proposed
clinical investigations with respect to their safety or their design and potential as controlled clinical trials
to support marketing of the drug.]
[INSTRUCTIONS: Under each heading below are listed the regulatory requirements per the above
regulatory reference. Note: Each section should be addressed and, if not applicable, state “not
applicable” and provide an explanation as to why it does not apply here.]
10. Additional information
10.1
Drug dependence and abuse potential
[INSTRUCTIONS: Drug dependence and abuse potential. If the investigational drug is a psychotropic
substance or has other abuse potential, a section describing relevant clinical studies and experience
and studies in test animals should be included here. Below is web address for an FDA draft guidance
on the assessment of abuse potentials.]
[FDA DRAFT Guidance: Assessment of Abuse Potential of Drugs:
 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM198650.pdf]
10.2
Radioactive drugs
[INSTRUCTIONS: If this application is for an investigational radioactive drug, please discuss the
placement of information within the application with the Research Navigators. For more information
on radioactive drugs, please review information available at the FDA‟s Medical Imaging and Drug
Development website (provided below).]
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[FDA Medical Imaging and Drug Development website:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm092895.htm]
10.3
Pediatric studies
[INSTRUCTIONS: Describe the plans for assessing pediatric safety and effectiveness here. If there
are not plans to assess pediatric safety and effectiveness, explain why here. The FDA site on
Pediatric Drug Development has more information on pediatric safety and effectiveness assessment
and their web address is provided below.
[FDA website on Pediatric Drug Development:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm049867.htm]
10.4
Other information
[INSTRUCTIONS: Provide any additional information here which you believe will add to the FDA
review of this IND application.]
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Section 11: Relevant Information
[SECTION INSTRUCTIONS: Per regulatory requirements, include in this section any relevant
information requested by the FDA that may be needed for the review of this IND application.]
[REGULATORY REFERENCE: 21CFR312.23(a)(10) - Relevant information. If requested by FDA, any other
relevant information needed for review of the application.]
11.0
Relevant Information
[INSTRUCTIONS: Per the section instructions and regulatory reference, provide any relevant
information the FDA requested be submitted with the application. If the FDA did not make such a
request, then either remove this section or insert text stating the FDA did not request relevant
information be submitted with this application.]
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Section 12: Bibliography
[SECTION INSTRUCTIONS: Provide a list of references cited in the IND application here. Note:
The bibliographical information may instead be provided after each of the above IND
application sections. If the Sponsor-Investigator chooses to do this, delete this section here
and from the table of contents.]
12.
Bibliography
[INSTRUCTIONS: Insert bibliography/literature cited.]
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Section 13: Appendices
[SECTION INSTRUCTIONS: Provide a list of the appendices in order of appearance in the
sections of the IND application. Before each appendix, include a cover page describing the
document(s) that will be found in that appendix.]
[ADDITIONAL INSTRUCTIONS - Copies of selected papers referenced in the IND application:
While not required, it is strongly suggested that the Sponsor-Investigator provide copies of key papers
that are referenced in the body of the IND application. Providing copies of any key papers will make it
easier for the FDA reviewers to access the papers if they want more information. As with the other
Appendices, include a cover page with this appendix, listing in order of appearance the citations for
the papers being submitted with the IND application.]
13. Appendices
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