Download Initial IND Submission Checklist

IND Content and Format Checklist
A sponsor who intends to conduct a clinical investigation with an investigational new drug/biologic
that is subject to 312.2(a) must submit an Investigational New Drug Application (IND). Detailed
information can be found on the FDA website, Code of Federal Regulations, 21 CFR 312
(http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312). An
outline of the contents is provided below:
Cover Letter
Transmittal letter introducing original IND submission
Cover Sheet (FDA 1571)
FDA Form 1571
Table of Contents
There is no standard format for the table, however FDA requires that the
format be “in the interest of fostering an efficient review of the application”
Introductory Statement and General Investigational Plan
This section should be brief, no more than three pages. The statement should
provide a description of the drug and the goals of the proposed investigations.
Specific elements should include:
i) A brief statement describing the drug, broad objectives, and planned
duration of the proposed clinical investigation
ii) A brief summary (if applicable) of previous human experience with the drug
iii) If the drug has been withdrawn from investigation or marketing in any
country, explain reasons for withdrawal
iv) A brief description of the overall plan for investigating the drug product for
the following year. This may include: rational for study, indication(s) to be
studied, general approach, types of clinical studies, target enrollment, and any
anticipated risks
Investigator’s Brochure
 An investigator’s Brochure may be obtained from the drug manufacturer or
referenced in a Letter of Authorization (see note below).
 For guidance on writing an Investigator’s Brochure, see ICH GCP Efficacy
Guidelines – E6 (http://www.ich.org )
i) A brief description of the drug substance and formulation
ii) Summary of the pharmacological and toxicological disposition of the drug in
animals and in humans (if known)
iii) Summary of safety and efficacy in humans obtained from prior clinical
studies
iv) A description of risk and side effects based on prior experience with the
drug under investigation or with related drugs, and any special monitoring
required as part of investigational use of the drug
Version: October 2010
Included
Protocol(s)
Include a protocol for each planned clinical study (Protocols for studies not
incorporated into the initial submission of the IND application should be
subsequently submitted as a Protocol Amendment
Format:
DF/HCC Biomedical Protocol Template (located in the Clinical Investigator Toolkit)
FDA Form 1572 for each clinical site conducting the protocol
A sample Informed Consent Form (if available)
FDA Form 3674 (ClinicalTrials.gov certification) for each applicable clinical trial
Chemistry, Manufacturing and Control Information
The CMC section should describe the composition, manufacture, and control of the
drug substance and the drug product. Information included in this section should
assure the proper identification, quality, purity, and strength of the investigational
drug.
Information regarding the Chemistry, Manufacturing, and Control section may be
obtained from the drug manufacturer or referenced in a Letter of Authorization
(see note below).
i) Description of the drug substance
ii) Description of the drug product
iii) Description of any placebo used in the studies
v) Specify any environmental analysis performed on investigational product or
indicate a claim for exclusion under 21 CFR 25.30 or 21 CFR 25.31
Pharmacology and Toxicology Information
The section should include information about pharmacological (no more than 5
pages) and toxicological studies (no more than 15 pages) involving laboratory
animals or in vitro, on the basis of which the sponsor has concluded that is
reasonably safe to conduct the proposed clinical investigations.
Information regarding the Pharmacology and Toxicology section may be obtained
from the drug manufacturer or referenced in a Letter of Authorization (see note
below).
i) Pharmacology and drug disposition
ii) Toxicology
iii) A statement that the study was conducted in compliance with GLP regulations
as outlined in 21 CFR 58
Version: October 2010
Previous Human Experience with the Investigational Drug
The section should indicate whether the investigational drug, or any of its active
ingredients, has been marketed or tested in humans previously. Include the
following:
i) A summary of previous human experience known to the sponsor
ii) If drug is combination product, a summary of previous human experience for
each active drug component
iii) A listing of countries in which the drug has been marketed and a listing of
countries in which the drug has been withdrawn from marketing for reasons
potentially related to safety or effectiveness
Additional Information
i) DF/HCC Institutional Data and Safety Monitoring Plan (located on the QACT
website)
ii) Letter of Authorization to Cross-Reference (if applicable)
iii) Certificate of Analysis (if applicable)
iii) A copy of all labels that will be assigned to the drug product and if applicable, all
labels that will be provided to each investigator. See 21 CFR 312.6 for labeling
requirements.
iv) Information regarding drug dependence and abuse potential (if applicable)
v) If the drug is radioactive, data from animal or human studies used for justifying
acceptable absorbed radiation calculation dose for human subjects (if applicable)
vi) Plans for assessing pediatric safety and effectiveness (if applicable)
FDA Forms 1571, 1572 and 3674 along with completion instructions can be located at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsare
DevelopedandApproved/ApprovalApplications/InvestigationalNewDrugIND
Application/ucm071098.htm
Letter of Authorization:
A letter of authorization is an authorization that the manufacturer is allowing FDA to refer to their IND or
marketing application in providing the technical information supporting the proposed clinical investigation.
The letter of authorization can be used for the Investigator’s Brochure, Chemistry, Manufacturing and
Controls, and the Pharmacology and Toxicology sections of the IND. Please note, it is recommended that the
Sponsor-Investigator and any site PIs have a copy of the Investigator’s Brochure as a reference throughout
the clinical trial. A sponsor-investigator submitting an IND not subject to a manufacturer's IND or marketing
application is ordinarily required to submit all technical information, unless such information may be
referenced from the scientific literature. (312.22 (d))
Version: October 2010