INITIAL TOBACCO PRODUCT APPLICATION
Title
Name of Sponsor Investigator, MD
X Professor, Department
DUKE UNIVERSITY MEDICAL CENTER
Date of Submission
1. Table of Contents
1. Table of Contents 2
2. Introduction 3
2.1. Introductory Statement 3
2.2. Name of the Tobacco Product 3
2.3. Investigator(s) 3
2.4. Rationale 3
2.5. References 3
3. Protocol 4
3.1. Study Protocol 4
3.2. Informed Consent 5
3.3. Internal Review Board 6
3.4. Other 7
4. Chemistry, Manufacturing and Control Information 8
4.1. Manufacturer 8
4.2. Ingredients 8
4.2.1. Control of Raw Materials 8
4.3. Harmful Constituents 8
4.4. Manufacturing of the Tobacco Product 8
4.4.1. Manufacturing Process and In-Process Testing 9
4.4.2. Analytical Testing of In-Process Products 9
4.5. Labeling 10
4.6. Stability 10
5. Summary of Nonclinical or Clinical Studies 11
6. Informing Investigators 12
7. Investigator’s Brochure 13
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2. Introduction
2.1. Introductory Statement
Overall project description and specific purpose(s)/objective(s) of the clinical investigation and rationale for study (including the type of FDA submission, if any, that it is intended to support)
2.2. General Investigation Plan
Brief description of the study design including planned number of subjects.
2.3. Name of the Tobacco Product
Name or other identification to specifically identify the tobacco product
2.4. Investigator(s)
Name(s) and title(s) of the person(s) responsible for monitoring the conduct and progress of the clinical investigation
2.5. References
List any references for Section 2
3. Protocol
3.1. Study Protocol
Please insert study protocol
Rather than insert the protocol within this document, we recommend that you assemble the ITP after separately printing this ITP document and the protocol. To ensure that the TOC on Page 2 reflects the true number of pages in the ITP, format the page number on the Informed Consent page to reflect the additional pages in the protocol.
To format the page number, highlight the page number in the footer, right click and choose “Format Page Numbers”. Then click “Start numbering at” and put the new number accounting for the number of inserted pages. Also note, to be able reformate page numbers, you need to insert a “section break (next page)” rather than a simple page break.
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3.2. Informed Consent
Please insert informed consent
Rather than insert the Informed Consent within this document, we recommend that you assemble the ITP after separately printing this ITP document and the informed consent. To ensure that the TOC on Page 2 reflects the true number of pages in the ITP, format the page number on the Internal Review Board page to reflect the additional pages in the informed consent.
To format the page number, highlight the page number in the footer, right click and choose “Format Page Numbers”. Then click “Start numbering at” and put the new number accounting for the number of inserted pages. Also note, to be able reformate page numbers, you need to insert a “section break (next page)” rather than a simple page break.
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3.3. Internal Review Board
Name and address of reviewing IRB
Plus a statement like “We commit to not beginning any study related activities until we receive IRB approval for the study.”
OR – attach IRB approval documentation
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3.4. Other
This section is for other appropriate attachments such as assessment tools, questionnaires, and case report forms. Add additional Section headers as needed.
Follow appropriate page formatting/numbering instructions from Sections 3.1 and 3.2 as needed.
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4. Chemistry, Manufacturing and Control Information
If you have Letter of Authorization referencing another ITP, IND or MF regarding information that would normally be included in this section, place a copy of the LOA in this Section.
4.1. Manufacturer
Name and address of the tobacco product(s) manufacturer.
4.2. Ingredients
A list of all ingredients, including tobacco, substances, compounds, and additives that are added by the manufacturer to the tobacco, paper, filter, or other part of each of the investigational tobacco products. The list should include the quantities, specifications, and function of each ingredient.
4.2.1. Control of Raw Materials
The ingredients used in the manufacture of XY are listed bellow
Item Description/Name / Manufacturer / Quantity / Function / Acceptance Criteria/ Specification /4.3. Harmful Constituents
The quantities of harmful and potentially harmful constituents in or generated by each of the investigational tobacco products. Minimally, this should include nicotine, total particulate matter, and carbon monoxide.
4.4. Manufacturing of the Tobacco Product
A detailed description of the manufacturing and packaging processes for each of the investigational products including, but not limited to, all manufacturing phases and test methods used in each phase. The details should include the manufacturing requirements, specifications, and testing results.
Please make a general manufacturing diagram describing how the manufacturing flow looks like. Two examples are shown below (flow diagram or table).
General manufacturing flow diagram:
4.4.1. Manufacturing Process and In-Process Testing
Step / Description / In-process testing / Release testing1.
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2.
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5.
4.4.2. Analytical Testing of In-Process Products
Please describe the analytical testing performed on the tobacco product(s) during the manufacturing.
To fully identify and characterize the products, please provide a comprehensive description for each product you propose using in your study including, but not limited to, the following:
• Cigarette Weight (mg);
• Cigarette Resistance to Draw (mm H2O);
• Cigarette Length and Circumference (mm);
• Puff Count;
• Burn Rates(s);
• Tobacco Filler Weight (mg);
• Tobacco Filler Cut Width (mm);
• Tobacco Filler Oven Volatiles (OV) or Moisture (%);
• Tobacco Filler pH;
• Tipping Paper Ventilation (%);
• Tipping Paper Length (mm);
• Filter Length (mm);
• Filter Efficiency (%) - If no filter efficiency data is available for the products, please include information sufficient to show that the cigarette filter is unchanged (denier per filament, total denier, etc.);
• Filter (Plug) Pressure Drop (mm H2O); and
• Fire Standard Compliant (FSC) – If the products use FSC paper, provide the Base Paper Porosity (CU), Band Porosity (CU), Band Width (mm) and Band Space (mm).
For each of these parameters, provide full test data (including test protocols, quantitative acceptance (pass/fail) criteria, data sets and a summary of the results) for all testing performed.
4.5. Labeling
Copies of all labels and labeling provided to each investigator (please note that the labels should state "for investigational use only")
4.6. Stability
Information sufficient to ensure that the investigational products are stable during the planned study
5. Summary of Nonclinical or Clinical Studies
Results of any nonclinical or clinical studies that have been conducted previously on the specific investigational tobacco product (published or unpublished).
If you have Letter of Authorization referencing a MF regarding information that would normally be included in this section, you may refer to the DMF here.
If you have Letter of Authorization referencing another ITP, IND or MF regarding information that would normally be included in this section, place a copy or reference the LOA here.
6. Informing Investigators
Your plan for informing FDA and investigators of important new information including unexpected adverse events and changes to the protocol or statistical analysis plan
.
7. Investigator’s Brochure
The Investigator’s Brochure (recommended if there are multiple investigators or co-investigators) with the following information:
• brief description of the product
• summary of the pharmacological and toxicological effects, to the extent known
• summary of the pharmacokinetics, to the extent known
• summary of any information obtained from prior investigations of the product in humans relating to the health risks, including risk of abuse liability
• description of possible health risks, including abuse liability, to be anticipated based on prior experience with the tobacco product or with related tobacco products; also any precautions or special monitoring to be done as part of the investigation
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