Revised November 2014
To assist investigators that seek NIDA funding for studies evaluating electronic cigarettes (e-cigarettes) in humans, this FAQ provides information to help determine the need for submitting to FDA an Investigational New Drug (IND) application. Because FDA makes determinations about investigational new drug applications (INDs) on a case-by-case basis, investigators should discuss their study protocol with FDA regarding any questions on whether the IND requirements apply to their planned clinical investigation. This document does not take the place of Institutional Review Board (IRB) requirements, FDA regulations, or NIH policies.
What is an IND?
An IND is an investigational new drug application. A sponsor must submit an IND to FDA if the sponsor intends to conduct a clinical investigation with an investigational new drug that is not exempt from the IND requirements in 21 CFR Part 312. For studies that require an IND, a sponsor may not begin the clinical investigation until the IND is in effect. An investigational drug covered by an IND is exempt from the premarketing approval requirements that are otherwise applicable to new drugs and may be shipped lawfully for the purpose of conducting clinical investigations of that drug.
When is an IND required for a planned clinical study of e-cigarettes?
- An IND is required if the e-cigarettes are intended for use in a clinical investigation for a therapeutic purpose (e.g., smoking cessation). The requirement that a study proceed under an IND is independent of the constituents of the e-cigarette (e.g., nicotine content or flavoring agents) or the type of e-cigarette being studied (e.g., disposable, sealed cartridge or tank system). Rather, the requirement for an IND depends on the intended use. If the study is examining a potential therapeutic purpose, then an IND is required.
- Additional information about when an IND is required can be found in the FDA guidance document entitled “Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND.” This guidance document is available on FDA’s Web site at http://www.fda.gov/downloads/UCM229175.pdf (PDF, 295 KB). You can also contact Alina Salvatore at FDA via email: Alina.Salvatore@fda.hhs.gov
- For NIDA grantees and applicants, further questions regarding e-cigarettes and planned clinical studies should be directed to your program officer or Dr. Kevin Walton, firstname.lastname@example.org.
If an IND is required for my clinical study of e-cigarettes, what do I do?
If an IND is required for a planned clinical study of e-cigarettes, an IND application must be submitted to FDA’s Center for Drug Evaluation and Research (CDER). Once the IND is submitted, the clinical investigator generally must wait 30 calendar days before initiating the study described in the IND. During this time, FDA reviews the IND for safety to assure that research subjects will not be subjected to unreasonable risk.
An e-cigarette clinical study requiring an IND is not eligible for the IND exemption at 21 CFR 312.2(b)(1). To qualify for this exemption, a clinical study must involve the use of a lawfully marketed drug product. At this time, there are no lawfully marketed e-cigarette drug products.
What information is included in an IND application?
Specific details to be included vary based on the application; however, they generally include information in the following broad areas:
- Animal Pharmacology and Toxicology Studies - Preclinical data to permit an assessment as to whether the constituents and product is reasonably safe for initial testing in humans.
- Manufacturing Information - Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.
- Clinical Protocols and Investigator Information - Detailed protocols to assess whether the trials will expose subjects to unnecessary risks; information on investigator qualifications; and, commitments to obtain informed consent from research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.
Who determines whether an IND is required for a planned clinical study of e-cigarettes?
- It is the responsibility of the sponsor (or the sponsor-investigator) to determine whether an IND is required for a planned clinical study.
- A clinical investigator may obtain information from FDA if there are questions about whether a planned clinical study requires an IND. Follow the guidance provided below.
Investigator Inquiry to FDA on the Need for an Investigational New Drug (IND) Application to Conduct a Clinical Study with Electronic Cigarettes
FDA has a pre-IND consultation process to help you determine the applicability of IND requirements to a planned clinical investigation. If you are uncertain whether your planned clinical investigation requires an IND, we recommend you contact FDA. We recommend that you submit the following information to assist FDA in advising on the applicability of IND requirements to your planned clinical investigation.
For the FDA to respond to your inquiry, email the information to Alina Salvatore at: Alina.Salvatore@fda.hhs.gov. Alternatively, mail it to FDA/CDER/CDR; Attention: Division of Nonprescription Clinical Evaluation; 5901-B Ammendale Road, Beltsville, MD 20705-1266. Please use only one method to submit this information.
- Your name, complete postal mailing address, phone number, fax number, email address, and organizational affiliation.
- The title of the study protocol.
- The name and a brief description of the substance(s) to be administered, the source (e.g., animal, synthetic, etc.), dosage form(s), sterility (if applicable), supplier(s) and manufacturer(s). If the specific product you plan to use has a trade name, list it.
- State whether the study subjects will receive the marketed product (modified or unmodified) or a special preparation.
- A brief summary of the study including the purpose, hypothesis, number of subjects, patient population, condition or disease (if applicable), dose, route, and duration of substance administration, and endpoint measures.
- A copy of the full protocol.
- A brief explanation of why you consider the substance(s) safe for administration to human subjects under the conditions of the study (append references, if necessary).
- A brief explanation of whether the protocol involves a therapeutic purpose or not.
Please contact FDA if you have questions or need more information.
**Note: The foregoing information is not endorsed or approved by FDA