Initial IDE submission


IDE Template

Maintain all of the headings in this document. If some are not applicable, simply state this under the appropriate headings.

When the submission is finalized, be sure to save as a PDF and rename according to e-copy guidelines.

IDE Template

Sections of an Initial IDE Submission

While the FDA has not officially outlined how they prefer the contents of an IDE submission to be presented, including the information listed in the sections below will provide the FDA with the information necessary to conduct a successful review.

Although a manufacturer may be supplying the device being investigated, the FDA defines the study "sponsor" as the person, company, or institution who is responsible for the regulatory aspects of the study. Often in an academic setting the investigator is called a "sponsor-investigator" because they assume both roles of the research.

Provide the following information in this section:

Sponsor Name
Address
Phone Number
Fax Number
Email Address

It is also strongly encouraged to also provide information for a designated alternate contact who is authorized by the sponsor to correspond with the FDA in the event that the sponsor cannot be reached. This person often the project manager, or regulatory coordinator for the investigation.

Alt. Contact Name
Address
Phone Number
Fax Number
Email Address

In this section, the sponsor should provide a complete report of prior investigations of the device.

General

The report of prior investigations shall include reports of all prior clinical, animal, and laboratory testing of the device and shall be comprehensive and adequate to justify the proposed investigation.

Specific Content

  • A bibliography of all publications, whether adverse of supportive, that are relevant to an evaluation of the safety or effectiveness of the device, copies of all published and unpublished adverse information, and, if requested by an IRB or FDA, copies of other significant publications.

  • A summary of all other unpublished information (whether adverse or supportive) in the possession of, or reasonably obtainable by, the sponsor that is relevant to an evaluation of safety or effectiveness of the device.

  • If information on nonclinical laboratory studies is provided a statement that all such studies have been conducted in compliance with applicable requirements in the good laboratory practice (GLP) regulation in 21 CFR part 58. If the study was not conducted in compliance with such regulations, a brief statement of the reason for the non-compliance.

At the beginning of this section, the sponsor can give a brief overview of the investigation plan, logic and need for this trial, is it a single-site study, what are the end points etc.

Purpose

The name and intended use of the device and the objectives and duration of the investigation.

Protocol

A written protocol describing the methodology to be used and an analysis of the protocol demonstrating that the investigation is scientifically sound.

Rather than insert the protocol within this document, we recommend that you assemble the IDE after separately printing this IDE document and the protocol. To ensure that the TOC on Page 2 reflects the true number of pages in the IDE, 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.

Risk Analysis

A description and analysis of all increased risks to which subject will be exposed by the investigation; the manner in which these risk will be minimized; a justification that the risks are reasonable in relation to the expected benefits; and a description of the patient population including the number, age, sex, and condition.

The risk analysis should include the anticipated benefits and potential clinical effects of failure identified in the device evaluation strategy, as well as risks independent of the device that may be related to the underlying disease comorbidities, or inherent to the procedure, and benefits unique to the device concept. For example, a risk analysis may include the risks associated with use of anesthetic and contrast agents and the benefits of a less invasive intervention.

Methods to minimize risks may include the use of standard approaches, with additional mitigation strategies to protect individual study subjects and future study participants during the ongoing study. Examples of both standard and additional risk mitigation strategies include:

  • use of study sites that have sufficient expertise and resources to manage adverse events and provide appropriate alternative therapies if needed;

  • identification of qualified investigators with adequate training to conduct the early feasibility study;

  • a plan to capture human factors information during the course of the study to modify the procedures or device as necessary based on the information obtained;

  • specifying appropriate study inclusion and exclusion criteria;

  • limiting the sample size to a reasonable number for an early feasibility study (e.g., 5-10 initial subjects);

  • follow-up assessments at regular intervals to monitor subject safety and device effectiveness (i.e., potentially more frequent than for a traditional feasibility or pivotal study);

  • timely reporting of serious adverse events (e.g., after each occurrence rather than only in a periodic progress report);

  • timely reporting of device performance parameters, which help determine whether the device functions as intended (e.g., measurements of deliverability, stability, handling, visualization, patency, integrity);

  • non-sequential enrollment, that is, initial device use in subjects with more favorable anatomical characteristics as compared to the population otherwise eligible for the early feasibility study (e.g., selecting subjects that meet study eligibility requirements but do not have anatomic features that may increase the difficulty of device use); and

  • a pre-specified plan for periodic patient outcome assessments and reporting prior to enrollment of additional patients (e.g., as frequently as after each use of the device).

One way to present the risk/benefit assessment is through a device evaluation strategy table.

The process of constructing the device evaluation strategy table can be divided into four parts:

  1. Device Deconstruction – identify the attributes needed for the device to achieve the design goals (Column 1), the potential failure modes (Column 2), and the effects of failure (Columns 3 and 4).
  2. Knowledge Base and Mitigation Strategies – describe what is known from the device design (Column 5), leveraged nonclinical and clinical information from internal or external sources (Columns 6 and 7), and the clinical study mitigation strategies (Column 9) applicable to the attributes and failure modes.
  3. Evidence Gaps – identify gaps in the existing information indicating that additional testing may be needed to justify study initiation, considering the Knowledge Base and focusing on the following:
    • attributes most important for the intended use;
    • potential failure modes most likely to be associated with catastrophic failures; and
    • basic safety requirements (e.g., biocompatibility).
  4. Filling the Gaps – identify in Column 8 the bench, laboratory, analytical, and/or animal testing to complete the evaluation of the device attributes and the potential associated failure modes, considering the following:
    • Evidence Gaps;
    • clinical context for the early feasibility study;
    • potential types, frequency, and severity of the clinical effects of failure that may be associated with the device or procedure; and
    • Mitigation Strategies.

Description of Device

A description of each important component, ingredient, property and principle of operation of the device and of each anticipated change in the device during the course of investigation. Include any drawings, photos, videos, or design information.

Make sure your device description is clear and describes ALL elements of your proposed device (e.g., physical description, figures, materials of construction, software documentation), in addition to providing its dimensions and all of the dimensions of its components. Diagrams of both your device and an exploded view of your device with all of the components identified are very helpful.

Clearly identify how all components of your device fit together and are held together.

Clearly describe the functional purpose of each element of your device. This helps FDA both understand the components of your device and your device as a whole.

Clearly identify all of the different sizes and configurations your device comes in. It is often helpful if this is done in a tabular format.

Always make sure you use consistent terminology for each component of your device in your submission.

Monitoring Procedures

The sponsor's written procedures for monitoring the investigation and the name and address of each monitor.

The following language can be used for studies conducted at a single site where only one investigator, the sponsor-investigator, is involved in the study:

"A risk-based monitoring plan will be developed and implemented for the proposed clinical study."

Based on the latest FDA guidance on IDE policies and procedures (January 20, 1998), the submission of written monitoring procedures is not required for a sponsor-investigator initiated study where only one investigator will be involved in the study. The sponsor-investigator, Dr. [insert name], will serve as the study monitor for the clinical study proposed under this IDE.

If you are using a marketed device, then it is appropriate to refer to the product label and provide copy or a URL to the most current product label. If any modifications have been made, provide details on all changes.

If you have a Letter of Authorization (LoA) from another sponsor referencing their FDA submission (IND, NDA, BLA, IDE, DMF, etc), include the LoA in this section. The LoA serves the purpose to allow the FDA reviewer to review their submission on file in relation to your IDE application.

If you are manufacturing the device, include a description of the methods, facilities, and controls used for the manufacture, processing, packing, storage, and, where appropriate, installation of the device, in sufficient details so that a person generally familiar with good manufacturing practice can make a knowledgeable judgment about the quality control used in the manufacture of the device.

An example of the agreement to be entered into by all investigators to comply with investigator obligations under this part, and a list of the names and addresses of all investigators who have signed the agreement. Information that must be included in the written agreement can be found in §812.43.

A template for the investigators agreement is available upon request.

Investigators CV should be attached as a part of this section. Where applicable, a statement of the investigator's relevant experience (including the dates, location, extent and type of experience); If the investigator was involved in an investigation or other research that was terminated, an explanation of the circumstances that led to termination; and

Also, a statement of the investigator's commitment to:

  • Conduct the investigation in accordance with the agreement, the investigational plan, Part 812 and other applicable FDA regulations, and conditions of approval imposed by the reviewing IRB and FDA;

  • Supervise all testing of the device involving human subjects; and

  • Ensure that the requirements for obtaining informed consent are met

  • Investigator's commitment to provide sufficient and accurate financial disclosure information and update information if any relevant changes occur during the investigation and for one year following the completion of the study.

A statement that all investigators who will participate in the investigation have signed the agreement, that the list of investigators includes all the investigators participating in the investigation, and that no investigator will be added to the investigation until they have signed the agreement.

The following statement can be used to satisfy this requirement: "As required for an IDE study, we commit to obtain a signed investigator agreement from all current investigators who are participating in the investigation. Additionally, no future investigators will be added until they have signed the agreement."

A list of the name, address, and chairperson of each IRB that has been or will be asked to review the investigation and a certification of the action concerning the investigation taken by such IRB.

The name and address of any institution at which a part of the investigation may be conducted that has not been identified in accordance with section 7.

If the device is to be sold, the amount to be charged and an explanation of why sale does not constitute commercialization of the device.

A claim for categorical exclusion under § 25.30 or § 25.34 or environmental assessment under § 25.40.

Please maintain this header and include the following statement: "Please note that an environmental assessment as required under 21 CFR 25.40 or a claim for categorical exclusion under 21 CFR 25.30 or 25.34 is no longer required [§25.34(g)]."

Include copies of all labeling for the device. (If you are using a marketed device, then it is appropriate here to refer to the most current product labeling and provide and URL link to the most current labeling.)

Labeling is defined as "all labels and other written, printed, or graphic matter upon any article or any of its containers or wrappers, or accompanying such article at any time while a device is held for sale after shipment or delivery for shipment in interstate commerce."

An investigational device or its immediate package must bear a label with the following information:

  • The name and place of business of the manufacturer, packer, or distributor;

  • The quantity of contents, if appropriate; and

  • The statement, "CAUTION ­­ Investigational device. Limited by Federal (or United States) law to investigational use."

The label must also describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.

The labeling of an investigational device must not contain any false or misleading statements nor imply that the device is safe or effective for the purposes being investigated.

Any other relevant information FDA requests for review of the application.

This is a good place to include Form FDA 3674 and a good place to list any references that will be attached to the application.

Additionally, a complete IDE template can be downloaded:

IDE Template

Formatting Information, Mailing Instructions, and e-Copy Instructions

How many copies do I send?

  • Three Copies:

    • One original hard copy

    • 2 electronic copies with a single cover letter that contains a signature and an adequate eCopy statement

      • "the eCopy is an exact duplicate of the paper copy"

      • Or, "the eCopy is an exact duplicate of the paper copy, with the exception of..."

  • Three Hole Punched Documents

  • Use at least a 1 ½" wide left margin to allow for binding into jackets

  • Submit in ACCO-like Report Covers

    • Preferred Colors for Report Covers:

      • Original hard copy - grey

      • eCopies with single cover letter - color other than grey

What is an eCopy and where can I find information on the eCopy program for medical device submissions?

An electronic copy (eCopy) is an electronic version of your medical device submission stored on a compact disc (CD), digital video disc (DVD), or a flash drive. Including an eCopy with your submission has been required since January 1, 2013. A submission with an eCopy that does not meet the technical standards outlined in the eCopy guidance will be placed on eCopy hold until a valid eCopy is received.

The following resources will help you in understanding the eCopy program and how to successfully create and submit your eCopy:

If you have additional questions about the eCopy program, please contact the eCopy Program Coordinators at CDRH - eCopyinfo@fda.hhs.gov or 240-402-3717.

Where do I send my IDE?

These are current addresses, but please confirm on the FDA website:

  • For devices regulated by the Center for Devices and Radiological Health (CDRH):

    U.S. Food and Drug Administration
    Center for Devices and Radiological Health
    Document Mail Center - WO66-G609
    10903 New Hampshire Avenue
    Silver Spring, Maryland 20993-0002
  • For devices regulated by the Center for Biologics Evaluation and Research (CBER):

    U.S. Food and Drug Administration
    Center for Biologics Evaluation and Research
    Document Control Center - WO71-G112
    10903 New Hampshire Avenue
    Silver Spring, MD 20993-0002

Important note:

You must state on the outer packaging (e.g. The FedEx label) of each submission what the submission contains. For example, an "IDE application", a "supplemental IDE application" or a "correspondence concerning an IDE application". This should also be clearly stated on your cover letter in the "RE:" section.

Whom do I address in the submission?

The initial submission is usually sent to the attention of the Division Director. Organization charts on the FDA website can be helpful in identifying the proper division and director to be addressed.