Improving patient access to new medical devices by strengthening and streamlining the clinical trial enterprise is a priority for CDRH. An important part of reaching that goal is to better track milestones in clinical trial development, Investigational Device Exemption (IDE) approval, study initiation, and study completion. FDA’s commitment to reporting certain metrics associated with IDE approval can be found the MDUFA III Commitment Letter to Congress .
On Aug. 18, 2013, CDRH will update our system used to process IDE and Emergency Use Authorization (EUA) submissions. The changes will provide a mechanism for tracking multiple studies—such as feasibility or pivotal studies—under a single original IDE submission number. Each subsequent submission to an IDE will be assigned to the appropriate study, so that the FDA can track milestones in clinical trial development, IDE approval, study initiation, and study completion.
The following changes will impact all IDE and EUA submissions received on or after Aug. 18, 2013. However, these changes will not impact the review period for these submissions; FDA will continue to review IDE submissions in 30 days and EUA submissions as quickly as possible. There are no new eCopy or other IT requirements for IDE and EUA submitters; however, FDA has outlined recommendations related to the submission process that are important for a smooth transition (see “Recommendations for IDE Submitters” below).
Changes to the IDE Submission Structure
The submission structure for IDEs will change in two key ways, both of which better align with the current structure for Pre-Market Approval (PMA) and Humanitarian Device Exemption (HDE) submissions.
After submission of an original IDE, the FDA will track subsequent submissions to that IDE as Supplements, Reports, or Amendments, as described below. Reports will now be tracked as a distinct submission type and will no longer be considered Supplements. In addition, the FDA will no longer consider responses from submitters to FDA deficiency letters to be Supplements. Instead, FDA will track deficiency letter responses as Amendments to the original IDE, IDE Supplement or IDE Report for which we issued the deficiency letter.
The FDA will track requests for a new protocol, changes to the approved protocol, or changes to the device, such as device design or manufacturing change, as supplements.
Submission reasons tracked as Supplements include:
- Change in correspondent, manufacturer, or sponsor
- Change in design or manufacturing
- Change in informed consent or protocol
- 5-day notices
- Request for compassionate use, live case demonstration, or other deviation from approved protocol
- Expansion of study (patients and/or sites)
- Extension of time to respond to FDA letter
- Request for waiver
- Institutional Review Board (IRB)certification
- Request for Centers for Medicare and Medicaid Services (CMS) recategorization
- Notification of study suspended or resumed
- Acknowledgement and response to clinical hold
- Termination of study without final report
- New study or protocol
The FDA previously tracked IDE reports as IDE supplements. IDE reports will now be tracked as a report and not as a supplement.
Submission reasons tracked as Reports include:
- Adverse Effect
- Final, Study Completed
- Annual Progress
- Interim Progress
- Semiannual Investigator List
- Failure to Obtain Informed Consent
- Compassionate Use Follow-Up
- Emergency Use
- Live Case Follow-Up
The FDA will track any IDE submission sent as a response to deficiencies communicated in an FDA disapproval, approval with conditions, or deficient report letter as an IDE Amendment to that submission.
For example, if you receive an “approval with conditions” letter after you submit your original IDE, your response intended to address deficiencies in that letter will be logged in as an Amendment. (Previously, such a submission would be tracked as a Supplement).
Amendments may be submitted to Supplements and Reports, as well as to the Original IDE.
Submission reasons tracked as Amendments:
- Response to Disapproval
- Response to Approval with Conditions
- Response to Refuse to Accept
- Response to Report Deficient
- Voluntary Withdrawal by Sponsor
Changes to Submission Structure for EUAs & PEUAs
Section 564 of the Federal Food, Drug, and Cosmetic Act was established to support preparedness efforts and rapid response capabilities for a range of stakeholders, such as federal partners like the Department of Defense and the Centers for Disease Control and Prevention, as well as state and local public health agencies in the event of a chemical, biological, radiological or nuclear attack, or an emerging infectious disease emergency.
Emergency Use Authorizations (EUAs) may be granted by FDA to allow medical countermeasures to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by such agents, when there are no adequate, approved, and available alternatives. The FDA can also begin review of such products prior to the declaration of an actual emergency through a request for Pre-Emergency Use Authorization (PEUA).
FDA will now track EUAs and PEUAs separately from IDEs.
Recommendations for IDE Submitters
1. Each IDE submission should address only one submission reason (for example, a request to modify the study protocol, a deficiency letter response, and an adverse event report are three different submission reasons).
The following examples illustrate the challenges that arise when one submission includes multiple submission reasons:
- A submission contains both a response to deficiencies from a disapproval letter and a request for a design change. The FDA finds the deficiency responses acceptable, but finds that the design change raises new safety concerns. Because FDA makes only one decision per submission, the FDA would disapprove the entire submission and the proposed study would remain disapproved. Therefore, we recommend separate submissions for responses to deficiencies and unrelated change requests so that study initiation or progress is not unduly delayed.
- A submission intended to report the progress of a study also includes a request to change the study protocol. Because changes to the study protocol require FDA approval prior to implementation and would be deemed approved if a decision is not made within the 30-day review period, the FDA will prioritize review of the change request over review of the report. As such, FDA will consider the submission to be a Supplement. In this case, the reporting requirement would not have been met and a separate report would be required. Therefore, FDA recommends separate submissions for reports and requests to change the device or study.
For these reasons, FDA recommends that sponsors not include multiple requests or combine a change request with a deficiency letter response or report within a given submission. During a three month transition period, FDA will work interactively with submitters to address any submissions that mistakenly contain multiple submission reasons, such as those described in the examples above.
2. Clearly identify in your cover letter the specific reason for your submission.
3. When responding to an FDA deficiency letter, include the date of the FDA letter to which you are responding as well as the original IDE, IDE Supplement or IDE Report number.
- We will accept multiple amendments (responses to deficiency letters) until all of the outstanding deficiencies have been resolved.
- Please note that the FDA does not consider “Study Design Considerations” (SDCs) to be deficiencies. If a submission responds to both SDCs and deficiencies from an approval with conditions or disapproval letter, we will track it as an Amendment. A submission that only responds to SDCs will be considered a request to modify the protocol and be tracked as a Supplement.
The IDE Staff can help answer any questions at 301-796-5640.
Improving patient access to new medical devices by strengthening and streamlining the clinical trial enterprise is a priority for CDRH. An important part of reaching that goal is to better track milestones in clinical trial development, Investigational Device Exemption (IDE) approval, study initiation, and study completion.