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SOP on FDA-Regulated Investigational Device Exemption (IDE) Application

 Title: Standard Operating Procedure for FDA-Regulated Investigational Device Exemption (IDE) Application

Introduction and Purpose

Conducting a clinical investigation, often referred to as a clinical trial, under the umbrella of an FDA-Regulated Investigational Device Exemption (IDE) application entails navigating a complex set of FDA regulations, requirements, and obligations. The FDA places the responsibility for ensuring compliance with these regulations, requirements, and obligations squarely on the sponsor of the IDE application, as delineated in 21 CFR Part 812, Subpart C. While sponsors of IDE applications are typically pharmaceutical and device companies, the FDA's IDE regulations extend the sponsorship eligibility to individuals, governmental agencies, or academic institutions (21 CFR Part 812.3).

The primary purpose of this Standard Operating Procedure (SOP) is threefold:

  • To assist in determining when an IDE is required.
  • To provide guidance and resources to individuals conducting clinical investigations, including sponsor-investigators, on obtaining an IDE for the device under study.
  • To address the process for compassionate use, also known as expanded access, and emergency use of an investigational device.

IDE Definitions and Acronyms

  • 510(k) Pre-Marketing Notification: An FDA application type for high-risk Class III devices. In most cases, an IDE is required to clinically evaluate devices subject to PMA (Premarket Approval) requirements.
  • Classes of Devices: The FDA classifies devices into three categories based on safety and effectiveness levels.
  • Class I: Low-risk devices, generally exempt from FDA regulations. Exceptions exist if the device's use is of substantial importance in preventing health impairment or presents unreasonable risk.
  • Class II: Moderate-risk devices that often require 510(k) clearance. Clinical investigations may be necessary in specific cases to demonstrate substantial equivalence.
  • Class III: High-risk devices mandating Premarket Approval (PMA) due to a need for safety and efficacy establishment. Clinical investigations are usually essential.
  • Device: Any instrument, apparatus, implement, or other article intended for diagnosing, curing, mitigating, treating, or preventing disease, or affecting the body's structure or function, not relying primarily on chemical action and not needing metabolism to function. This also includes investigational software.
  • Emergency Use: An FDA Emergency Use exemption allowing the use of an investigational device in a life-threatening situation when no standard treatment is available. Emergency use is considered clinical care, not research.
  • Expanded Access: Mechanisms allowing the use of an investigational device outside of a formal clinical trial. Also known as compassionate use, it permits patients to access the product when they're ineligible for or no clinical trials are available.
  • HUD (Humanitarian Use Device): A device benefiting patients with a disease or condition affecting fewer than 4,000 individuals in the U.S. per year.
  • Investigational Device Exemption (IDE): Authorization from the FDA to use an investigational device in human subjects, typically when the device lacks FDA marketing approval.
  • IDE Application: Document submitted to the FDA seeking permission for clinical studies involving significant risk devices that are new or not approved for a specific use.
  • Nonsignificant Risk Device: An investigational device not classified as significant risk, usually exempt from IDE requirements.
  • PMA (Premarket Approval): FDA's review process to assess safety and effectiveness for Class III medical devices, mandatory before marketing.
  • Significant Risk Device: An investigational device meeting specific criteria indicating potential serious risks to subjects' health, safety, or welfare.
  • Sponsor-Investigator: An individual initiating and overseeing the investigation, responsible for both investigator and sponsor duties.
  • Clinical Research: Research involving human participants.
  • Clinical Trial: A specific type of clinical research designed to evaluate an intervention's effect on health-related outcomes.
  • CFR (Code of Federal Regulations): The codification of general and permanent rules and regulations published in the Federal Register by the executive departments and agencies of the federal government.
  • FDA (United States Food and Drug Administration): The federal agency responsible for regulating and supervising various aspects of food, drugs, medical devices, and more.
  • IRB (Institutional Review Board): A committee responsible for the ethical and regulatory oversight of research involving human subjects.
  • SOP (Standard Operating Procedure): A documented set of instructions and protocols to standardize and guide specific processes.

IDE Guidance

IDE Requirements: Clinical investigations involving devices vary in regulatory control based on risk levels. IDE regulations differentiate between significant and nonsignificant risk device studies, with different approval processes. Every clinical investigation involving devices must possess an approved IDE or be exempt from IDE regulations. Exemptions include the use of legally marketed devices, non-invasive diagnostic devices, veterinary devices, and devices for research with laboratory animals, among others.

IDE Pre-Submission Process: Sponsor-investigators are encouraged to engage with the FDA before submitting an IDE application. This is especially valuable for first-time sponsors or those exploring new technologies or uses. Early interaction helps sponsors understand FDA requirements, regulations, and guidance, expedites the regulatory process, and fosters mutual understanding. Pre-submissions can be used to discuss potential IDEs and to determine their risk classification.

Initial IDE Submission: Sponsor-investigators bear the responsibility of preparing and submitting the IDE application to the FDA. Each IDE application's content varies depending on the investigational device and the study's specifics, but it generally includes a complete protocol, informed consent, and information about the device. The FDA has 30 calendar days to review the IDE submission, during which they may request additional information. The investigator must not begin the clinical study during this review period. After 30 calendar days, assuming no clinical hold, the study can commence.

IRB Requirements: Sponsor-investigators must ensure that an Institutional Review Board (IRB) reviews and approves the study before initiation. The IRB may require proof of IDE submission or waivers with the initial submission. The Pre-IDE Audit must be completed before IRB approval. This audit process is initiated automatically upon IRB submission and includes a Pre-IDE Checklist.

Significant Risk Devices: These devices pose serious risks and require both FDA and IRB approval before initiating a clinical study. The FDA notifies the sponsor upon receiving an IDE application and may approve, approve with modifications, or disapprove it. The sponsor can provide requested information or request a hearing if dissatisfied. Clinical investigations can begin 30 days after FDA receipt of the IDE application if IRB approval has been obtained.

Non-Significant Risk Devices: These devices have lower risks and only necessitate IRB approval before starting a clinical study. Sponsor-investigators of nonsignificant risk device studies do not submit IDE applications to the FDA. Instead, submissions are made directly to the IRB. If the IRB disagrees with the nonsignificant risk determination, this should be reported to the FDA within five working days.

IDE Reporting Requirements: Sponsor-investigators must adhere to specific reporting obligations during the study, including IDE supplements, changes in the investigational plan, development changes, protocol deviations, and more. Annual reports are due within 60 days of the IDE anniversary date, even if the study hasn't begun. A final study report is submitted upon study completion for IDE closure.

IDE Submission Documentation: Comprehensive records of IDE submissions, FDA responses, and relevant correspondence must be maintained for the study's duration and afterward, following Clinical Research SOP, "Study Records Management." 

References

  • 21 CFR Part 812: Investigational Device Exemptions
  • 21 CFR Part 812, Subpart C: Responsibilities of Sponsors
  • 21 CFR Part 812.3: Definitions

Document Approval

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