In July 2020, Switzerland-based medical device development company, Carag AG received U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) approval for its Carag Bioresorbable Septal Occluder (CBSO). The device is designed to help treat atrial septal defects (ASD). Earning the IDE gave Carag AG an opportunity to conduct a clinical trial with its device prior to submitting a premarket approval application (PMA). The study can provide valuable data regarding the device’s safety and effectiveness in treating patients with ASD.1
What is an FDA IDE Designation?
An investigational device exemption (IDE) is a regulatory option set up by the FDA that allows an investigational medical device to be used in a clinical study in order to collect safety and effectiveness data. This data is then used to support a PMA application as part of the 510(k) process.
Medical device companies may seek an IDE when clinical experience is necessary because nonclinical testing methods are either not available or not adequate to provide the data needed to develop the device. The IDE also applies to clinical evaluation of certain modifications or new intended uses of existing, legally marketed devices. All clinical evaluations of investigational devices must have an approved IDE before launching a study.2
Because the IDE is for investigational devices, the medical device developer works with an institutional review board (IRB) to initiate the application process. According to the FDA IDE guidance, the company and IRB need to determine if the device is considered a significant risk or nonsignificant risk prior to beginning the clinical study. However, the FDA has the ultimate authority to determine the level of risk. Significant risk means the device:
- Can pose serious risk to the health, safety or welfare of a subject.
- Is purported to sustain human life.
- Is substantially important in treating disease or preventing impairment of human health.
Clinical Study Requirements
To conduct a clinical evaluation of an investigational medical device, the medical device developer must complete these IDE requirements outlined by the FDA:3
- Complete the application process, which includes submitting an investigational plan for approval to the IRB.
- Receive informed consent from all clinical subjects.
- Label the device “for investigational use only.”
- Monitor the study.
- Produce the required records and reports from the study.
The IDE application must clearly state that the proposed study is an early feasibility study. Include the justification, using an appropriate benefit-risk analysis, for conducting this type of study. Addressing the following questions in the IDE application will help with achieving approval:
- What clinical condition will the device treat or assess?
- What is the standard of care for the clinical condition and expected outcomes associated with the standard?
- What are the anticipated benefits of the study device?
- Is the information included in the report of prior investigations adequate to support initiation of the study?
- Does the investigational plan include a thorough risk analysis, sufficient risk mitigation strategies, adequate subject protection measures and an appropriate clinical study protocol?
- Is initiation of the clinical study justified based on the clinical need for the device, and are the anticipated benefits likely to outweigh the potential risks?
Initiating an IDE application involves developing an investigational plan. This critical part of the IDE needs to be well thought out and comprehensive. It should identify the novelty of the device and the medical need as well as the limited nature of the investigation. In addition, the plan includes the following items:4
- Description of the device and its intended use – The name of the device, its purpose and objectives of the clinical study.
- Device study protocol – The methodology, including a description of the subjects, study endpoints, endpoint assessment methods and adverse event definitions.
- Risk analysis and mitigation – A description and analysis of the type and estimated severity of risks to the subjects. Identify how the risks will be minimized and adequately justify that the risks are reasonable in relation to the expected benefits.
- Monitoring processes – The FDA guidance on a risk-based approach to monitoring states that companies need to identify critical study data and processes. Then, identify the risks that could affect the collection of critical data or the performance of critical processes. The monitoring plan focuses on the important and likely risks to critical data and processes.
- Additional records and reports – Include any additional data and information that support the need and benefits of conducting a clinical study.
The IRB uses the information in the investigational plan to determine if there is significant risk with the device and study. If the study is deemed to pose significant risk, the FDA must also review and approve the investigational plan.
Good Clinical Practices for IDE
During an investigational device clinical trial, medical device companies must comply with good clinical practices (GCP) specific to the IDE regulations detailed in 21 CFR 812:
- 812:20 – Explains the requirements and process for submitting an IDE application, including the information the application must contain such as the investigational plan and report of prior investigations.
- 812:25 – Lists the information that must be included in the investigational plan.
- 812:27 – Specifies what information needs to be included in the report of prior investigations, i.e., all prior clinical, animal and laboratory testing of the device.
- 812:35 – Applies to supplemental applications, which explains when changes to the device and investigational plan must have prior FDA approval as well as the protocol for notifying the FDA of changes that do not require prior approval.
Conducting an early feasibility study under an IDE provides a unique opportunity to obtain clinical experience with a new or modified device or new clinical use of an existing device. A study environment enables companies to use appropriate subject protection measures and GCP study practices. Data obtained from the study can provide valuable insight, which can be used to optimize device design, risk controls and quality processes.
- “Carag Receives U.S. FDA IDE Approval to Conduct Clinical Study of First Transcatheter Septal Occluder With Bioresorbable, Metal-free Framework,” Ken Dropiewski, CardiacVascularNews, July 2, 2020, http://cardiacvascularnews.com/carag-receives-u-s-fda-ide-approval-to-conduct-clinical-study-of-first-transcatheter-septal-occluder-with-bioresorbable-metal-free-framework/
- “Investigational Device Exemption (IDE),” U.S. Food and Drug Administration (FDA), Dec. 13, 2019, https://www.fda.gov/medical-devices/how-study-and-market-your-device/investigational-device-exemption-ide
- “Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies: Guidance for Industry and Food and Drug Administration Staff,” U.S. Food and Drug Administration (FDA), Oct. 1, 2013, https://www.fda.gov/media/81784/download
- “Understanding FDA Regulatory Requirements for an Investigational Device Exemption (IDE) for Sponsor-Investigators,” M. E. Blair Holbein and Jelena Petrovic Berglund, U.S. National Library of Medicine National Institution of Health, National Center for Biotechnology Information, Oct. 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448842/