CREATE Devices: Regulatory Guidance

Section I. Brief Synopsis

Although the field of neural engineering is full of promising proof-of-concept device studies with potential clinical applications, the proportion of these studies that actually lead to clinical use is unfortunately small.  Many basic science researchers have little experience with the regulatory process - a process that can be difficult to navigate - creating a potential barrier to clinical translation.  

The FDA typically provides guidance to individuals/businesses seeking 510Ks or Investigational Device Exceptions (IDE) for medical device clinical applications through more official interactions (e.g. pre-IDE and IDE meetings– See Section II, Definitions).  The onus is on the investigator/business to come to these meetings fully prepared.  This goal of this document is to identify resources for the reader to develop an overview of the FDA regulatory process sufficient to assist applicants in writing a U01 or SBIR/STTR application.  Note that it is permissible for an investigator to include expenses for consulting for regulatory and quality issues as part of the budget for a U01 or SBIR/STTR application.

Section II. Definitions

Note: Many of the following concepts are further explained in the CDRH Learn educational videos (Center for Devices and Radiological Health), which are discussed in Section III of this document.

Device Classification - The FDA device classification ranges from Class I to Class III, and depends on the intended use of the device and also upon indications for use.  In addition, classification is risk-based, that is, the risk the device poses to the patient and/or the user is a major factor in the class it is assigned. Class I includes devices with the lowest risk and Class III includes those with the greatest risk. 

Premarket Approval - Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices.  

510(k) - A 510(k) is a premarket submission made to the FDA to demonstrate that the device to be marketed is at least as safe and effective (substantially equivalent) as a legally marketed device that is not subject to Premarket Approval (PMA).  

Investigational Device Exemption (IDE) -  An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. Clinical studies are most often conducted to support a PMA.  

Please note near the bottom of the above web page, under the heading Good Clinical Practices (GCP), the regulations and requirements that must be complied with while conducting a clinical study.

For more information, please see a memorandum detailing the goals and initiatives for the IDE Program.

Pre-IDE meeting- In order to facilitate the initiation of clinical trials under IDE regulation, the FDA encourages sponsors to begin communicating with the reviewing division prior to the submission of the original IDE application.  Pre-IDE meetings should occur early in the IDE preparation process so that any advice/guidance by the Office of Device Evaluation (ODE) can be used in the development of supporting pre-clinical data or incorporated into the IDE application.  See attachment A for more details:

See the relevant sections of the FDA modernization Act of 1997 (section 201 and 205) pertaining to pre-IDE meetings, along with additional guidance from the FDA on those sections.

Section III. CDRH Learn

The FDA’s Center for Device and Radiological Health (CDRH) has a webpage dedicated to industry education.   It consists of a series of training modules describing many aspects of the medical device and radiological health regulation, covering both premarket and post-market issues. 

For those unfamiliar with the regulatory process, we recommend looking at the videos under the following categories:

  • Overview of Regulatory Requirements: Medical Devices
  • Overview of the Premarket Notification Process – 510(k)
  • Investigational Device Exemption Process - IDE
  • Quality System Regulation 21 CFR Part 820
  • CDRH Regulated Software: An Introduction

Section IV. Developing U01 Milestones

The U01 mechanism is a cooperative agreement, meaning that the NINDS program staff will have a significant, although not dominant, role in the planning and execution of the supported activities. Consequently, we highly recommend contact program staff at least six weeks prior to submission.  This is necessary to allow for discussion of the readiness and appropriateness of a plan for the specific FOA, as well as obtaining any necessary approval for acceptance of the application (e.g., for applications requesting $500,000 direct costs or more in any year).

It is intended for the extramural research community to use translational research initiatives flexibly and creatively, and in whatever combinations necessary, to achieve the most rapid and effective development of clinical interventions for neurological disorders.  Specific milestones of progress will be established at the time of the award with input from program staff that must be met prior to funding of each subsequent period.

Section V.  FDA Guidance for Retinal Prostheses

On April 17th, 2009 the FDA released a guidance document for industry and FDA staff concerning IDEs for retinal prostheses.  Note that projects pursing the development retinal prosthetics fall under the mission of the National Eye Institute, not NINDS.   However, this document provides guidance about developing pre-clinical and clinical tests for an implantable neuromodulation device, the retinal prosthesis, and describes pre-clinical tests a sponsor should conduct to characterize device safety before initiating any clinical testing.  This document is not directly applicable to implantable devices outside of retinal prosthetics; however, the general framework as an example should be of substantial use to a sponsor unfamiliar with the regulatory path.  

Section VI.  Other Notes

Unless specifically justified, pre-clinical laboratory studies need to comply with 21 CFR Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies (21 CFR 812.27(b)(3))).  

In addition, sponsors must develop a quality management system (QMS), including specific requirements for employee training, documentation and design controls/verification/validation activities.  This can be the most cumbersome aspect of the regulatory process, and often requires outside consulting from experience individuals to develop the quality systems infrastructure.   A CDRH training video detailing quality systems is available on CDRH learn (see Section III).

Finally, the FDA regulations are always in a state of evolution.  Sponsors can sign up for the CDRH News updates under CDRHNEW.