The FDA regulatory gauntlet can be a daunting challenge.

That's especially true for startups new to the field. But it need not be. The process serves an important purpose—ensuring that new drugs and medical devices marketed to the public are safe, effective, and result in the intended health outcomes.

That's why in my 30 years of advising tech and life sciences companies, I often have to remind eager entrepreneurs of this:

Having great science is not enough.

The pathway for getting a product to market does require great science, but that science must also be grounded in a practical understanding of what it takes to clear Food and Drug Administration (FDA) requirements. In the case of a new medical device, this includes navigating the premarket approval (PMA) or 510(k) process.

In short, the PMA process (or the 510(k) for devices that are deemed “substantially equivalent” to an already approved device) provides the FDA the information it needs to determine if a medical device is safe, effective, and ready to market to the public. In most cases, a device sponsor will also need to first conduct clinical studies in support of its PMA or 510(k) application. To conduct these clinical studies, a sponsor must first submit an investigational device exemption application or IDE.

The IDE process is designed to ensure that a clinical study is well-designed, that the anticipated benefits outweigh the potential risks to human subjects, and that appropriate safeguards are in place to minimize those risks. As such, successfully navigating the IDE process is a critical frontrunner to receiving PMA or 510(k) approval.

What is an IDE and when do you need one?

Medical devices vary widely and so too do the regulations regarding their testing.

For example, a tongue depressor is minimally invasive and low risk, so it requires much less stringent pre-marketing and testing approval requirements than a pacemaker or artificial organ. The regulatory scheme appreciates this variability by providing different pathways for approval depending on the relative risk posed by the intended use of a particular device.

Class I devices present the lowest risk and are subject to general controls but are generally exempt from FDA approval and premarket notification requirements. Manufacturers must still comply with baseline general controls including registration, manufacturing, labeling and device listing requirements.

Class II devices present a moderate risk of harm and while still subject to the same general controls as Class I devices, may also require 510(k) approval from the FDA before marketing. The 510(k)-approval process is designed to determine whether the device is substantially equivalent to an already approved predicate device. While clinical data, and consequently an IDE, is not typically required for most 510(k) applications, a small percentage of applications do require clinical testing and an IDE.

Class III devices present the highest risk and generally require a premarket notification (PMN) approval from the FDA before marketing. Class III devices typically require evidence from animal studies and clinical trials to judge the relative safety and effectiveness of the device. Consequently, most Class III devices will require IDE approval.

Still, not all Class III devices require an IDE prior to clinical studies. The need for and level of FDA review and approval required to conduct a clinical study largely depends on the level of risk posed by the proposed clinical trials.

Exempt and Diagnostic Device Studies

As the name implies, exempt device studies require no federal filings or additional FDA approval prior to conducting a clinical study. Exempt devices generally include:

1. Those already in use in a manner that is consistent with their labeled use;
2. One that is substantially equivalent to another device already in distribution;
3. A device being studied for consumer preference, veterinary use, research in laboratory animals, and customary devices, and;
4. Non-invasive diagnostic devices that do not present a significant risk to humans.

Non-Significant Risk Devices

Non-significant risk (NSR) devices require filing an abbreviated IDE but do not require FDA approval. The sponsor must only receive approval from the reviewing institutional review board (IRB) at each institution where the investigation is being conducted. If the IRB considers the device to pose a significant risk, it must report this to the FDA and the sponsor must receive FDA IDE approval before commencing any studies.

Significant Risk Devices

A medical device that is deemed by the sponsor or IRB to pose a significant risk must file an IDE and obtain approval from the FDA before beginning clinical studies. FDA regulations define a significant risk (SR) device as one that is

• “intended as an implant and presents a potential for serious risk to the health, safety or welfare of a subject;
• purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
• for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety or welfare of a subject;
• or otherwise presents a potential for serious risk to the health, safety or welfare of a subject.”

The FDA provides additional guidance on determining a device's risk classification.

Notably, a device that is otherwise considered to pose a nonsignificant risk may fall in the significant risk category if its proposed use presents a novel significant risk, such as by increasing surgery time or when used in combination with another device that increases the risk.

The IDE Application

There is no standardized form for the IDE application, but the FDA has issued helpful guidance that details what information should be included. The FDA has 30 days to approve or disapprove the application. Along with a cover letter, the application should include:

• Prior investigations, including prior clinical and other testing and any adverse information
• Manufacturing information about the quality control of the device
• Investigator information and commitment statement
• Institutional review board information
• Device sale and labeling details
• Informed consent materials for use in clinical trials
• Any other relevant materials

In addition, the IDE must include information about the investigational plan, including:

• A detailed description of the device, name and objectives of the study
• The study protocol, including a description of its methodology, study subjects, study endpoints, endpoint assessment methods and adverse event definition
• Risk analysis and justification of the relative risk to subjects along with an explanation of how risks will be minimized
• A detailed device description and anticipated device changes during the investigation
• Description of the monitoring process and contact information of monitors
• Additional records and reports that may be required

Getting Early Feedback

The FDA has established several pathways by which medical device sponsors can engage in early conversation and receive helpful feedback about the PMA, 510(k), and IDE process. Early interaction opportunities with the FDA should be used to the greatest extent possible. Doing so can improve the quality of IDE submissions, shorten review times and streamline the development process.

Study Risk Determination Meetings

Study risk determinations can be requested to receive FDA guidance on whether a proposed study is exempt or considered a significant or non-significant risk for the purposes of requiring an IDE. The FDA provides detailed guidance on risk determination and meeting availability here.

Informational Meetings

Informational meetings may be appropriate where a sponsor wants to familiarize the FDA with a new device or to provide an overview of device development when multiple submissions may be planned in the coming year. The FDA does not give feedback in an informational meeting. If a sponsor wants to receive FDA feedback, they should utilize the pre-submission or early collaboration meeting process.

Pre-Submission

The FDA encourages new sponsors or those who are proposing studies with new technologies or new uses for existing technologies to utilize the pre-submission process. The pre-submission process provides an opportunity for the sponsor to request and receive formal feedback on its IDE request from the FDA in writing or via a telephonic or in-person meeting.

Formal Early Collaboration Meetings

Formal early collaboration meetings provide an opportunity for the agency to provide early feedback to sponsors on the proposed bench/animal testing and clinical trial design. An informal version of this process was once referred to as a “pre-IDE” meeting but has more recently been formalized under the FDA Modernization Act (FDAMA). Under the new formal meeting regulations, any advice given must be in writing and is generally binding on the agency.

Two types of formal early collaboration meetings can be requested:

1.   Determination Meeting

A determination meeting may be appropriate for sponsors anticipating submitting a PMA. The meeting can help the sponsor better understand what type of evidence will be necessary to demonstrate device effectiveness and whether clinical studies are needed. The FDA will also work with the applicant to determine the least-burdensome way to evaluate the device's effectiveness and that also has a reasonable likelihood of success.

2. Agreement Meeting
An agreement meeting is available to sponsors investigating a class III device and who intend to submit a 510(k) request. The purpose of the meeting is to agree on clinical protocol and other key parameters of the investigational plan.

The Pathway to IDE Success

The IDE is a critical step in new device development and requires careful and informed planning. Utilizing early communication channels with the FDA can help you secure IDE approval and ultimately smooth the pathway to market. Approaching the agency with a spirit of cooperation and transparency is paramount. It will help establish trust and reveal potential concerns at an early stage when it's more likely they can still be easily remedied.

An experienced consultant can help you successfully navigate the IDE process and set the foundation for PMA and 510(k) success. Crowley Law LLC is a full-service law firm for tech and life science companies with an extensive network of experienced FDA consultants with whom we can work to optimize your overall business, legal and regulatory strategy.

Crowley Law LLC is a full-service law firm for tech and life science companies. Contact us for a consultation on how we can best assist you in the IDE application process and ensure you have the greatest legal advantage moving forward.