What’s the best way to go about obtaining FDA authorization to market a medical device? This is the million-dollar question frequently put to us at TSG. Naturally, every situation is different, but the single most important factor is a regulatory strategy. And the earlier this can be developed, the better.

A regulatory strategy brings focus and purpose

Put simply, a regulatory strategy aims to achieve FDA authorization in the most efficient way possible for the device in question. It clearly sets out steps that need to be taken to reach the desired goal, which for many medical device companies is obtaining FDA clearance for the proposed indication via 510(k) premarket notification. For that reason, we focus on 510(k) notices in this discussion, although the general principles also apply to other types of premarket submissions.

How to develop and implement a successful 510(k) regulatory strategy: six key steps

1. Do the groundwork

Assess the product concept, look at the technologies involved and consider how well known and widely used they are. If there’s an established regulatory path for devices of this type, there’s a good chance that the new product will follow a similar route. With 510(k)s, it’s important to think about how ‘substantial equivalence’ might be demonstrated. Getting this right results in a more streamlined route to authorization.

2. Take advantage of FDA’s pre-sub option when appropriate

A pre-submission (pre-sub) is a voluntary step whereby companies submit a formal written request for FDA feedback ahead of a premarket submission. The goal is to convince FDA to accept the company’s proposed approach.

This step should be considered when it is not clear whether FDA would agree with the proposed predicate device(s) and/or the type and amount of performance data needed to demonstrate substantial equivalence to the predicate(s). In such cases, the pre-sub typically describes the device, identifies the most significant similarities and differences between that device and its predicate(s), summarises any testing already conducted and provides protocols for proposed testing. The pre-sub explains how the company intends to demonstrate substantial equivalence based on the proposed comparison and the results of testing. It can also include specific questions for FDA about the key regulatory issues.

3. Meet with the FDA

If the pre-sub is accepted, FDA will schedule a meeting with the company, and provide written responses to the company’s questions before this takes place. Such meetings are a valuable opportunity to work through any remaining issues regarding the proposed regulatory pathway and to take on board any suggestions regarding predicates, if applicable, or testing that might be conducted.

It’s important to be well prepared for these meetings, and to understand the type of guidance that can be given. FDA representatives cannot answer overt questions about whether a certain approach will lead to clearance. However, the meeting should provide a good understanding of the quantity and quality of data required to evaluate the safety and efficacy of the device, as well as how to obtain it.

4. Obtain the required data

Armed with FDA feedback, companies can take a decisive and well-informed approach to the generation of data surrounding device performance and capabilities. This might involve bench, animal, and/or clinical (human) data. Either way, this important stage of the process is better defined than it would be without FDA input. Incorporating FDA’s feedback into the test protocol is more likely to result in the depth, breadth and type of data that will be needed to evaluate whether the device is at least as safe and effective as its predicate(s) and thus, substantially equivalent.

5. Prepare premarket notification

Following completion of testing, the 510(k) submission can be compiled, drawing on supporting data and outlining substantial equivalence to the primary and any secondary predicate devices. Care must be taken to ensure the submission is clear, concise and free from mistakes to reduce the risk of FDA misunderstanding the device, requesting unnecessary additional testing, and/or questioning the validity or relevancy of the data. At this stage, it’s always a good idea to pass the documentation to a trusted third party for an impartial review. They may notice inconsistencies or ambiguities that the core team has overlooked due to close involvement with the project.

6. FDA’s 510(k) review and decision whether to clear the device

Once 510(k) documentation has been submitted, an FDA response naming the lead reviewer and Acceptance Review status will be received within 15 days. If the submission is not accepted for review, it’s placed on Refused to Accept (RTA) Hold and the submitting company has 180 calendar days to address any deficiencies cited.

The ideal outcome at this stage is for FDA to accept the 510(k) and progress to Substantive Review where a comprehensive analysis of the submission takes place. FDA’s goal is to provide substantive feedback within 60 days of receipt of the 510(k) if it accepts the original submission. The same timeframe applies to responses to an RTA decision that resulted in FDA’s acceptance of the submission.

In many cases, the substantive feedback is a request for additional information (RAI). The company has 180 days to respond to an RAI, or the 510(k) is automatically withdrawn. FDA usually stops the review clock until an RAI response is submitted unless it believes that the requested information could be provided in a short period of time (often a week or less). In this case, it may decide to let the review clock run and work interactively to address any remaining issues by a certain date. FDA’s goal is for its total review time for the initial 510(k) plus the company’s responses to be 90 days or less.

Based on information and data provided in the 510(k) notice and responses to RAIs, FDA determines whether the device is substantially equivalent. If FDA determines that the device is Not Substantially Equivalent (NSE), it will identify the grounds for that determination in its decision letter. The company would have to address those deficiencies in any subsequent premarket submission to market the device. The type of subsequent premarket submission required (another 510(k) notice, a de novo request, or a premarket approval application) would depend on the grounds for NSE.

If FDA finds that the device is substantially equivalent, it will issue a letter granting premarket clearance, with indications for use specified in an attached statement. The company can then market the device for those indications if the manufacturer complies with FDA’s device establishment registration and listing requirements and the applicable quality systems regulations.

What are the benefits of a 510(k) regulatory strategy?

Taking a proactive and premeditated approach from the outset puts the company in the driving seat. It can satisfy any existing FDA requirements for demonstrating that the type of device is substantially equivalent, or define those requirements and apply them to its device.

Should the company seek FDA input, feedback is likely to be constructive as it would be based on a concrete plan. If the company then modifies its plan based on FDA feedback prior to submitting the 510(k) notice, it minimizes the risk of a delayed decision. For instance, the agency is less likely to request a major change or additional performance data during its review of the device. Ultimately, a well-conceived regulatory strategy increases the likelihood of FDA clearing the device and accelerates time to market.

Laurie Clarke has previously worked as FDA partner for several US law firms. Her more than 30-years of FDA regulatory experience regarding medical devices means she brings valuable insights to support companies developing new device concepts.

For more information contact Laurie at [email protected]