Approaching FDA ahead of formal premarket submission can make the regulatory process smoother for medical devices. But deciding the best moment to make contact requires careful consideration.

Medical device companies often want to find out the type of premarket submission FDA will require for their devices (510(k) premarket notification, De Novo review of automatic Class III classification (a De Novo request), or a premarket approval application (PMA)). They are also keen to determine what clinical data, if any, FDA would require as part of the premarket submission.

Obtaining FDA feedback on these key regulatory issues is best achieved through a pre-submission to the Agency.

Preparing a pre-submission

Ideally, a pre-submission should propose a regulatory path for the device as well as clinical study design. Alternatively, it might suggest that clinical data is not needed and present the rationale for this.

A pre-submission should also contain a detailed description of the device, including its proposed indications for use and technological characteristics, providing preliminary evidence of its safety and effectiveness to support the company’s regulatory plan. This proactive approach increases the likelihood that FDA will concur with the company’s basic plan and provide constructive feedback.

To obtain the full benefit of a pre-submission, the company would need to:

• Determine the device it wants to market
• Conduct performance testing to evaluate it
• Possibly refine the device based on the results of such testing
• Analysis of the potential regulatory impacts of any refinements

FDA might be more willing to review the device via a quicker and less expensive premarket process (possibly requiring clinical data from a smaller or shorter study or with a primary endpoint that is easier to achieve) based on this information and data. However, obtaining FDA feedback before the design of the device is finalized helps minimize the costs of satisfying the Agency’s requirements.

In other words, it is easier to modify a device based on early feedback from FDA, but the Agency is likely to give more positive feedback if it can review data that becomes available later. So, the timing of the pre-submission often involves finding a balance between these objectives.

Finding the sweet spot for FDA contact

Achieving this balance is not easy. Approach the agency too soon and the feedback is likely to be too general to provide much guidance. It may also be more conservative. Approach too late and the feedback could be hugely disruptive, especially if the company needs to modify a technological characteristic of the device. Unless a device is truly novel, the quantity and/or quality of feedback from FDA is likely to diminish with multiple pre-submissions, so getting the timing, as well as the content, of a single submission right is critical.

Since the sweet spot for FDA contact varies between cases, it’s useful for the product development team to have an open discussion with commercial advisors and regulatory experts. This ensures all relevant factors are considered when deciding on the timing and focus of a pre-submission.

Establish what you need to know

In many cases, an experienced regulatory professional will be able to say with some certainty which regulatory path a device is likely to follow. Based on this knowledge, it may also be possible to ascertain the type of performance data that FDA expects in a premarket submission for that type of device.

When the regulatory path is clear, contact FDA later

For instance, it may be advisable to wait until initial data is available before approaching FDA with a pre-submission. The best time to do this might be after a pilot study but before a pivotal study, to ensure the conversation is focused, not just theoretical.

The company can highlight any issues identified in the pilot study, explaining how the device has been modified in response. Endpoints for a clinical trial can be proposed, as well as factors such as the number of patients, their age range and the possible exclusion of patients with certain underlying conditions. In this scenario, direct questions can be put to FDA about the validity of the proposals. This enables the agency to give meaningful and constructive feedback that adds value to the process.

When there is regulatory uncertainty, contact FDA sooner

Sometimes it’s not so clear which regulatory path a device will take. Uncertainty about substantial equivalence to predicate devices may introduce risk to the 510(k) route. Or in the case of a truly novel device, it may not be easy to determine whether it will be eligible for De Novo classification or if it will have to undergo PMA.

With cases like this, it is beneficial to contact FDA at an earlier stage, possibly before design inputs have been established, to determine whether the PMA route will be pursued.

When it comes to novel device concepts for which FDA has not yet determined the regulatory path, FDA representatives will be wary. They won’t be able to offer firm guidance, but may indicate that the more stringent PMA is the likely regulatory outcome. Crucially, the company will come away from the pre-submission process with a better understanding of what is required.

Take a collaborative approach

Ultimately, reaching out to FDA ahead of formal premarket submission should bring greater clarity, confidence and assurance to the product development process. We’ve written before about how regulatory strategy should be integral to product development from the outset. This is especially true when it is unclear what type of premarket submission or clinical data is required. Companies that facilitate collaboration between regulatory experts, product developers and commercial teams have a better chance of getting FDA pre-submissions just right. It’s about understanding exactly what you need from FDA, and how you will act on the guidance you receive, so that the interaction is positive, constructive and well-timed.

Contact [email protected] to speak with Laurie Clarke, our VP and Principal of Medical Device Regulatory, and find out how we can support your company.