Neil Buckley, head of quality and regulatory affairs at Sky Medical Technology, outlines the process of applying for FDA clearance and suggestions for best practice.
Sky Medical Technology has gained nine FDA clearances for its geko™ device. The small wrist-watch sized device sends a painless electrical pulse to the common peroneal nerve to activate the calf and foot muscle pumps. This results in increased blood flow in the deep veins of the calf to address life threatening blood clots and complications related to swelling after orthopaedic surgery – conditions experienced by more than 1 million US patients with unmet need every year.
What is the FDA and why does it matter?
The US Food and Drug Authority (FDA) is the American regulator for all pharmaceuticals, medical devices and related products. In short, what this means is, if you want to bring any certain medical product to market in the US it must be approved or cleared by the FDA for the specific indication for which you are suggesting it can be used.
For medical device companies, products that present a relatively low risk are genarlly placed in Class I or Class II and require the manufacturer to seek clearance from the FDA via the 510(k) premarket notification route prior to marketing, unless exempt from regulation (as many Class I devices are). Whereas, a Class III classification is reserved for devices posing a greater risk. These undergo the premarket approval process, which requires the manufacturer to prove the safety and effectivness of the device to the FDA’s satifacton.
The geko™ device is classified Class II. Successfully navigating the FDA regulatory process has developed our know-how and this has enabled us to gain FDA clearances for VTE prevention across all patients groups, including non-surgical patients, and for the reduction of oedema to address complications related to swelling – and it is this experience and a few tips that I share here.
Although FDA approval or clearance is only legally necessary when looking to bring products to market in the US, the impact this recognition has globally can be significant. Many markets follow the FDA’s lead when it comes to approval, and if your product is already FDA cleared, the approval process for other territories can be much quicker.
To add to this, clinicians outside the US often find FDA approval or clearance reassuring, as they know the product will have undergone a rigorous approval process to prove it is safe and effective for use. There is a perception within the global market that FDA clearance or approval is a very high bar to achieve, so products that have made the FDA cut are often more desirable.
The application process
When seeking Premarket Notification (FDA ‘clearance’), there are two routes to take.
The first, and most straight forward, is demonstration of substantial equivalence. When presenting a product via this route, the medical devices company will have to demonstrate that the new product, and the indication for its use, is “at least as safe and effective” as an identified predicate that has already gained clearance.
To prove that the products are substantially equivalent is not to say they have a similar design, but instead that they use similar technology. When the geko™ device first gained clearance, the initial predicate was much closer in physical appearance to a Hi-Fi system than the wristwatch-sized geko. However, as we were able to prove there was a similar technology used, and any differences were only minor, we gained clearance.
Having found a predicate and proven substantial equivalence for your product for one indication, you are able to use your own product as the predicate in other instances. Once a device is cleared it is possible to add new indications for use using clinical data as evidence of safety and effectiveness.
If you are submitting a product that is so unique or novel that there is nothing else like it on the market, the process known as ‘de novo’ is a little more difficult, and you will have to submit enough relevant clinical data to convince the FDA that the product is safe and effective for use on patients.
FDA and the geko™ device
Our first clearance for the geko™ device was for increased local blood circulation. Once we had achieved clearance for this indication, we were able to use the device time and time again as a predicate for further applications. By making adjustments to the indication for use based on real-world clinical data, we were able to support claims for clearance for other uses, including for the reduction of oedema, for immediate post-surgical stimulation of the calf muscles to prevent venous thrombosis. This is a well-worn path in terms of how the FDA operates, and at this stage all the indications for use that we had presented had already been cleared by the FDA for other devices.
However, when it came to our most recent FDA clearance for the geko™ device, for stimulation of the calf muscles to prevent venous thrombosis in non-surgical patients at risk for venous thromboembolism, the application was slightly more difficult. This was because there were no other FDA approved products using the same technology, which had previously been cleared for this particular indication.
In this instance we used the geko™ device as a predicate for the technology, alongside our own data, to prove the product was safe and effective for this therapy area.
What was unusual about the data submitted in this case was that it was real-world data. Traditionally, when submitting data to the FDA, Randomised Control Trials (RCTs) are used, as these are considered the gold standard in clinical evidence. However, with medical devices this is not always feasible – especially in the case of the geko™ device, where patients can feel a physical sensation, preventing blinding.
As long as the data is statistically significant and proves the efficacy of your product, real-world vs RCT data likely will not matter. The results of our clinical evaluations were binary – either our patients were affected by VTE or they were not – which helped in making the effectiveness very clear.
What is the standard timeline?
Once a standard or ‘traditional’ 510(k) clearance application is submitted, the FDA has 90 days in which to respond. They can respond by accepting the application and giving clearance, or by rejecting it on the grounds that it is not substantially similar and/or the data provided is not strong enough. There is a third FDA response, which is probably the most common, which allows the FDA to ask further questions about the application.
If this happens you have a few options. You can either respond quickly and the clock will continue to tick. Or, if the FDA comes back with a tricky question that requires additional data, you have the option to pause the application and pick it back up later. Finally, you can withdraw the application and resubmit at a later date. None of these options would harm your chance of a successful application.
The fastest the FDA could possibly approve an application is 60 days, which we are fortunate enough to have achieved twice with the geko™ device; however, it is not unusual for it to take months or even years in some cases.
Tips for submitting your application
Are you convinced?
When you – as the person in charge of or responsible for quality assurance or regulation – receive the clinical data, your first port of call should be to decide if you are convinced by it. Would you allow the product or device to be used on your loved ones? If there is any doubt in your mind, go back a few steps. Once you are convinced the data is robust and speaks for itself you can move onto the next step.
Use stepping stones
Once you have robust data, be careful not to make leaps. All the data you submit has to be linked really closely to the specific indication you are seeking clearance for. Do not expect the assessors to make large intellectual leaps, because they will not. Instead, plan for the possibility that you may have to make applications for indications you do not intend to take to market. These can act as the stepping stones towards your end goal.
Create a narrative
The assessors are people too, and if they get bored they can miss a step or misunderstand the application. Ensure that your narrative is engaging, follows a clear and logical process, and holds the attention of the reader. This will give you the best chance of gaining clearance.
Have a plan
Seeking clearance can take a long time, so it is essential to have a robust plan of action and a clear timeline of which products you would like to take to market and when. As mentioned previously, plan every aspect of the process and build a timeline that includes stepping stone applications where necessary. With the geko™ device, we have planned two years ahead for clearances and my regulatory team asks to receive any clinical data two months ahead of the proposed application date so we can begin structuring our FDA application appropriately.
How FDA clearance has impacted Sky Medical
The direct impact is that Sky Medical Technology is able to market its products in the US for its nine specific indications. Having this access to the US market has enabled us to raised further capital as FDA clearance and access to the US represents a huge opportunity.Read the article