The goals of most medical device clinical trials are the same: collect sufficient safety and efficacy data to obtain regulatory approval, support marketing claims and product launch/adoption, and provide evidence for reimbursement. That said, while the overall goals are the same, each trial has its own pathway to success. This blog will explore the different roads to regulatory approval through the Food and Drug Administration (FDA) with an examination of the pros and cons behind each approach.
The FDA has three types of regulatory approval of medical devices for commercialization:
- Premarket approval (PMA)
- 510(k) clearance
- de novo clearance
The following presents a brief overview of each pathway:
1. Premarket Approval (PMA)
The PMA pathway is typically the longest, most complicated, and most rigorous approval pathway. It is primarily used for Class III significant risk (SR) devices. These are devices intended as implants or used to support and sustain life that are defined by FDA (21 CFR 812.3) as having a potential for serious risk to the health, safety, or welfare of a patient. Examples of Class III devices include stents, valves, cochlear implants, pacemakers, defibrillators, artificial joints and discs, and injectable devices, such as certain applications of hydrogel. Clinical trials being conducted on Class III devices must receive both FDA and Institutional Review Board (IRB) approval prior to commencement. Such trials are designed to show the investigational device is superior in efficacy with the same safety profiles as the standard of care currently being used to treat the target condition. However, not all implantable devices fall into this tightly regulated classification. For example, for many years, spinal cord stimulators and leads were Class III devices, but after many years on the market with a satisfactory safety profile, the FDA classified them down to Class II devices in 1999.
2. 510(k) Clearance
Conversely, the 510(k) pathway is a simpler, often faster path to approval. It is used for Class II nonsignificant risk (NSR) devices. These are devices with a similar device already approved and on the market in the United States that do not meet the definition for significant risk. To take advantage of the 510(k) pathway, the study sponsor must first identify the predicate product to use for comparison, then demonstrate the investigational device is “substantially equivalent” to the predicate device and “non-inferior” to it in terms of safety and efficacy. The predicate device and investigational device must have the same indication for use, including target condition and patient population, as well as a similar mechanism of action. Examples of Class II NSR devices include endoscopes, low-power lasers, externally worn glucose monitors, vascular access devices, a variety of diagnostic tools, and temporary use devices, such as catheters.
3. de novo Clearance
The de novo pathway was created by the FDA in 1996 to allow novel NSR devices with no predicate device to follow a regulatory pathway with the speed and simplicity of 510(k) clearance rather than the burdensome requirements of PMA. However, in order to follow the de novo pathway, a request must be made prior to the start of the clinical trial to obtain an FDA agreement that there is currently no predicate device on the market. Fortunately, once a de novo device is cleared by the FDA, it may be used as a suitable predicate device by any sponsor for future product approvals.
The Pros and Cons
Each of these pathways has its own pros and cons, meaning your initial choice in regulatory strategy can have big implications for your trial’s overall timeline.
Premarket Approval
As noted above, the PMA pathway is typically the longest, most complicated, and most rigorous approval pathway. Effective planning may require a number of pre-trial conversations, pre-submission feedback, and proactive communications with the FDA to agree on trial design and conduct. From there, the trial itself and the final PMA application will also take a significant amount of time to complete. All in all, these factors produce long lead times to product commercialization, resulting in protracted market adoption, delayed revenue generation, and higher trial costs to the sponsor. These costs include direct fees to clinical sites for study participation and overhead to support internal and external staff, including contract research organizations (CROs) and similar service vendors.
That being said, it may still be beneficial for Class II devices to follow the PMA pathway rather than pursue 510(k) or de novo clearance because premarket approval creates a barrier to other manufacturers hoping to bring similar devices to market. In other words, if you use the PMA pathway for your device, similar devices will also need to follow the PMA pathway. Other sponsors won’t be able to use your device as a predicate device, and if they request a de novo classification, it will most likely be denied by the FDA. Therefore, while following the PMA pathway for Class II devices requires more time, more work, and more money, it can also act in defense of your device’s long-term viability.
510(k) and de novo Clearance
One advantage to using the 510(k) and de novo clearance pathways is that FDA approval is not required before the study begins. Depending on the device and target condition, you may still want to engage in discussions with the agency to ensure your clinical strategy and study design are acceptable, but your trial startup is undeniably shorter. Other advantages include more relaxed study demands, such as fewer subjects, shorter follow-up, and less risk of serious adverse events, which translates into accelerated timelines and lower costs. However, one disadvantage of the 510(k) process is its unique regulatory requirement: you must demonstrate your device is substantially equivalent or non-inferior to the predicate. This starting point can make it challenging to market your new product effectively when all you can claim is you’re similar to what is already available! The de novo pathway avoids this conundrum, but you need to obtain FDA agreement that your device has no predicate prior to using this pathway, which carries its own set of challenges and considerations.
Define Your Regulatory Strategies
While determining your FDA regulatory pathway is often straightforward and defined by device class, there is a measure of flexibility that allows sponsors to be more strategic in choosing the most advantageous approach for your company and product. The strategic consultants at Avania have the experience and expertise needed to identify the best pathway for your short-term and long-term objectives, then provide precise, end-to-end guidance for successful approvals. When you need to find the right path, It Takes Avania.