As any medical device manufacturer knows, obtaining 510(k) clearance can represent a significant milestone in the product development journey. It can also be perceived as a major hurdle. This article looks at key elements of the process and how to manage it effectively.

What is 510(k) clearance?

Under section 510(k) of the US Food, Drug and Cosmetic Act (FD&C Act) a premarket submission is required to notify the Food and Drug Administration (FDA) of intent to market a medical device. The process allows FDA to determine whether the device is ‘substantially equivalent’ to at least one legally marketed predicate.

A device can be a predicate if:

1. FDA previously cleared it through the 510(k) process
2. It is exempt from 510(k) requirements
3. The Agency granted it de novo authorization; or
4. That specific device was commercially available before the May 28, 1976 enactment date of the Medical Device Amendments to the FD&C Act

And a device may be considered ‘legally marketed’, for the purposes of serving as a predicate, unless FDA has removed it from the market or a judicial order states that it violates the FD&C Act.

Should FDA determine a device is substantially equivalent, it clears the 510(k) notice. In which case, the device does not need a premarket approval application (PMA), which is the most rigorous type of premarket submission. It’s worth noting that PMA-approved devices cannot serve as predicates.

Understanding substantial equivalence

The path to 510(k) clearance is more straightforward when you know how the process works and what reviewers need. These elements may have a bearing on the design of the device itself as well as information and data provided in the submission, so thinking about it in the early stages of product development is key.

It’s important to understand that ‘substantial equivalence’ does not mean a device has to be identical to the predicate(s) cited in the submission. FDA’s regulations state:

A device is substantially equivalent if, in comparison to a predicate it:

• Has the same intended use as the predicate; and
• Has the same technological characteristics as the predicate; or
• Has different technological characteristics and
  • The device does not raise different questions of safety and effectiveness; and
  • The information and data submitted to FDA demonstrate that the device is as safe and effective as the legally marketed device

A guidance document issued by FDA interprets the above criteria. It includes examples of differences between new and predicate devices (including labeled indications for use, materials, features, and methods of operation) that affect whether the new device is or is not substantially equivalent. A flowchart is also included to help companies compare devices and evaluate their differences. However, FDA has broad discretion in determining whether a new device satisfies the substantially equivalent criteria.

How can an incremental approach help?

In general, the more similar a new device is to its predicate, the smoother its path to 510(k) clearance is likely to be. However, there are often some differences between the new and predicate devices’ indication for use, in other words, the diseases or conditions that they are intended to treat, diagnose, prevent or cure in their intended patient population.

In this situation, FDA needs to evaluate whether the devices have the same general purpose and thus satisfy the criterion that they have the same intended use. Where there are technological differences, FDA will determine whether the new device qualifies for 510(k) review. If so, FDA will likely require performance (bench, animal, and/or clinical (human)) data to evaluate the impact of differences on the safety and effectiveness of the new device. So, rather than combining numerous product indications and/or features into a first-generation device, there are times when it is better to phase them in gradually across multiple 510(k) submissions to minimize the differences between the new device and its predicate(s).

When is it best to take this approach?

Circumstances vary, but a small business or start-up might do well to consider this strategy. From a commercial perspective, getting ‘something’ to market, such as a basic version of a device, can help generate sales and/or secure investments. Such funding may fuel the next phase of product development. Achieving this in the shortest possible time can accelerate future progress.

Both large and small device companies may also derive other benefits from an incremental approach. If a company can conceive a version of a device that is 510(k) exempt, it could list the device as such on FDA’s website and then use it as a predicate for the second generation of the device (in some cases, never intending to market the initial device).

Alternatively, a company can use its own 510(k)-cleared or de novo-authorized device as a predicate for its next-generation device. In this situation, FDA’s review of the 510(k) for the new device would focus only on differences between those devices.

It is possible for a company to submit sequential 510(k) notices for increasingly complex versions based entirely on its own predicates. This can represent a more efficient route to 510(k) clearance for a device that might otherwise have required de novo or PMA review if clearance had been sought earlier.

It may be possible to achieve the same benefits using competitive devices as predicates. However, evolution of the predicates will be outside the company’s control. Furthermore, this strategy risks constantly playing catchup unless each version offers more than the predicate device(s).

Strike an effective path

A cautious, measured approach to 510(k) premarket notifications can allow manufacturers to achieve their end goal sooner. It may result in a more streamlined product development journey where capabilities and features evolve over time. However, there is no one size fits all solution. The ‘right’ strategy depends on numerous factors, including FDA’s current resources and priorities.

A recent article for our sister company Sagentia Innovation considers how the FDA’s Center for Devices and Radiological Health has adapted its premarket submissions review process for IVDs following a surge during the COVID-19 pandemic. As explained in that piece, FDA review of pre-submissions and premarket submissions for most in vitro diagnostic (IVD) devices that are not related to COVID-19 is facing extended timeframes. So, it might be more advisable for manufacturers of other IVD device types to submit a single 510(k) if clearance would ultimately have been sought, rather than encounter multiple delays.

The most effective strategy is to identify any hurdles a device is likely to face then find ways to overcome them. In this way, R&D and Regulatory teams are empowered to work together to make informed decisions. It also helps bring clarity to 510(k) submissions. This is an important factor since FDA receives thousands of 510(k) submissions each year; any ambiguities must be addressed by the company making the submission which might delay FDA’s review.

Developing and implementing an effective regulatory strategy from the outset enables a faster, more streamlined review process for medical devices. This helps ensure patients have access to safer and more effective devices sooner, which is the end goal of FDA and manufacturers alike.

Here at TSG Consulting, we help you understand the regulatory requirements associated with medical devices, then identify the best way forward for your product.

Get in touch at [email protected] to speak with Laurie and find out how we can support your company.