Case Study – US Clearance: Product Overhaul After More Than 10 Years on the Market
The Initial Situation
In 2010, a client we work closely with obtained 510(k) clearance for their core product in the United States. Since then, various changes were made to the product; however, each of these – and their cumulative effect – were assessed as non-significant, meaning an updated clearance was never deemed necessary.
The time had now come for a comprehensive overhaul and facelift of the product: a new color scheme, new features – the competitive landscape had shifted in the meantime, and a series of incremental improvements were to be implemented for a re-launch, making a new clearance necessary.
The Challenge
Obtaining clearance for product changes as part of a new or updated variant is a standard scenario – a prototypical 510(k) case. The challenge in this project lay more in the time elapsed since the initial clearance. Regulatory mechanisms and requirements have evolved and become more stringent; the bench test configurations originally devised by the manufacturer and the internal capacities for executing them have also advanced considerably. It was necessary to strike a balance between a body of evidence that was adequate at the time but is now outdated, and the demonstration of "substantial equivalence" to the established predecessor version as it stood at the time of initial clearance.
In addition, development work on a further variant of this product was still ongoing, with no clear timeline for completion. The goal was to bring the finalized facelift of the core variants to submission as quickly as possible, while avoiding the need for a separate, subsequent clearance for the trailing variant.
Approach and Solution
Since a large-scale facelift of this nature does not appear out of thin air, we were able to identify critical issues early, assess them appropriately, and thereby reduce associated risks to the clearance project:
New Color Scheme
While changes were made to the design, the materials used and the manufacturing processes were not materially altered. The only addition was the incorporation of a colorant into an established component. Admittedly, the colorant was new – however, less than 0.5 mg is used per product. The question therefore arose as to how the FDA could be convinced on matters of biocompatibility. Thanks to early engagement with this issue, the topic was addressed with the FDA in a Q-Submission. The outcome was that standard biocompatibility tests would be required – a requirement that, at the very least, could be addressed at an early stage.
The Bench Test Battery – Then and Now
Many of the bench test configurations submitted at the time of initial clearance had since changed and improved. It was necessary to examine whether the current test cases address the same questions that had been relevant at the time of first clearance.
In fact, there was one test case that is no longer covered in today's test battery. In coordination with the FDA, the original test setup was updated and conducted with the new variant.
Accommodating an Additional Variant Not Yet Finalized
The core variants are complete; a trailing variant should not delay the clearance but should also not require its own separate clearance effort. This is understandable – and in principle feasible with the FDA – through a Pre-Determined Change Control Plan (PCCP).
The concept: foreseeable product changes are included in the clearance submission; the PCCP describes the change and specifies how it is to be evaluated through verification and validation (V&V) measures. The FDA can then review – and ideally approve – this implementation plan as part of the same submission. When the time comes, the negotiated change can be implemented in accordance with the FDA-authorized plan, which must be documented accordingly. Another round with the FDA is then no longer required – provided the modified product passes the previously agreed-upon V&V measures.
The FDA initially introduced the PCCP mechanism for software-based products utilizing AI and machine learning. For such products, updates to newly trained algorithms are commonplace. If an update follows the same V&V logic as the initial clearance, such updates can in principle proceed via PCCP without requiring a separate clearance. In August 2024, the FDA extended this mechanism to physical medical devices, and it was successfully applied here.
In Summary
Obtaining clearance for changes to an existing 510(k)-regulated product in the US is a standard process. What matters is the delta between the last cleared product configuration and the current product design, as well as the time elapsed in the interim – since the regulatory landscape continues to evolve. Potentially time-sensitive aspects relating to biocompatibility and bench testing were resolved with the FDA, with a significant impact on the clearance outcome. In addition, the relatively new concept of a Pre-Determined Change Control Plan was successfully implemented here. The additional product variant now "simply" needs to clear the hurdles agreed upon with the FDA.
