While a radically different treatment approach may be necessary when no adequate treatment exists, these novel technologies introduce a level of uncertainty that can be difficult to assess and adequately control. Because of this, the regulatory requirements to demonstrate safety and effectiveness for devices with no established precedent (i.e., a PMA or de novo) are much more stringent and rigorous than for moderate-risk devices with established predicates [i.e., 510(k)]. In addition, this performance uncertainty introduces a risk to companies, which may devote large financial resources and time to a device that proves to be less effective than expected or introduces an unanticipated safety concern. While the 510(k) pathway is limited to moderate-risk devices that demonstrate equivalence to legally marketed predicate devices in the United States, the U.S. Food and Drug Administration (FDA) allows for innovation through an incremental approach, providing a level of control over potential uncertainty.
Proven Treatment Techniques
Specifically in the orthopedic space, many current treatment options, such as interbody cages for spinal fusion or hip arthroplasty systems, have well-understood mechanisms of action and an established history of successful outcomes. A recent meta-analysis conducted by MCRA found the 24 month fusion rate for lumbar interbody cages to be 92 percent with significant improvements in function and pain scores.1,2 Similar results have been reported for cervical interbody cages.3 For metal-on-poly hip arthroplasty systems—the current gold standard—survivorship has been reported to be approximately 96 percent through 13 years per the U.K. National Joint Registry.4
Because of this demonstrated performance, interbody cages and certain hip arthroplasty systems are classified as Class II devices that can be cleared through a 510(k) pathway. While this track is designed for new devices that demonstrate equivalence to previously cleared devices, companies have continued to innovate in an incremental approach to improve device performance.
However, due to the differences between interbody cages and joint arthroplasty systems in both clinical objective and functional lifetime, these innovations have taken different forms.
Examples of Innovation via 510(k)
Because the functional lifetime of interbody cages only lasts up to the point of spinal fusion (usually around 12 months), companies have focused improvement efforts on augmenting the implant-bone interface through coatings to improve physical and biological compliance with bone, introducing polymeric cages such as polyether ether ketone (PEEK) to reduce imaging artifacts, reconfiguring cage design to allow for a more minimally invasive approach, and developing improved manufacturing techniques such as 3D printing.
Alternately, hip implants have a functional lifetime that lasts the life of the patient; therefore, innovation efforts have been focused on improving the long-term function of these devices, including enhancing materials to reduce wear of articulating surfaces and modifying implant design and component surfaces to improve long-term fixation.
In the last decade, interbody cages have shifted from being primarily composed of metallic materials such as stainless steel or titanium alloy, to polymers like PEEK, as these polymeric materials provide improved mechanical properties that reduce the risk of subsidence and allow for controlled visibility with radiographs for easier placement verification and healing site assessment. These polymeric implants were further improved with the addition of porous titanium coatings that allow for increased bone compliance and fixation.
Interbody cage design has also improved incrementally over time. Early iterations of cages were indicated for use with supplemental fixation plates to provide structural support. Next-generation cages introduced integrated fixation with screws to eliminate the need for supplemental fixation plates. Other design improvements include modifications to allow for different and less invasive surgical approaches through a transforaminal (TLIF) or lateral approach (LLIF). The indications for use have also evolved to include the use of allograft and multilevel use in the cervical spine.
Similar to interbody cages, hip arthroplasty systems have improved incrementally through the 510(k) pathway. This innovation has been largely focused on addressing the two primary modes of failure of these systems: polyethylene liner wear and loss of fixation. Improvements in polyethylene include the introduction of highly cross-linked UHMWPE in the early 2000s and the introduction of anti-oxidants such as Vitamin E to improve acetabular liner wear performance.
Another example of incremental innovation in hip arthroplasty systems involves improvement to femoral stems to enhance fixation and reduce the risk of device loosening. While the first generation of hip systems used cemented femoral components, implant design shifted to cementless designs to allow for greater bone tissue preservation. The most common reason for revision in hip arthroplasty systems is implant loosening, accounting for approximately half of all revisions.5,6 The primary cause of loosening is stress shielding, which occurs when a stronger, stiffer material (e.g., metal femoral component) absorbs the majority of the load passing through a long bone like the femur, resulting in a long-term reduction in stress passing through the bone and leading to bone resorption over time.
Femoral stems have slowly evolved in the past 20 years to preserve bone, reduce stress shielding, and improve bone compliance of the implant surface. One example of this is short femoral stems, which were designed to minimize bone removal, reduce pain (as the implant will not stimulate the diaphysis), and diminish stress shielding on the proximal femur. Similar to interbody cages, the introduction of plasma spray and porous surface coatings such as hydroxyl apatite (HA) provides improved bone compliance and subsequent device fixation.
Implementing Incrementalism into Regulatory Strategies
Utilizing an incremental approach to design changes allows for a more straightforward evaluation process for regulators and reduces the risk of unanticipated safety events. Instead of being tasked with evaluating a complex, novel device system, incrementalism allows regulators to asses a single modification and its impacts on safety and performance compared to a predicate. This allows for a more predictable and simplified review.
When modifying existing devices, a successful regulatory approach often entails utilizing precedent in design, materials, indications, and manufacturing as much as possible when submitting to FDA or other regulatory body. For instance, if a company wants to introduce a new surface coating for a currently marketed medical device, maintaining the same device size, indications, and implant material will provide an increased level of assurance of performance and allow regulators to focus on the performance implications of the new coating without any confounding variables.
For new device companies looking to introduce a first generation system that incorporates unique design principles such as a new surface coating or product design, the best regulatory strategy often is to utilize a stepwise approach, introducing the system without the unique design feature or limiting the number of unique features. This allows the company to reduce the time to market, as the simplified device will be more similar to predicate devices and thus, will introduce fewer unknowns for FDA assessment. Following clearance, a subsequent 510(k) can be submitted that includes the desired novel features, allowing FDA to evaluate these new considerations on their own, rather than assessing a brand new device, company, and manufacturing process.
Similarly, if a device company is considering modifying a currently marketed device to allow for expanded indications, a successful approach often entails first submitting the modified product for the currently cleared indications. This allows FDA to assess the modifications without having to consider the increased risk or uncertainty associated with expanded indications. Following clearance, a second 510(k) can be submitted with the desired indications, enabling FDA to assess the implications of the new indications on their own.
In this way, a company can limit the potential for unexpected regulatory concerns to arise and better plan for FDA requests. While this stepwise approach often increases the time to get the final, desired product to market, if long-term testing on the novel features is required, it can allow a new firm to at least get a product on the market earlier while the testing process for the novel features is underway. It is important for a company to weigh the time and monetary costs with these different regulatory approaches. However, an incremental approach to innovating in the medical device industry often proves to be a successful strategy, as it reduces the business risk and financial burden to companies, provides increased certainty of device performance for regulators, and delivers improved treatment options for surgeons, all while assuring patient safety.
- Gornet, Matthew F., et al. “Lumbar disc arthroplasty with Maverick disc versus stand-alone interbody fusion: a prospective, randomized, controlled, multicenter investigational device exemption trial.” Spine 36.25 (2011): E1600-E1611.
- Blumenthal, S. L. “A prospective, randomized, multi-center FDA IDE study of lumbar total disc replacement with the CHARITE artificial disc vs. lumbar fusion: I. Evaluation of clinical outcomes.” Spine 30 (2005): 1565-1575.
- Fraser, Justin F., and Roger Härtl. “Anterior approaches to fusion of the cervical spine: a metaanalysis of fusion rates.” Journal of Neurosurgery: Spine 6.4 (2007): 298-303
- National Joint Registry. “NJR 14th Annual Report.” (2017).
- Delaunay, Christian, et al. “What are the causes for failures of primary hip arthroplasties in France?.” Clinical Orthopaedics and Related Research 471.12 (2013): 3863-3869.
- Ulrich, Slif D., et al. “Total hip arthroplasties: what are the reasons for revision?” International orthopaedics 32.5 (2008): 597-604.
Samuel Pollard is a senior regulatory associate at Musculoskeletal Clinical Regulatory Advisors (MCRA), primarily focusing on developing regulatory strategies and submissions for the U.S. Food and Drug Administration, as well as international regulatory agencies. He has an extensive knowledge of regulatory pathways with experience developing PMAs, IDEs, 510(k)s, de novo submissions, and Clinical Evaluation Reports, with a focus in orthopedic devices. He attended Clemson University and graduated with a bachelor of science degree in bioengineering with a concentration in biomaterials.