Explore how groundbreaking devices like transcatheter heart valves and the artificial pancreas navigated FDA’s PMA pathway. Learn strategies from staged approvals, Breakthrough designation, supplements, and postmarket commitments.
One illustrative PMA journey is that of the first transcatheter aortic heart valve (TAVR) device. This device enables replacement of a diseased aortic valve via catheter without open-heart surgery – a high-risk, groundbreaking technology at the time. Let’s see how its PMA pathway unfolded:
The manufacturer initially targeted TAVR for patients who were so high-risk (or inoperable) that they couldn’t undergo open surgery – a clear unmet need. A pivotal clinical trial was conducted in this population, showing that the TAVR device significantly improved survival and quality of life compared to medical therapy alone. Because this was a first-of-kind device, FDA convened an advisory panel. The panel reviewed the trial data and, noting the dramatic benefits for patients with no alternatives, voted in favor of approval for inoperable patients. FDA approved the PMA for that narrow indication in 2011, marking the first catheter-based aortic valve approved. Importantly, FDA mandated a post-approval study to follow patients for 5 years to monitor long-term outcomes and device durability.
With the device on the market for inoperable patients, the company gathered more data in broader patient groups. In subsequent years, they submitted PMA supplements to expand use to “high-risk” surgical patients, then to “intermediate-risk” patients, and eventually to “low-risk” patients. Each expansion was backed by new randomized trials comparing TAVR to surgical valve replacement in those risk groups. For example, in 2016, FDA approved an expanded indication for intermediate-risk patients after a trial showed TAVR was as good as surgery in outcomes. This approval was significant – FDA noted it was the first time a transcatheter valve was approved for a moderate-risk population. The decision was supported by robust data and an advisory panel endorsement. Similarly, by 2019, data in low-risk patients led to FDA approving use in essentially all risk categories. Each time, the manufacturer strategically used PMA supplements (panel-track for major expansions) to broaden the label, rather than trying to get everything in the initial PMA. This stepwise approach allowed FDA to gain confidence gradually and allowed the company to address concerns (like stroke risk, durability) iteratively.
Throughout these approvals, postmarket surveillance played a role. FDA required continued follow-up of clinical trial cohorts and also set up a national registry to track real-world outcomes (the Transcatheter Valve Therapy registry). These data gave FDA reassurance on safety in wider use. Additionally, specific warnings were included in labeling (e.g., noting stroke risk, need for proper imaging during implantation). The company also improved the device and procedure iteratively (e.g., better delivery systems to reduce complications), submitting those improvements as PMA supplements (some as 180-day supplements for design changes).
This case shows how a company can strategically navigate the PMA process for a paradigm-shifting device: starting with the sickest patients to demonstrate benefit, using strong clinical trials to expand indications, working closely with FDA and advisory panels, and committing to extensive post-approval studies. It also highlights FDA’s flexibility – as confidence in the technology grew, FDA’s requirements evolved (for low-risk patients, FDA still needed an RCT but was willing to approve because earlier phases went well). Essentially, the PMA pathway was used as a framework for ongoing innovation and evidence generation, not just a one-and-done approval.
Our second case involves the first FDA-approved hybrid closed-loop insulin delivery system for type 1 diabetes – often dubbed an “artificial pancreas.” Approved via PMA in 2016, this device automatically monitors blood glucose and adjusts insulin delivery, a major advance for diabetes care. Here’s how its PMA process exemplified strategic FDA engagement:
The device was recognized as a breakthrough technology given its potential to reduce burden and risks for Type 1 diabetics. FDA’s Center for Devices (CDRH) worked closely with the company during development. In fact, FDA officials noted they interacted from the earliest stages to expedite bringing this device to patients. For example, the company and FDA likely discussed study designs and reliability testing early through Pre-Subs. This collaboration helped in designing a pivotal trial that would meet FDA’s needs without unnecessary complexity. As a result, the PMA included data from a single-arm clinical study in 123 patients over 3 months using the system, showing it was safe and maintained glucose control within target range without serious hypoglycemia. Given the chronic nature of diabetes, FDA could have asked for longer studies, but due to the breakthrough status and urgent need, they accepted this data with conditions.
Interestingly, FDA did not convene an advisory panel for this device – possibly because it was a breakthrough and the data were straightforward, or because the risks were well-understood (since it’s built on existing pump/monitor tech). Instead, FDA expedited the review and approved the PMA in just 6 months after submission, which was ahead of expectations. The news was widely covered; FDA’s press release emphasized the “first-of-its-kind technology” and its potential to improve lives. They quoted CDRH director Dr. Jeffrey Shuren, highlighting how this device gives patients greater freedom. That quote reflected FDA’s perspective that benefits were clear.
With approval, FDA required some follow-up: a post-market study to monitor real-world performance in a larger group (including younger children as the initial approval was age 14+), and labeling updates as needed when that data came in. Indeed, the device’s use was later expanded to younger pediatric patients after additional studies, via PMA supplement. The initial PMA approval was conditioned on further evidence for those populations.
From a case study viewpoint, the company’s strategic moves included obtaining Breakthrough designation, leveraging that for frequent FDA feedback (so the PMA content met FDA’s expectations), and being prepared to commit to postmarket data collection to mitigate any uncertainties. For instance, one might note the relatively short 3-month pivotal study – normally, FDA might want longer data for a chronic device. But the sponsor likely argued that any issues (like diabetic ketoacidosis or device glitches) would appear in 3 months, and they proposed to gather extended data post-approval. FDA agreed, as reflected in the approval with required postmarket surveillance.
The artificial pancreas case demonstrates the impact of strategic FDA engagement and a strong benefit-risk case. By working closely with FDA, the sponsor managed to get a complex PMA through on a relatively small dataset, because the device addressed a critical medical need and the risk mitigation strategy (like training users, extensive device alarms for malfunctions, etc.) was solid. It underscores that FDA can be pragmatic and flexible – if approached the right way. The public FDA statements even acknowledged how the agency “worked interactively” with the company to speed development. This is a blueprint for other innovators: invest in a cooperative relationship with FDA, and approach your PMA not as a hurdle but as a joint effort to safely bring innovation to patients.
Both case studies highlight several themes:
For anyone preparing a PMA, these real-world examples reinforce the importance of tailoring your strategy to your device’s context: if it’s breakthrough, capitalize on that; if it’s high-risk but life-saving, demonstrate that clearly; if it’s incremental improvement, you might face a higher evidence bar since the unmet need is less. Case studies show it’s possible to achieve PMA approval on first attempt, even for revolutionary devices – but smart planning, quality data, and adept regulatory navigation are common denominators of success. By studying these and other PMA stories, you can better map out your own path to a successful FDA approval.
