David vs. Goliath: How a Small Startup Managed to Slingshot the FDA Approval Process

By Dawn A. Lissy, President & Founder, Empirical | November 22, 2016

I chose a career in the medical device industry because I wanted to help people. Specifically, I wanted to help my father, a man who suffered lifelong neck problems because he worked as a mechanic for 40 years. I sought to create a solution to ease his and other people’s pain.

I believe most of us in this industry have a similar story; we’re all here to help patients. That includes the U.S. Food and Drug Administration (FDA). While the agency is often cast as the giant we must battle to bring products to market, it exists to safeguard those we’re all working to help.

When it comes to Class III devices—cutting-edge, disruptive technologies with no comparable products—FDA is extra cautious. The agency requires a longer and more demanding path to the consumer than it does for Class II devices, which are essentially improvements to existing technologies. In addition to mechanical testing, report submissions, and other processes required for Class III devices, submitters must conduct extensive randomized, multi-center clinical studies and face a panel of experts who grill the applicant about the clinical outcomes and the device. It’s an arduous, time-consuming, and expensive process.

For Cartiva Inc., a venture-backed startup with 20 employees, Class III premarket approval was the only way to get its innovative device to market. The company bet its entire future on its key product, the Cartiva Synthetic Cartilage Implant (SCI). The breakthrough implant resurfaces the metatarsophalangeal joint to treat osteoarthritis.

During a year when at least four other major orthopedic companies failed their panel reviews, Cartiva not only passed the rigorous panel meeting, it received approval to sell Cartiva SCI 71 days later. As of 2014, the average span from panel meeting to FDA approval was 159 days. SCI not only succeeded where so many medical giants have failed, its approval came in less than half the expected time.

So what’s the company’s secret? The quick turnaround at the very end followed nine long years of careful and diligent work. From the beginning, Deborah J. Moore (Cartiva’s vice president of regulatory, quality, and clinical affairs) and her team took the approach of honest, objective reviews of the product’s internal strengths and weaknesses.

“I think being from a small company in general, you have to think outside the box,” Moore said. “You tend to have a lot of people here who are innovative to begin with. That’s part of being in a startup environment.”

Another part of being a startup is the intense pressure to succeed placed on a small team.

“We’ve got limited resources—people and money,” she said. “We are gonna live or die based on the outcome [of the PMA].”

Moore knew the company had a strong regulatory and clinical team that was determined to be directly involved in clinical trials performed at 12 leading institutions in Canada and the United Kingdom.

“I didn’t want to outsource study management to a [contract research organization] because I think it’s important to have and maintain those relationships at the clinical site and be familiar with data,” she said. “I think a company has better success when they’re very hands-on with the clinical trial.”

She attributes the high rate of follow-up to her team’s direct involvement—97 percent of subjects completed the entire two-year process, she said.

However, there were other areas where it paid to pay someone else to run the show. She selected my company, Empirical Testing Corp., for mechanical testing. Moore recognized her firm had neither the equipment nor the extensive orthopedic testing experience to run the full battery of tests or develop the customized test fixtures required for the panel submission.

“It really didn’t make sense for us to invest in all that equipment and fill out the learning curve for things that would only be required at key junctures,” she said. “For us, it was really important to work with people that have that knowledge and have successfully worked with the FDA in the past.”

The ticking of the clock also echoed in Moore’s head as she considered whether to outsource another aspect of their project.

“We might have the expertise to do a given thing, but if we can get it done quicker [by outsourcing], we might do that as long as the level of quality is where it should be,” she said.

In addition to knowledge and experience, a smooth partnership is built on trust and ongoing, honest communication. A good consultant or vendor doesn’t try to take over a project, but rather works behind the scenes to ensure you shine brightest when it counts the most.

“We were looking at relationships and expertise—what they had done previously, what their track record had been,” Moore explained.

Recommendations from clients and other vendors were a critical part of that decision-making process, she said. International law firm Hogan Lovells, who advised Cartiva on regulatory strategy, was a trusted source of direction and references for Moore.

“I think, again, it’s really in talking to each of the vendors, really understanding what they’ve done, how recent has that work been, how successful has it been,” she remarked.

Cartiva also outsourced data management and statistical support for clinical trials, attorneys and regulatory strategy consultants, and panel meeting preparation. While each outside vendor made significant contributions along the way, Moore said the two full-on mock panel presentation preps prior to meeting with the FDA’s experts were invaluable.

“When you hear what’s involved, initially as a company you think, ‘We don’t need to do that, it seems like overkill,’” she recalled. “But absolutely that was what was a key to success.”

During the first mock panel, five panelists grilled Moore and her team as if they were representing the FDA. For the second panel, nine medical device experts put them through their paces. Both times, Moore employed a data presentation company as information support. A team of five people, “the bullpen,” each with different areas of expertise, wore headphones and manned laptops with a prepared deck of 1,000 slides covering a range of topics they anticipated the advisory panel would inquire about. During the mock and actual panel, the laptop team anticipated the appropriate slides and sent those slides in preview mode to the Cartiva presenter, who could then choose which slide to share. 

“It was pretty intense,” Moore remembered. “I was having to listen to the question that was coming at me and make a judgment on slides. It demonstrated to the panel members that we were confident and well prepared, we had information at the ready, we had anticipated the questions, and we could answer them with a lot of depth.”

Panel meeting preparation was a very costly and time-consuming process, Moore said. But it was time and money well spent, and she’d do it all over again without hesitation.

“The panel prep was expensive and exceeded our budget, but it was absolutely worth it,” she noted. “Your panel meeting, you have that one day. It’s only eight hours. The future of your company is decided on that particular day.”

This is the first column in a series. Upcoming installments will focus on how to find other experts to help bring a Class III device to market. 

Dawn Lissy is a biomedical engineer, entrepreneur, and innovator. Since 1998, the Empirical family of companies (Empirical Testing Corp., Empirical Consulting, LLC, and Empirical Machine, LLC) has operated under Lissy’s direction. Empirical offers the full range of regulatory and quality systems consulting, testing, small batch and prototype manufacturing, and validations services to bring a medical device to market. Empirical is very active within standards development organization ASTM International and has one of the widest scopes of test methods of any accredited independent lab in the United States. Because Lissy was a member of the U.S. Food and Drug Administration’s Entrepreneur-in-Residence program, she has first-hand, in-depth knowledge of the regulatory landscape. Lissy holds an inventor patent for the Stackable Cage System for corpectomy and vertebrectomy. Her M.S. in biomedical engineering is from The University of Akron, Ohio.