Class III Devices from 10,000 Feet: The Big Picture on Getting Premarket Approval

It takes a certain level of passion and perseverance to break new ground. For the innovator introducing a disruptive technology to improve patient outcomes and lives, the creativity fueling the process of getting a Class III device to market is rivaled only by the determination and dedication to prove that device’s safety and effectiveness.

I admire clients who take on the challenge—it’s not for the faint of heart. It typically takes years to make it from the initial concept to a successful panel meeting with the U.S. Food and Drug Administration (FDA).

Based on my series on Cartiva Inc.’s quick approval of the Cartiva Synthetic Cartilage Implant, here’s what Class III innovators should consider when steering their device to market.

Know Your Market and Device
It takes more than a great idea to improve patient lives and health options. It takes demand for the device and understanding of the social, medical, and economic landscape supporting it. In addition to medical benefits for patients, it will need buy-in from surgeons and healthcare plans. No matter how good the device, it will never make it to the end-user without reimbursement.

You should be the ultimate expert on your device, said Kevin Prebula, attorney and partner at Hogan Lovells, a global consulting firm Cartiva hired for legal and regulatory support. If you don’t know everything about your product, how will you convince FDA to approve it?

“You have to have a clear idea about what your technology is and what you want your technology to do,” he said. “FDA will apply the same rules whether you’re a small company or a large company based on those two things. If you don’t have a clear idea of what that is, no amount of outsourcing will help you figure it out.”

Know What You Don’t Know
Take a serious, objective self-assessment to help develop a realistic timeline and identify areas to outsource. From the 10,000-foot view, do you have the time, funds, and staff to see this project through several years of development? Do you openly communicate with the FDA and understand how to navigate its processes? Do you know who to contact for guidance at critical junctures?

Then consider specifics, such as meeting FDA’s standards for proof of safety and efficacy. Do you have the proper test frames and expertise to run your device to failure points? Can you manage clinical trials from start to finish, including compiling statistics? Who’s on your legal team, and what are those potential challenges? What about a liaison with FDA who knows how to format reports and answer follow up questions? How are you protecting intellectual property?

Know Where and When to Spend
Finances are often tight for smaller companies, and purse strings may be held by well-meaning investors without a full understanding of what it takes to thrive in the medical device industry. Upfront costs appear large and daunting, but are typically smaller and more manageable than those required to course-correct further into the process. Saving more by initially spending more is a smart use of funds. Your honest self-assessment should identify where you need to pay to bring in experts.

Time is literally money for most Class III devices. The sooner you can reach market, the sooner you can start recovering investment and generating a profit. Glenn Stiegman is senior vice president of clinical and regulatory affairs with Musculoskeletal Clinical Regulatory Advisers LLC. His firm partnered with Cartiva to support its journey to market. He said specific concerns and expenses vary depending on the device, but it’s not worth it if cutting one cost adds risk to overall success.

“If you don’t do it right, it’s more expensive in the long run,” he said. “You can spend triple the money going through appeals and going back to fix [earlier mistakes]. No one thanks you for saving money if you fail.”

Practice for the Panel
The panel presentation is a make-or-break point for most Class III devices. It’s an unbiased set of experts interviewing both the applicant and the FDA about the device—what it is, how it works, the need it addresses, etc. After review, the panel submits its opinion on whether the device should be approved to the FDA. The FDA can then follow or ignore the panel’s advice on next steps.

Deborah Moore, vice president of clinical, regulatory, and quality affairs for Cartiva, said participation in in-depth, complex, expensive, and stressful mock panels made the actual panel presentation much easier. She hired a “bullpen” of five people with different areas of expertise, each ready to anticipate and send information from a deck of 1,000 slides compiled to answer various questions.

“It was pretty intense,” Moore said. “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.”

Respect Regulatory
After over 20 years in the medical device industry, I have great respect for the men and women making the tough calls concerning medical devices. We’re all committed to best outcomes for patients, but agencies like FDA have the final call on what “safe” and “effective” mean. I can’t stress enough the importance of a strong, open, honest relationship with reviewers and other regulatory agents.

These people share your passion for the industry, viewed from a different perspective. If you understand those perspectives and make their jobs as easy as possible, they’ll likely reciprocate. Contact them early in the process, answer their questions quickly and effectively, and consider outsourcing if this is outside your comfort zone. I’m not saying you should never challenge or question their feedback—misunderstandings and mistakes happen. But if you do, have clear, conclusive data to support your concern. And be polite, no matter who’s asking questions or raising concerns.

Pick the Right Partners
The companies and people accompanying your journey to market are key to success. More than subject matter experts, they’re an integral part of the team, often for years. Ensure you share values, vision, and work ethic. Get recommendations from colleagues, trusted vendors, and companies that have brought a Class III device to market.

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

Ensure the firms you select truly understand your specific market segment.

“You want somebody that knows the anatomy and patient population, knows the study design that FDA would expect, knows that review group at the FDA so you already have that established working relationship,” Stiegman said. “You have to understand the dynamics of the whole regulatory and clinical environment.”

You also want someone willing to say what you don’t want to hear.

“If I’m not willing to say ‘probably not,’ I’m doing a disservice to my client,” Prebula said. “They’ve hired me to not only be their advocate but also an adviser. I have to be willing to do both. If you find a consultant who only wants to say yes or only wants to tell you things that can go wrong, you probably want to look for someone who’s a little more balanced.”  

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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.