Copy to clipboard 
Startups must be diligent about how they spend money during the regulatory process. Novel technologies may require costly studies and clinical trials for regulatory approval, but even missteps for a 510(k) product can lead to extra work and delayed timelines.
Experts recommend that orthopedic startups gain clarity on regulatory and quality requirements early in the product development phase. This requires determining the best regulatory path for your device, choosing the best markets for launch and understanding pertinent guidance and standards.
Prepare for the Submission
It’s rare for startups to possess regulatory prowess, making it important for companies to seek wise counsel from experts. Conducting an assessment to define a product’s regulatory pathway and requirements for a successful submission should be a priority.
“Understanding what needs to be done is critical,” said Christine Scifert, Founder and Partner of MRC Global. “Companies come to us and say that their submission is ready, and we find certain things haven’t been done. That significantly delays the submission process.”
Engage with a regulatory expert early to ensure that you’re doing the right work in the correct order, she said. The 510(k) pathway is a reasonably straightforward process. But if your device doesn’t follow standard testing or requires premarket approval, you should engage with FDA through the Q-Submission Program.
When it comes to the European market, Ibim B. Tariah, Ph.D., Technical Director, Business Development Medical Devices at SGS, said companies should engage a Notified Body as soon as they freeze their product design. This allows the Notified Body to understand the technology and provides an opportunity for the two parties to agree on the best path forward.
“It’s time to market, not speed to market,” Dr. Tariah said. “That includes time to submit, time for the Notified Body to perform their reviews and time for back-and-forth communication.”
When building your submission, teach reviewers about the technology and tell its story, said Dave McGurl, Vice President of Regulatory Affairs – Orthopedic, Musculoskeletal Clinical Regulatory Advisers. Companies with novel products are often engaged with regulatory bodies for multiple years, so the review team is likely to change. When this happens, McGurl recommends calling the new reviewer to introduce yourself and your company and bring them up to speed on the product and the process.
“You’ve been working on your product for years, and a new reviewer is picking up your submission and learning it in days,” McGurl said. “You need to educate them about your device.”
Pick the First Market Wisely
Startups once thought the European Union was an easy market to enter due to less stringent regulatory processes. However, the new, complex Medical Device Regulation (MDR) has made it difficult and expensive for companies to compete in European countries.
“Europe has become a second destination to the U.S.,” Dr. Tariah said. “The cost of getting an MDR is high compared to the former MDD, and the maintenance cost is even higher.”
He noted that the European Parliament finally heeded industry complaints that MDR is too bureaucratic and an innovation stifler and announced plans to review the regulations by the end of the first quarter of 2025. While this is a positive step, Dr. Tariah said, the government made no promise to change the regulations.
“A lot of companies ask me about EU MDR, and I tell them not to do it,” Scifert said. She cited years-long waits for reviews by Notified Bodies, the cost to collect clinical data and the difficulty of transferring an MDR. Startups seeking to be acquired may be less attractive to purchasers if they only have products on the EU market because MDRs aren’t easily transferable from one company to another.
Startups previously looked favorably at the EU market because it cost less to collect clinical data there than in the U.S. European-headquartered companies might still find it easier to gather data in the region, though. McGurl said that there is a potential route for companies to collect data in the EU and use it for an FDA regulatory submission.
He noted that FDA guidance on using foreign data for a submission focuses on the quality and generalizability of the data. Companies must be able to show that the patient population or orthopedic procedures are similar, and they should be prepared for FDA to require a post-approval study.
Know the Issues of the Day
Current events and emerging technologies can force regulatory bodies to scrutinize specific topics. You should be aware of which issues are gaining attention from regulators to stay ahead of requirements. Biocompatibility and cybersecurity are priorities today.
“Biocompatibility is a big topic for submissions globally, but specifically in the U.S.,” Scifert said. She noted that orthopedic companies are often surprised by the requirements for a device manufactured with well-established materials like titanium. “The ISO 10993 standard was updated, and FDA came out with a number of guidances for biocompatibility 10993 implementation. Chemical characterization requirements are heavily encouraged on final finished devices, which takes a lot of time and money to complete.”
If your orthopedic device is made of a unique material, a polymer or it absorbs, you should conduct an animal study to prove biocompatibility, McGurl said. He noted that FDA examines testing methodologies and often has a significant number of questions that put companies in a long feedback loop. “An animal study is ultimately going to be faster than other testing options,” he added.
Companies are also running into issues related to the integrity of biocompatibility testing data. FDA issued a memo to medical device manufacturers about an increase in fraudulent data and handed out warning letters to firms. McGurl and Dr. Tariah stressed that you should contract certified labs for your biocompatibility testing.
The growing adoption of enabling technology and software in orthopedics has also caught the attention of regulators.
“One of the biggest things we’re seeing is FDA’s focus on cybersecurity,” McGurl said. “Cybersecurity is going to be the next biocompatibility. If you have software or firmware in your technology, FDA is going to ask to see everything. Companies need to be prepared to take on that amount of work.”
Scifert said companies hesitate to provide FDA insight into their proprietary algorithms. Still, the agency will ask to see complete documentation on validations and change management during submission.
Dr. Tariah said startups with connected and enabling technologies will face similar scrutiny when they enter the EU market.
“Europe also adopted the AI Act,” he added. “They are cognizant of the fact that technology will continue to evolve. Oftentimes regulations lag innovation, so they’re doing their darndest to stay abreast of advancements.”
