On November 26, 2018, the U.S. Food and Drug Administration (“FDA”) announced the process for clearing most medical devices for marketing is being updated to incorporate changes the FDA laid out in an April draft guidance. For over forty years, most medical devices have entered the United States market through the 510(k) clearance process. The 510(k) process offers an expedited approval process available only for products that are substantially equivalent to products already on the market (known as predicate devices). The FDA is considering no longer allowing sponsors to rely on predicates older than ten years and making public information about cleared devices that relied on predicates more than ten years old. In addition, the FDA intends to finalize guidance establishing an alternative 510(k) pathway with different criteria that reflect current technological principles.

In a statement, FDA Commissioner Scott Gottlieb reasoned that newer products relying upon older predicates might not reflect new performance standards or latest scientific and medical understanding. Commissioner Gottlieb believes this change will promote the continual improvement of medical devices. However, the announced change received quick pushback. Many manufacturers argue that reliance upon older predicates can be necessary when no newer predicates are available, and older predicates can provide data that helps sponsors make new devices safer. In addition, many industry-observers believe the FDA’s plans may contradict and exceed its statutory authority, and therefore require additional support from Congress.

If the current proposal becomes law, the implications will include increased costs for manufacturers forced to innovate because of the inability to rely on older predicates. The agency’s statement indicates that new medical devices that utilize the 510(k) pathway should be better than predicates, rather than the applicable legal standard of substantial equivalence. Thus, manufacturers can anticipate increased agency scrutiny when submitting information in the 510(k) summaries. In addition, manufacturers may need to make alternative plans if developing a new device based on an older predicate.

In early October, FDA held a public workshop to discuss the challenges of regulating medical devices made through additive manufacturing (also known as 3-D printing). Additive manufacturing gives designers the ability to build devices directly from 3-D images, like patient CT or MRI scans. As the push toward personalized medicine continues, 3-D printed devices hold incredible potential for advancing the ball. While additive manufacturing isn’t completely mainstream yet, FDA and industry stakeholders expect to see major growth in this field in coming years. Experts project that the global market for healthcare 3-D printing will reach $1.13 billion by 2020.

With industry innovators moving forward, FDA’s goal for last month’s workshop was to get a handle on the technical challenges and patient safety concerns that come with 3-D devices.

What’s Already Out There?

3-D-Printed-Hand-640x480FDA has already begun receiving (and clearing) submissions for 3-D printed devices. For example, additive manufacturing company, Oxford Performance Materials (OPM), has received 510(k) clearances for two 3-D printed devices over the past two years (the OsteoFab Patient-Specific Cranial Device (cleared in February 2013) and the OsteoFab Patient-Specific Facial Device (cleared in July 2014).

Following the clearance of its 3-D printed facial device, OPM’s CEO, Scott DeFelice, noted, “Until now, a technology did not exist that could treat the highly complex anatomy of these demanding [facial reconstruction] cases. With the clearance of our 3D printed facial device, we now have the ability to treat these extremely complex cases in a highly effective and economical way, printing patient-specific maxillofacial implants from individualized MRI or CT digital image files from the surgeon.” OPM plans to continue innovating in the additive manufacturing space. In fact, the company recently announced a partnership with Yale University to pursue new 3-D printed biomedical technologies.

Other types of 3-D printed devices have also recently hit headlines, including 3-D printed tracheal splints and vertebrae.

FDA Evaluation of 3-D Printed Devices 

As mentioned earlier, OPM’s two implant devices were cleared through FDA’s 510(k) process. To obtain FDA clearance through this process, a manufacturer must show that its device is “substantially equivalent” to another device that is legally marketed in the U.S. (a “predicate device”). In each of its 510(k) applications, OPM compared its proposed 3-D printed device to predicate devices that had similar intended uses (i.e., replacing bony voids in the cranial skeleton (for its 3-D printed cranial device) and correcting trauma/defects in facial bone (for its 3-D printed facial device) and similar technical specifications (i.e., customized for each patient). The fact that the suggested predicate devices had not been manufactured using 3-D printing did not prevent FDA from determining that the new proposed devices were “substantially equivalent” to the predicates.

However, in light of the highly individualized nature of many 3-D printed devices, some commentators have questioned whether the 510(k) process (or any of the typical premarket pathways for that matter, i.e., PMA, de novo, etc.) are appropriate for these devices. Part of the argument is that the traditional tools manufacturers have used to support a proposed device’s safety and effectiveness (e.g., clinical trials) hardly apply for many 3-D printed devices.  For example, how do you create a clinical trial where the intended user of a device is just one patient?

Yet, at this point, FDA is not evaluating 3-D printed devices in a way that is vastly different than how it evaluates any other medical device. FDA has stated that depending on its use, “[a]dditive manufacturing may or may not present new questions.” Still, FDA acknowledges that additive manufacturing is a complex process (that will likely become increasingly more complex) and is actively seeking input from stakeholders in industry and academia to help shape its regulatory approach (including future guidance documents). Going forward, it appears that a key Agency focus in reviewing 3-D printed product submissions will be on process verification and validation, which according to FDA, “are especially important when devices are produced individually or in very small batches.”

3-D printed devices have clear promise for providing treatment solutions that are both patient-specific and cost-efficient. Guided by stakeholder discussion and feedback, FDA will hopefully be able to come up with a regulatory approach that appropriately addresses the risks posed by 3-D printed devices without significantly impeding patient and clinician access to these valuable innovations.