3D printing of medical devices will revolutionize and disrupt healthcare as we know it. The U.S. Food and Drug Administration (FDA) has already cleared more than 80 medical devices and one prescription drug that are produced by 3D printing techniques. Those devices (and drug) were cleared (and approved) using FDA’s existing regulatory framework and were considered nothing more than another form of advanced manufacturing. If, when, or how the FDA would clarify the submission requirements and regulatory framework for 3D printed medical devices has long been in doubt — that is, until earlier this month, when the agency released a draft guidance for Technical Considerations for Additive Manufactured Devices.
By setting forth technical assessments that manufacturers of certain 3D printed medical devices should consider, the FDA’s draft guidance is meant to provide a transparent evaluation process for future submissions. It is not meant to be a comprehensive document addressing all regulatory requirements; but it does highlight the technical considerations and makes recommendations for the design, manufacturing, and testing of medical devices that include at least one fabrication step using additive manufacturing.
Introduction to the draft guidance
The FDA realizes that the draft guidance is not a one-size-fits-all approach, and that is why the FDA categorizes it as a “leap-frog” guidance. It is simply meant to provide the FDA’s “initial thoughts” on 3D printing of medical devices. The draft guidance is split between two main areas of focus: 1) design and manufacturing and 2) device testing. Both sections overlap in substance, and the device testing section in particular provides strong, detailed recommendations for what a device manufacturer should include in a premarket submission for a device that uses additive manufacturing.
The FDA has evidently put a lot of time into thinking about the unique technical aspects involved in 3D printing of medical devices — and ensuring that the manufacturers of those devices consider these issues when submitting a premarket application. The FDA is clearly aware that 3D printing has numerous advantages for medical devices but at the same time poses significant challenges. While the draft guidance is a necessary step in the right direction and resolves some questions, many issues still remain unclear.
What the draft guidance resolves
In general, the draft guidance does not change the current regulatory pathway to market for medical devices, whether 3D printed or traditionally manufactured. Manufacturers who use additive technology in their medical devices will continue to use traditional pathways. This is no different than how the FDA has handled the already more than 80 medical devices cleared by the FDA to date.
The draft guidance does, however, pay particular attention to the unique technical considerations involved in 3D printing (generally) and how those procedural issues should be assessed and documented in premarket submissions. The draft guidance is helpful in the sense that it outlines what the FDA is looking for in premarket submissions for 3D printed medical devices, and also how the FDA considers such products in its regulatory framework — basically the same as any other medical device.
The draft guidance also pays particular attention to patient-matched devices (devices that are “tailored” for a specific patient’s anatomy, usually based on medical imaging data). Patient-matched devices are one of the numerous advantages of 3D printing in the healthcare space, because this type of personalized medicine helps deliver the right device, that is the right size, to the right patient. While these devices are considered “custom” in the 3D printing industry, the draft guidance clarifies that patient-matched-devices do not fall into the Federal Food, Drug, and Cosmetic Act’s (FDCA’s) custom device exemption under section 520(b)(2) [21 U.S.C. § 360j(b)]. Under section 520(b)(2), the FDCA exempts certain generic medical device types (i.e., a grouping of devices that do not differ significantly in purpose, design, materials, energy source, function, or any other feature related to safety and effectiveness) from some, but not all, FDA regulatory oversight.
For instance, although manufacturers do not need to seek premarket approval or conform to mandatory performance standards, they still need to comply with the FDA’s quality system (QS) requirements and standards. Medical devices falling within this custom device exemption must be made to the specifications of a single patient based on their prescribed needs as determined by a healthcare professional, and must not be generally available in the United States in finished form. Notably, the exemption is available only when less than five of custom device types are manufactured per year. Thus, assuming a 3D printed medical device could qualify for the threshold criteria for the FDCA exemption, the statutory limit of “no more than five units per year” would prohibit any large-scale 3D printing operations. In the draft guidance, the FDA is clearly sending a warning (or reminder) to those who mistakenly believe the exemption might apply broadly to 3D printed devices.
The FDA also provides that a manufacturer should take several things into account regarding the unique nature of patient-matched devices, such as drafting labeling, making sure to include the patient identifier, identifying use, file design iteration, and that the patient is surveyed for potential anatomical changes (between the time of imaging and surgery).
The draft guidance will undoubtedly help 3D printed device companies design, manufacture, and test their devices, especially those who manufacture patient-matched devices. It provides a baseline framework for 3D printing that will help many in the industry prepare for engaging the FDA early in product development.
What remains unanswered
Although the draft guidance is a start, there are still many unresolved regulatory issues that need to be addressed, especially as the technology continues to evolve and more innovative products are brought to market. One still-pressing, unanswered regulatory issue associated with 3D printing is how the FDA intends to approach non-traditional device manufacturers.
As background, under the existing FDA regulatory framework, a manufacturer is defined broadly to include “any person who designs, manufactures, fabricates, assembles, or processes a finished device.” As 3D printers become increasingly accessible, a person (or entity) with a 3D printer does not need the financial capital, infrastructure, or resources historically associated with traditional manufacturing operations. While the draft guidance acknowledges point-of-care manufacturing, it does not provide much discussion on non-traditional entities, such as healthcare providers and suppliers becoming “manufacturers” of medical devices.
Complicated regulatory problems are associated with this possibility, and there are still many unanswered questions. If production occurs in a non-traditional manufacturing site, such as a hospital, clinic, or academic center that is not under control of the device sponsor, how will or should the FDA regulate that site? Should the site be subject to all of FDA’s QS requirements and other standards, such as requirements related to the facilities themselves and controls for, and methods used in, purchasing, manufacturing, packaging, labeling, storing, and installing medical devices? Will the FDA take enforcement action because a 3D printed medical device is technically adulterated when it is not manufactured under QS-compliant conditions?
The FDA is also careful to warn that the guidance does not apply to any devices that use bioprinting — which incorporates biological, cellular, or tissue-based products into the additive manufacturing process. These products have some of the greatest potential to change healthcare, yet the draft guidance is virtually silent on the regulatory framework and impact that such devices will have. How FDA will ultimately regulate bioprinting remains unclear.
Combination products also are not mentioned in the draft guidance. These would also include some of the most innovative and cutting-edge new healthcare products that combine, in some conjugation or another, drugs, devices, and biologics, whether entirely or partially 3D printed.
The great unknown
Researchers in the 3D printing space are doing things today that were only dreamed of a few years ago, such as 3D printing living tissue and cells or using conductive, 3D printable ink, to create proof-of-concept biomedical products. Although further research is needed before these concepts evolve into viable commercial applications for use in the healthcare industry, it is likely not too far away. How the FDA will approach these and other innovative products remains unknown.
We also do not know how the FDA intends to resolve the legal and regulatory issues associated with point-of-care manufacturing.
The answer might be found in how the FDA (through the FDCA) regulates dental laboratories. Dental laboratories customize medical devices, such as dentures, bridges, and crowns that are manufactured to patient specifications and prescribed by a dentist. The FDA does not consider these finished dental products as medical devices, so there is no need to obtain premarket approval for them. Instead, the manufacturers of the dental devices must submit for premarket approval the component materials used in the devices. Once the component materials are cleared by the FDA, no further clearance or approval is necessary, and the dental devices can be customized at the laboratories.
Extrapolating these rules to 3D printing, it seems that FDA can clear the materials used for 3D printing (whether plastic, biomaterial, metal, etc.). After the materials are cleared, 3D printing laboratories, which would have quality control specifications and could potentially be inspected by the FDA, would be responsible for printing the product, which would be customized to a patient’s specifications. This regulatory approach would align with FDA’s risk-based approach to medical device regulation, but it also would require revision to FDA regulation and likely the FDCA.
Many other unknowns associated with point-of-care manufacturing may need to be addressed before it might revolutionize the practice of medicine. For example:
- How will physicians and hospitals be reimbursed for devices made at point-of-care facilities?
- Will point-of-care manufacturing sites transition to mobile manufacturing sites (e.g., similar to mobile dental laboratories or mobile CT scanning operations)?
- How will the FDA and state regulatory agencies regulate mobile printing operations?
- Will the regulatory approach differ between 3D printers that are designed solely for patient-specific diagnostic assessments versus non-diagnostic 3D printers?
- For 3D printers that are designed solely for patient-specific diagnostic assessments, will the Centers for Medicare & Medicaid Services (CMS) need to create coverage policies to govern the services, similar to the way in which CMS currently covers services of portable X-ray suppliers?
Looking forward, some 3D printing technology (such as specialized 3D printing for emergency departments) may cause a surge of point-of-care manufacturing at healthcare facilities and practitioner offices, as these facilities and offices obtain their own 3D printers — or at regional and local 3D printing hubs (and mobile 3D printing laboratories) that service the facilities and offices. But for this to occur, the healthcare industry needs guidance from the FDA about how the current system for oversight and regulation of medical device manufacturing, processing, and distribution applies to 3D printing.
As the FDA (and other regulatory authorities) begin to confront these questions and establish a framework for regulating 3D printing, it is important that companies and users are aware of these issues so that they can be on the forefront of emerging 3D printing technologies and the complex legal issues that are on the horizon.
ABOUT THE AUTHORS
Matt Jacobson is an associate in Reed Smith LLP’s Life Sciences Health Industry Group. He focuses his practice primarily on product liability litigation for medical device companies. Matt can be reached at firstname.lastname@example.org.
Kevin Madagan is counsel in Reed Smith’s Life Sciences Health Industry Group. His practice focuses on advising clients from across the life sciences and health care industry sectors on FDA regulatory issues related to manufacturing, distribution and sale of drugs, biologics, medical devices, and dietary supplements. He can be reached at email@example.com.