On May 10, 2016, FDA issued the draft guidance “Technical Considerations for Additive Manufactured Devices: Draft Guidance for Industry and Food and Drug Administration Staff”. Additive manufacturing, or 3D printing, is considered an emerging technology; FDA’s efforts to communicate its initial thoughts and expectations via guidance prior to full emergence of the technology is considered a “leap-frog” guidance. A main advantage of 3D printing for medical devices is the ability to create “patient matched” devices, which are those that are matched to the patient’s own anatomy and unique for that individual patient. For example, “patient matched” implants, prosthetic devices, surgical instruments, and dental restorations are possible by 3D printing. Another use for 3D printing is the creation of devices with complex structures that would be difficult to produce using other fabrication methods. FDA states on its website that as of December 2015, more than 85 3D-printed medical devices have been cleared by the Agency.
3D printing involves a layered fabrication process (very thin layers of raw material built upon each other) that is guided from a digital 3D computer file or patient image. This fabrication process creates unique challenges related to device verification testing and process validation. Accordingly, in the draft guidance, FDA’s insights are broken into two main parts to address these challenges: (1) design and manufacturing process considerations, which provides considerations for fulfilling Quality System requirements for 3D-printed devices, and (2) device testing considerations, which provides recommendations for the type of information that should be included in premarket submissions. In the draft guidance, FDA provides specific recommendations on patient-matched device design. However, the guidance specifically states that these devices “are not custom devices meeting the FD&C Act custom device exemption requirements unless they comply with all of the criteria of section 520(b)”.
Although some recommendations in the guidance may be applicable to non-printed devices (e.g., biocompatibility), there are several interesting aspects related to testing of 3D printed devices that FDA brings to consideration. For example, due to the unique fabrication method, FDA notes that 3D-printed devices have an orientation (i.e., anisotropy) associated with them, which should be considered when conducting certain verification testing and selecting “worst case” device samples for testing. Also, the Agency recommends manufacturers provide evidence that the material recycling that occurs with some 3D printing fabrication processes does not negatively impact the final device. In addition, there are software compatibility concerns related to the use of multiple software packages from different manufacturers. Finally, FDA discusses the idea that expiration dates for patient-matched devices “may be driven by the patient imaging date or the design finalization date rather than the standard methods of determining device shelf life”.
The guidance does not cover 3D printing of biological, cellular, or tissue-based products. FDA also notes in the guidance that “point-of-care device manufacturing may raise additional technical considerations”. Point-of-care printing would involve 3D printing “on demand” in the healthcare setting and could also raise important regulatory challenges. With the increasing development and use of the technology, 3D printing at point-of-care will likely be the topic of future FDA guidance or additional Agency discussions.
FDA’s website also states that two of its own laboratories in the Center for Devices and Radiological Health, Office of Science and Engineering Laboratories are researching the technology. The labs are investigating how design changes affect the safety and performance of devices in various patient populations as well as how printing methods affect the strength and durability of the device materials. FDA will likely use knowledge of their own research results to aid in their review of 3D-printed medical devices.
The FDA held a public workshop in October, 2014 that discussed the technical considerations of 3D printing for medical devices with various stakeholders; the feedback from the workshop helped to shape the recommendations in FDA’s draft guidance. It is recommended at several points in the draft guidance for manufacturers to consider using the Agency’s Pre-Submission process to obtain more detailed feedback related to 3D printed devices.
Public comments on the draft guidance can be submitted until August 8, 2016 at http://www.regulations.gov (search for docket number FDA-2016-D-1210-0001).