Additive manufacturing (AM) held a prominent place in the response to the COVID-19 pandemic, which was explicitly acknowledged by the FDA. The agency collaborated with other federal government agencies to encourage rapid innovation in manufacturing for the pandemic, but with the pandemic having come to a close, it may be time to examine the FDA’s standing guidance for AM.
AM holds tremendous promise for patient-matched and customized medical devices but creates an unusual convergence between software development and the hardware manufacturing process. The 2017 FDA guidance for technical considerations for devices fabricated with AM highlights some of the attendant complexities, but there may be enough opportunity to motivate a software developer to steer its efforts into this realm.
The guidance is divided into two general sections: one for device testing considerations and one for design and manufacturing considerations. The FDA emphasized that this guidance does not address the establishment of a quality system for the operation of an AM manufacturing system.
No Indication of Near-term Changes
The FDA described this guidance as a leapfrog guidance — a document type that is explicitly provisional. However, there is no impending rewrite of this guidance, as it does not appear on the FDA’s guidance agenda for fiscal 2023, although there are calls for an update on a broad policy level. The guidance’s content for device testing applies to all device premarket applications, including De Novos, 510(k) Premarket Notifications, Premarket Approvals, Investigational Device Exemptions, and Humanitarian Device Exemptions.
The guidance includes several recommendations for testing, including mechanical testing for properties such as modulus and device creep/viscoelasticity. Among the recommendations for material physical property testing are in vitro degradation testing for devices manufactured with absorbable materials. Test coupons can be used to validate the manufacturing process, but coupons must themselves be validated to ensure they accurately represent the part or parts within the described build volume. Bioprinting is not within the scope, as such activities would be regulated by the Center for Biologics Evaluation and Research (CBER).
Imaging Accuracy Requirements May Vary
The section of the guidance on design and manufacturing considerations states that AM devices will generally follow the regulatory requirements imposed upon all medical devices. Anatomical imaging is often used to guide the additive manufacturing process for patient-matched devices, but the required degree of imaging accuracy is not uniform across all device types. Among the points of interest in this context are:
- The minimum image feature quality and resolution used to provide matching for the patient’s specific anatomy;
- The use of algorithms for smoothing or otherwise processing the images when these processes may affect the dimensions of the final device design;
- The inherent rigidity of the imaged anatomical structures; and
- The clarity of anatomical landmarks used to match the manufactured device to the patient’s anatomy.
The FDA suggests that small changes in device size or device geometry be validated to control for mismatch with the patient’s anatomy. A mismatch might only be identifiable during device use or implant, but another hazard is that devices intended for use with non-rigid and soft tissues may encounter some variability in the size and conformation of those tissues in the patient’s body. The guidance also advises that the software be developed with the understanding that the patient’s anatomical features may change over time, such as when those features are affected by progression of the underlying disease.
Image File Format Considerations Potentially Crucial
The discussion of software workflow emphasizes the need to ensure that image file format practices are sufficient to avoid any need for revalidation of the software due to image file conversion errors. One file format that might help avoid such issues is the use of the additive manufacturing file format described in ISO/ASTM 52915.
In some circumstances, the manufacturer/developer will have to revalidate the device, including the software used to guide the manufacturing process. Among the conditions that may necessitate such a step are:
- Changes to the software, including an update to the build preparation software;
- Changes to the software workflow;
- Relocation of the manufacturing system to a new site;
- Changes in manufacturing material or material handling; and
- Alterations in the spacing or orientation of the device or device components within the volume of the device build.
The FDA emphasized the importance of this guidance in a December 2017 statement, which stated that the agency had approved or cleared more than 100 devices manufactured by AM. The statement highlighted the role of AM in drug manufacturing as well, citing an example which Scott Gottlieb, who at the time was the FDA commissioner, said was just the tip of the iceberg where the use of AM in drug production is concerned.
Orientation of AM Materials Drive Differences in Device Testing
There are several interlocking guidances for the actual production of devices, such as the recent draft guidance on patient-matched implants (see table below). There is also an AM Center of Excellence administered by the American Society for Testing and Materials, so there is no lack of resources for developers.
The data and the history of implanted medical devices would seem to suggest that a well-run software company could avail itself of a field with a tremendous future.
Some have estimated that the compound annual growth rate for AM medical devices will average approximately 18% per year over the next seven years. This is driven in large part by skyrocketing domestic and global demand for hip and knee implants, the effectiveness of which will be particularly improved by AM technologies that produce patient-matched implants. Bear in mind that orthopedic device implant failures have been particularly closely scrutinized by regulators in the past 10 years, but the data and the history of implanted medical devices would seem to suggest that a well-run software company could avail itself of a field with a tremendous future.
| Guidance | Purpose | Issuing center | Status/date | Docket |
| Custom device exemption | Limitations to exemptions | CDRH | Final 09/14 | FDA-2013-D-1601 |
| Patient-matched implants | Premarket submissions | CDRH | Draft 06/23 | FDA-2023-D-2370 |
| Devices used with regenerative therapies | Risk classification | CDRH/CBER | Final 02/19 | FDA-2017-D-6154 |
