FDA guidance is a first step
3D printing promises to be a revolution in orthopaedic device manufacturing. In 3D printing, parts are built up layer-by-layer by adding to a workpiece using a variety of materials and energy sources. 3D printing is more technically called additive manufacturing (AM) to distinguish it from traditional machining, which “subtracts” material from a solid billet or from a rough part that was cast or forged.
Although AM has been used in nonmedical industries for some time, it is still a relatively new technology, particularly in medical applications, and requires a careful analysis of risk before new products are introduced into clinical use. Currently, most commercial activity in orthopaedics has been for standard-sized implants. However, some applications of 3D printing have also been for patient-specific implants.
Many of these implants are not truly custom, but cover a large range of size parameters cleared by the U.S. Food and Drug Administration (FDA) in a so-called “envelope submission” (a range of sizes and design parameters). A smaller set of applications have been used for 3D printing of truly custom implants, specific to one patient for complex reconstructions following trauma or surgical treatment of tumors. The regulatory distinctions among standard sizes, “patient-specific” implants, and truly “custom” implants are very stringent and clear, as detailed in FDA guidances. The use of 3D printing does not change these definitions or their regulatory requirements.
In orthopaedic surgery, both metallic and polymeric (plastic) parts are currently fabricated using AM. Many clinical applications have been proposed for 3D printing, using patient-specific data or allowing complex geometries. Commercial applications have thus far included the following:
- metallic implants, such as tibial baseplates, acetabular shells, and spinal cages with porous or complex geometries
- polymeric instruments such as patient-specific jigs
- custom polymeric and metallic implants for complex reconstructions, such as tumor surgery and craniomaxillofacial surgery
The explosion of such leading-edge applications has created a need for careful regulation to ensure such devices are safe and effective.
Regulation in orthopaedic surgery
The majority of orthopaedic products are devices regulated by the Center for Devices and Radiological Health (CDRH) of the FDA. The FDA does not regulate the practice of medicine directly. Instead, it regulates the claims that manufacturers can make regarding their orthopaedic devices.
While basic surgical instruments may be class I, most orthopaedic surgical products are class II and class III devices. Class II devices are moderate to high risk. They can be cleared for marketing if they are shown to be substantially equivalent to a previously cleared predicate device, and no new questions of safety and effectiveness arise in comparison to the predicate. This 510(k) pathway is named for the section of the regulations that define it. The FDA considers class III devices to carry the highest risk. They must be approved by FDA prior to marketing, often in conjunction with data from clinical trials conducted under an investigational device exemption (IDE).
In that the predicate products for most 3D-printed devices in orthopaedic surgery are class II, most of the regulatory activity around these printed devices follows the 510(k) pathway. Therefore, the FDA worked to clarify and publicize its expectations for the regulation of 3D-printed orthopaedic devices.
Fig. 2 A patient-specific 3D-printed guide for spinal instrumentation.
Courtesy of Medacta SA
2016 FDA Draft Guidance
On May 10, 2016, the FDA issued the draft guidance document “Technical Considerations for Additive Manufactured Devices.” This guidance was finalized by the FDA on Dec 5, 2016.
The scope of the 2016 final guidance is very technical and broad. It is divided into two major sections: design and manufacturing considerations and device testing considerations. Each section contains multiple topics critical to the safety and effectiveness of 3D-printed orthopaedic devices. Although each is important, many topics are quite technical and geared toward engineers rather than practicing surgeons.
The two most clinically important drivers of 3D printing identified by the FDA are “facilitating the creation of anatomically matched devices and surgical instrumentation (called patient-matched devices) by using a patient’s own medical imaging” and “fabricating complex geometric structures, allowing the creation of engineered porous structures, tortuous internal channels, and internal support structures.” The FDA further divided these considerations into those for standard-sized devices and those for patient-specific devices.
Porous and complex metallic implants
One of the clinical opportunities for 3D printing is in the manufacturing of complex geometric structures. Here, much of the commercial activity has focused on metallic implants with complex structures, especially porous structures. Although porous materials were clinically useful before the era of 3D printing, the new technology allows integration of porous structures with other geometric complexities, such as fine surface features, internal channels, and nonporous structures (Fig. 1).
Implants fabricated by 3D printing may also have post-build processing to minimize any unconsolidated or loosely sintered powders and to achieve specific surface features at the micro-, meso- and nanoscale levels. Patient safety issues relevant to engineering take on new importance for such complex geometries; the FDA guidance also addresses how to ensure sterility of fine features and cleanliness, including removal of any endotoxin and immunogenic or inflammatory contaminants.
One of the clinical opportunities for 3D printing is patient-specific devices based upon imaging data. For this application, most commercial activity has been in patient-specific instruments such as jigs and cutting guides manufactured from polymeric materials (Fig. 2). Patient-specific jigs and guides have been produced for spinal instrumentation, as well as for total knee arthroplasty and other applications.
Although many basic surgical instruments are class I devices, instruments specific to an implant take on the device-class of the implants themselves, generally class II. As such, patient-specific guides have received considerable regulatory scrutiny. Patient-specific cutting guides for total knee arthroplasty have also received considerable clinical scrutiny focused on effectiveness and cost-benefit analysis. The promise of 3D printing may be substantial, but must be supported by significant evidence. Increasingly, clinical trial designs are focused not just on regulatory questions, but also on the payer dialogue and cost-effectiveness analysis.
The FDA guidance has gone far to clarify what data are needed to ensure safe and effective 3D-printed devices. Also, it is important to note what the guidance does not cover—biologic, cellular, tissue-engineered, or combination products. Regulated through the Center for Biologics Evaluation and Research (CBER) or jointly between CBER and CDRH, this broad class of devices has a high potential for technical and regulatory complexity. However, due to the lack of commercial activity, these devices have not been given regulatory priorities. Finally, no matter what the promise of any new technology, careful clinical research is needed to prove safety, clinical effectiveness, and cost-effectiveness for patients, surgeons, and payers alike.
S. Raymond Golish, MD, PhD, MBA, is a member of the Orthopaedic Device Forum and chair of the AAOS Biomedical Engineering Committee. He can be reached at firstname.lastname@example.org.
Steven M. Kurtz, PhD, is a member of the Orthopaedic Device Forum and is the leader of ASTM F04 division task groups for medical grade UHMWPE and PEEK. He can be reached at email@example.com.
Barbara D. Boyan, PhD, is a member of the Orthopaedic Device Forum, co-chair of the preclinical assessments subcommittee of the F04 division, and member of the additive manufacturing group of ASTM. She sits on the board of directors of the Commonwealth Center for Advanced Manufacturing and is dean of the school of engineering at Virginia Commonwealth University. She can be reached at firstname.lastname@example.org.
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