3D Printing Medical Devices: The New Frontier in Personalized Medicine and its Impact on Quality Compliance
Kari Miller, Vice President of Regulatory and Product Management, Pilgrim Quality Solutions
3D printing or Additive Manufacturing is the new frontier in the Life Sciences industry and personalized medicine, where medical devices and even pharmaceuticals can be produced on demand, with specifications suited to a specific patient. For the Life Sciences industry, it means the potential to transform the way patients are treated, improving the efficacy of their treatment and their quality of life.
A “New” Technology That’s Been Around Awhile
3D printing has been around since the 1980’s. In the past few years we’ve witnessed rapid development in this technology, along with rapidly decreasing prices. These two factors have moved 3D printing from the realm of prototyping into manufacturing fairly quickly. We’re seeing Additive Manufacturing being used to build knee replacements, spinal cages, dental implants, tracheal splints, and even 3D printed drugs. The industry expects to see this technology to expand into bio printing as well, which is 3D printing with human tissue.
As the price of 3D printers continues to come down, there is an opportunity for manufacturing to move out of the realm of the “traditional” manufacturing to manufacturing at the point of care including hospitals, dental offices, and other healthcare providers. This brings us to a new frontier for quality and compliance. To understand the quality compliance frontier for Additive Manufacturing, some background is helpful.
Additive Manufacturing is a very descriptive name for this manufacturing process. It is a process that literally builds up the component layer by layer. This allows for the creation of complex medical devices as a single piece. This is a contrast to traditional manufacturing where you start with more than you need and take away what isn’t needed until the final product emerges.
Validation is the First Key to Quality Compliance
The Additive Manufacturing process relies heavily on other technologies, not just those deployed in the printer itself. For example, when 3D printing medical devices, especially patient specific devices, use of medical imaging data as well as design manipulation software (sometimes several) is required, so the issue of compatibility across these technologies is key.
Also key is the validation of the software used to convert the digital design into a format that can be used to build a device or component. This is referred to as “Build Preparation Software” in the Technical Considerations for Additive Manufactured Devices, Draft Guidance for Industry and Food and Drug Administration Staff.
However, validation requirements don’t end there. The additive manufacturing system, including the hardware, machine control software, required setup software, and peripheral accessories, will also require validation.
Quality System Requirements Still Apply When 3D Printing Medical Devices
21 CFR 820.30 Design Controls still apply for Class II, Class III, and select Class I devices. Manufacturers must establish and maintain procedures to control the design of the device to ensure it is fit for purpose.
This includes validation of the process and procedures for the monitoring and control of process parameters to ensure specified requirements continue to be met.
Because Additive Manufacturing technologies are many, as are the processing steps that can be deployed, it is critical that each step in the printing process is clearly identified. This identification includes a description, the process parameters, and output specifications. Additionally, when the optimization of one design parameter may influence another, these tradeoffs must be indicated. Finally, as with any manufacturing process, risks and risk mitigation for each process step must be documented.
Complex Device Builds Requires Rigorous Process Validation
The most commonly used Additive Manufacturing techniques include powder fusion, stereo lithography, fused filament fabrication, and liquid based extrusion. Each of these techniques relies on a power source—be it laser, electron beams, light, heat, solvent evaporation, or other chemical processes. Additive Manufacturing allows for the creation of complex geometric structures that can include porous, tortuous internal channels and internal support structures not easily achieved by other methods. Due to the potential complexity of devices produced via Additive Manufacturing, one or more of these additional preparatory processes will be required:
- Build Volume Placement (Orientation and placement affect material properties)
- Addition of Support Material (can affect geometric accuracy)
- Slicing (layer thickness)
- Creating a Build Path (The path traced by the energy or material delivery system can impact the quality of the finished device)
Since multiple devices and components can be produced simultaneously, the variability is endless. When variability occurs, as in any of the processes mentioned above, each combination must be documented. For this reason, optimal process validation and acceptance criteria will require rigor. Finally, the test methods used for process monitoring and control must be documented and validated.
Any changes to the additive manufacturing process, or process deviations will most likely create the need for revalidation. Revalidation triggers include, but are not limited to, software changes, changes in material, change in placement or orientation, moving of the machine, or changes to post-processing.
And Don’t Forget Calibration, Cleaning, Training
Each Additive Manufacturing technology has parameters and settings that can be configured by the device manufacturer. Performing proper calibration and preventive maintenance, and keeping records of the aforementioned for 3D printers are as crucial as they are with any piece of manufacturing equipment. Additionally, adequate cleaning between builds ensures that residual material contamination does not occur in the next build. Proper training and certification of staff to perform these tasks is key to producing a quality device that is fit for purpose.
This All Sounds Familiar
There are a plethora of additional topics to examine, including post-process cleaning. Sterilization of the 3D printed medical device or component, for example, can be much more complex because of the sophisticated geometric builds made possible by 3D printing. We could also look at how to handle raw material reuse and final quality testing. Even with those topics added in, from a quality perspective you might be thinking it all sounds familiar (more complex maybe due to the plethora of combinations to consider) but familiar, and you would be right. The quality compliance practices of traditional manufacturing still apply to Additive Manufacturing. The draft guidance on Additive Manufacturing from the FDA, issued on May 10, 2016, confirms this.
Where (or When) it Gets Interesting
What the industry and regulators need to consider is the future. When a 3D printer moves into point-of-care facilities for either the build of a device, or personalization of a “standard sized” device for an individual patient, that point-of-use facility becomes a manufacturer.
- Are point-of-use facilities prepared for these quality compliance requirements?
- Will they have the skill sets needed for proper maintenance and calibration of these devices?
- What about final QC, cleaning, and sterilization of the end product?
- Are regulators prepared to inspect these point-of-use facilities?
- If an adverse event or nonconformance occurs with a device produced at a point-of-use facility, who owns the product liability? Is it the 3D printer provider or the point-of-use device manufacturer?
Today, most 3D devices produced at point-of-use facilities are low-risk devices. Most Additive Manufactured devices are still produced and distributed in a traditional way: by a manufacturing facility who produces the device. Even personalized devices are typically manufactured in-house and then distributed to the point-of-use facilities. However, as the trend for personalized medicine continues to grow, point-of-use production, or at a minimum, point-of-use personalization, will grow. With that growth will come the need to consider the quality compliance requirements and regulatory oversight needed at point-of-use facilities to ensure patient safety, while transforming the way patients are treated, thereby improving the efficacy of their treatment and their quality of life.
Prepare to Succeed: Stay Ready for Your Next FDA Audit
A Guidebook for FDA Audit Readiness
This e-book gives you actionable strategies to prepare yourself, your team, your site, your quality system, and even prepare the FDA inspector for a successful quality system audit. Plus, we’ll discuss how automating key quality processes will help you quickly demonstrate compliance.
How do you prepare for FDA audits? Please share your thoughts in the comments below.