3D Printing in Healthcare
Brief overview of the technology
3D printing is a type of additive manufacturing, which is the process of creating an object by building it one layer at a time. There are several types of additive manufacturing, but the terms 3D printing and additive manufacturing are often used interchangeably. 3D printing is a process that creates a three-dimensional object by building successive layers of raw material. Each new layer is attached to the previous one until the object is complete. Objects are produced from a digital 3D file, such as a computer-aided design (CAD) drawing or a Magnetic Resonance Image (MRI).
My interest in 3D printing is focused on the current and future impacts of the technology in healthcare — the medical device industry; the medical device testing industry; and the regulation driving those industries who ultimately allow these 3D printed products to go market.
The Medical Futurist does great job giving a high-level overview of the primary healthcare products which may currently be impacted by 3D printing.
Below I have added another image depicting the current capabilities of the 3D printing technology in healthcare:
3D printing in the context of the healthcare industry
More recently, FDA-reviewed products developed via 3D printing have been medical devices such as orthopedic implants, with more than 100 devices having been reviewed. This manufacturing approach offers several clinical advantages. For example, manufacturers have used 3D printing technologies to create devices with complex geometries such as knee replacements with a porous structure, which can facilitate tissue growth and integration. 3D printing also provides the ability to create a whole product or device component at once while other manufacturing techniques may require several parts to be fabricated separately and screwed or welded together.
Since this type of manufacturing does not rely on molds or multiple pieces of specialized equipment and designs can be rapidly modified, 3D printing can also be used for creating patient-matched products based on the patient’s anatomy. Examples include joint replacements, cranial implants, and dental restorations. While some large-scale manufacturers are creating and marketing these products, this level of customization is also being used at the site of patient care in what is called point-of-care (PoC) manufacturing. This on-demand creation of 3D-printed medical products is based on a patient’s imaging data. Medical devices that are printed at the point of care include patient-matched anatomical models, prosthetics, and surgical guides, which are tools that help guide surgeons on where to cut during an operation. The number of U.S. hospitals with a centralized 3D printing facility has grown rapidly in the past decade, from just three in 2010 to more than 100 by 2019. As the technology evolves, this point-of-care model may become even more widespread.
3D printing also has potential applications in other product areas. For example, research is underway to use 3D printing to manufacture pharmaceuticals with potential for unique dosage forms or formulations, including those enabling slower or faster absorption. FDA approved one such 3D-printed drug in 2015, an epilepsy treatment formulated to deliver a large dose of the active ingredient that can disintegrate quickly in water. 3D printing could also one day be used to make personalized treatments combining multiple drugs into one pill, or a “polypill.” Additionally, researchers are using bioprinters to create cellular and tissue constructs, such as skin grafts and organs, but these applications are still in experimental phases.
Current and future state of 3D printing in healthcare
Key takeaways from the graph:
· By component type, the system segment generated 51% revenue share in 2021. However, the materials segment is registering growth at a compound annual growth rate (CAGR) of 21.3% over the forecast period.
· By technology, the droplet deposition segment held 29% revenue share in 2021.
· By application, the external wearable devices segment accounted 38.7% market share in 2021.
· By end user, the medical & surgical centers segment exhibited revenue share of around 45% in 2021. However, the academic institutions segment is growing at a CAGR of 21.6% between 2022 to 2030.
· By region, North America garnered highest revenue share 43% in 2021 and registering a CAGR of 19.5% from 2022 to 2030.
· Asia-Pacific is expected to grow at a CAGR of 21.8% over the forecast period 2022 to 2030.
Major 3D printing players in healthcare
- Stratasys Ltd. (US & Israel)
- 3D Systems Corporation (US)
- GE Additive (US)
- Materialise NV (Belgium)
- Renishaw plc (UK)
- SLM Solutions Group AG (Germany)
- Desktop Metal, Inc. (US)
- Prodways Group (France)
- Carbon, Inc. (US)
- CELLLINK (Sweden)
- Organovo Holdings, Inc. (US)
- Electro Optical Systems GmbH (Germany)
- Biomedical Modeling, Inc. (US)
- Formlabs (US)
- 3T Additive Manufacturing Ltd. (UK)
- DENTSPLY Sirona, Inc. (US)
- DWS Systems SRL (Italy)
- Roland DG (Japan)
- HP, Inc. (US)
- regenHU (Switzerland)
Is the Future Bright for 3D Printing in Healthcare?
Key features and benefits
3D printing is revolutionizing the medical device landscape through its ability to rapidly create patient-specific anatomic models, surgical instruments, and implants. Recent advances in 3D printing technology have allowed for the creation of point-of-care 3D printing centers. These PoC centers blur the line between healthcare provider, medical center, and device manufacturer, creating regulatory ambiguity. The United States Food & Drug Administration (FDA) currently regulates 3D printed devices through existing medical device regulations. However, the FDA is increasingly interested in developing guidelines and regulations specifically for PoC 3D printing due to its rapid adoption across the healthcare institutions.
PoC 3D Printing Trends
Broader 3D printing applications
In 2020, shortages of essential healthcare materials — due mostly to long supply chains that were repeatedly disrupted by the pandemic — increased awareness of the value of having 3D printing capabilities at the point of care. Offering speed and versatility, 3D labs can easily and quickly adapt to changing circumstances, repurposing resources as needed, e.g. shifting focus from printing anatomical models for surgical planning to printing personal protective equipment.
Digital communication and remote collaboration
With social distancing firmly established in our everyday lives, new ways to communicate and collaborate effectively are becoming more necessary than ever before. In terms of healthcare, this rapid acceleration in digitization will lead to increased demand for and provision of telemedicine, i.e. remote diagnosis and treatment of patients. Digital technologies for patient-clinician, clinician-clinician communication, as well as communication between clinicians and point-of-care 3D printing labs, will become essential, and barriers to their widespread adoption will be much lower than in the past.
Complementing 3D printing activities with virtual and augmented reality
Once only in the realm of video games, advanced visualization technologies like virtual and augmented reality are now gaining pace and importance in clinical practice as a complement to 3D printing applications. Their potential has been amplified by advances in hardware capabilities and the availability of targeted software applications. Accessibility has also increased dramatically thanks to more affordable devices. This is sure to boost adoption not only for visualizing clinical cases and training purposes but also to support the rapid prototyping of devices and possibly even aid surgeons in the operating room.
Increasing importance of quality management systems
Delayed by a year due to COVID-19, the European Union’s new Medical Device Regulation (MDR) will be fully applicable as of May 2021. Across the EU’s Member States, point-of-care 3D printer manufacturers will be able to operate under the MDR’s article 5 exemption on several conditions. These conditions include a stipulation that printed medical devices are only used within the legal entity in which they were created, and that the hospital has an appropriate quality management system (QMS) in place.
Further integration of 3D printing in the clinical workflow
The update to the Digital Imaging and Communication in Medicine (DICOM) standard to include DICOM encapsulated Stand Tessellation Language (STL) and Wavefront OBJect (OBJ) files has paved the way for greater integration of 3D printing and planning in the clinical workflow. 3D printing files can now be easily archived and retrieved in hospitals’ picture archiving and communication systems (PACS). This allows for easier traceability as it facilitates the linking of 3D imaging files with patients’ medical records.
Increased accessibility of 3D printers
3D printing technology is constantly improving, and 3D printing manufacturers are not only focusing their efforts on increasing quality but are also striving to make their machines more affordable. As a result, high-quality, medical-grade 3D printers are becoming more accessible.
To understand the importance of PoC 3D printing, a basic understanding of how medical devices are currently regulated by the FDA is needed. The following visual depicts the medical device classifications from simplest to most complex:
The FDA classifies devices based on their level of risk and the regulatory controls necessary to provide a reasonable assurance of safety and effectiveness. Class I devices are low risk and include products such as bandages and handheld surgical instruments. Class II devices are considered moderate risk and include items such as infusion pumps, while Class III devices, which are considered high risk, include products that are life-supporting or life-sustaining, substantially important in preventing impairment of human health, or present an unreasonable risk of illness or injury. A pacemaker is an example of a Class III device.
Regulatory scrutiny increases with each corresponding class. Most Class I and some Class II devices are exempt from undergoing FDA review prior to entering the market, known as premarket review; however, they must comply with manufacturing and quality control standards. Most Class II devices undergo what is known as a 510(k) review, in which a manufacturer demonstrates that its device is “substantially equivalent” to an existing device on the market, reducing the need for extensive clinical research. Class III devices must submit a full application for premarket approval that includes data from clinical trials. FDA then determines whether sufficient scientific evidence exists to demonstrate that the new device is safe and effective for its intended use.
The FDA also maintains an exemption for custom devices. A custom device may be exempt from 510(k) or premarket approval submissions if it meets certain requirements articulated under Section 520(b) of the Federal Food, Drug, and Cosmetic Act. These requirements include, for example, that the manufacturer makes no more than five units of the device per year, and that it is designed to treat a unique pathology or physiological condition that no other device is domestically available to treat. In addition, FDA has the option to issue emergency use authorizations as it did in response to the COVID-19 pandemic for certain 3D-printed ventilator devices.
The FDA expects that all devices, unless specifically exempted, adhere to current good manufacturing practices, known as the quality system regulations that are intended to ensure a finished device meets required specifications and is produced to an adequate level of quality.
Keys to successful implementation of PoC 3D printing
Ensuring devices 3D printed at the PoC are safe and effective: FDA regulation is designed to provide a reasonable assurance that devices are safe and effective; this assurance applies regardless of where and how a product is manufactured.
Assuring appropriate control of devices 3D printed at the PoC: Appropriate controls during product design and manufacturing help assure that product specifications are met; these approaches are well-defined for traditional manufacturing but are less defined for 3D printing at the PoC.
Clarifying the responsible entity: There are specific requirements that apply depending on the activities an entity conducts across a device’s life cycle. There may be uncertainty regarding responsibilities for activities related to 3D printing at the PoC, including device design, testing, FDA premarket submissions, manufacturing, quality control, complaint handling, adverse event reporting, and corrective actions. The entities responsible for 3D printing at the PoC should understand the requirements related to these activities.
PoC training and capabilities: Under many circumstances, the PoC facility could be responsible for complex processes, such as patient-matching or post-processing activities, to generate a final finished device. Additionally, devices can vary in risk depending on their intended use and technological characteristics. Therefore, the entities responsible for 3D printing at the PoC should have the requisite knowledge and expertise to conduct these activities.
International 3D printing standards, quality assurance and control are the next challenges the 3D market needs to overcome. Governing bodies will likely need to tackle the issue of international standards and quality control in the near future.
So, how is 3D printing regulated?
The FDA does not regulate 3D printers themselves; instead, FDA regulates the medical products (products that are intended for medical purposes, including software interfaces and image segmentation systems) made via 3D printing. The type of regulatory review required depends on the kind of product being made, the intended use of the product, and the potential risks posed to patients. Devices — the most common type of product made using 3D printing at this time — are regulated by FDA’s Center for Devices and Radiological Health and are classified into one of three regulatory categories, or classes (as depicted above). The agency may also regulate the imaging devices and software components involved in the production of these devices, but these are reviewed separately.
What are the challenges and risks?
In 2017, FDA released guidance on the type of information that should be included for 3D-printed device application submissions, including for patient-matched devices such as joint replacements and cranial implants. However, the guidance does not specifically address point-of-care manufacturing, which is a potentially significant gap given the rapid uptake of 3D printers by hospitals over the past few years. FDA has also cleared software programs that are specifically intended to generate 3D models of a patient’s anatomy; however, it is up to the actual medical facility to use that software within the scope of its intended use — and to use it correctly.
For medical 3D printing that occurs outside the scope of FDA regulation, little formal oversight exists. State medical boards may be able to exert some oversight if 3D printing by a particular provider is putting patients at risk; however, these boards typically react to filed complaints, rather than conduct proactive investigations. At least one medical professional organization, the Radiological Society of North America, has released guidelines for utilizing 3D printing at the point of care, which includes recommendations on how to consistently and safely produce 3D-printed anatomical models generated from medical imaging, as well as criteria for the clinical appropriateness of using 3D-printed anatomical models for diagnostic use. Other professional societies may follow suit as 3D printing becomes more frequent in clinical applications; however, such guidelines do not have the force of regulation.
To summarize, there are many different levels with which a medical device may be integrated with 3D printing technology. Therefore, the scope of regulation is harder to assess. Regulatory bodies cannot make the mistake of narrowly defining requirements for specific devices because of the 3D printed device varieties currently available in the world, which makes exceptions to every rule they attempt to establish. There is a uniformity of regulation that exists for non-3D printed devices that took a years to establish. So, it is fair to assume we are still in the data collection phase of how to regulate 3D printing in healthcare. Devices, specifically made at the PoC, will continue to be evaluated on a case by case basis until more data exists for specifically classifying these devices. While the unknown poses many future ethical challenges for devices seeking market approval, there are many opportunities for entities (i.e., medical device testing companies) potentially involved in the device approval process who can assert themselves as leaders in this technology space.
What are the 3D Printing Implications for Medical Device Testing Companies?
How does my company benefit?
We must do the following:
· Understand our current non-3D printed medical device submissions in relation to the graph above, as well as the future impacts on those current devices from 3D printing, specifically Point-of-Care 3D printing.
· Perform a gap assessment of our capabilities, both current and future state integration with medical device 3D printing.
· Begin to build relationships with current manufacturers/key industry players of 3d printed medical devices (which also includes software and quality management developers, as well as healthcare facilities utilizing PoC 3D printing technology).
· Do our own research and data collection to understand what is required to create an infrastructure model needed to evaluate 3D printed medical devices.
· Archive current regulatory 3D printing case studies (see 3D printing PoC discussion paper link above) for evaluation and use as talking points for future regulatory conversations.
As mentioned earlier, there is a lack of information and regulatory direction toward the future landscape of 3D printing in the healthcare, but we can set the narrative that allows us to become eventual leaders in this emerging area of the healthcare industry.
