July 13, 2021 PAO-07-21-NI-01
While AM is still considered an emerging technology, many businesses are adopting it for its potential to lower costs and reduce timelines, while simultaneously providing precision products for their customers. AM allows for the creation of single or small batches, with objects that have complex geometries and a wide variety of material properties. Because every patient is unique, AM has significant potential in personalized solutions that can be customized for individuals in a more precise and cost-efficient manner, resulting in better outcomes for both manufacturers and patients.
Additive manufacturing is the process of creating a 3D object by building it layer by layer; this is the opposite approach of the more traditional subtractive manufacturing (SM) in which objects are created by cutting away at larger materials to arrive at a final product. Technically, AM can refer to any process where a product is created by “adding to” as opposed to “taking away,” but it is colloquially synonymous with 3D printing (3DP). AM was originally used for rapid prototyping, allowing full-scale models to be manufactured quickly, without the typical setup processes and costs associated with SM prototyping.1 Over time, AM expanded to rapid tooling to create molds for final products, and, by the early 2000s, AM was finally being used to create functional products.1 Typically, designs are created through computer-aided (CAD) software or by scanning an object, and the designs are sent to a 3D printer that uses liquid, powder, sheet material, or other materials to add successive layers.1
There are several 3DP techniques for AM in healthcare applications. One of the more popular 3DP approaches is fused deposition modeling (FDM), which utilizes a thermoplastic polymer that is melted and forced through a mobile heated nozzle.2 The polymer is then extruded layer by layer along the x, y, and zaxes, and the desired final shape is achieved upon solidification. Multiple dosage forms, such as implants and zero-order release tablets that include polymer as a part of their formulation, can be created using FDM.2 FDM offers fast manufacturing speeds, cost efficiency, on-demand preparation, and personalization. However, FDM only supports a few thermoplastics, offers lower resolution quality when compared to other printing techniques, and presents manufacturing difficulties for filaments with small diameters.2 FDM has potential for manufacturing surgical instruments, implants, orthoses, and prostheses, and is the only current method of manufacturing personalized catheters with promising results.2
Inkjet printing (IP) is utilized for advanced and complicated ceramic structures like scaffolds and tissue engineering.2 A fixed ceramic suspension like zirconium oxide powder in water is pumped and accumulated as droplets, then pushed through an injection nozzle onto a substrate.2 The droplets form a continuous pattern that solidifies enough to add subsequent layers. The process is quick, efficient, and flexible, but sometimes yields a coarse end product that lacks adhesion between layers.2 IP is applicable for both polymer and ceramic biomaterials and has pharmaceutical applications for controlled drug delivery, personalized medicine, and prostheses.2
Stereolithography (SLA) is one of the primary approaches of AM.2 UV light in the form of an electron beam is used to initiate a chain reaction on a resin layer or monomer solution.2 The monomers are UV-active and are immediately converted into polymer chains following exposure to light.2 A pattern is solidified inside the resin layer after polymerization, which keeps subsequent layers in place.2 When printing is complete, the unreacted resin is eliminated, and post-process treatments like photo-curing or heating provide the finishing touches.2SLA offers high quality but it is more costly and time consuming than other 3DP approaches, and the overall process is more complicated.2 Products manufactured using SLA include Invisalign® orthodontics and hearing aids, and it is also being explored as a technique for tissue engineering, drug-release manufacturing, and regenerative medicine.2
Powder-bed fusion (PBF) composes thin layers of fine powders that are dispersed and packed closely on a platform.2 The powders are fused in each layer with a binder or laser beam, and each powder layer is joined atop previous layers until the product is fully constructed.2 Excess powder is discarded, and finishing techniques like infiltration, sintering, or coating are performed if required.2 PBF shows promise for tissue engineering and bio-devices and has been used to fabricate metallic scaffolds for bone grafting.2
Digital light processing (DLP) is similar to SLA but, in DLP, the light source works in tandem with LCD screens that cause the resin to react in an instant, making it much faster than SLA.2 DLP creates parts with high accuracy and fewer inputs, making it a more cost-effective than other 3DP approaches.2 DLP has various applications, including medical devices (models, implants, functional devices), tissue engineering (liver, lung, bone, heart, spinal cord), and pharmaceutics (drug discovery, development, and delivery).2
Multiphoton polymerization (MPP) also utilizes light like SLA and DLP, but it works by polymerizing a light-sensitive material by simultaneously absorbing several photons at higher wavelengths.2 Parts manufactured using MPP are typically small and not suitable for constructive tissue scaffolding of implants, but it is utilized for understanding the interactions of cell scaffolding.2
3D slurry printing (3DSP) uses a photocurable matrix as a binder that can be incorporated with various ceramics powders to form slurries, which are then photocured using a light source to shape whatever is being manufactured.2 This technique has been primarily utilized for dental implants.2
Perhaps one of the most exciting and promising applications of AM and 3DP is 3D bioprinting (3DBP). 3DBP allows for assembling and patterning living and non-living materials for producing bioengineered structures that serve in pharmacokinetic, regenerative medicine, and basic cell biology studies.2 It is critical for 3DBP to be precise and well controlled, and techniques generally include extrusion-, laser-assisted–, IP-, and SLA-based approaches.2 3DBP requires a sterilized environment with a constant temperature of 37 °C.2 Despite a myriad of challenges associated with 3DBP, considerable progress has been made over the past decade in the areas of organ and tissue printing, and, if the technology is perfected, there would be significant global health gains, as it would mitigate organ donor shortages and allow for better treatment of chronic conditions.2
The aforementioned technologies are just a sampling of the robust approaches and possibilities 3DP has to offer. As processes become more refined, patents expire, and end products are proven efficacious, there will likely be an influx of organizations using 3DP as their primary manufacturing approach owing to the efficiency and specialized precision it has to offer.
Traditional processes, such as milling, granulation, compression, and mixing, can lead to quality irregularities in drug manufacturing, as factors such as drug release, stability, and dosage heavily rely on precision in the manufacturing process. 3DP can improve safety and efficacy due to its precise, replicable nature.2 Beyond technical and mechanical advantages, 3DP also offers personalization, speed, and sustainability that outperforms traditional manufacturing approaches. 3DP allows for specific dosing requirements to be integrated into small batches for individual patients while remaining time- and cost-effective. A specific example of this is in pediatric medicine, where there is more variation in dosing and size/shape requirements, as well as the need to mask medicinal taste.2 3DP also allows for more granularly controlled, targeted drug release by printing a binder in the layers of the matrix powder and creating a barrier between the active pharmaceutical ingredient (API) layers to affect the release profile.2 3DP could also potentially be leveraged to allow patients to print their medications on-demand, without the need to leave their homes — although there are a bevy of regulatory challenges that would need to be overcome for this to become a reality.
3DP could allow for pharmacists and physicians to work collaboratively to make modifications between doses or explore new drug combinations based on the needs of individual patients, and, with improved outcomes, adherence would also likely increase.3 3DP is also ecofriendly, as it is energy efficient and reduces manufacturing waste typical of SM through the discarding of unused raw materials.2 Shorter production times and reduced maintenance and engineering requirements also make 3DP an increasingly favorable option for drug manufacturing.3
In 2015, the U.S. Food and Drug Administration (FDA) approved the first 3D-printed pharmaceutical, SPRITAM (levetiracetam), created by Aprecia Pharmaceuticals for the treatment of seizures.4 What makes SPRITAM unique is that it is printed in layers until the correct dosage is achieved, allowing for customization for patients with varying degrees of epilepsy. It utilizes ZipDose® Technology, which allows for rapid disintegration regardless of the dosage level.5 Although it is currently the only FDA-approved 3D-printed drug, the numerous advantages of 3DP makes SPRITAM the model upon which a broad regulatory framework can be built, and it is likely only a matter of time until we see 3D-printed drugs become more ubiquitous across healthcare.
3DP proved invaluable in efforts to combat the COVID-19 pandemic. As shortages of lifesaving medical equipment and personal protective equipment (PPE) were prevalent, 3DP mitigated supply shortages across a number of products and industries. 3DP was utilized in the production of PPE, medical and testing devices, personal accessories, visualization aids, and emergency dwellings, among other materials.6 FDM has also been utilized in the production of face masks.7 Face shields, hand sanitizer wrist bands, gloves, hands-free door openers, personal protective suits, swabs, and ventilator parts are all examples of products created through AM processes.7 With businesses shut down and production lines severely impacted, 3DP played a large role in ensuring that the supply chain did not completely dry up, and it will likely be leveraged for future health crises that put a strain on the global healthcare supply chain.
The global healthcare AM market was valued at $1.34 billion in 2020 and is projected to expand at a compound annual growth rate of 21.8%.8 Market drivers include the need for customized medical products coupled with the need for manufacturing complex designs.8 As emerging players create varied applications of the same technology at reduced costs, competition in the market should continue to increase. AM stands to change the medical manufacturing landscape due to its portable, decentralized nature and its ability to create “just the right amount” of something. The FDA has reviewed more than 100 devices manufactured using 3DP, including customized, patient-matched devices, such as cranial implants and knee replacements.8
The increasing demand for customized products and products that range in complexity are driving market growth. AM could be the driver of the next industrial revolution in manufacturing, with great potential to provide cost-effective methods to manufacture complex and customized products, medicines, and possibly even organs and tissues. High demand, short supply, and unmet needs in the healthcare sector will likely set the stage for continued growth in AM in the years to come.
David is a writer, content creator, and marketing strategist with experience that spans various industries. He is adept at research and seamlessly crafting stories from disparate sources to bring clarity to complex topics, as well as skillfully articulating company and product value propositions. Beyond content and writing, David also spent nearly a decade working in various capacities in education, and leverages all of these skillsets to deliver engaging pieces for Nice Insight.
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