Factory settings

A majority of us only became aware of additive manufacturing a few years ago and it sounds like the cutting edge of 3D printing. But additive manufacturing has been around for a while in the medical device space. The technique, which involves fusing materials – usually plastic or metal – into tiny layers to produce an object in 3D, was first used in the late 1980s and has grown in popularity since.

According to data from the Boston Consulting Group, global sales of additive manufacturing equipment grew by 25% from 2009 to 2016, with the medical device market making up a large portion of that growth. From early experiments in dental implants and custom prosthetics, medical device companies now use additive manufacturing to produce a dizzying array of products, from bones, windpipes and eyeglasses to stem cells, organs and new kinds of drug delivery devices.

“A lot of the early adopters of these technologies tended to be dental and craniofacial applications,” says James Coburn, senior research engineer at the US FDA’s Centre for Devices and Radiological Health (CDRH). “Practitioners in these areas had more experience doing 3D and computer-aided design. But it has quickly worked itself into orthopaedics and other areas such as hearing aids, braces and tooth alignment technologies.”

According to Robert Cohen, vicepresident of R&D at the UK-based medical technology giant Stryker, cheaper manufacturing costs and improved equipment have helped enable this increase in popularity. “Ten to 12 years ago, additive manufacturing was very different,” he says. “The cost of equipment was extraordinary, and most of it was used as a rapid prototype configuration rather than for commercialised implant systems. It reduced the lead time on prototypes, but the amount of human labour required to come up with a configuration of the part and get the machine programmed correctly became problematic. But as additive manufacturing equipment became more consistent in process around six years ago, adoption levels became greater even if it wasn’t being used for anything very creative.”

Public interest

The key public health benefit of additive manufacturing remains its ability to customise medical devices. Coburn says 3D printing allows additional design freedoms that companies really can’t get with other types of manufacturing. “These often manifest in personalised medicines: you can use 3D printing to make things that are exactly like a patient’s anatomy,” he says. “You can make a model of their anatomy, for example, to help a physician hold something that looks exactly like their patient on the inside, or you can make an implant that exactly matches the patient.”

The use of 3D printing offers similar benefits for companies, Cohen says. “The whole objective of additive manufacturing, and especially what it means to Stryker, is to be able to do things that we couldn’t do before,” he says. “We can take designs, shapes and configurations, and make something that conventional manufacturing processes would not allow. It allows the R&D engineers a brand new process for innovation to handle and address clinical issues that we could not do before.”

Stryker’s flagship 3D-printed product is the Triathlon Tritanium knee replacement implant. It’s porous surface allows bone to grow into the metal, eliminating the need for bone cement. “With younger patients that have good-quality bone, surgeons have a preference to implant what we refer to as a cementless component,” Cohen explains. “Bone can’t grow into an implant overnight, however, so engineers have to do two things. First, provide initial stability: a shape and configuration that makes the implant stable for a period of time. Second, products need to have a longer-term biologic fixation phase. In the past, this had worked badly, because engineers using conventional manufacturing processes could not design a product with enough initial stability.”

Additive manufacturing has allowed Stryker to develop a device that can solve this problem. “We produced a material that has a frictional surface against the bone, and can provide the initial stability,” Cohen says. “That same geometry then allows the bone to grow into the implant, stay in there and thrive. In other words, we have achieved long-term biologic fixation.”

He adds, “Because of that success, we’ve also been able to tackle one of the more challenging total knee procedures, which is not when you get your first knee, but when you get a secondary replacement. We have now made pieces of metal, additivemanufacturing produced, that allow biologic ingrowth that can fill voids in the bone from when the first implant came out.”

Knee implants aren’t the only additivemanufactured product Stryker offers either. It also has a spine division that is focused on using 3D printing for spinal fusion. “We have made devices that go between and help stabilise the vertebrae, allowing interbody fusion,” Cohen says. “Released last year, it puts us in additive manufacturing for hips, knees and now spine.”

According to Cohen, Stryker’s success in additive manufacturing is predicated on retaining a variety of competencies at an in-house 3D printing facility in Cork, Ireland. “If you buy an additive manufacturing piece of equipment, you don’t just plug it in and it works,” he says. “It takes months, in fact years, to get a consistent process. The machine does not know what you are producing. We are industry leaders because we have our own equipment and we design, manufacture, program and quality check everything ourselves. This means R&D engineers can design and test things quicker and we can control our own destiny from the cost of manufacturing through to the creativity process.”

Regulation for beginners

While Stryker’s ten years of experience in additive manufacturing has given it a good understanding of regulation, many companies remain wary of 3D printing due to confusion around FDA rules. With this in mind, FDA issued draft guidance in 2016 that was designed to clarify its thinking on the subject. “We are helping to create standards and best practices for the industry, so that we can find more transparent and easy ways to help them brings things to market,” Coburn says.

In 2014, before the guidance was written, FDA held a workshop and created an internal working group that brought together industry leaders, clinicians and patient groups. “We talked about the different regulatory and technical concerns that these groups had for 3D printing,” Coburn says. “We wanted to focus the guidance on these technical areas to make sure people who do 3D printing in medical devices know what they need to be looking at, and to make sure that they do things safely.”

Coburn says two primary areas of concern arose for the industry at the initial workshop. Firstly, clarifying the rules around patientmatched devices, where a device is designed to mirror a person’s precise anatomy. “Patient matching is not a fully automated, easyto- do process,” Coburn says. “You have to take a patient scan such as a CT or MRI, turn that image into a digital 3D model, and then perfectly match the biomechanics and anatomy of that person. Throughout this process, you need to make sure your workflow is validated. At the workshop, people said they wanted to understand the best way of doing that and we talk about it in the guidance.”

A second concern was the manufacturing process itself. “Unlike traditional manufacturing, where you have, say, a slab of titanium, with 3D printing you have a bunch of very fine powder,” says Coburn. “For a metal device, you are making the metal and then designing and manufacturing the implant all at once. You might even be making multiple at the same time. Monitoring that, and making sure it goes according to plan, takes understanding and time. People spoke to us about the problems they had and how they overcame them. Again, we’ve tried to capture that in our guidance.”

Keeping pace

For the time being, Coburn says FDA – which has cleared a number of 3D-printed devices over the past few years – will view and regulate additive-manufactured products in the same way it regulates other areas. Only in rare cases does it expect “ different questions of safety and/or effectiveness” to arise.

“We regulate 3D-printed devices pretty much along the lines of any other device,” Coburn explains. “We have these classifications for medical devices: Class One, which is low risk; Class Two, which is medium risk; and Class Three, which is high risk. If a device is going to fall into one of these classes, the fact that it is 3D printed is not likely to change anything. It might just affect how we approach the review and how the sponsor should evaluate it.”

Keen to keep up with the pace of industry innovation, FDA has also initiated its own research programme, which Coburn currently leads. “We are using it for several different types of research,” he explains. “We have medical device research, looking at implants and surgical tools. We are researching 3D-printed drug manufacturing, and even 3D tissue engineering. We want to better understand the technology and its application, so that when somebody comes in and says to us, ‘we have this great idea’, we are able to review it in an efficient and appropriate manner.”

As companies like Stryker, which has already implanted over 100,000 additive manufacturing parts look to the future, that regulatory expertise will certainly be needed. “This is just the start,” says Cohen. “We will continue to innovate with additive manufacturing and are currently looking at less-invasive, early intervention procedures.”