Made to fit: 3D-printed medicine

Additive manufacturing is increasingly used to make plastic or metal objects. But using 3D printing to create pills – or even living tissues – is opening the door to revolutionary new medical applications.

One layer at a time: How 3D printing works

Additive manufacturing, or 3D printing, is a fundamentally different way of making things compared to traditional manufacturing processes.

“This novel approach, which involves adding material one layer at a time to build an object, is opening a range of new opportunities across the health-care industry,” explains Christoph Huels, founder of OneZeroMed™ Additive Manufacturing of Tablets.

The process starts with a digital 3D model, which is then sliced up into ultrathin digital layers and turned into a set of instructions for the printer to follow. Some 3D printers will melt the starting material into “glue” which is then directed through a precision nozzle onto the preceding layer. Alternatively, a laser or electron beam is used to selectively melt thin layers in a bed of powdered material. As the materials cool or are cured, they fuse to form a 3D object.

Since the release of the first 3D printer in 1987, the technology has advanced at a staggering pace [4]. In 2018, there were 1.42 million 3D printers sold globally, and this is projected to exceed 8 million by 2027 [1]. Additive manufacturing is already in extensive use across a range of heavy industries – such as the automotive, electronics, aerospace, and health-care sectors. Some predict that one-half of all manufactured goods will be made using 3D printing by 2060 [2].

In the health-care sector, 3D printing is now being used to build custom-made prosthetics, dental implants, and other medical devices. And researchers are exploring other applications for this revolutionary technology, such as “digital pills” or to create artificial living human tissues to help accelerate drug development.

Did you know?

  • 1.42M

    3D printers were sold in 2018 – and this number is predicted to exceed 8 million by 2027 [1].

  • 50%

    of manufactured goods could be made by 3D printing by 2060 [2].

  • 2015

    saw the approval of the first-ever 3D-printed medication [3].

Where drug adaptions just need some clicks

Millions of people around the world take prescription pills or tablets every day. These are traditionally manufactured by compressing a powder formulation containing active ingredients and helper constituents (excipients) into a solid form.

“This is an established process that’s been used for many years,” states Huels. “It’s very efficient for the large-scale production of a single formulation to produce billions of pills.”

But the approach is not ideal for making smaller batches of experimental drugs, which are usually needed during clinical development. It is also costly and time-consuming to make changes to the initial formulation, which is usually required as the drug moves through the phases of testing and into commercial production.

“You will need to make a new stamp to compress the pill, which is expensive and time-consuming,” says Huels. “Your active ingredient can easily cost up to 200,000 euros per kilogram during the early phases of drug development.”

But additive manufacturing has the potential to revolutionize the way that tablets are produced – moving the industry toward digitalization. In 2015, the first 3D-printed medication was approved for the treatment of epilepsy, opening the door to the development of customized pills [3].

“It offers much greater flexibility; we can easily change the shape, size, or dosage of a pill – just by making a few changes to the digital file,” explains Huels. “By hugely simplifying the process, this could lead to a dramatic reduction in cost and time in clinical trial supply.”

As well as helping to get new medicines to patients faster by speeding up clinical trials, 3D printing could also benefit patients with rarer conditions – and help to deliver personalized medicine.

“You can imagine having small batches made for groups of patients,” predicts Huels. “But the ultimate goal would be the customized pill that can meet specific individual needs.”

Additive manufacturing could also lead to the decentralization of drug production, which could help to secure the supply chains.

“Currently, there may only be one or two manufacturing centers for a pill that is then shipped to different countries,” says Huels. “In the near future, 3D printing will enable tablets to be produced locally, where they are needed, and according to different market requirements.”

Please exchange the collagen cartridge

Other researchers are exploring the potential of 3D bioprinting. This involves applying the technology to print a biomaterial, such as gelatin or collagen, combined with living cells, into layers on laboratory dishes.

“You can print with different cartridges, so you might have one with collagen and one cell type and another with a different material mixed with another type of cell,” explains Petra Macht, a senior scientist in our Analytical Services Department. “You can then combine them into a very defined structure using the bioprinter.”

Although the technology is still in its infancy, it offers exciting opportunities to build laboratory-engineered complex tissues. For example, our skin has different layers, opening the possibility of printing each layer using different cell types.

“The holy grail of bioprinting is organ regeneration, such as skin grafts using the patient’s cells,” says Macht. “It’s still a very long way off, but it would be a total game changer.”

The development of advanced cell-culture models created using 3D bioprinting also has the potential to improve drug development. Traditionally, 2D cell cultures are used in the early stages of drug discovery to select which compounds to progress. But these models do not provide an accurate reflection of human physiology.

“Cells grown in monolayers are not in their correct 3D environment,” says Macht. “In the body, a tissue contains many different types of cells that will interact with each other.”

This can be a challenge in early drug discovery. Around 86% of drug candidates entering clinical trials will never gain approval [5], and it takes an average of 12 years for an experimental drug to enter the medicine cabinet [6]. Selecting the wrong compounds during early laboratory testing is likely to play a part in this high failure rate.

“Developing better laboratory models that mimic how cells normally grow and function in the body would help rule out unsuitable compounds early on,” says Macht. “This should increase the chance of success of experimental drugs that progress into clinical trials.”

The next chapter of medicine will be 3D printed

Our Innovation Center is partnering with 3D printing specialist AMCM, a sister company of EOS, the world-leading technology provider for the industrial 3D printing of metals and plastics, to apply additive manufacturing for producing tablets. The project, which also involves experts from across our health-care business, focuses on a process based on powder fusion technology.

“The machine puts a powder, typically 100-micrometer thick, onto a building plate,” explains Huels. “We use a laser to melt the powder into a semi-solid or solid state, and then the next layer is added – and that process continues layer by layer.”

This process should be simpler and faster than traditional tablet manufacturing – and easy to scale up.

“We’re now at the stage of testing out the process at an industrial scale, complying with good manufacturing practice (GMP) to make sure it can deliver pills that are safe for patients,” says Huels.

“I find it so exciting to revolutionize an area that’s been very traditional in its processes for so long,” he adds. “It’s fun to shake this industry up a bit with something new.”

We are also aiming to develop 3D bioprinting for drug testing applications. Like any new system, the technology will first require extensive validation – and currently, reproducibility is a major challenge.

“We need to print lots of very small structures into tiny wells to enable the testing of many drug substances at different concentrations,” describes Macht. “And these must be identical – so the first well needs to be the same as the hundredth.”

But despite these challenges, 3D bioprinting is an exciting technology to work on.

“It’s a unique technique because you have the cell biology, the printing technology, and the material – and also the unlimited possibilities of how you change it,” enthuses Macht. “And just seeing how the cells behave in a different environment, that’s fascinating for me.”

And progress in the development of 3D bioprinting is set to disrupt drug testing and regenerative medicine.

“It’s fun to try something different – it’s always exciting!” enthuses Macht.

Ready to revolutionize the future medication?

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