It’s finally here: 3D-printed pills and technology in pharma

Credit: Jonathan Juursema

The notion of tailor-made drugs, which are customised to an individual patient’s needs, has seen remarkable progress of late. This has culminated in the achievement of recent ground-breaking pharma innovation in the area of technology known as three dimensional (3D) printing.

The progression within the industry in the potential use of this technology is obvious, with the recent announcement of the first 3D printed drug in the world to gain approval from a regulator, in this case the FDA’s green light for Aprecia’s Spritam (levetiracetam). Although 3D printing has already been incorporated in other medical fields such as prosthetics, it is the first time technology of this kind has been adopted and approved for the production of drugs for human use.

How 3D printing works

Spritam has been developed by the Ohio-based pharma company Aprecia, and is a drug that controls epileptic seizures. It employs the company’s trademark ZipDose technology, a concept developed by Michael Cima and colleagues at the Massachusetts Institute of technology (MIT).

The technology uses 3D printing to create a more porous pill by layering the active and inactive ingredients, and using an aqueous fluid to stitch together multiple layers of powder. The structure of the pill means it is able to dissolve more quickly on contact with liquid, making it easier to swallow in higher doses, compared to conventional tablets. The 3D printing process allows layers of medication to be packed more tightly, in precise dosages.

The idea is that medicines can be customised to individuals in a way that can be tailored in terms of its dose, size, appearance and delivery, all of which can be designed to suit an individual and make the drug safer and more effective. This new and unique manufacturing technique also benefits patients, as building each dose individually can make each pill more porous and therefore more potent compared to traditional techniques. Pills printed through this process are thought to disintegrate in less than 10 seconds, which is unusually fast for high-dose drugs.

This novel way of creating drugs has other advantages, such as creating pyramid-shaped pills, that release drugs more rapidly than traditionally manufactured cylinder tablets. The advantage of 3D drug printing means drugs can be made on demand at a custom dose, to the nearest microgram. Also, 3D drug printing means that there may no longer be obstructions in the cost of making niche medicines. Innovation of this kind could be a major movement in the pharma industry.

What could the market be worth?

Getting approval for technology of this kind in an environment such a pharma is challenging. The safety of the manufacturing process, as well as the drug, is under scrutiny. However, for pharma companies that crack the market, there is the potential for mass applications of the technology.

A 2014 pharma report by Vision Gain predicted the advance in manufacturing could be worth more than $4 billion by 2018 to the global healthcare industry, and forecasts high sales growth to 2024. As well as manufacturing and packaging, there are also implications for the pharma supply chain, as 3D printing will also enable medication to be manufactured closer to its desired destination, which in turn will reduce distribution costs.

Pharma interest in 3D printing

The idea of 3DP has caught the attention of a number of academics and pharma companies within the UK, who are aiming to discover and develop methods and ideas using 3D printing technology to take the UK pharma market forward. What used to be a dull trip to the pharmacy could soon be livened up if individuals can have custom made medications printed to specific shapes and dosages to match their needs.

Researchers at the University College London School of Pharmacy are looking at ways to print 3D pills in different shapes such as pyramids and doughnuts, using a technique known as ‘hot melt extrusion’. The different shapes release drugs at different rates, an effect which would be hard to produce using standard production techniques.

UCL’s Dr Stephen Hilton believes technology of this kind ‘will change the NHS in many ways’. He told Pharmafocus: “One thing we have seen at the UCL School of Pharmacy is how to save costs. Everyone is trying to save money; this is technology that can save money. These machines aren’t expensive and we make objects from our laboratory already and do it for other laboratories. We are taking objects which typically cost about £10,000 and now make them for £1,000, giving us money to do other things – and the NHS can do the same.”

Even though 3D printing can help to bring the long-heralded era of personalised medicines closer, it is not suitable for all drug manufacturing processes. Dr Hilton sees specific situations where pharma companies would be able to use the technology to their advantage. But he also cautions companies: “It’s not the panacea that everyone says it’s going to be. What it gives you is the ability to cope with a range of variations in patients. You will still have your standard tablets that are mass produced. But for patients where you need individual control, that’s where it will help out. Rather than covering 30-40% of the population, you can now cover dosing for 100% of the population based on their individual needs. And that’s where it is useful – because it is so cheap to have individualisation.”

In anticipation of the growing demand from the UK and globally, the research group started its very own pharma company, called FabRx, in 2014. It is based in Ashford and is helping the university to commercialise its 3D printing concepts and innovations. The team is led by Dr Hilton, who is a director and founder, along with three other University College London academics, who saw the potential of 3D printing technology for making better medicines.

FabRx develops printed medicines and drug-loaded medical devices, as well as designing and developing drug-loaded polymers for fusedfilament printing into controlled or modified release tablets and caplets, or polymer-drug blends for SLA printing into tablets and medical devices.

The interest of pharma companies in 3D printing is stepping up following the FDA’s approval of Spritam. Pharma giants GlaxoSmithKline is thought to be running an R&D project looking at 3D printing drugs at the company’s site in Upper Merion, Pennsylvania. Although the project is still at an early stage, GSK is assessing if there is potential to invest in the 3D printing of drugs. First the firm has to determine whether there are certain types of drugs that might benefit from being mass-produced using the method of 3D printing and if so, what materials and systems they may need to start a printing programme.

The future for 3D printing in pharma

While 3D printing principally changes the physical structure of a pill, researchers such as Professor Lee Cronin, Regius chair of chemistry at the University of Glasgow, has been working on a ‘chemputer’. This technology focuses on developing new drugs at a molecular level, by creating a 3D printed chemistry set using a £1,250 system to create a range of organic compounds and inorganic clusters, which can be programmed to make chemical reactions and produce different molecules.

He told Pharmafocus: “We use 3D printers to control the architecture of the test tube to show how different test tube shapes can give you different molecular discoveries. So 3D printing can indirectly help towards the outcome of reactions. We are working with stakeholders in academia and the industry, all around exploring the potential and expand our horizons.”

He is already 3D printing ibuprofen in his lab, but has his sights set higher. “I think the chemputer will revolutionise drug discovery and change it completely. The problem with drug discovery at the moment is that it is a very labour-intensive process. The approach we are taking in the lab will allow us to discover more diverse molecules more quickly, according to a design. “The idea is we are going to try and design new molecules according to specification, which will allow us to discover new molecules in a new way. Then once we have done the discovery, we will have a digitisable platform so we can digitise drug chemistry.”

Regulating a new industry

The introduction of this type of technology in the NHS could change the UK’s healthcare system. However access to technology of this kind opens itself to many possibilities but also brings with it the potential disadvantage of counterfeit and illegal drugs.

It requires regulations to be heightened and adapted, which could be a major issue for pharma companies. The Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines and medical devices in the UK. Currently the Agency has received not received any applications for printing 3D drugs. In the longer term, as the cost of the equipment and production falls, and the speed of manufacture increases, 3D printing medicines is likely to become commonplace in the UK.

A spokesperson from the MHRA told Pharmafocus that 3D printing will change the NHS: “When the costs reduce and speed of production improves, manufacturing can happen closer to where it is needed by patients. They are likely to be for specialist use and would not compete with conventional largescale manufactured tablets. All of these methods of production, including those using 3D printing, need to be appropriately controlled so that patients and healthcare professionals can be assured with the quality of the products.”

The future of 3D printed drugs may be closer then we think, as the MHRA spokesperson suggested this is already on the regulator’s agenda. “The support of safe and timely introduction of all healthcare innovations, including 3D printing, for the benefit of patients is a key strategic objective for the MHRA. Over the last few years we have significantly increased our work to support innovation.”

However, customised products like Spritam are simply adaptations of existing materials. The truly exciting future innovation will be the ability to make fully tailored materials, through the use of 3D printing, that improve patient care and the treatment of illnesses.

Top Ten: Uses of 3D printing in life science

• 3D printed hip implants for patients with bone cancer
• Researchers at the University of Twente in the Netherlands have built 3D printed scaffolds to improve the regulation of glucose and insulin in diabetic patients
• Researchers at the Wake Forest School of Medicine have created 3D printed beating artificial heart cells called organoids
• An Italian research studio called MHOX has developed the ‘EYE’ (Enhance Your Eye), which uses a bio-ink that contains cells found in the human eye to construct 3D printed eyes
• Researchers at the Brigham and Women’s hospital in Boston hospital have 3D printed blood vessels
• Surgeons from Morriston Hospital in Swansea are using 3D printing to build implants for patients with facial injuries
• Gabriel Villar, a researcher at the University of Oxford, has created a 3D printer that can print watery droplets, similar to living human cells
• Printing a new knee for patients with joint problems
• Creating life-size models of patients’ heads as a guide during face transplantation surgeries
• An Israeli company is using 3D printing technology to design marijuana inhalers