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3D printing starts to take hold in pharma

3D printing is starting to stimulate interest in the pharma sector for uses including drug screening and the tantalising prospect of manufacturing medicines on-demand at a location where they are needed

3D printing starts to take hold in pharmaChances are that if you keep track of developments in science and technology you will be aware of the emerging phenomenon of 3D printing, a rapid prototyping technology that is starting to change the way people think about manufacturing and distributing goods.

The premise is simple, and the applications seemingly almost limitless and worthy of any science fiction movie. Using a device similar to an inkjet printer, 3D objects are built up a layer at a time in a process – known as additive manufacturing – that can make use of materials as diverse as plastics, edible foodstuffs and even metals.

The technology is advancing so rapidly that it is now feasible to scan an object using off-the-shelf software, import it into standard 3D modelling applications like Lightwave or Google SketchUp and then either print it yourself using a home 3D printer – now available from a few hundred dollars apiece – or have it printed for you for a few tens of dollars by online companies such as iMaterialise and 3D Systems' Cubify.

So far, so cool (or geeky, depending on your viewpoint). But while the technology may have started out as a tool for enthusiasts and inventors and generally used for prototyping, 3D printing is now starting to make its mark in serious industrial and medical applications, and even has a possible role to play in the pharmaceutical industry.

Medical magic

One early and obvious application of the technology has been the production of 'bespoke' prosthetics for people who have lost a limb or require a hip or dental implants – a business that is already valued at more than $2bn and growing at around 30 per cent a year, according to consulting firm Wohlers Associates.

Another emerging medical use of 3D printing is in surgery. For example, if a surgeon needs to remove a tumour from a patient but runs the risk of hitting a nerve or artery in doing so, he or she can practise on a 3D model of the cancer – created using the patient's own CT scans and a 3D printer – before working on the patient. 

Earlier this year, for example, doctors in Belgium applied the technology in the country's first face transplant. Digital 3D modelling was used to develop a surgical plan for the procedure, while 3D-printed anatomical models served as reference guides during the procedure.

Furthermore, the ability to create 3D structures raises the tantalising prospect of using the technology to print artificial organs and tissues – known as bioprinting – and while this is clearly still years away from the clinic, some early successes have been recorded.

A team led by Anthony Atala at the Wake Forest Institute for Regenerative Medicine in the US made history more than 10 years ago when it implanted an engineered bladder into a patient – made using a similar technique to 3D printing using his own cells – via a procedure which has now been repeated dozens of times.

Atala and colleagues have also started printing early prototype kidneys that are being studied experimentally but still years away from clinical use. It has proved very hard to get complex engineered tissues to be viable – mainly because of difficulties in creating vascular systems to keep them supplied with oxygen and nutrients.

In 2011 however, researchers at Germany's Fraunhofer Institute successfully used 3D printing to create biocompatible blood vessels small enough to be used to deliver nutrients to cells. And earlier this year, a team at Massachusetts Institute of Technology (MIT) and the University of Pennsylvania in the US created a sugar-based framework using 3D printing that it believes could – in time – allow artificial blood vessels to grow into and so keep cells in engineered tissues alive.

Meanwhile, Atala's team is designing a 3D printer technology that can print directly on to the patient, for example scanning a wound and then using living cells supported by a gel to build up skin tissue, and there are dozens of other groups around the world working on novel medical uses.

Pharma applications

These medical applications could revolutionise the practice of medicine in time and transform the pharmaceutical industry; imagine the impact of successfully developing a functional artificial pancreas on the multibillion dollar diabetes treatment market for example.

In the meantime, 3D printing is starting to stimulate interest in the pharma sector for more immediate uses, including drug screening and, amazingly, the possibility of manufacturing medicines on-demand at the location they are needed.

Professor Lee Cronin of the University of Glasgow in the UK made headlines earlier this year when he provided a first glimpse of the potential applications of 3D printing in chemistry. 

These medical applications could revolutionise the practice of medicine in time and transform pharma
Cronin's team successfully synthesised the non-steroidal anti-inflammatory drug ibuprofen by using a 3D printer to initiate chemical reactions by printing reagents directly on to a 'reactionware' matrix – printed reactor vessels that incorporate catalysts and components for electrochemical and spectroscopic analysis.

This allows reactions to be monitored so that different reactionware architectures could be screened for their ability to handle a process, according to Cronin, who noted that the whole project has been built using open-source technology provided via the Fab@home project. 

“For centuries chemists have used glass as the accepted medium in which you make a molecule,” says Cronin. “This technology allows people to think differently, and opens up the possibility of doing chemistry in a fundamentally different way.” 

Ongoing work has already shown that small molecules can be purified within the system, for example by printing in a filter or column, or crystallising the molecule. The team is now looking at developing more sophisticated networks that can accommodate multiple layers of reactions to produce more biologically-relevant molecules.

The dream at the moment, according to Cronin, is to include a final layer that will allow the compounds to interact with printed live cells or microorganisms. While he was reluctant to speculate on the possible applications for these complex systems, drug screening seems an obvious extrapolation of the current work, raising the possibility in time of 3D-printed devices that could serve as drug discovery engines.

“What new science might be accessible if you could discover the drug in the context of the particular cell you are interested in,” he asks?

Ongoing work has already shown that small molecules can be purified within the system …
Meanwhile, Cronin's lab has just started a new project called Splotbot – making small chemical robots with 3D printers that provide a cheap way of doing array chemistry compared to current robotic techniques used in the pharma industry.

Extrapolating from the current trajectory of the technology – with no real need for developments in science – it may be possible to make molecules that are not made easily at present by tapping into the reactionware's ability to house molecules such as proteins, peptides and sugars, combining very reactive fragments together.

“If we can learn how to make relatively simple molecules using standard precursors in these devices, it may become possible to make molecules in areas of the world where there is no access to pharmacies,” says Cronin.

That raises the intriguing prospect of what has been dubbed in the press as a 'chemputer', which in the future could allow a portfolio of drugs to be made at the point of use in a validated device, avoiding the need for lengthy and expensive distribution chains and the risk of patients being exposed to adulterated, denatured or counterfeit medicines.

3D printing is never likely to rival the economies of scale afforded by mass production in the context of speed and cost-effectiveness, but there is clearly a multitude of uses for more tailored manufacturing. For example, rather than make shoes or spectacle frames in vast quantities, why not print them in the shop to a customer's exact size and specification?

From that point the mental leap to applications in pharmaceuticals is not huge, if you consider the change in R&D focus that is already moving drugmakers away from the blockbuster model of 'one-drug-fits-all' to personalised medicine.

This is clearly long-range thinking, and Cronin is at pains to point out these concepts will require years if not decades of work and refinement. 

“Hype aside, this is a new way to do chemistry, and that is interesting in and of itself,” he concludes.

Phil Taylor

The Author
Phil Taylor is a freelance journalist specialising in the pharmaceutical industry.

1st November 2012

From: Research, Healthcare



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