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Three-dimensional (3D)-printing technology is on track to change the way we make things and drug manufacturing is no exception. After more than two decades of research on the application of 3D printers in drug manufacturing, the FDA has approved for the very first time a drug formulation produced using 3D-printing technology. The approved drug, Spritam (levetiracetam), is a prescription medicine used as an adjunctive therapy in the treatment of seizures in adults and children with epilepsy. Spritam is based on the ZipDose® platform technology, which uses 3D-printing technology to manufacture a porous formulation that rapidly disintegrates with a sip of liquid. The ZipDose platform is based on a powder-liquid 3D-printing technology that enables the delivery of a high drug load in a single dose (up to 1,000 mg) and each dose is individually packaged so there is no need to count pills or measure liquids. This technology was originated at the Massachusetts Institute of Technology (MIT) and is expected to revolutionize patient experience and dramatically improve treatment compliance. Pharmaceutical rights to MIT's 3D-printing, patent-protected process are exclusively licensed to Arpecia Pharmaceuticals. Arpecia filed the NDA for Spritam, its first product using advanced ZipDose technology, in December 2014. Spritam is expected to be available in the first quarter of 2016.

Treatment outcomes can be seriously undermined by patient factors such as not taking medications as prescribed , or poor adherence to regimens. 3D-printing technology has the potential to transform the patient experience by enabling the printing of drugs on demand with personalized doses and shapes. 3D-printed drugs might be the answer to swallowing problems, and thus could have a major impact on pediatric medications.

Investigators from the University College of London published a paper describing a method combining hot melt extrusion (HME), a technique used to manufacture sustained release polymer-based pellets of various freely soluble drugs, and 3D printing. This new method enabled the printing of five different tablet geometries (cube, pyramid, cylinder, sphere and torus), which are difficult to produce via traditional manufacturing techniques such as powder compaction. The influence of the geometric shape of the pill on drug release into the patient's bloodstream depended on the surface-to-area ratio. Overall, the printing process did not affect the stability of the drug.

To fully comprehend the potential impact of this approach on the pharmaceutical industry, a radical shift in thinking about how we take medications is needed. We may think that taking a pill is a no-brainer, but non-compliance with drug treatment is widespread; the fact is that under some circumstances taking medication is tough. For instance, children are often resistant to taking medicines. Potentially, this method may allow children to choose the shape and flavor of a pill, making it easier for them to comply with treatment. Also, this will greatly impact patients taking chronic medications with a high drug load and patients with swallowing problems. In these cases, the ability to customize the geometric shape of the pills and to alter drug delivery by enabling high drug loads in smaller tablets may greatly improve patient experience and ultimately quality of life.

In addition, the experience of buying medication may soon shift away from mass-produced drugs. In a moment when the pharmaceutical industry is evolving from mass manufacture toward personalized medicine, 3D printing could play a key role in accelerating this change and become a very important part of the drug production line. In the near future, going to the pharmacy may involve answering questions about your body constitution so the drug can be printed to suit you as an individual, making it more effective and safer. The appearance, size, dose and rate of delivery of the drug could be modified to match your unique needs.

Digitalization of chemistry

To further explore the potential of 3D-printing technology, we talked to Professor Lee Cronin. Prof. Cronin is Regius Professor of Chemistry in the School of Chemistry at the University of Glasgow and Founding Scientific Director of Cronin Group plc, a company listed on the AIM stock market in the UK. The company is focused on the discovery, development and manufacture of small molecules and nanomaterials using proprietary chemistry developed at the University of Glasgow and enabled through the application of 3D printing and related technologies.

"In this context 3D printing should be a pseudonym for cheap modular robots," said Prof. Cronin.

While Arpecia Pharmaceuticals is focused on customizable technology to control dosing, Cronin's team is looking at this technology from a different perspective. The aim of their research is the digitalization of chemistry for the discovery and design of molecules, formulations and nanomaterials using technologies like 3D printing and robotics. “3D printing is a way we should control deposition or removal of material in three dimensions,” Cronin argues. According to Cronin’s group, robots could be used as ‘automated bartenders,’ manipulating the components, similar to making a cocktail, in order to carry out chemical reactions under extremely well controlled and easily reproducible conditions. This would ultimately bring down the cost of discovery in the chemical space, e.g. drugs, catalysts, formulations and so on.

"What we are doing is aiming to create the equivalent of the chemical internet," stated Prof. Cronin.

One of the things that made the internet possible was that html, the standard language to create web pages, was very cheap and easy. In the same way, Cronin's team is focused on developing cheap and easy-to-use robots that can do chemistry. “If the robots are too complicated they will fail and no one will use them,” Cronin pointed out.

The digitalization of the chemical space may represent a major change in the discovery process in chemistry. In the future, it might be possible to develop an application for a robot to create a molecule and do design according to a specification. Once a discovery is made, the coordinates of the new molecule in the chemical space could be stored as a code, making reproducibility cheap and easy, and hence changing the manufacturing process as we know it. The code could be used again and again. The potential of this system in the pharmaceutical industry is massive. Complicated drug manufacturing processes could be simplified and done at once. Drug discovery and formulation is a very complex process that demands a significant investment in effort, time and money. By using inexpensive robotics and improving reproducibility, the cost of either drug discovery, formulation or manufacture could be greatly reduced.

The rate of discovery of new molecules is decreasing. Current technology enables investigators to access a simple chemical space, which has already been extremely well searched. Therefore, another primary objective of Prof. Cronin's academic research is to develop a system that allows opening up the chemical space, which would increase the number of drug candidates dramatically.

"In the future, we want to open up drug discovery, make many more drugs and explore the stratification approach to medicine," stated Prof. Cronin.

This technology would enable drug manufacture in local facilities, like pharmacies, and a shift from mass production toward personalized medicine. If the discovery and manufacture of drugs were easier, it might be possible to put a code (a blueprint for a drug or molecule) in a library or in an app store and run it every time it was needed. “We could have an iTunes for chemistry,” stated Cronin. Although still far away, this goal is technologically possible.

"If the system was to be realized in the next 20 or 30 years, suddenly we would not be limited by big manufacturing," hypothesized Prof. Cronin.

Currently, it is not possible to use computer power to discover new molecules; they have to be discovered in the lab. The digitalization of chemistry would change drug discovery and thus, the drug manufacturing game. “We are going to do for chemistry what Google did for the internet; we aim to be a chemical Google,” he said. In addition to indexing molecules that are already known, Cronin aims to create a system that can discover new molecules, formulations and nanomaterials.

"Academically I’m doing this because I want to develop search engines to discover the key molecules, and molecular systems that were present at the onset of the origin of life on planet earth," proclaimed Prof. Cronin.

Cronin and his team are in the process of developing a simple robot that manufactures a very simple commercial drug. "You press the button and it makes the drug," Cronin stated. The robots have a chemical operating system, which they call a "chemputer."

The next challenges for this technology are to discover blueprints and to make chemistry more uniform. "Our main goal is to make chemistry modular and digital, trying to find a way to make reactions reproducible to enable discovery," Cronin added.

So, will 3D printing and robotics completely replace drug manufacturing as we know it? Or will these technologies only be used to produce niche drugs? Will precision medicine be a reality much sooner than we expect? Although we cannot answer these questions yet, we can be sure that 3D-printing technology is going to turn manufacturing upside down.