There is plenty of hype about 3D printing, across multiple industries, but could it also make its mark on pharmaceutical manufacturing? Natalie Healey meets the man who believes it can. Lee Cronin, Regius professor of chemistry at the University of Glasgow, discusses his unconventional research and its implications for changing the process of drug making, producing personalised medicine and giving remote parts of the world unprecedented access to healthcare.
Lee Cronin wasn’t exactly blown away when he first came across a 3D printer at an architecture conference at University College London, but the chemistry professor soon found inspiration in the process he had, on first impression, written off as lacklustre.
"I thought the machine looked like a nice piece of robotics, but the plastic shapes it was printing were relatively boring," he reveals. "But then, I realised we could reconfigure the robot and make it do chemistry."
Cronin, Regius professor of chemistry at the University of Glasgow, has often pondered ways of making chemistry more efficient. As anyone who has worked in a laboratory will know, things can go wrong, reactions can fail, and making a method reproducible is a big challenge. When Cronin laid eyes on the 3D printer, he saw a chemist in the making. But not just any chemist; a scientist for whom nothing is left to chance. In short, Cronin reckons he can ‘app’ the discipline and make a universal chemistry set with implications for drug discovery, manufacturing and accessible medicine in remote parts of the world.
"I’m basically going to make an iTunes for pharmaceutical chemistry," boasts the scientist and TED speaker.
He is quite clear that to understand his work, you have to divorce the idea of the 3D printer and instead think of the system as a convenient, configurable robot.
"A lot of people misunderstand that what we do and what a 3D printer does are two quite separate things," says Cronin, the leader of a world-class team of 45 researchers at Glasgow, spanning disciplines as diverse as artificial intelligence and nanoscience.
However, there certainly is at least some printing of plastic involved. Firstly, the group uses the prototype machine (dubbed the chemputer) to print an object for the reaction to take place in; essentially a glorified beaker or a test tube. Once the reactor is complete, the equipment can mix reagents inside it like "a cheap cocktail maker" until the sought-after molecule is printed.
The process requires software, hardware and chemical inks – likely simple reagents from which more complex molecules can be made. Cronin’s theory is that with the right tech and just a few specialised printer inks, you could make any organic molecule you wanted.
And if 3D printers can do organic chemistry, it follows that they might also be able to make drugs, offering up a new potential frontier in pharmaceutical manufacturing; a way of making the process faster, cheaper and more democratic. After all, such practices haven’t changed for decades. The industry is said to waste $50 billion a year thanks to its old-fashioned way of making drugs.
However, Cronin believes that instead of the huge reactors and the complicated robots used by major companies and which cost many millions of pounds, a 3D printer could produce similar results cheaply, and nothing would go to waste.
But as regular World Pharmaceutical Frontiers readers will be well aware, the sector is already talking of a manufacturing revolution. Vertex Pharmaceuticals, for instance, is building a $30 million, 4,000ft2 facility in Boston, US, for its new cystic fibrosis drug, while GSK, Novartis and Johnson & Johnson (among others) are trying to move the industry towards a method where some pharmaceuticals can be manufactured without using time-consuming, chemical-heavy batch processes.
Cronin shrugs this off. Continuous manufacturing, touted as the method to shake up pharma’s inefficient approach to drug making, will be no match for what he and his colleagues are proposing, he says. In his opinion, the sector just isn’t thinking big enough.
"This is about as disruptive as it gets," he opines. "This is going to destroy the current pharmaceutical industry as we know it."
Continuous manufacturing is a way of making the API manufacture cheaper and more efficient, he says, but it doesn’t necessarily make it more flexible. And although he even admits to currently being involved in several such projects, Cronin believes what continuous manufacturing will ultimately offer patients isn’t comparable to what he is suggesting.
"What I’ve got in mind is literally being able to download the codebase you need to make the molecule or the formulation of the molecule that is suitable for you," he says.
He’s talking about personalised medicine and believes every pharmacy, if not every home, will have one of his chemputers in the future. That way, drugs can be assembled and printed in accordance to several factors unique to you, such as your age, sex or genome. It would not only open up the number of drugs but also the ways in which they can be formulated.
No barrier
Aside from personalised medicine, Cronin believes there are other aspects of healthcare that can be challenged with such technology. For one, he’s particularly excited about the possibilities for more accessible healthcare. He sees remote places or poor countries as no barrier to his proposals. Cronin wants to democratise complex chemistry, allowing pharmaceuticals to be distributed anywhere in the world and delivered to those who need them. And in implementing his chemputer, or something similar, he believes the prevalence for ineffective counterfeit drugs in regions with low GDP could effectively be reversed.
"If you live in a remote place, or you’re in a poor country but you’ve got cheap ingredients, you could still use the technology," he reveals. "Because remember, chemistry is about taking small molecules and building them up in unit operations to more complicated ones. If you have your chemicals and you have the robot, you’ll be able to download the code and turn those chemicals into the range of drugs you need. So therefore, it decentralises the process. You might be able to give the entire population of the world access to drugs."
And as the average patient comes to rely on more than one prescription to take throughout the day, Cronin also thinks a print-on-demand process could be used to make things more convenient, by combining all the pharmaceuticals a person needs into one daily pill. He does point out, though, that there are several companies working on similar technology at the moment, suggesting the concept is not too far away from becoming mainstream.
Emphasis on biologicals
It must be said, however, that in recent years pharma has turned its attention away from small molecule drugs and the sort of chemical reactions Cronin’s printer will administer. Instead, the emphasis is on biologicals, products such as antibodies and interleukins derived from living cells. Such therapies are littering the bestsellers list. But Cronin does not seem to think the days are numbered for pure chemistry in drug development. Quite the contrary, actually. He believes pharma is only moving towards these more complex molecules because they haven’t been making the most out of chemistry. It won’t do well to abandon small molecules, he cautions.
"I think if we can open up the chemical space, we won’t need biologics – that’s the whole point," he explains. "Biologics are quite complicated. There’s a lot of baggage with them because to get that molecular action, you need all the scaffolding. But if you have access to a bigger chemical space, you might be able to get it more cheaply. It would seem smart to have access to all of chemistry rather than all of biology."
Cronin appears to have many answers, but what do pharmaceutical companies actually think of his ideas? The professor claims he’s had contact with most of the major players in the field.
"There’s some scepticism," he admits, "because the chain from drug discovery to clinical validation of manufacturing is very long. But the technology I’m developing actually combines a lot of that. On the whole, people are positive, but obviously conceptually it’s quite a leap."
So what are the next steps for the Cronin Laboratory?
"World domination," Cronin teases. But he’s not far off. This chemist is nothing if not ambitious. In fact, the group first formed to see if they could create ‘life’ from non-biological building blocks. Lofty aspirations aside, though, and thinking more short term, the group plans to develop the platform and will set up a collaborative network where other organisations can test the technology and see what they can achieve with it.
As for how long it will be before such equipment could be taken up by a pharmaceutical company, Cronin says he isn’t sure, while he hints that the regulatory worries might be harder to solve than the science.
"I have no idea how long it’ll take," he says. "Are there big technological barriers? There are some. There are no show-stoppers there though, and probably very little new science. How cheap is it going to be? How useful is it going to be? Those are the questions. And once we’ve proven the cost and how useful it’s going to be, I guess it will take off quite quickly, and if it works in a discovery setting and moves to a manufacturing setting, I’d say pretty damn quickly, as long as quality can be assured."