Digital Health

Medicine straight out of the printer

3D printers have long been part of everyday life in many industries, such as medicine. Printed dental implants, prostheses and bone replacements have become almost indispensable. Now comes the next stage of evolution, and it could be spectacular. Or is it just the next hype? //next author Ronald Voigt spoke with Christian Franken, who plans to put the first 3D printer into operation in pharmacies this year with his start-up.

A good decade ago, 3D printing was already hype. Many who believed in it lost a lot of money on the stock market. Even if it became quiet afterwards: The industry - alongside the increasingly agile maker scene - has tinkered on, step by step.

In the summer of 2019, news rushed around the world, a medical sensation: An Israeli research team had 3D-printed a human heart for the first time. The artificial organ had no functionality whatsoever, and was also no larger than a cherry. However, the experiment substantiated the proof that printing with bio-ink - an artificial mixture to which living, human cells are added - works. However - and this is also part of the truth - it will be decades before the printer can replace a donor heart.

Christian Franken is quicker on the uptake: Before the end of the year, he and his start-up plan to put the first 3D printer into operation in pharmacies. Tablets with a wide variety of active ingredients, compositions, dosages and sizes from one and the same printer - that's what he's all about. Inkheart vs. 3D tablet, it's like comparing a Hollywood blockbuster with a YouTube video. And yet the pill from the printer could radically change the medical supply situation.

Franken has a doctorate in pharmacy, was a member of the management board of DocMorris mail-order pharmacy for many years and is now responsible for Dihesys, a start-up that builds the pill printers, supplies the ingredients containing the active ingredients and programs the necessary software - in short, plans the 360-degree supply.

He holds a 3D pill between his thumb and forefinger. It looks like a normal tablet, elongated, oval, inconspicuous at first. However, it is not white, but consists of several layers of color, like toothpaste. Blue, red, pink, white on the outer sides. Each color is a filament, a bioresorbable polymer that contains an active ingredient. The polypill he brought contains five active ingredients - five tablets built into one. Each active ingredient with the individual dose that the patient needs.

 

"Turn 15 pills into one"

Franken brought a tablet portioner from his father-in-law: "There are about 15 tablets in there that he has to take every day. He's multimorbid, like many of his peers."

If you turn 15 pills into one: What is the advantage?

Swallowing one is more comfortable than swallowing 15. We need to make it easier for patients to take it. Adherence is a big problem in healthcare. Patients simply stop taking their pills because they are feeling better at the time, for example. With psychotropic drugs, several months can pass between taking the medication and its effect. The bill comes with a significant delay. It is estimated that 30,000 to 40,000 people die from medication errors in Germany every year.

40,000 dead just because they stop taking their pills?

No, there are many reasons: Some patients take cocktails of tablets prescribed by different doctors who are not communicating with each other. Active ingredients can reinforce each other under certain circumstances, even negatively. Or look at the susceptibility to errors when filling pillboxes, as was the case for my father-in-law: Those who fill the plastic boxes, the nurses and relatives, fill them by hand. Mistakes can happen.

And the 3D printing pill is the solution to everything?

Whether you swallow one pill or 15 - or whether you have to stock them for patients as a caregiver - there is a difference. Many things are possible to increase adherence. The costs of non-adherence are estimated at up to ten billion euros per year in Germany alone, and up to 300 billion dollars in the USA. 3D compounding of drugs dramatically reduces the number of therapeutic agents: complexity decreases, adherence increases. Other key parameters are also greatly improved. So an individualized dose will also reduce side effects and optimize effectiveness - and that brings us to the second very big advantage: the individualization of medicine.

Individual medicine as a megatrend

Like everything that comes out of the printer, the additively produced pill has one decisive disadvantage - the number of units. A really good printer can currently produce 250 tablets per hour. The limiting factor is the limited speed of the print head. Industrial presses in the pharmaceutical industry, on the other hand, spit out up to 250,000 tablets per hour. All pills are identical, usually designed for an average male patient - to the concentration and dose that suits him.

If you are a woman, a child or a non-average patient, this can mean that one tablet is too many. Then it is divided or even quartered, the gap in the middle seems made for it. But you never get exactly half or a quarter. However, many diseases require exact dosage. And with children, for example, the necessary low dosage is often not available at all. With the printer, you can dose individually, but not with the press.

Every person is different, and medical treatment must take this into account. Under the buzzwords "individualization" and "personalization" of medicine, a paradigm shift is currently underway. With gene sequencing and CrisprCas9, the possibilities are suddenly there to make the individual in people visible and to tailor treatment accordingly.

Christian Franken is a pioneer of this megatrend; he wants to make the individual pill socially acceptable. The dosage of the active ingredient is just one of many possibilities. Another is to increase the individual effect and reduce side effects. In his wishful thinking, the pharmacist types in the ingredients that the patient has brought with him on his prescription, or better yet, transferred via e-prescription. Wait a minute or two - and the individual tablet is ready.

Even for small patient groups or rare or little-researched diseases that are less in the spotlight for economic reasons, medications can now be produced much more easily with the individualized 3D printing processes.

Precisely timing the release of the active ingredient

3D pills have been on the market for some time now, and the first drug (to treat epilepsy) from the printer was approved by the drug authorities in 2015. Since then, the technology has developed enormously. In particular, the diversity in the area of pharmaceutically important material properties, such as elasticity and heat resistance, has increased enormously.

In the FDM/FFF-process, which is used to print several drugs in one tablet, the individual drugs are stored in different filament layers. The temperature problem, where heat could damage the active ingredients during printing, has also been solved. The print head temperature is now very low.

It is also fascinating that it will soon be possible to "program" when, where and in what gradation each individual active ingredient printed in the 3D capsule is released in the body. Anything between "in seconds" and "for hours" is possible - and individually adapted, just as the body needs it. To achieve this, each active ingredient is packaged with a polymer wall of varying thickness. Five different release times in one capsule? No problem!

 

"Why not in the shape of a heart - with licorice flavor?"

During the conversation, Christian Franken takes a small, rectangular wafer, the size of a postage stamp, 2D printed, in his hand. A QR code has been printed in blue on the white wafer, which is a tablet. During the conversation, he swallows it.

Don't worry, it's just a placebo.

What is the blue?

That's the actual medicine. We can print it as a QR code on the carrier. This allows the patient to watch a short film on the effect or the correct application before taking the medicine, for example.

Isn't that more of a gimmick?

That's something everyone has to decide for themselves. But we have already addressed the problem of adherence. If we manage to increase adherence, we will have healthier patients. My goal is to make every patient a fan of their disease - and the 2D and 3D tablet offers fantastic opportunities for that.

For example?

For example, I wonder: Why does the tablet always have to be white and round or oval? Why not heart-shaped and red? Or like a little soccer ball? The question must be: How do I motivate the patient to take the tablet? A soccer ball or even a Harry Potter figure can be quickly programmed in the printer. If this increases adherence to therapy, then the shape alone has a decisive effect.

Christian Franken has won three innovation awards with Dihesys by 2020. He is even more pleased that the first pilot project has started together with two university hospitals and a health insurance company. Other projects have also started in other European countries and also outside Europe.

So 3D printing is gaining momentum again in the post-hype phase. Incidentally, the Corona pandemic is helping: With borders closed and supply chains interrupted, printers were running at full speed - for masks, for test kit rods, through to valves, intubation materials and syringe pumps. More was printed than ever before. Could be time to look again at 3D printing stocks.

Text: Ronald Voigt