3D-Printed Meds: Better Living Through Chemistry or 3D Printing Novelty?

Leroy Cronin brought media attention to the concept of 3D-printed medications with a 2013 TED Talk discussing the topic. Since then, the idea has received a great deal of hype, but actual progress has taken place mostly behind the closed doors of research facilities. Only in the past year or so have we seen an increased number of stories revealing that 3D-printed medicine is a bit closer than we might think. This includes not only the first FDA approval of a 3D-printed medication, but also a number of related advances taking place at labs around the world.

Cronin’s lab at the University of Glasgow has published a breakthrough study that may lay the foundations for a new era of 3D-printed medicine. What might that era look like?

Reactionware: A Genie in a 3D-Printed Bottle

Cronin’s concept for 3D-printed medicine is among the first to have reached the ears and eyes of mainstream media. It’s also probably the most complex of the ideas, practically and conceptually, behind 3D-printed drugs.

To demonstrate how the process works, the lab recently developed reactionware for the affordable and accessible muscle relaxant baclofen. The set is made up of five 32 ml modules 3D-printed on an Ultimaker 3D printer. During the printing process, the researchers paused the printer to insert non-printable parts, such as magnetic stirrer bars for reaction modules, fritted glass filters for filtration modules and hydrophobic filters for extraction filters.

Then, over the course of 12 steps—which included the introduction of chemical ingredients into the various modules, as well as heating and cooling various modules and pushing chemistry from one module to the next—the chemists were able to obtain 98 mg of baclofen that was over 95 percent pure, a process that took 40 hours to complete.

Cronin ultimately envisions reactionware as 3D printable by labs and pharmacies on demand. Technicians could download the designs and order a drug-specific kit, made up of prefilled syringes, and produce the medications by following a strict series of steps. The researcher refers to such a process as the “digitization” of medicine, essentially making drug fabrication as easy as following a simple series of steps.

For reactionware to reach this point, Cronin and his team need to ensure that the drug fabrication process is reproducible to exact standards so it can receive approval from the FDA and other regulatory bodies.

Custom Meds from FabRx

Ultimately, one of the goals of 3D-printed pharmaceuticals is custom medication, tailored specifically to the patient. While Cronin’s reactionware may be used for highly specialized drugs, it may be possible to customize more regular medications more immediately.

One startup, FabRx, spun out of and based at University College London, has developed a method for 3D printing custom tablets, or printlets as FabRx refers to them, for producing patient-specific doses. Currently, pharmacies have no way of manufacturing pills in different doses. According to Dr. Alvaro Goyanes, the company’s director of development, by 3D printing medicine directly, it may be easy to modify the dose just by changing the size or infill of the printlet.

“This could be a game-changing technology in pediatric medicine, where the dose of medicines changes depending on the age or weight of the child,” Goyanes said.“On top of that, it will be possible to combine two or more drugs in one tablet, reducing the number of tablets that one person has to swallow. That is important in geriatric populations.”

As for SLS, Goyanes said, “One of the advantages of SLS is that instead of using plastic, ceramic or metal powder, we can fill the printer with a drug and GRAS-pharmaceutical excipients. The process is very simple, and we get printlets that are perfectly safe. It is not necessary to get a filament by hot melt extrusion like in the fused deposition modeling technology, and, depending on the excipients we select, we can get very fast release or targeted release of the medicines to specific regions of the gastrointestinal tract.”

Each technology offers its own advantages. For instance, using a semi-solid extrusion technique, FabRx has been able to create flavored, chewable printlets—for which the startup recently launched a crowdfunding campaign—which would make taking medicine much more appealing to kids.

“We have identified different treatments that could get benefit from personalized medicine by 3D printing,” Goyanes said. “Those treatments include some rare diseases and gene therapies.”

This differs from a business like Aprecia, a company with a focus on mass manufacturing that made history with the first FDA-approved 3D-printed drug.

Mass Manufactured 3D-Printed Meds

As futuristic as 3D-printed medicine may be, the concept already is a reality. In 2015, drug manufacturer Aprecia became the first to receive FDA approval for 3D-printed medication before being released to the market in 2016.

The medicine, Spritam, is a variety of the epilepsy medication levetiracetam. Unlike other varieties of levetiracetam, Spritam is manufactured with binder jet 3D printing technology. While binder jetting is typically used to produce full-color gypsum models, metal parts or sand molds for sand casting, Aprecia is able to mass produce water soluble tablets by binding layers of levetiracetam powder, a process the company calls ZipDose.

In this way, Aprecia is mirroring the approach used by medical device manufacturers like Stryker, which is not yet pursuing 3D printing for patient-specific devices but is instead leveraging the technology for the unique characteristics it can produce. When Spritam was approved by the FDA, Aprecia CEO Don Wetherhold said, “This is the first in a line of central nervous system products Aprecia plans to introduce as part of our commitment to transform the way patients experience taking medication.”

Though it may not have been initially designed for patient-specific use, it doesn’t mean such a use is out of the question. Binder jetting can be used to produce various parts in a single batch. Dental and medical devices, invisible braces and hearing aids, respectively, are mass manufactured with 3D printing. Combining these two facts, it’s not difficult to imagine patient-specific doses mass manufactured using ZipDose technology.

The Future of 3D-Printed Meds

A mass manufactured pill is much easier to standardize and, therefore, its ability to pass regulatory requirements is that much easier. Patient-specific pills, let alone chemically complex reactionware, may require entirely new ways of thinking about regulation.

So far the FDA has only issued guidance for 3D-printed medical devices, focusing on the material and processes used to make them. It’s possible that similar guidance for medicine could be issued when the technology reaches that level of maturity, but specific regulations for 3D-printed devices have yet to be drawn up.

“It also depends on the regulations. Right now it is not clear how the approval process is going to be; if the printing process is going to be considered a manufacturing step, with much higher control and regulation, or a compounding step, which is done every day in hospitals so has less strict regulation.”

Once the technology does mature, what will this mean for patients? As it stands, medication is produced with a one-pill-fits-all approach. With 3D printing, doses could be perfectly tailored to a patient’s weight and even metabolism. It could even change depending on what a person ate during the day. It’s even possible to envision 3D printers installed in homes that, once the proper reactionware was installed, could produce pills on demand.

Of course, to think that such a world is possible in our current political and economic climate may be absurd. Pfizer recently demonstrated that drug companies may be more interested in profits than research into treatments for crucial afflictions. After the recent U.S. tax bill was passed, which is expected to benefit large corporations like Pfizer, the company announced that it was laying off 300 employees and ending research into treatment for Alzheimer’s and Parkinson’s diseases.

This isn’t due to a lack of money. Pfizer paid no federal income taxes to the U.S. government from 2010 to 2012, while receiving $2.2 billion in tax refunds during that time. Nine out of the top 10 drug manufacturers spend more on marketing than research. The pharmaceuticals and health products industries spent $209,395,967 on lobbying in 2017, with Pfizer in particular spending $8.5 million. At the same time, manufacturers are able to increase prices on critical medications, as we’ve seen from the Martin Shkreli saga and Mylan’s move to increase the price of its EpiPens.