A pilot study that was conceived by the pharmacy team at St. Jude Children's Research Hospital in Memphis, Tennessee, is helping set the stage for pediatric patients to receive 3D-printed formulations of select nonsterile compounded oral medications.
Led by Brooke Beavers Bernhardt, the hospital’s chief pharmaceutical officer, the study evaluated the characteristics of oral gel tablet, water-free troche, and orodispersible film (ODF) formulations of hydrocortisone produced by a semi-solid extrusion process using a modular 3D-printing system. The target concentration of each formulation — 3.2-mg gel tablets, 2.8-mg troches, and 1.2-mg ODFs — represented doses typically used by the hospital.
The study results, which were recently published in Pharmaceutics, demonstrated that all three oral hydrocortisone formulations reliably and reproducibly met U.S. and European pharmacopeial criteria for mass and content uniformity. Each hospital-compounded formulation also satisfied US Pharmacopeia criteria for drug release (75% or higher within 30 minutes).
The pilot study is part of a larger exploration of 3D-printing technology by the pharmacy department.
“We’ve actually done some meticulous validation on several products,” Bernhardt said. “This was just the first paper to be published.”
One of Bernhardt’s priorities since she came to St. Jude two years ago has been to find better methods to produce compounded medication doses for young patients. Her main partner in the effort is Cindy Brasher, the hospital’s compounding manager and a coauthor of the Pharmaceutics report.
Together, they hope to use 3D-printing technology to create personalized medication formulations that are more palatable and easier to administer than traditionally compounded doses.
“We get a lot of adult manufactured dosage forms,” Brasher said. “That’s ideal for them. But when we have our pediatric patients, either we need partial doses or it needs to be prepared as a liquid or something else that they can take.”
The first 3D-printed medication entered the U.S. market in 2016 with the launch of Spritam, a levetiracetam oral tablet product. Other 3D-printed commercial drug products are in development.
Bernhardt and Brasher said they first became aware of the potential for 3D printing in pharmacy compounding after seeing the technology in use at a European hospital. Their interest was further spurred by a visit to the University of Mississippi School of Pharmacy, which uses 3D printing for research purposes and even offers a course on 3D printing of medications.
“We didn’t realize it was this close to reality until we went to visit other hospitals,” Bernhardt explained.
The tentative plan at St. Jude is to begin producing 3D-printed compounded nonsterile products for patients this year.
“We’re still working out the details, but we’ll probably start with three products,” Bernhardt said. “We’re going to start with a really carefully measured approach.”
Bernhardt reached out to several manufacturers of 3D-printing systems while planning the study that was reported in Pharmaceutics.
Each step in the production process, including mixing, dose production, packaging, and validation, was first performed at the manufacturer’s facilities. The validated process was then implemented at St. Jude in Tennessee to produce compounded hydrocortisone formulations for analysis.
“We were able to reproduce those same doses with that same concentration and strength, using the machine, no matter where we were,” Brasher said.
In addition to studying and validating 3D printing, the pharmacy team is also ensuring that its use of the technology meets regulatory requirements for pharmacy compounding.
Bernhardt said the 3D-printing technology replaces manual processes in nonsterile compounding in a way that’s loosely analogous to using robotics in sterile compounding.
“So it should not be held necessarily to a higher standard — it should fall under the existing standards. And it’s actually better than what we’re doing now, we believe,” Bernhardt said. “This is really taking compounding to the next level.”
Brasher said portions of the hospital’s compounding area have already undergone construction to ensure compliance with US Pharmacopoeia standards for nonsterile and hazardous materials compounding.
“We’re making sure that we’re meeting those existing standards and then figuring out how the 3D technology fits within those parameters,” Brasher said. She also worked with the state pharmacy board about issues such as whether the 3D system should be housed on a table in a negative-pressure room or installed inside a hood.
Brasher noted that typical dimensions of 3D pharmaceutical printers are roughly 2-3 by 2-3 feet. But operating the system requires additional space in the compounding area.
“There’s the device itself. And then you’re figuring out, does it open from the top or open from the front, and then adding on things like mixers for mixing together the base and the ingredients,” Brasher said. The system also requires workspace in one or more hoods for weighing out active pharmaceutical ingredients and excipients.
“That’s probably been one of our biggest learning curves,” Brasher said.
Once installed, she said, the system is simple to operate. And it has attracted the interest of staff members who own personal filament-based 3D printers.
“They are the ones that are coming to us saying, ‘I’m intrigued about this, I want to get involved, how do I do that?’” Brasher said. “I love the idea of how it can kind of generate that interest within your staff to learn and do something new.”
Bernhardt said she’s pleased to have contributed to the evidence base for 3D printing in nonsterile compounding, and she’s excited about the potential for 3D printing to improve patient care at her own hospital. But she said technology is likely to remain largely a niche area in pediatrics, geriatrics, and other specialized areas of pharmacy practice where standard product formulations don’t work for many patients.
“For us, it opens the possibility of greater precision, improved medication adherence. It allows us to find better ways to deliver lifesaving medications to pediatric patients that we treat,” she said.
