Researchers at the University of Glasgow developed a new method for drug manufacturing which uses 3D printers to create pharmaceuticals on demand. The study on 3D printed drugs, published in a new paper published today in the journal Science, could lead to a ‘Spotify for chemistry’. This would mark a new approach to the manufacturing of pharmaceuticals using a digital code, one that many are looking at as a potential breakthrough.
In the UoG study, digital code is used by a 3D printer as a portable factory, which can make the drug by adding the chemicals in a pre-defined fail-safe sequence. This approach could dramatically increase the number of useful drugs available regardless of patent-life, no longer requiring a limited number of dedicated manufacturing facilities
First, the researchers claim that the ability to ‘print’ drug factories on demand could reduce cost. Furthermore, they would increase the choice available to clinicians and reduce the risk of counterfeiting. Finally, they would also help personalize drug delivery to the needs of individual patients.
In the paper, the team of researchers from the University’s School of Chemistry demonstrated the potential of the system by producing the pharmaceutical Baclofen. This is a muscle relaxer used to treat muscle symptoms caused by multiple sclerosis, including spasm, pain, and stiffness.
The team’s chemical factories are designed using a chemical-to-digital converter to digitize the process so that it can easily be reproduced in a 3D printer. The researchers compared this process to converting a compact disc to an MP3 file. With a simple instruction manual, the drug can be produced when and where it is needed.
The approach was designed and developed by Professor Lee Cronin, the University of Glasgow’s Regius Chair of Chemistry. He and his team are paving the way for the manufacture of drugs outside of specialist facilities.
“[This approach] is a key step in the digitization of chemistry, and will allow the on-demand production of chemicals and drugs that are in short supply, hard to make at big facilities and allow customisation to tailor them to the application. We will also use this approach to make a ‘Spotify for chemistry’, allowing scientists to develop better code to make important chemicals.” said Professor Cronin.
This research is funded by the University of Glasgow complex chemistry initiative along with the European Research Council and the Engineering and Physical Sciences Research Council. Professor Cronin has a long-standing relationship with EPSRC; support provided by EPSRC over the last 16 years has aided in the development of diverse research areas, ranging from the development of inorganic fuels for water splitting to the use of configurable robotics for the programming of drug discovery and novel materials.
He is currently the principal investigator for projects in receipt of EPSRC grants worth £7.6 million and is co-investigator on a further four grants totaling £9.9 million, while EPSRC has supported 20 previous research projects since 2002. Additionally, the business activity of Cronin Group Plc, of which Professor Cronin is the founding scientific director, is the digitization of chemical space.
Drug delivery, a key application for 3D printing and bioprinting
The idea of 3D printing drugs for more efficient and accurate delivery is not new. In fact, it is one of the most interesting medium-term business opportunities for 3D printing and bioprinting technologies alike. Researchers at ETH Zurich are also working on 3D printers to create on demand, customized drug delivery vehicles.
In 3D printing, computer-aided design and computer-assisted manufacturing are combined to construct complex 3D objects without the use of molds, offering a high degree of flexibility in the structural design. Specifically, in the pharmaceutical sciences, there is a unique opportunity for innovation since most of the advances so far made are limited to simple oral dosage forms (i.e. tablets).
The aim of the team at ETH is to develop 3D printing as a leading-edge technological platform to manufacture innovative drug-eluting devices with precise spatial compositions, controllable drug release patterns and most importantly, with unprecedented customizability. The possibility to readily 3D print drug-eluting devices represents a remarkable step towards personalized medicine as it will allow to select the drug used, the dose loaded and the release kinetics, as well as tailor the size and geometry of the device to completely accommodate the anatomic features and medical needs of patients.
In this project, the researchers generated a library of printable “pharmaceutical inks”, a comprehensive database of their properties, and the procedures that can be used to 3D print and characterize drug-delivering devices. As a result, they investigated different 3D printing technologies, such as fused deposition modeling and stereolithography.
The $50M business opportunity for bioprinted medical devices
In its latest report on bioprinting technologies and materials, leading AM market research firm SmarTech Publishing includes bioprinting of drugs and devices for customized drug delivery in humans in the medical devices segment. This is a field that has no current commercial applications today. However—according to industry operators interviewed by SmarTech—it holds a very significant potential in the medium- to long-term. In fact, by relatively conservative estimates it has the potential to grow into a $50 million yearly business within the next ten years.
One of the most active companies researching practical and commercial applications of 3D printed/bioprinted pharmaceuticals is UK-based FabRx. Established in 2014, FabRx is a rapidly growing biotech business that is developing printed medicines and drug-loaded medical devices. The company is the creation of academics from University College London, who saw the potential of 3D printing technology for making better medicines. FabRx is primarily a research-driven company. In addition to its IP portfolio, its staff frequently publish papers in International Journals.
Their latest published paper -Patient acceptability of 3D Printed Medicines- focused on patient-centric medicine is a derivative term for personalized medicine. Thus, the pharmaceutical product is expected to provide the best overall benefit by meeting the comprehensive needs of the individual. In this research, FabRx considers the end-user from the beginning of the formulation design process through development to an end product. 3D printing is seen as a way one way to obtain personalized medicines, on-site and on-demand. The aim of this study was to investigate the influence of the shape, size and color of different placebo 3D printed tablets (Printlets) manufactured by fused deposition modeling (FDM) on end-user acceptability regarding picking and swallowing.
From bioprinting to FDM, SLA and SLS
Other recent studies published by FabRx members focus on the use of selective laser sintering (SLS) as a manufacturing method for pharmaceuticals as well as the use of 3D printed tablets loaded with polymeric nanocapsules. Earlier research focused on the use of stereolithography (SLA) technology for local drug manufacturing.
They are not the only ones. Many other institutions around the world are researching 3D printing technologies as a key opportunity for better drug manufacturing and delivery. Truly personalized is no longer just a cool idea.
Ten different printlet shapes were prepared by 3DP for an open-label, randomized, exploratory pilot study with 50 participants. The torus printlet received the highest PRO cores for ease of swallowing and ease of picking. Printlets with a similar appearance to conventional formulations (capsule and disc shape) were also found to be easy to swallow and pick which demonstrates that familiarity is a critical acceptability attribute for end-users.
3D printed drugs are already here
In 2016 Aprecia Pharmaceuticals announced that SPRITAM (levetiracetam) tablets, for oral suspension, are commercially available as adjunctive therapy in the treatment of partial-onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures. SPRITAM is the first prescription drug product approved by the U.S. Food and Drug Administration (FDA) that is manufactured using 3D printing technology.
“As we explored potential applications for our 3D printing technology in prescription drug products, it was important that we identified disease areas with a real need for patient-friendly forms of medication,” said Don Wetherhold, CEO of Aprecia. “SPRITAM is designed to transform what it is like to take epilepsy medication, and is the first in a line of products we are developing to provide patients and their caregivers with additional treatment options.”
SPRITAM is formulated with Aprecia’s proprietary ZipDose Technology, which combines the precision of 3D printing and formulation science to produce rapidly disintegrating formulations of medications. Manufactured in a regulated commercial-scale facility, SPRITAM is available in four unit-dose strengths, including 250 mg, 500 mg, 750 mg and 1,000 mg. Nearly three million people in the United States were living with active epilepsy in 2013, and about 150,000 new cases are being diagnosed every year in the U.S. Swallowing challenges can make taking medication difficult.
Using 3D printing Aprecia is able to maintain rapid disintegration properties even at high dose loads (up to 1,000 mg). The company can also provide a wide range of taste-masking capabilities while delivers unit-doses for precise and convenient administration. Aprecia has just signed a new partnership with Cycle Pharmaceuticals to use 3D printing to produce orphan drugs. These are drugs that are used to treat extremely rare conditions, making them an ideal fit for the customization that is possible with 3D printing processes.
That’s personalized medication, it’s already here and it’s just the beginning.