Big Pharma’s 3D Focus

My team at the University of Nottingham started work in the area of printing formulations around 2005, based on conversations within our EPSRC (Engineering and Physical Sciences Research Council) Centre for Doctoral Training in Therapeutics. Our discussions with Morgan Alexander, an expert in developing new materials for medical applications, and Paul Gellert, a leading formulation scientist at AstraZeneca, led to a PhD project where we explored the basics of printing formulations and showed the principal of emulating a commercial formulation. Following this successful project, we nevertheless struggled to attract interest in the idea of printing formulations – not so much from sponsors, but from students wanting to take up such a ‘crazy’ project! Eventually, an adventurous student, Shaban Khaled, joined us and took up the challenge. And we got a boost when the EPSRC Centre for Innovative Manufacturing in Additive Manufacturing arrived at the university, along with Ricky Wildman, a professor with expertise in modeling and 3D printing.

Shaban had demonstrated that 3D printing based upon extrusion can produce viable solid dosage forms capable of passing regulatory tests (1, 2). These tablets have become increasingly complex, starting as simple bilayer tablets, moving onto osmotic pump release tablets, and recently polypills containing several different drugs, each in a separate compartment and released independently. We continue to partner with AstraZeneca on developing novel inkjet printed solid dosage forms and on pushing the limits of 3D printing towards nanoscale resolution. We are also working extensively with GlaxoSmithKline to explore the wider possibilities in manufacturing.

Working with industrial partners really helps us focus on the key issues that must be resolved if this methodology is going to become commonplace in medicines manufacture. Some people say that pharma companies can be wary of new technology, but in my experience big pharma is always keen to explore promising new technologies and ideas, even if they may seem a bit far-fetched to begin with. 3D printing is an accessible idea; it’s an easy concept to ‘sell’, albeit challenging to deliver.

The main issues preventing widespread adoption are the regulatory view of 3D printing as a manufacturing process (particularly if it is distributed away from a large central facility), a need for new safe materials for formulating the printable ‘inks’ and viability in fast mass manufacture. The FDA’s first approval of a medicine that uses 3D printing will go a long way to addressing the concerns about regulation. The tablets, made by Aprecia, use an aqueous fluid to hold together multiple layers of powder in a reformulation of the anti-epileptic seizure drug levetiracetam. As the tablet is very porous it very quickly disintegrates in liquid. This is a very clever ‘niche’ product and now there is some real validation of 3D printing in the pharma industry, I expect interest to grow even further.

As to the latter issue of manufacturing speed, the technology of printers is moving at such a breathless pace that it’s hard to imagine the speed of manufacture being a long-term issue, especially as, ultimately, 3D printing is likely to be used to produce complex medicines, not to make billions of off-the-shelf tablets.