Understanding the “why” behind usage of 3D printing technology in pharmaceutical industry

Introduction

3D printing technology has been widely used to produce medical devices since more than a decade. There is 200+ FDA-approved 3D-printed devices available that can be tailored to fit a patient’s personalized care. However, use of this technology for drug products is still not popular due to many regulatory questions that need to be addressed.

The only 3D printed commercially available drug product in the US market is Spritam? tablets used in the treatment of epilepsy, which is developed and marketed by Aprecia Pharmaceuticals, LLC headquartered in PA, USA. The product was approved on July 31st, 2015.

Why Aprecia Pharmaceuticals, who owns first USFDA approved Spritam? tablets uses 3D printing technology?

Their aim was to make medicines easier to take and reduce the number of pills a patient need. They developed proprietary ZipDose Technology, which allows tablets to hold a high dosage load of up to 1,000 mg of levetiracetam and still rapidly disintegrates with just a sip of water.

Why 3D printing technology in not widely used in drug products?

There are several questions regulatory standpoint which needs to be answered on which the scientists from The Office of Testing and Research (OTR) in CDER’s Office of Pharmaceutical Quality are working on. Here are some important questions regulators have in mind and are working on –

o??What are the critical parameters affecting the printability of various materials into drug products?

o??What are the critical process parameters for each 3D printing technology?

o??How can we assess the performance of 3D printed drug products?

o??Can we use traditional in vitro testing methods for 3D printed drug products?

o??How can we determine when and how a certain 3D geometric design may not perform as it should?

o??What are the critical characteristics of the intermediate products for 3D printing, such as 3D printing inkjets, filaments, substrates, and cartridges?

o??What are the critical factors in 3D-printed design that affect the drug release rates and mechanisms?

CDER is also considering the regulatory challenges associated with 3D-printed drug products, and to what extent the 3D-printing process may be controlled to ensure the quality of 3D-printed drug products. For example, the multiple components associated with 3D printing processes, namely 3D printers, printing materials, and intermediate products and processes, should be considered. Nextly, the functions of commonly used inactive ingredients may not be applicable for 3D printing processes as their behavior is likely to change which is another challenge in using this technology.

Why 3D printing technology is said to have a great potential of usage in the pharmaceutical drug product manufacturing?

Conventional drug production relies on large-scale batch manufacturing, which is very efficient at churning out large volumes of drugs with uniform characteristics. But it becomes time-consuming and expensive when it comes to small scale batch manufacturing, such as for clinical trials where the doses need to be adjusted. The process is also associated with an environmental burden resulting from inefficient use of raw materials, expired stock and production of toxic and non-toxic waste.?

3D printing can allow efficient small-scale production of medicines. This approach uses 3D modeling software to build an object layer-by-layer; for solid drugs, the 3D printer stacks ink with an excipient — inactive substances in drugs added for specific functions like improved stability and bioavailability — and the active pharmaceutical ingredient to print out a finished product. By adjusting the printing parameters, the drug dosages, drug combinations, release profiles and even flavors can be personalized.

Here are five companies that are leveraging 3D printing to produce customizable drugs –

1.??????Aprecia Pharmaceuticals, PA, USA

They are the first to get USFDA approval for Spritam? tablets used in the treatment of epilepsy. The product is manufactured by using their proprietary ZipDose 3D printing technology which helped them create a more dissolvable pill and which can accommodate higher drug load.

2.??????FabRx, London, UK

Founded in 2014 as a spin-out of University College London, FabRx aims to revolutionize medical treatments by facilitating the production of personalized medicines, where the size, shape, dosage and dosage combinations can be customized. In 2020, the company released M3DIMAKER, the first pharmaceutical 3D printer for personalized medicine, allowing clinicians and other professionals to “print” tailored medicines on demand.

Using their 3D printing technology, FabRx has also created a range of personalized Printlets — medicines with customized shapes, flavors, colors, dosages and release profiles, such as tablets with Braille and moon patterns for patients with visual impairments as well as Polypills, which combine several drugs in one pill.

FabRx technology is also being used to print personalized pills for children with a rare metabolic disorder called maple syrup urine disease, which requires treatments to be strictly tailored based on age, weight and blood concentrations of the amino acid isoleucine. Current manual preparation methods are time consuming and costly, so FabRx’s approach could save time and money for caregivers.

3.??????Merck, Darmstadt, Germany

The biopharma giant Merck is working on next-generation tablet manufacturing through 3D printing. In 2020, Merck announced a cooperation with ACMC — sister company of EOS, a worldwide provider of 3D printing solutions — to produce 3D printed tablets for clinical trials at first, before moving towards commercial-scale manufacturing. This partnership aims to advance the industrial applications of 3D printing technology and digitalization.

4.??????Triastek, Inc., Nanjing, China

Triastek is a global leader in pharmaceutical 3D printing, with 41 patents that account for more than 20% of global 3D printing pharmaceuticals applications. Using their proprietary MED 3D printing technology, Triastek develops their own in-house drugs and partners with others to provide drug development solutions.

The MED 3D printing platform allows for the customizable design of tablets, with the different shapes and geometries controlling drug onset time, duration, and drug interactions with the body. This platform was accepted into the FDA’s Emerging Technology Program in 2020, and two of their 3D printed drugs have been granted investigational new drug clearances from the FDA. The first is a chronotherapeutic drug for rheumatoid arthritis, where the drug is taken at bedtime but its release is delayed until the early morning hours, when pain and joint stiffness are at their peak. The second is a one-dose pill alternative to the twice-daily marketed drug for cardiovascular and clotting disorders.

5.??????GlaxoSmithKline, Brentford, UK

GSK was one of the first big pharma companies to show interest in 3D printing as a manufacturing tool, partnering with the University of Nottingham to study the feasibility of 3D inkjet printing and curing with ultraviolet light to produce solid drug forms; in 2017, researchers demonstrated the successful 3D printing of ropinirole tablets for Parkinson’s disease.

3D inkjet printing deposits liquid materials or solid suspensions layer-by-layer but each deposited layer must first be dried, or “cured,” between the deposition steps. GSK is exploring how to convert active pharmaceutical ingredients into curable ink to enable 3D drug printing.

References –

1.??????https://www.fda.gov/drugs/news-events-human-drugs/cder-researchers-explore-promise-and-potential-3d-printed-pharmaceuticals#:~:text=To%20date%2C%20one%20FDA%2Dapproved,manufactured%20using%203D%20printing%20technology.

2.??????https://www.accessdata.fda.gov/scripts/cder/ob/results_product.cfm?Appl_Type=N&Appl_No=207958#32011

3.??????https://www.computerworld.com/article/3048823/this-is-the-first-3d-printed-drug-to-win-fda-approval.html

4.??????https://www.labiotech.eu/best-biotech/five-companies-personalizing-treatments-with-3d-printed-drugs/

5.??????https://www.iiprd.com/3d-printing-in-pharmaceutical-industry/ (newsletter picture credit)