3D printing is ushering the pharmaceutical industry into a new era of personalised medicine. We explore how additive manufacturing is helping researchers to create truly personalised pharma solutions.
With projects such as prosthetic limbs and functional bridges to its name, 3D printing has already redefined the line between possible and impossible. It’s not surprising, then, that its medical applications have been well ahead of mainstream product development for some time now.
We see examples of 3D printing in healthcare almost every day. 3D-printed anatomical models have been used for complicated surgeries for 20 years now, and 3D printing for hearing aid cases is now standard practice. What is perhaps harder to imagine is the full potential of customised, 3D-printed additive manufacturing in the pharmaceutical industry.
Why are personalised pharma solutions important?
“The pharmaceutical industry has a little secret: even as it invents futuristic new drugs, its manufacturing techniques lag far behind those of potato chip and laundry soap makers.”
This quote from FDA Commissioner Mark McClellan has fueled an ongoing debate over the efficiency of the pharmaceutical industry. For over a century, pharmaceutical manufacturing has relied on batch technologies and fixed recipes - an expensive and inefficient approach.
A 2006 study reported losses of $50 billion/year in manufacturing costs from inefficient processes, and as a result the cost of pharmaceuticals has continued to soar ever since. A 2016 Gallup report reiterated that inefficiency continues to be a crucial problem for the industry, with Gallup’s Senior Economist Jonathan Rothwell explaining,
“The complicated practice by which pharmaceutical companies develop new drugs and set their (often very high) prices continues to come under scrutiny and provides the opportunity for potential reform.”
The good news is that we’ve recently seen slow progress in improving efficiency. As Director of Health Care Innovation at the Brookings Institution, Mark McClellan has progressed from his damning statements about manufacturing techniques to suggest that,
"If we can not only speed development but use it to foster competition among treatments, and if we can make progress on cheaper and better ways to deliver health care, I'm fairly optimistic about the outlook for drug innovation over the next decade or so."
Overall, the industry’s history of inefficiency has led to expensive and flawed pharma solutions that are delayed by an over-reliance on the restrictive batch and fixed recipe approach. A shift towards continuous manufacturing and personalised medicine could take us some way towards fixing this - and 3D printing is an essential piece of that puzzle.
How does pharmaceutical 3D printing work?
3D printing refers to the fabrication of physical objects from digital models. A 3D printer uses computer-aided design (CAD) software to process a design and reproduce it in thin layers until the buildup of layers results in the designed object.
In the pharmaceutical world, this technique allows the architecture of drugs to be precisely controlled, meaning that chemists can create pills with high-level precision, complex geometries and intricate internal structures, such as hollow channels to decrease dosage, with well-defined size dimensions.
So far, different 3D printing ‘inks’ have been used to print everything from edible pizzas to functional heart valves. By lacing 3D printer inks with active medications, researchers can start to experiment with the size, taste and structure of tablets.
Advances in custom dosage
Simon Gaisford, a pharmaceutical scientist at University College London, has come up with an innovative combination of 3D printing and hot-melt extrusion (HME), which is used in the pharmaceutical industry to make polymer blends of insoluble drugs. In this process, a drug and polymer are heated, mixed and squeezed through a small aperture. This disperses the drug into the polymer, which can then be shaped into a custom tablet.
By using the unique abilities of the HME process in conjunction with the bespoke options that 3D printing offers, Gaisford hopes to manufacture drugs with variable doses and configurations.
Gaisford and his team have tested their printing prowess on two aminosalicylate drugs used to treat inflammatory bowel disease. They printed tablets in a range of shapes and found that the different shapes affected the speed at which the drug was released in the body. For example, a pill with a hollow middle dissolved at a faster rate to a solid tablet.
Eventually, he sees this technology developing so that pharmacists can tailor-make drugs to suit each patient’s needs. Polymers are already used by pharmaceutical companies, and Gaisford suggests that in the future pharmacists could purchase polymer inks pre-loaded with a drug, then print out pills at a local dispensary.
The trouble with this technology is finding the right materials. Any polymer used in drug manufacture needs to be not only biocompatible but also capable of withstanding the high temperatures used during the 3D printing process.
Additive manufacturing for paediatric medicine
The array of possibilities for shape, size and colour is one reason why many believe that children could benefit the most from 3D printing advancements in the pharmaceutical industry. Research into medicated inks could make pills easier to swallow or dissolve, and more aesthetically appealing to children.
While ordering children's drugs in the shape of their favourite animal may seem a novel idea, these kinds of gestures could reduce a lot of stress for children recovering from intense illnesses or surgeries.
Their parents or carers would also benefit from knowing that the drugs had been designed with a specific dosage, customised to each child’s unique requirements.
Steve Tomlin, consultant pharmacist at Evelina London Children’s Hospital, explains that the enormous weight range among children can make dosing very difficult:
“This technology could revolutionise the way we look at children’s medicines, both in terms of what they take and the ability to keep changing the dose as they grow,” says, UK. Having a 3D printer in a hospital pharmacy could make weekly medication changes simple, personalised, and even fun.”
A shift toward continuous manufacturing
In the longer term, 3D printing could change the entire paradigm with which drug manufacturers view the production process. The industry currently relies heavily on batch processing and blended processes with a variety of technologies.
This is costly in terms of both time and money, meaning that some of the most effective drugs remain out of reach of those who need them most. Lee Cronin, the Glasgow University chemist behind 3D-printed reactionware (customisable kit for performing molecule synthesis) believes that additive manufacturing can help to combat this deficit across the world:
“Personalisation is the ‘sexy’ driver but I think distribution and reach are the winners here — especially in the developing world.”
Moving away from batch production to a continuous process has been a focus for the pharmaceutical industry for some time, primarily for its efficiency and cost saving benefits. However, there are many further benefits to continuous manufacturing. A continuous process will also improve quality, sustainability and containment.
A focus on quality control
Niklas Sandler, Professor in Pharmaceutical Technology at Finland’s Åbo Akademi University, is focusing his research on the quality control aspect of 3D printing, using a process called hyperspectral imaging to ensure that each drug has the ideal dose, layer by layer.
This method takes tens of thousands of spectral images of each drug sample, comprising an overall image of what the sample contains on each layer of its printed makeup. This should benefit clinicians by ensuring that dosage is accurately controlled, as well as regulators who will be given a highly accurate overview of what patients are receiving.
By building processes such as these into a continuous system, 3D printing technology can speed up the entire process of getting drugs on the market, with the potential for customisable dosages negating much of the time spent researching an ideal blanket dosage.
The industry has already come a long way towards a continuous approach, but many are still using blended processes with varying technologies. However, Andrew Sinclair, president and founder of Biopharm Services, has noted an uptake in single-use technologies:
“Single-use process technologies took 20 years to be fully adopted and accepted in clinical manufacturing, and they are only just making their way through commercial manufacture.”
The challenges ahead
Before 3D printing revolutionises the pharmaceutical world for good, however, there are some significant challenges for researchers to work on overcoming.
Firstly, the question is raised as to who will be responsible for product liability. If a pharmaceutical company licenses its 3D printing ink and digital designs to local healthcare providers, it can’t oversee the printing process as it would with batch-produced drugs.
Were any complaints or serious adverse events to be raised regarding the printed drugs, the pharmaceutical company may still be liable as the designer of the product blueprint. However, many agree that the healthcare provider would also be partly responsible for product defects.
However, a number of parties including the printer manufacturer, software designer and material suppliers could also be held liable. As there’s no precedent for such events, it’s unclear what the eventual strategy for legally and financially protecting different key players in the production process will be.
Another concern is raised with regard to digital plagiarism. As with any files shared digitally, 3D printing drug blueprints could potentially be hacked into and the medications reproduced by competing parties. Counterfeiters could even adjust the recipe or dosages in the blueprint, leading to widespread chaos for users.
Not only is this a significant risk to manufacturers themselves, it also increases the chance of drugs being made improperly and posing a risk to patients who, knowingly or not, purchase the unregulated counterfeits.
While the path toward readily available custom medication has many obstacles to overcome, the plethora of advances made in recent years suggest that we’re closer than we think to replacing traditional drug manufacturing altogether.
As reactionware pioneer Cronin suggests, “In the end it will replace big plant manufacturing all together. That’s my vision, anyway.”
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