3D Printing: Democratizing Precision Medicine
With rapid printing technology, we could be on the cusp of a revolution. But is it a manufacturing or a compounding process – and how do we regulate it?
Dayanjan Wijesinghe, Tom Knapman |
As increasing numbers of personalized and precision therapies are approved by regulatory authorities, modern technologies – like additive manufacturing – are being employed to help realize this rapidly emerging medical paradigm. In 2015, the FDA approved the first 3D printed drug pill – Aprecia’s seizure medication SPRITAM (levetiracetam). The tablet formulation is rapidly disintegrating and high-dose, which is especially useful for patients with epilepsy who may be experiencing a seizure. The tablet dissolves in seconds with a sip of liquid. The approval was a clear signal that additive manufacturing could be used to create formulations tailored to the needs of the patient.
Easily customizing the dose and/or release kinetics of the API for the patient is one clear benefit of 3D printing, but we may also see the rise of on-demand personalized polypills – single pills that comprise multiple APIs at specific doses and combinations for specific patients. This could take place in hospital pharmacies, doctor’s surgeries, or perhaps even at patient homes. Not only will this disrupt how we make and supply drugs, it could also expand our drug repertoires and access. Without the need for long-term stability and shelf life, more drugs could become available for prescription. Flexible dosing could also make the difference for many pediatric and adult patients who cannot get tablets at low but accurate doses.
So, what might this future look like? And how could it work with other potential advances in clinical care and developments underway in biomedical science? Imagine, you are unwell and go to hospital. You do not know what is wrong. A sample of your blood is taken, which is analyzed using automated omics and mass spectrometry-based systems. They scan your blood to sensitively and selectively detect and quantify multiple genomic, proteomic, lipidomic, and metabolomic biomarkers, both known and unknown. Novel, unknown markers are identified and characterized by AI-driven iterative processes that run automated experiments using innovative untargeted methods, such as SWATH acquisition, with reference to the wealth of human knowledge published in research literature and databases online. Thus, from one sample, you and your doctor are provided with a readout that comprehensively describes your unique physiology, biochemistry, genetics, and even lifestyle. It can even account for existing comorbidities and medications. The readout will not only inform diagnosis but also the choice of treatment options.
For example, your diagnosis indicates that you need a course of antibiotics. But that will disrupt your gut microbiome, so you will also need a probiotic. Disrupting your gut flora will also deplete your vitamin B levels, so you should also take a vitamin B supplement to keep your levels topped up. At that point, you could take three different pills – the antibiotic, the probiotic, and the vitamin B supplement – all at standard doses, or you could opt for a single bespoke polypill, 3D printed there and then at the point of care, where the doses and API release kinetics have been personalized specifically for you. Even the tablet shape and taste could be tailored to your preference.
The metabolomics component of the readout will also be able to determine a person’s metabolic rate so that the drug dose and API release can be adjusted accordingly. Moreover, readouts of blood taken after treatment can flag any drug-drug interactions as well as provide early indications about whether the treatment is working. After all, the initial blood analysis revealed the biochemical dysfunctions underlying the person’s disease. These biochemical markers of dysfunction should disappear if the treatment is working to reverse or mitigate the disease. Such early indications empower patients and doctors to make early decisions regarding whether to stay the course or switch to another treatment option.
The reality of 3D printed precision medicine may not be as far-fetched and distant as you might believe. With new enabling technology on the horizon, such drugs may become routine and commonplace as soon as the next 5–7 years. Interest is growing quickly in the pharmaceutical industry – especially among developers and regulators. However, many questions remain regarding the logistical and regulatory hurdles. For instance, in a scenario where pharmaceutical companies mass produce 3D printer ink cartridges containing APIs and excipients and distribute them to community pharmacists for printing and dispensing, how will this be regulated – and by whom?
Although the manufacture of medical products falls within the FDA’s remit in the US, oversight responsibility can be less clear when the manufacture occurs at the point of care. No specific guidance has yet been issued regarding how the regulatory framework will adapt to ensure that such 3D printed products are safe and effective for their intended use. However, some argue that the 3D printing of drugs is not a manufacturing process so much as a compounding process. As such, the compounding of drugs is a practice and not a product. The practice of medicine is not directly regulated by the FDA and is instead overseen by state medical boards. Regardless, regulatory authorities are engaging early to keep pace with advances in the field.
Certainly, there are many moving parts in the development of 3D printed drug tablets. Indeed, our team at Virginia Commonwealth University are currently working with collaborators on multiple aspects, including printer instrumentation and open-source platforms, with the aim of advancing the 3D printing of drugs into clinical trials to demonstrate proof of efficacy and safety. Another critical aspect is the automated metabolomics platform and workflow, which relies on advanced analytical instrumentation and methods, allowing us to analyze and predict the biochemical networks and identify the dysregulated biochemistries. There are a wide range of 3D printing applications, many of which we are considering; for example, supplying medicines to rural areas, low-income countries, disaster sites, war zones, and even space!
The potential is huge. And if the industry can figure out the regulatory hurdles, we may be on the cusp of a revolution: the democratization of personalized precision medicine.