Before any new drug is introduced in the market, it undergoes a series of pre-clinical and clinical trials to ensure it is safe, efficacious and meets regulatory requirements. In pre-clinical trials, the efficacy of the drug is tested using living cells in a petri plate and animal models such as rodents and rabbits. If the medicine effectively passes the pre-clinical trials, it is tested in human subjects by randomized control trials.
Given the differences between animal models and actual human systems, it is not surprising that about 90% of all drugs that clear pre-clinical trials, either fail to be effective in clinical trials or are toxic to humans. Moreover, most marketed drugs are bulk manufactured without considering the wide spectrum of patients that are prescribed it. The drawback of today’s pharmaceutical industry to translate efficacy of drugs from bench to bedside makes it extremely likely for a disruptive technology to take the center stage in the coming years and change the way our medicines are developed.
THE DISRUPTIVE TECHNOLOGY
Additive manufacturing, or in popular terms, 3D Printing (3DP), has already revolutionized the way we produce objects- from tools, toys, clothing, food to even body parts. Generally, in this computerized technique, a digital design of a 3D structure is fabricated using a building material, layer by layer to create the object. The building material (just like ink in a regular work printer) can be plastic, metal, silicone, pharmaceutical compounds or even living cells! Computer Aided Design (CAD) is used to make the blueprint of the desired product. For this the dimensions of the object are first converted to a machine readable format. Slices of the surface are then printed as layers when the building material is loaded, giving a solid shape on a platform.
PERSONALIZED MEDICINE THROUGH 3D PRINTING
3DP has recently been used for making PPEs for healthcare workers in India. But, hang on! The use of 3DP does not end here. Now, even our medicines can be printed! Yes, you read that right. For drug manufacturing, the Active Pharmaceutical Ingredient (API), inactive ingredients (excipients) and binder solution together make the building material and gets printed as a drug of customized shape and size. Before we dive right into the manufacturing of medicines, let’s first discuss how 3DP holds the potential to replace the cumbersome pre-clinical trials.
In a number of laboratories, bioprinted tissues are being used to test the efficacy of novel drugs, bypassing the tedious and less accurate pre-clinical trial phase. For bioprinting tissues, the patient is required to donate a few of his/her own cells, which are reprogrammed to differentiate into a specific cell type. They are cultured in an incubator that mimics the environmental parameters inside human body. Next, these cells, along with biological scaffolds are printed to get the desired 3D bioprinted, living, functional tissue or even organ! In other words, bioprinted self-tissues have replaced the animal models that are not exactly similar to human cells.
Since the patient’s self-cells are used to check drug release kinetics and toxicity, the drug is expected to show similar effects when administered to the patient. Further adjustment in dosage of API and precision can be made as per the patient’s treatment needs, age, gender and co-morbidities. It is obvious that the ‘one-size-fits-all’ model is not ideal for healthcare where a broad spectrum of patients have to be treated. In all, the potential of 3D printing not just lies in its flexibility to fabricate dosage forms for personalized regimens but also in its ability to tailor drug release profiles, produce combination drugs (polypill), simplify the supply chain for rare therapeutics, extend the shelf-life and to act on a specific target location inside the body.
RISKS AND FUTURE PROSPECTS
Despite being a promising method of developing personalized, safe drugs, 3DP technology does have some manufacturing risks. These include variable layer thickness, print-head clogging, inconsistent binding between layers and friable tablet production. Subsequent control strategies need to be worked on to grow this technology further in order to shape the future of patient-centric drug delivery.
2015 marked a milestone in the pharma industry when Spritam (levetiracetam) tablets became the first 3DP FDA prescription- approved drug for epilepsy. Currently, the FDA is updating the regulations on medical product designing, encouraging further research for the advancement of this technology and promoting the use of 3DP to solve public health problems. Hopefully, in the next 5 years we will see similar disruptions in technologies with lower risk profile getting regulatory clearance and advanced technologies in the proof-of-concept stage move toward commercialization.
Further reading:
1) 3D PRINTING – 3D Printed Drugs Hold Great Potential for Personalized Medicine https://drug-dev.com/3d-printing-3d-printed-drugs-hold-great-potential-for-personalized-medicine/
2) 3D Printing in Drug Development & Emerging Health Care https://www.fda.gov/media/125479/download
Lets Interact!
Do you think 3D Printing is indeed the game changer for the pharma sector? In your opinion, what other drawbacks of today’s pharma industry need to be addressed? Leave your thoughts in the comment section and we can all learn something. Thank you for reading!
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