With advancements in 3D printing technology, material, and formulation developments, There is a definite increase in the number of research publications [Figure 1] and startups in the space. The intrinsic advantages of additive manufacturing include mass customization and complexity for free are empowering pharmaceutical professions in creating innovative solutions. According to one report, “The potential market for other 3D printed drugs (moderate growth scenario) is estimated to be $278 million in 2020, and would reach $522 million by 2030, growing at a CAGR of 6.5% from 2020 to 2030.” Spritam by Aprecia, a seizure medication with a quick-release profile, remains to be the only FDA-approved 3D printed medication in 2015, but more newcomers are successfully challenging the regulatory barriers. For example, very recently, Chinese startup Triastek has received Investigational New Drug (IND) approval from the US Food and Drug Administration (FDA) for its first 3D printed drug product, T19, a medication for rheumatoid arthritis. Upcoming European/UK regulatory update on point of care 3D printing may potentially enable widespread adoption of 3D printing in extemporaneously compounded medications per Anna Worsley from FabRx in a recent 3DHEALS conference focusing on the same subject.
In this guide, we will address the major questions related to 3D-printed drugs. This guide does not include discussion related to other 3D printed drug delivery medical devices. The following main questions will be addressed:
- What additive manufacturing process has been used to 3D print pharmaceuticals?
- Which are the major additive manufacturing applications of 3D printed drugs?
- How can 3D printed drugs benefit patients?
- Some of the major technical challenges facing the industry
- What are the key regulatory questions and challenges facing the industry?
- What are the main financial challenges facing the industry?
- Who are the major players in the space?
- What are some of the latest industrial trends?
Figure 1. Number of publications focusing on “3D printed drugs” by year
Which additive manufacturing process has been used to 3D print pharmaceuticals?
There are about seven major manufacturing processes that are used in 3D printed pharmaceuticals. Startups working in the area are indicated next to the process types below:
- Vat Photopolymerization
- Material Jetting
- Binder Jetting – Aprecia
- Powder bed fusion
- SLS-FabRx, Sinterit
- Material Extrusion:
- FDM (Fused Deposition Modeling) – FabRx, CraftHealth
- DPE (Direct Powder Extrusion) – FabRx
- MED (Melt Extrusion Deposition) – Triastek
- SSE (Semisolid Extrusion) – FabRx
- Direct Energy Deposition
- Sheet Lamination
What are the major applications of 3D printed drugs?
The markedly increased freedom in design in 3D printed tablets allows more customizations in many different aspects of existing pharmaceuticals. Here we list some of the major applications and potential markets as the following:
- Well-controlled complex release profile by design. This is largely affected by complexity in geometry according to professor XiaoLing Li (Triastek) during the 3DHEALS conference.
- Pattern (e.g. Braille, data matrix)
- Different formulations (e.g. chewable tablets)
How can 3D printed drugs (potentially) benefit patients?
- Personalization of tablets with unique release profiles that fit a patient’s unique biometrics (i.e. weight, size, metabolism, renal function, etc.)
- Improved compliance – For example, better flavor, color, and texture for pediatric patients
- Decentralized drug delivery process – For example, researchers at FabRx recently published a paper demonstrating a smartphone based 3D printing process that can allow patients to create variable tablets fitting their treatments at home.
- Significant reduction in formulation development time
- Reducing batch manufacturing cost
- Revival of some abandoned drugs due to small target market
- “Endless (design) possibilities”
Some of the major technical challenges facing the industry:
As with any emerging technologies in healthcare, there are quite a few challenges before the industry can be well-adopted and scaled. These are identified as some of the major challenges:
- Lack of materials selection that is 3D printable and safe in 3D printed drugs
- Lack of knowledge in matching 3D printing processes and APIs (Active Pharmaceutical Ingredients). For example, it is hard to 3D print insoluble APIs, although some startups are tackling this challenge by creating compartments that can contain the insoluble components.
- Lack of longer term clinical validations
- Inability to scale to the same level as conventional mass manufacturing methods
- Lack of well defined quality control process
What are the key regulatory questions and challenges facing the industry?
While FDA-approved 3D printed drugs are currently scant as pointed out at the beginning of this article, the uptick in research activities [Figure 1] ensures more commercialization in the space. In fact, the FDA CDER (Center for Drug Evaluation and Research) already has dedicated resources in the space, indicating a more clarifying future drug approval process.
The top questions FDA wanted to address also parallel the top regulatory challenges. Drug and equipment developers should pay close attention to the following technical questions:
- What are the critical parameters affecting the printability of various materials into drug products?
- What are the critical process parameters for each 3D printing technology?
- How can we assess the performance of 3D printed drug products?
- Can we use traditional in vitro testing methods for 3D printed drug products?
- How can we determine when and how a certain 3D geometric design may not perform as it should?
- What are the critical characteristics of the intermediate products for 3D printing, such as 3D printing inkjets, filaments, substrates and cartridges?
- What are the critical factors in 3D-printed design that affect the drug release rates and mechanisms?
Additional regulatory challenges from the FDA perspective also include the following:
- 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.
- What are some of the best ways to approach existing questions, while understanding that the technology is changing rapidly.
Some of the main financial challenges facing the industry:
- Extemporaneously compounding may not be a profitable enough business model for technology startups to survive.
- Larger pharmaceutical players are still hesitant in adaptation. Partly, this is because the 3D printed drug industry is still early with many technical and regulatory challenges mentioned above.
Who are the major players in space?
- Researchers (complete list to come)
- Startups – (Updated version of this group can be found in 3DHEALS Company Directory)
What are some of the latest industrial trends?
- Holistic innovation process – Almost all the companies at the recent 3DHEALS conference described a holistic approach to scale up their technologies. These include:
- Software/Database innovation
- Heavy reliability on existing materials, design database
- Artificial intelligence and machine learning in future formulation development
- Software development:
- FabRx in fact has a currently free software researchers can try out: https://m3diseen.com/predictions/
- Many companies have dedicated software targeting both formulation development and manufacturing process.
- Design to scale up manufacturing using other emerging technologies such as robotics and automation to achieve continuous manufacturing processes.
- Software/Database innovation
- Orphan drug – Given current limitations in mass quantity production, most companies are now focusing on orphan drugs which could be a perfect economical fit.
- Nutrition – While personalized nutrition has been a past innovation target in the space, with the advancements in 3D printing technologies and digital health at large, the chance of succeeding in the space economically is potentially higher.
- More decentralized delivery – For example, patients can create personalized tablets at home with a smartphone as described earlier in this article.