Frost & Sullivan releases the 'Pharmaceutical 3D Printing Industry Report', with 3D printing technology driving a paradigm shift in the pharmaceutical industry

Frost & Sullivan (Frost & Sullivan, abbreviated as 'Frost & Sullivan') continues to monitor emerging technologies in the field of drug development and production, and has officially released the 'Drug 3D Printing Industry Report'.This report is the first multi-dimensional industry analysis of drug 3D printing, providing the most comprehensive in-depth analysis at the levels of technological development, industry trends, and commercial potential. The report points out that drug 3D printing technology will advance the digitization and intelligence of the pharmaceutical industry, becoming an accelerator for modern drug research and development by pharmaceutical companies, as well as an advanced method for manufacturing drugs. Frost & Sullivan looks forward to bringing better medication options to patients through this emerging technology in the future.

This article delves into technology and industry development,Analyze the potential of 3D printing technology for revolutionizing how drugs are designed, manufactured, and used.

3D printing technology, also known as additive manufacturing technology, is a process controlled by computer programs that directly manufactures three-dimensional solids from materials such as metals, polymers, and adhesives through 'layer-by-layer printing and stacking'. Compared to traditional manufacturing techniques, 3D printing can reduce complex processes and produce objects with special shapes or complex internal structures at higher production efficiency. 3D printing technology has initially been used for producing simple plastic prototypes but has now expanded to the pharmaceutical field.

According to the classification standards of the American Society for Testing and Materials (ASTM) F42 Additive Manufacturing Technology Committee, six 3D printing technologies based on four principles—material extrusion molding, binder jetting, powder bed fusion, and photopolymerization curing—are applied in the pharmaceutical field. These six technologies are: Melt Extrusion Deposition (MED), Fused Deposition Modeling (FDM), Semi-Solid Extrusion (SSE), Powder Binding (PB), Selective Laser Sintering (SLS), and Stereolithography (SLA).

In the late 1980s, various 3D printing technologies emerged like mushrooms after rain. In 1996, Therics, the world's first drug 3D printing company, boldly attempted to introduce 3D printing technology into the traditional pharmaceutical field. In 2015, 3D printed drugs became a reality. Aprecia's antiepileptic drug Spritam received FDA approval for marketing. The drug uses 3D printing technology to create an internal porous structure that can achieve rapid disintegration, solving the clinical need for swallowing difficulties. The launch of the world's first 3D printed drug marked the recognition of this emerging technology by regulatory authorities and also sparked a wave of research on 3D printed drugs. Currently, about fifty companies and institutions around the world have entered the field of drug 3D printing, including dozens of multinational pharmaceutical companies. The report sorts out information on representative professional drug 3D printing companies, multinational pharmaceutical companies, and research institutions in terms of business direction, technical routes, equipment capacity, intellectual property rights, and regulatory registration, as shown in the following figure.

The report analyzes the literature and patents on drug 3D printing technology. Before the global launch of the first 3D-printed drug, both Therics and Aprecia developed their technologies based on powder bed fusion (PB) principles. In recent years, 3D technology based on material extrusion has become mainstream due to its ability to produce satisfactory drug appearances, design complex formulation structures, achieve precise drug release, as well as having shorter formulation development times and lower drug production costs.

The report collates the performance of 3D printing technology for six drugs in terms of print accuracy, print temperature, print materials and drug loading, print equipment, and pharmaceutical structure formulation.Among them, MED technology is universal in the field of solid preparations and has great clinical application value.

MED directly mixes and melts the powdered active ingredient and excipients, then extrudes them with high precision for layer-by-layer printing and molding to prepare a pre-designed three-dimensional structured pharmaceutical preparation.MED uses a mixing and extrusion device, which can effectively achieve the mixing, melting, and conveying of raw material powder and excipients, making continuous feeding and printing possible; precise extrusion devices enable high-precision printing; and through creative engineering techniques such as collaborative printing at multiple stations and print head arrays, it uses multi-materials to construct complex internal three-dimensional structures of drugs and achieve high-efficiency, high-throughput mass production, addressing the shortcomings of 3D printing technologies based on material extrusion forming principles like FDM and SSE in drug preparation.

MED can achieve the design of complex dosage forms and precisely control drug release.The San Diego-based company, TriDiox, has developed T19, a product utilizing MED technology, which can precisely control the timing of drug release for the treatment of rheumatoid arthritis. Patients take T19 before bedtime, and the drug concentration in their blood peaks on the morning when symptoms are most severe, alleviating joint stiffness, pain, and functional impairment after waking up. Product T21 can also precisely control the site of drug release for the treatment of ulcerative colitis, working locally within the colon to limit systemic exposure, reduce adverse reactions, and improve medication safety and efficacy.

In the historical development of the pharmaceutical industry, although processes and costs have been optimized, their lack of flexibility may not necessarily be compatible with drug development or diverse clinical needs. On the other hand, drug 3D printing has a high degree of flexibility, and its production process is digital and continuous, holding the potential to transform existing designs, manufacturing, and methods of using drugs. In terms of drug design, drug 3D printing can control the appearance shape and internal structure of drugs through the selection of printing materials, model design, and adjustment of process parameters, thereby better controlling the drug release cycle, location, and rate, and thus addressing various clinical needs. In terms of drug manufacturing, compared to traditional pharmaceutical processes, drug 3D printing has a simplified production process, requires less equipment, and can achieve on-demand production. In terms of drug use, drug 3D printing makes personalized medication possible due to its high flexibility, by individually setting dosages or customizing compound drugs for each patient, improving medication safety and compliance.

As an emerging technology, drug 3D printing technology can be applied in the field of solid dosage forms.Solid dosage forms are dominated by small molecule drugs. In recent years, the market for small molecule drugs has grown rapidly. According to Frost & Sullivan data, from 2016 to 2019, the global market size increased from $932.8 billion to $1,038 billion, and the Chinese market size increased from 722.6 billion yuan to 819 billion yuan. In 2020, the COVID-19 pandemic affected pharmaceutical distribution, resulting in a slight decline in both global and Chinese market sizes. It is expected that market sizes will continue to grow, with the global market size increasing to $1,181.3 billion by 2025 and the Chinese market size to 975.2 billion yuan by 2025.Compared to traditional solid dosage forms, 3D-printed drugs can better control drug release, improve therapeutic efficacy, reduce side effects, and lower the frequency of dosing. Currently, several 3D-printed drugs have been approved for IND (Investigational New Drug) and entered clinical trials. In the future, with the commercialization of more 3D-printed drugs, it will provide patients with better medication options and accelerate the expansion and application in the solid dosage form market dominated by small molecules.

In the pharmaceutical industry, new technologies require decades or even longer to go through trial and error, improvement, and development from discovery to clinical application. Since the establishment of the world's first drug 3D printing company in 1996, the industry has developed over more than 20 years, turning scientific hypotheses into reality with 3D printed drugs. Today, drug 3D printing, with its digital and personalized manufacturing methods, has injected new momentum and models into the development of solid dosage forms, which dominate the drug market.

Currently, companies in the drug 3D printing industry do not share the same technical path, each having its own technical preferences and developing along their respective commercial development directions. The main development directions of the drug 3D printing industry are large-scale production and personalized pharmaceuticals.

Mass production:The current drug production model has been adopted, which conforms to the current laws of drug development, registration, and commercial circulation. The company has successively developed fixed-dose pharmaceutical products, conducted drug registration, and scaled up production, supplying them to markets in various countries.

The US company Aprecia and China's Sany Dynetics are developing in this direction, truly applying 3D printing technology to the development and commercialization stages of pharmaceutical products. Aprecia has developed a large-scale production system that meets GMP requirements, capable of producing 100,000 tablets per day, and has already launched a 3D printed drug on the market. Sany Dynetics owns an automated, continuous GMP 3D printing line with an annual capacity of 50 million tablets, and two drugs, T19 and T20, have received FDA clinical trial (IND) approval. In addition, the large multinational pharmaceutical company Merck is also exploring large-scale production, initiating a drug 3D printing innovation project. Currently, they produce clinical trial drugs using 3D printing technology and plan to use it for large-scale production in the future.Data prediction in clinical Phase I-III has reduced preparation time by 60%, and the raw materials required for drug preparation have been reduced by 50%.

Personalized medicine:Due to the flexibility of 3D printing technology in adjusting drug dosages, combinations, and production methods, customized drug manufacturing can be carried out based on individual patient needs, genetic characteristics, disease status, gender, and age.

FabRx, a professional company in drug 3D printing, is at the forefront of personalized medicine. It has researched various technologies suitable for drug 3D printing, including FDM, SLS, SLA, SSE, and Direct Powder Extrusion (DPE). FabRx has previously prepared personalized drugs for children with maple syrup urine disease, and research clinical trial results show that it can better control the blood levels of leucine, isoleucine, and valine in patients, while also having a high acceptance rate among patients for its taste and color. Currently, FabRx has partnered with the Gustave Roussy Cancer Center in France to develop personalized drugs for the treatment of early breast cancer.

Drug 3D printing is the most visible next-generation technology capable of transforming drug manufacturing, but it still faces significant challenges in development and application.In terms of technology development, although there are currently various commercial 3D printers on the market, most are difficult to directly 'transfer' to pharmaceutical applications. It is necessary to start from scratch, developing specialized equipment to meet pharmaceutical requirements and drug regulations. Additionally, research on excipients is needed for pharmaceutical process and dosage form design, as well as in vivo and in vitro studies and validation of the release mechanisms of new three-dimensional structure drug formulations. The overall development of technology is challenging, requiring a high level of personnel expertise and the collaborative efforts of professionals from engineering, materials science, pharmacy, and other disciplines.

In terms of technological applications, since 3D printing drugs uses entirely new pharmaceutical technologies, for drug 3D printing companies, it is necessary to navigate regulatory pathways in specific countries to ensure the future commercialization of their products. Regulatory authorities need to adapt and accept 3D printing as a method of drug manufacturing and prepare for the changes brought about by the new technology. The continuous and digitalization of the drug 3D printing production process is a direction of industrial reform promoted by regulatory authorities around the world. In 2017, the FDA issued an industry guide to promote the use of emerging technologies for pharmaceutical innovation, with 3D printing drugs being one of the strategic directions. In 2022, China's CDE accepted an IND application for the T19 product from Dynacere, focusing on the application of 3D printing in the pharmaceutical industry.

Drug 3D printing technology will accelerate its gradual improvement and wide application.After years of technical accumulation, a leading company in the field of drug 3D printing has emerged. It possesses interdisciplinary talents and the capability for independent research and development as well as production. The top companies, multinational pharmaceutical enterprises, startups, and research institutions in the field of drug 3D printing will find their respective positions based on their strengths, construct a new ecosystem, and explore more scenarios for research and development, production, and commercial applications through cooperation. They aim to accelerate the gradual improvement and widespread application of new technologies.

Drug 3D printing will achieve commercialization earlier in the direction of large-scale production.Drug 3D printing has shown tremendous commercial potential in both large-scale production and personalized medicine. In the direction of large-scale production, a 3D-printed drug has been approved for market release with clear regulatory registration pathways. However, personalized medicine requires overcoming greater regulatory obstacles and changing the system of drug commercial distribution. Currently, regulatory departments in the United States and Europe are actively exploring guiding principles for personalized medicine through cooperation with pharmaceutical companies, helping new technologies address different clinical needs arising from individual differences among patients. It is expected that the era of personalized medicine will arrive within the next 10 to 20 years. Overall, drug 3D printing will achieve commercialization earlier in the direction of large-scale production.

Drug 3D printing will propel the pharmaceutical industry into a new era of intelligent drug developmentDrug 3D printing is a digital production technology based on computer models, which has laid the foundation for digital pharmaceutical manufacturing. It is more easily combined with advanced information technologies such as big data, artificial intelligence, and the Internet of Things, as well as precise online physical and chemical testing technologies, to be used in drug production processes and quality management. The large amount of process and testing data generated during the research, development, and production of 3D printed drugs can be fed back into and optimized using the models and algorithms established in technology development, thereby realizing intelligent pharmaceutical manufacturing.

Aprecia:Founded in 2003, as one of the pioneers in the field of 3D printed drugs, ZipDose Pharmaceuticals developed the technology based on powder-bonded 3D printing. The anti-epileptic drug product Spritam (levetiracetam) was approved by the FDA for marketing in 2015 as the world's first 3D printed drug, sparking a research boom in 3D printed drugs. However, due to the abundance of commercial competitors for the active ingredient levetiracetam, its market response was mediocre. Subsequently, Aprecia transformed into a pharmaceutical formulation technology platform company based on its technical advantages, focusing on new drug product collaboration and development and production in its business model. It engages in global commercial cooperation with large multinational pharmaceutical companies and biotechnology firms.

Triassic:Founded in 2015 by Dr. Cheng Senping, who has entrepreneurial experience in both China and the United States, and Professor Xiaoling Li, an expert and educator in the US formulation industry, it is a global leader in the field of 3D printed drugs. Stryker pioneered the MED technology globally, developing a proprietary 3D printing technology platform that covers the entire chain from drug formulation design, digital product development to intelligent pharmaceutical manufacturing. It possesses the richest 3D printing product pipeline in the world, with four 3D printed drugs either in clinical trials or having completed registration applications globally, three of which come from Stryker. Stryker is also the only Chinese pharmaceutical company selected for the US FDA's Emerging Technology Program and is participating in formulating industry standards for 3D printed drugs in the US Pharmacopeia.

After years of technical development, Stryker has become the organization with the most complete patent layout and the largest number of applications in the global field of drug 3D printing.The patent application covers three major categories: drug three-dimensional structure dosage form design, proprietary 3D printing equipment for drugs, and digital drug development methods using 3D printing. It has 156 patent applications, 22 patent families, and 38 authorized patents. The core patents are distributed in 10 countries and regions including China, the United States, Europe, etc.

FabRx:Founded in 2014 by two professors from University College London (UCL), Abdul Basit and Simon Gaisford, FabRx is one of the most active companies in the field of 3D printed drugs. FabRx has comprehensively explored and researched various technologies suitable for drug 3D printing: FDM technology, SLA technology, SLS technology, SSE technology, DPE technology. FabRx has clearly defined its commercial direction as personalized dosing, developing desktop 3D printers M3DIMAKER and software M3DISEEN. FabRx's newly developed Direct Powder Extrusion (DPE) technology can quickly and flexibly prepare a variety of drug dosage forms, making it better suited for personalized pharmaceutical scenarios.

Multiply Labs:Founded in 2016 by engineers from MIT and pharmaceutical scientists from the University of Milan, it is a startup located in South San Francisco, USA. Multiply Labs prepares personalized drug formulations through a two-step process. The first step involves printing capsules with compartments and adjustable compartment sizes using FDM technology. By designing the wire material and capsule compartments, it is possible to delay drug release time, achieving the effect of taking one dose and having the drug take effect at multiple points in time. The second step uses an automated filling production line to fill the capsule shells with drugs or nutrients. To improve patient compliance, multiple drugs are placed in different chambers within a single capsule formulation to achieve the effect of compound prescriptions.