The curtain of pharmaceutical industry 4.0 opens: one article to understand 3D printing of drugs

Author: Yu

The development and production of drugs is a rigorous and long process, and its technological progress and iteration are very slow.

In 2015, the world's first 3D printing drug was approved by the U.

Overview of 3D printing technology

3D printing technology (Three Dimension Printing, 3DP) is also known as additive manufacturing technology (Additive Manufacturing, AM).

3D printing technology has been widely used in the fields of machinery manufacturing, aerospace, construction engineering, medical engineering and jewelry.

Pharmaceutical 3D printing technology

Pharmaceutical 3D printing is an emerging technology field in recent years.

Table 1 Technical characteristics and applicable dosage forms of drug 3D printing

Note: The full English name and abbreviation of pharmaceutical 3D printing technology: Fused Deposition Modeling (FDM), Melt Extrusion Deposition (MED), Direct Powder Extrusion (DPE), Melt Drop Injection molding (Melt Drop Deposition, MDD), semi-solid extrusion (Semi-Solid Extrusion, SSE), drop-on-demand (DOD), powder binding (Powder Binding, PB), optional Laser sintering (Selective Laser Sintering, SLS), light curing molding (Stereolithography, SLA).

Figure 1 Schematic diagram of part of the 3D printing technology used in pharmaceuticals

1.

Thanks to good micro-control and spatial design capabilities, material extrusion molding technology can achieve control of drug release by constructing complex geometric shapes and internal three-dimensional structures.

As one of the most popular 3D printing technologies, Fused Deposition Modeling (FDM) is widely used in pharmaceutical 3D printing research due to its low equipment cost and flexible operation, but it also exposes many shortcomings.

1) Few optional materials.

2) Long prescription development time.

3) It is not conducive to continuous and large-scale production.

4) The medicine printing accuracy is poor.

5) It is difficult to realize complex internal structure of preparations using commercial FDM printers.

These shortcomings hinder the real application of FDM technology to the development and commercial production of preparations.

Also based on the principle of material extrusion, in order to be better applicable to pharmaceuticals, three new 3D printing technologies, namely hot melt extrusion deposition (MED), direct powder extrusion (DPE) and melt drip injection molding (MDD), came into being.

Compared with FDM, Direct Powder Extrusion (DPE) and Melt Drop Injection Molding (MDD) use powdered raw materials to reduce the restrictions on material selection, and at the same time avoid the tedious process of drug-containing wire prescription development.
Direct powder extrusion (DPE) can print tablets with only 8 grams of powder, which fully reflects the flexibility of 3D printing in on-demand production.
However, direct powder extrusion (DPE) and melt drip molding (MDD) technologies require pre-mixing of pharmaceutical raw materials and excipients through pre-processing steps such as grinding, crushing or granulation, and it is difficult to achieve continuous production.
Melt drip molding (MDD) also has the problems of difficulty in cleaning and mass production.
In terms of printing accuracy, these two drug 3D printing technologies are equivalent to FDM, and the quality deviations of the reported drug printing are mostly above ±10%.
The Hot Melt Extrusion Deposition (MED) technology is tailor-made for applications in the pharmaceutical field according to the characteristics of polymer pharmaceutical excipients.
In engineering, the equipment is designed and developed completely in accordance with the MED process.

Figure 2 MED 3D printing principle diagram

As shown in Figure 2, MED 3D printing can directly mix and melt powdered raw and auxiliary materials into a flowable semi-solid.
Through a precise extrusion mechanism and accurate control of the temperature and pressure of the material, the medicated melt can be High-precision extrusion, layer-by-layer printing and molding, prepared into a pre-designed three-dimensional structure pharmaceutical preparation.
There is no need to prepare wires and no secondary heating during the whole process.
Moreover, the advantage over direct powder extrusion (DPE) and melt drip molding (MDD) is that MED uses a mixing and extrusion device, which can effectively achieve the mixing, melting and conveying of raw materials and auxiliary powders, which is a continuous process.
Material and printing provide the possibility.
The unique precision extrusion device can achieve high-precision printing and control the tablet quality deviation below ±1%.
Multiple printing stations (corresponding to a variety of different materials) collaborative printing and print head arrays and other creative engineering techniques have realized the use of multiple materials to build complex internal three-dimensional structures of drugs, as well as high-efficiency and high-throughput scale The production solves all the shortcomings of the aforementioned 3D printing technology in the preparation of drugs with the principle of extrusion of several materials.
So far, MED is the most universal and clinically valuable 3D printing drug technology in the field of solid preparations.

2.
Adhesive injection molding

Binder injection molding technology is represented by powder-bonded printing (PB).
It is the first 3D printing technology to be applied to the pharmaceutical field and has been successfully industrialized.
There is no heating in the powder bonding production process, which can be used to prepare drugs with poor thermal stability and can achieve very high drug loading.
It is especially suitable for high-dose, fast-acting drugs for the treatment of central nervous system diseases.
The powder-bonded printed tablets have a loose and porous internal structure and quickly disintegrate within a few seconds after encountering water, which helps to improve the medication compliance of elderly patients and children with swallowing difficulties.

However, limited by the principle of powder bonding, it still has many defects in drug release and product production.
Only single-component materials can be used, and there is no flexibility in product design, making it difficult to achieve complex drug release or drug compounding.
In the process, it is necessary to prefabricate mixed powders of drugs and excipients with uniform distribution and good fluidity.
The dust control is difficult and the procedures are complicated.
After the production is completed, powder removal and powder recovery are required, and the tablets are dried.
Because the tablets are glued and formed by adhesives, the inside is porous, the appearance of the tablets is rough and easily broken, the packaging requirements are high, and it is not convenient to transport.

3.
Powder bed melt molding

The powder bed melt molding technology that can be used to prepare drugs is mainly selective laser sintering (SLS).
Similar to powder-bonded 3D printing, selective laser sintering (SLS) requires prefabricated powder containing drugs and laser absorbers in the process, and powder removal and powder recovery in the later stage, which have similar challenges to powder bonding.
SLS does not have flexibility in the design of the internal three-dimensional structure of pharmaceutical preparations, but the laser scanning speed can affect the melting degree of the drug-containing powder after absorbing the light energy, and then affect the compactness of the printed tablets.
This method can be used to a certain extent.
Realize the control of the drug release rate.
At present, most SLS printers used in pharmaceutical 3D printing are single laser beams.
The process of point-by-point melting and layer-by-layer stacking limits the application of SLS in the mass production of drugs.

4.
Material injection molding

On-demand inkjet printing (DOD) is the main material injection molding technology used for pharmaceutical 3D printing, which can eject tiny droplets at high frequency onto the printing platform or the carrier structure for accumulation and forming.
Drop-on-demand inkjet printing (DOD) can be used to prepare lipid delivery systems to improve the solubility and oral bioavailability of drugs.
It can also be used for the production of very low-dose drugs that are difficult in traditional pharmaceutical processes.
However, it has certain restrictions on the choice of materials, and generally only low-viscosity pharmaceutical excipients can be used.
Limited by the printing principle, drop-on-demand inkjet printing is slower, which limits its further application in 3D printing medicines.
This defect is expected to be improved in the future through array inkjet printing.

5.
Light polymerization curing technology

Light curing molding (SLA) also has a few cases of exploratory research applied to 3D printing drugs.
The monomers of most photopolymer resins are toxic and need to be separated from the tablets and cleaned up after printing.
Moreover, the types of photopolymerizable resins that can be used as pharmaceutical excipients are very limited.
At the same time, the free radicals generated by the photopolymerization reaction easily react with drugs.
These shortcomings all limit the application of this technology to 3D printing pharmaceuticals.

Research and development status of global pharmaceutical 3D printing technology

In 1996, the application of MIT's powder-bonded 3D printing technology (PB) in the pharmaceutical field was licensed to Therics, a New Jersey company, and the world's first 3D printing pharmaceutical company was born.
Based on the technical principle of powder bonding, Therics started to develop the drug 3D printing technology TheriForm.
Because of the high difficulty and long cycle of technology development, Therics did not succeed in realizing the industrialization of PB in the pharmaceutical industry.

In 2003, Aprecia, a 3D printing pharmaceutical company, was established, and they re-licensed the right to use PB technology for pharmaceuticals.
Based on the principle of PB technology, Aprecia has successfully developed ZipDose pharmaceutical technology that can be mass-produced after nearly 10 years.
On July 31, 2015, Aprecia's first 3D printing drug product, Spritam, developed using ZipDose technology, was approved by the US FDA, marking that 3D printing has been recognized as an emerging pharmaceutical technology by US regulatory agencies, and it has also set off a round of 3D printing.
The upsurge of drug research.

The Emerging Technology Team (ETT) established by the FDA in 2014 to help and encourage the pharmaceutical industry to implement innovative technologies also participated in product approval, ensuring the smooth approval of Spritam products using new pharmaceutical technologies.

Although in theory there are many 3D printing technologies that can be used in pharmaceuticals, each principle requires the development of special technologies to meet pharmaceutical requirements and pharmaceutical regulations.
The process of special technology development involves multiple links, including the complete machine design and manufacturing of special 3D printed pharmaceutical equipment, research on excipients for pharmaceutical technology and drug dosage form design, and in vivo and in vitro research on the release mechanism of drug three-dimensional structure dosage forms.
verification.
Therefore, the development of special technology requires the cooperation of talents in many professional disciplines such as engineering, materials science and pharmacy.
In each technical direction, the preliminary research results that these disciplines can really learn from are very limited, and it is necessary to build a scientific research system from the ground up, carry out systematic research work and technological development, and through the collaboration between disciplines and each discipline The phased research results obtained can influence each other and promote the progress and maturity of technology.
The process of industrialization of proprietary technology will also involve the large-scale production of 3D printing technology, which is in the early stage of exploration in the entire 3D printing field, and there is no mature model to learn from.
After the development of the proprietary technology is mature, it is necessary to cooperate with the regulatory department through the registration and application of the product to jointly formulate regulations and guidelines for the new technology.

Although the pharmaceutical 3D printing field is facing a blue ocean market of solid preparations of hundreds of billions of dollars, the development and industrialization of proprietary technologies require a lot of time and capital, and it also requires strong innovation and creativity, as well as a leader in the field.
A type of enterprise to follow the path of technology development, product development, and regulatory registration, and achieve commercial success.
At present, the global 3D printing pharmaceutical industry is still in its infancy.
From the perspective of the global pattern of 3D printing drugs (Figure 3), 3D printing drug companies and active research institutions are mainly distributed in Europe, the United States and China.
According to the technology maturity and application direction, they can be divided into commercial development of drug products and personalized medicine.
Three categories of medicine and early concept research.

Figure 3 The global pattern of 3D printing drugs

1.
Commercial development of pharmaceutical 3D printing products

Globally, there are only two companies that apply 3D printing technology to the commercial development of pharmaceutical products, Aprecia in the United States and Triassic in China, both of which are specialized companies in 3D printing drugs.
Two large multinational pharmaceutical companies, Merck & Co.
and Merck, Germany, are also exploring in this direction.

Table 2 Companies in the commercial development direction of 3D printed pharmaceutical products

1) Aprecia

As one of the pioneers in the field of 3D printing medicine, Aprecia established the goal of applying advanced 3D printing medicine technology to the development of pharmaceutical products and realizing commercial production since its establishment in 2003.
In 2007, Aprecia developed the prototype of ZipDose pharmaceutical technology based on the powder-bonded 3D printing technology (PB) of the Massachusetts Institute of Technology.
In the next 4-5 years, Aprecia developed this technology and developed a scale that meets GMP requirements.
The drug production system has realized the production of 100,000 tablets/day.
After the first anti-epileptic drug product Spritam (levetiracetam) was approved for marketing in 2015, although it has set off a research boom in 3D printing drugs, because the active drug ingredient levetiracetam has more commercial competitors, The response in the market was mediocre.
After that, Aprecia transformed into a pharmaceutical preparation technology platform company based on its own technological advantages, focusing on the cooperative development and production of new drug products in its business model, and carried out global business cooperation with large multinational pharmaceutical companies and biotechnology companies.

In terms of technology, Aprecia is seeking further breakthroughs by developing a new generation of ZipDose 3D printing technology for In-Cavity Printing (In-Cavity Printing) to enhance the flexibility of product design and production, and to improve the flexibility of product design and production before printing.
The "pre-processing" of the coating has created the possibility for the development and production of sustained and controlled release drugs.
In terms of equipment, Aprecia has developed a series of GMP 3D printing equipment with different capacities based on the principle of Zipdose, which can be used for the early development of pharmaceutical products and the on-demand production of orphan drug products.
At the end of 2020, Aprecia and Oak Ridge National Laboratory of the United States reached a long-term strategic cooperation, hoping to realize the upgrade of ZipDose 3D printing production equipment through cooperation, and further expand the application of ZipDose technology in the field of pharmaceutical 3D printing.

2) Triastek

Nanjing Triastek Pharmaceutical Technology Co.
, Ltd.
(hereinafter referred to as "Triastek", English name Triastek) was established in Nanjing, China in July 2015.
Co-founded by Dr.
Li Xiaoling.
Sandieji is committed to building a new 3D printing drug technology platform.
It pioneered the world's first MED 3D printing drug technology, and developed a proprietary 3D printing technology platform from drug formulation design, digital product development, to the entire chain of smart pharmaceuticals.
This emerging technology has overturned the development and production methods of traditional solid preparations, as well as drug delivery methods.

Through the unique internal three-dimensional structure design of the drug formulation, MED can accurately realize the programmed control of the drug release time, location and rate, and can also flexibly combine the drug release methods, which can solve the problems that cannot be solved by the existing formulation technology.
Various clinical needs provide a wealth of product design methods.
The pioneering "Formulation by Design (3DFbD)" digital formulation development method has revolutionized the traditional trial-and-error formulation development method, which can greatly improve the efficiency and success rate of new drug product development, and reduce development time and cost.
The continuous and intelligent MED 3D printing drug production line developed by Triassic, the preparation is produced at one time, and the quality is controlled in real time through process analysis technology (PAT), which is significantly better than traditional preparations in terms of product quality and production cost.
The digital production process will change the production management mode of pharmaceutical companies and the supervision of laws and regulations.

In April 2020, the MED 3D printing technology was established in the US FDA Emerging Technology Group (ETT).
ETT believes that this is a brand-new controlled release solid preparation production method, and is concerned with this fully automated integrated process analysis technology (PAT) And the process innovation of feedback control is highly recognized.
In January 2021, T19, the first drug product developed by Triassic using MED 3D printing technology, was approved by the US FDA for New Drug Clinical Approval (IND).
This product is the second 3D printed drug product in the world to submit an IND to the US FDA.
China's first 3D printed pharmaceutical product to enter the registration application stage.
This is a major breakthrough in 3D printing technology in the global pharmaceutical field.

Triassic changed the situation where 3D printing mother technology and patents were concentrated in European and American countries.
After five years of technological development, Tridecium has become the institution with the most complete patent layout and the largest number of applications in the field of 3D printing drugs in the world.
Patent applications cover 113 patent applications in 19 patent families in 3 categories, 3D-printed drug-specific equipment and 3D-printed digital drug development methods, including three-dimensional structure and dosage form design of drugs.
The core patents are in major pharmaceutical market countries such as China, the United States, Europe, and Japan.
There is a layout.

In addition to Aprecia and Triassic, Merck KGaA (Merck, Germany) and Merck (Merck & Co.
, USA) have also begun to lay out and try to use 3D printing technology to develop commercial drug products.
Currently, both companies are using 3D printing technology to accelerate The early stage of drug product development.

3) Merck KGaA (Merck, Germany)

Merck KGaA (Germany Merck) announced in February 2020 that it plans to use powder bed fusion 3D printing technology to develop and produce drugs for clinical trials, and cooperate with the world’s largest selective laser sintering (SLS) 3D printing equipment manufacturer, German EOS Its AMCM has signed a cooperation agreement to develop large-scale pharmaceutical 3D printing equipment for commercial production, and it is estimated that it can achieve a production capacity of 100,000 pieces/day in the future.
Compared with traditional pharmaceutical technology, Merck believes that 3D printing technology can provide a fast and flexible method to produce drug formulations with different ingredients, dosages or release characteristics.
A simple production process can make tablet manufacturing faster and cheaper, not only It can speed up the research and development of new drug products, and can also effectively save the consumption of expensive raw materials in the prescription development stage.

On the other hand, the pharmaceutical excipient company of Merck, Germany, also used FDM 3D printing to study the release behavior of the pharmaceutical excipients for the preparation of wires and the drug loading, and based on Arburg Plastic Freeforming (Arburg Plastic Freeforming, APF) technology developed Melt Drop Injection Molding (MDD) technology, but they are all in the early stage of exploration.

4) Merck (Mersk, USA)

Merck (Mersk & Co.
, USA) chose to use FDM technology as a tool to accelerate the early development of new drug products with drug release requirements.
Through the combination of FDM and perfusion printing, they quickly prepared small batches of drug dosage forms with different drug release characteristics, and screened out prototypes of drug dosage forms with ideal drug-time curves from early clinical trials, but in the mid- to late-stage clinical and commercial production stages , Merck still uses traditional pharmaceutical technology for production.

2.
3D printing personalized pharmacy

In addition to being used for drug product development and large-scale production, the flexibility of 3D printing technology in adjusting drug dosages, drug combinations and production methods makes it very suitable for personalized pharmaceuticals.
It is based on the individual needs of patients, genetic characteristics, and disease states.
Customized production of drugs based on gender, gender, and age provides the possibility.
Patients can customize the dosage of the drugs in the tablets according to their actual needs to reduce individual side effects caused by excessive intake of doses.
A variety of drugs that patients need to take can also be customized into a single tablet through 3D printing, avoiding missed and mistaken intakes, and improving medication compliance.
3D printing technology can also achieve personalized customization of appearance and taste, especially in children's medication.
It can improve the compliance of children patients by printing tablets of personalized shapes, colors and flavors.

In the direction of 3D printing personalized medicine, the main participants are the large multinational pharmaceutical company AstraZeneca (AstraZeneca, UK), the independent research institution TNO, and three professional 3D printing drug companies FabRx, Multiply Labs and DiHeSys.
The main business application scenario is for hospital pharmacies and outpatient clinics, instant printing of personalized tablets, providing a fast and automated choice for personalized therapeutic doses.

1) FabRx

FabRx was founded in 2014 by two professors Abdul Basit and Simon Gaisford from University College London (UCL), and is one of the most active companies in the field of 3D printing medicines.
Since its establishment, they have explored and researched various 3D printing drug technologies, including fused deposition modeling (FDM), light curing (SLA), selective laser sintering (SLS) and semi-solid extrusion (SSE), and published 3D printing drugs There are more than 40 related academic articles and a professional book named "3D Printing of Pharmaceuticals" has been published.
For personalized drug delivery, FabRx has developed a desktop 3D printer M3DIMAKER and software M3DISEEN, and conducted a clinical trial for children in a hospital in Santiago de Compostela, Spain in September 2019, for children with a rare metabolic disorder-Maple Diabetes (MSUD) Prepared personalized drug dosage forms.
FabRx's newly developed direct powder extrusion (DPE) technology can quickly and flexibly prepare a variety of pharmaceutical dosage forms, which can be better applied to personalized pharmaceutical scenarios, and may also be applied to accelerate the early development of pharmaceutical products in the future.

2) TNO

The Netherlands Organization for Applied Scientific Research (TNO) is an independent research institution established by the Dutch national government in 1932.
It has a deep technical accumulation in the direction of multi-material composite printing and high-speed printing.
In recent years, TNO has begun to enter the field of 3D printing food and medicine, and has conducted extensive research and exploration in this field using 3D printing technologies such as FDM, SLS, and PB.
Similar to FabRx, TNO's research on 3D printed drugs is mainly focused on personalized medicine and the use of 3D printing to accelerate the early development of drug products.
They developed a printer based on the principles of FDM, SLS and PB for 3D printing of medicines.
They also combined 3D printing technology with the InTESTine test platform, which can simulate the functions of different parts of the human digestive system in vitro, to study how to improve the oral bioavailability of drugs through 3D printing technology.

3) AstraZeneca

In 2019, AstraZeneca (AstraZeneca) announced that it will cooperate with the global industrial inkjet technology leader Xaar and 3D printing equipment company Added Scientific to explore the industrial production of clinical personalized medicines through inkjet 3D printing technology The feasibility.

Multiply Labs and DiHeSys are mainly committed to using FDM technology to develop personalized pharmaceutical production equipment, and to realize the terminal application of 3D printing technology in the preparation of personalized medicines.

4) Multiply Labs

Multiply Labs is a start-up company located in South San Francisco, USA.
It was established in 2016 by engineers from the Massachusetts Institute of Technology and pharmaceutical scientists from the University of Milan.
Multiply Labs specializes in personalized medicines and nutrients, and prepares personalized medicine dosage forms through a three-step method.
The first step uses FDM to print capsule shells with different thicknesses, and adjusts the time and location of drug release by changing the material and thickness of the capsule shell; The second step is to make a capsule mold based on the parameters obtained in the first step, and mass-produce the capsule shell by injection molding (IM); the third step uses an automated filling production line to fill the capsule shell with drugs or nutrients.
Different drugs can be placed in different chambers of the same capsule to achieve compound prescription, thereby improving patient compliance.

5) DiHeSys

The start-up company DiHeSys Digital Health Systems was established in Germany in 2018.
The company's main business is personalized pharmacy for hospital pharmacies and outpatient clinics.
It mainly uses FDM technology to print and prepare multi-layer tablets containing multiple drugs.
The company plans to conduct personalized drug delivery clinical trials in European hospitals in the first quarter of 2021.
The company also develops and produces 2D/3D printers, components and related software for sales.
In a new patent published by DiHeSys in December 2020, it demonstrated a concept of preparing a sustained and controlled release drug dosage form by inkjet printing of splicable drug units, indicating that the company will also be in the direction of inkjet printing pharmaceuticals in the next step.
To explore.

Compared with the development and production of commercialized products of 3D printing drugs, the integration of 3D printing technology into personalized medicine is facing more challenges and a longer implementation cycle.
However, the extremely high flexibility of 3D printing and the ability of on-demand production make it have great potential in personalized medicine, and it is also one of the development directions of future pharmaceuticals.
In addition to major breakthroughs in regulations and supervision, 3D printed personalized medicines also need to be regulated from multiple links such as pharmaceutical materials, pharmaceutical processes, quality management, and drug sales to ensure the safety of 3D printed personalized medicines.

3.
Early concept research on 3D printing of drugs

At present, most institutions in the global pharmaceutical 3D printing field are in the early concept research stage.
Large multinational pharmaceutical companies such as Bayer, GlaxoSmithKline and Pfizer mainly conduct global intelligence research by setting up inter-departmental virtual 3D printing teams, internally using commercial 3D printers for preliminary research, and externally and scientific research institutions for subject research and publication of papers.
University research institutions include the Roberts CJ research group of the University of Nottingham in the UK, the Alhnan MA research group of the University of Central Lancashire in the UK, and the Repka MA research group of the University of Mississippi in the US.
The research topics are basically concentrated in 1 or 2 3D printing technology fields.
All are in the conceptual stage.
The University of Nottingham owns the British National Additive Manufacturing Center.
The research of its Roberts CJ research group is mainly focused on the use of semi-solid extrusion (SSE) and drop-on-demand inkjet printing (DOD) to develop slow and controlled release 3D printing pharmaceutical dosage forms, and cooperate with Gülen.
Su Shi Ke jointly published related research results.
The research directions of the Alhnan MA research group at the University of Central Lancashire and the Repka MA research group at the University of Mississippi are mainly focused on the use of FDM combined with hot melt extrusion (HME) to prepare 3D printed drugs.

The development trend of the pharmaceutical 3D printing industry

1.
Drug 3D printing will become a hot spot in the pharmaceutical industry due to its fast, flexible and precise controlled release characteristics.

After years of technology accumulation, leading companies in the field of pharmaceutical 3D printing have emerged.
Compared with the traditional pharmaceutical process, the 3D printing technology of medicine shows significant technical advantages in clinical product design, accelerated drug development and advanced manufacturing.
These new technology companies pass the road of regulatory registration through their products, which will attract many traditional pharmaceutical companies to use such emerging technologies to develop and produce drugs.
Through technical cooperation with traditional pharmaceutical companies, pharmaceutical 3D printing companies will jointly explore more scenarios for R&D, production and commercial applications, and accelerate the improvement and widespread use of new technologies.

2.
Pharmaceutical 3D printing has shown broad application prospects in both large-scale production and personalized medicine, and its commercial potential is huge.

Because personalized medicine needs to break through greater regulatory barriers and at the same time change the system of drug commercial circulation, it can be predicted that large-scale drug 3D printing will first achieve commercial success.
European and American regulatory agencies are cooperating with pharmaceutical companies to actively explore the guiding principles of personalized medicine, and help new technologies to solve the different clinical needs of patients due to individual differences.
China and the United States have first-run advantages in the direction of large-scale pharmaceutical 3D printing, and European research and applications in the direction of personalization of pharmaceutical 3D printing are more active.
It can be predicted that the commercialization of 3D printed drugs will occur in these major drug market countries.

3.
Pharmaceutical 3D printing will become an important advanced technology for the development and production of solid preparations, as well as product updates and iterations in the future.

The production process of solid preparations has a history of more than 100 years, and the global market scale is as high as hundreds of billions of dollars.
Compared with other industries such as semiconductors and automobiles, the pharmaceutical industry is relatively slow in self-innovation and technological iteration due to its strict regulatory oversight and high difficulty in technological development.
Drug 3D printing is the most visible technology capable of changing drug manufacturing.
In 2017, the US FDA issued industry guidelines to promote the use of emerging technologies in pharmaceuticals, among which 3D printing and continuous production are important strategic directions.

4.
Pharmaceutical 3D printing is the core technology of smart pharmacy, which will push the pharmaceutical industry into a new era of smart pharmacy.

Pharmaceutical 3D printing is a digital production technology based on computer models, which builds the foundation of digital pharmacy.
Through the design of medical 3D printing equipment and production lines, other advanced information technology such as big data, artificial intelligence (AI), Internet of Things (IoT), and sophisticated online physical and chemical testing technologies , Can be used in pharmaceutical production process and quality management, many production and testing links are realized by robots to achieve unmanned production.
At the same time, the global unmanned production line can be monitored, fed back and managed through a data-based central control system.
The large amount of process and testing data generated during the R&D and production of 3D printing drugs, combined with the models and algorithms established in the technology development, enables big data analysis and artificial intelligence technology to be applied in the development and production of 3D printing drugs, feedback and optimization of the whole Process, and then realize intelligent pharmacy.