3D printing is an emerging manufacturing technology that builds physical objects layer by layer based on digital models. This technology profoundly impacts traditional processes, production lines, factory models, and industrial chain combinations, representing a disruptive technology in manufacturing. With the release of the EU’s 3D printing standardization roadmap, the establishment of a series of standards by international organizations regarding 3D printing, and the introduction of various regulations by the US FDA concerning 3D printing technology, 3D printing is gradually acquiring its universal language and direction.
Applications of 3D printing technology in the research and manufacturing of medical devices continuously empower the innovative development of medical instruments, forming products known as “3D printed medical devices,” which have been gradually widely used in the past five years. 3D printed medical devices primarily utilize metals, polymers, and other materials, enabling personalized customization of devices and the manufacturing of precise microstructures. However, while 3D printing brings “personalization,” it also introduces unique risks. Traditional regulatory approaches for standardized products may be difficult to apply, and there is a lack of analysis and evaluation methods and standards for the processes, quality, and risks associated with 3D printed medical devices, posing numerous challenges for their regulation.
Establishing Certification Standards, Regulations, and Evaluation Systems for Medical 3D Printed Products
To achieve the subsequent industrial application of medical 3D printed products, relevant institutions should work together, with higher authorities playing a key leading role.
The first breakthrough in medical 3D printing occurred in the fields of orthopedics and dentistry, and it is gradually maturing in these areas. As early as 2010, regulations for 3D printed medical implants were proposed for orthopedic and dental products.
Currently, the National Medical Products Administration has approved four types of 3D printed standard products for clinical applications. The National Medical Products Administration prioritizes their use in mature or already validated areas, such as orthopedics and dentistry, with customized product components manufactured by different provinces.
Since additive manufacturing products include customized products, the National Medical Products Administration plans to establish a complete evaluation system. So far, the National Medical Products Administration has formulated 40 guidelines regarding obtaining medical device registration certificates, of which 7 principles relate to additive manufacturing. In the future, a relevant standard system, regulatory system, guidelines, registration technical documents, and beacon system will be established to focus on developing clinical applications and achieving breakthroughs.
China’s “Regulations on the Supervision and Administration of Medical Device Production” lists the safety and effectiveness of medical devices as the primary requirements. Currently, the US Food and Drug Administration (FDA) primarily controls risks based on reasonable determinations and effective scientific evidence to ensure that medical products can be safely and effectively applied, thereby improving public health. For new medical devices in the field of additive manufacturing, corresponding regulatory science must be established to verify the performance of registered products. Important tasks to be completed before registration include conducting multicenter clinical trials and medical research, as well as producing products that are summarized and peer-reviewed and published in scientific literature, thus providing important evidence for clinical practice. Such research and production will assist in the development of innovative products and facilitate monitoring of the entire usage process during the clinical application of the products.
The Sichuan University Institute of Regulatory Science for Medical Devices is the world’s first academic institution dealing with regulatory affairs related to medical devices, tasked with establishing regulatory science for medical devices through pre-validation and risk control. This regulatory science should encompass the entire lifecycle of medical products based on background information such as users, product developers, and enterprise risk control.
There are differences between domestic and international regulations for customized products. In the UK, the core management philosophy regarding customized devices is as follows: except for material-related matters, the entire production process of additive manufacturing is the responsibility of the surgeon, including the acquisition of computer tomography (CT) or magnetic resonance imaging (MRI) image data from clinical patients, manufacturing, clinical physician confirmation, and subsequent clinical application.
The focus of Chinese enterprises is on obtaining a registration certificate issued by the National Medical Products Administration before market entry. The current situation in the UK indicates that China should quickly issue clear registration guidelines for customized medical devices and accelerate clinical translation. The relevant registration guidelines should balance technical feasibility with creating practical benefits for all parties—especially patients. The reproducibility of medical additive manufacturing and the characteristics of finished products (whether for humans, animal models, or cell models) must be achieved in a standardized manner. This topic warrants further consideration and discussion in future R&D and clinical applications.
All new technologies and novel materials—especially the three categories of medical products utilizing 3D printing—must undergo systematic evaluation and approval by regulatory agencies before clinical application. The medical additive manufacturing technology is still in its exploratory stage. Currently, in the clinical applications of 3D printing technology in orthopedics and dentistry, several major challenges remain: unclear risk responsibility definitions and excessively long clinical registration and approval times. This is due to the difficulty in assessing the expected clinical effects of such products, particularly those manufactured by 3D printing. Additionally, the product quality control system has yet to be perfected. Although the clinical research initiated by preclinical scientists is not aimed at clinical registration, the relevant management processes and quality control systems must meet the corresponding surgical medical requirements.
Key Points of Quality Control for 3D Printed Medical Devices
For the performance of 3D printed medical devices, safety is the most crucial aspect. To ensure safety, it is essential to control every link from the early design and manufacturing stages, namely, product quality control. Quality control of 3D printed medical devices involves many aspects of the manufacturing process and production management, including medical-engineering interaction, raw material quality control, printing equipment management, processing parameter control, post-processing management, and finished product quality control, with different quality control points for each aspect.
01 Medical-Engineering Interaction
Medical-engineering interaction is one of the prominent features that distinguish patient-matched 3D printed medical devices from non-customized medical devices. The norms, effectiveness of interaction information, close cooperation, and well-documented records are extremely important. The key links and components of the entire medical-engineering interaction process should be accurately defined, and research should be conducted on how to implement effective control over these elements.
The “Technical Review Guidelines for Registration of Passive Implantable Bone, Joint, and Oral Hard Tissue Personalized Additive Manufacturing Medical Devices (Document No. 70 of 2019)” also clarifies that the products should meet six requirements for medical-engineering interaction, including design software, printing equipment, raw materials, printing process validation, post-processing methods and validation, and product testing, and requires confirmation of the medical-engineering interaction capability of additive manufacturing medical devices from three aspects: personalized design, product delivery, and product usage.
02 Raw Material Quality Control
Quality control of raw materials is the foundation for ensuring the quality of printed products, with purity and performance being crucial. Currently, the raw materials primarily involved in additive manufacturing medical devices are metal powders used for 3D printing, including medical titanium alloys, medical pure tantalum, and medical nickel-titanium alloys.
The form of metal 3D printing raw materials is spherical powder, so characterization of the raw materials should be conducted from aspects such as roundness, sphericity, flowability, tapped density, and bulk density, and verification of their physical and chemical properties must meet the requirements for medical device production. Additionally, for the use of recycled old powders in 3D printing, manufacturers are required to clarify and validate the mixed powders, verify the impact of the printing environment on the powders, and demonstrate process stability and clinical acceptability. This information will help assess the potential impact of powder recycling on the printing process and results; otherwise, the use of recycled powder materials is not allowed.
03 Printing Equipment ManagementPrinting equipment is crucial hardware for the production of 3D printed medical devices. The stability of equipment operation and the stability of the printing process determine whether the batch-to-batch differences of the products are within acceptable limits. Printing parameters of the equipment must have strict validation procedures to ensure the feasibility and stability of the printing process. The reasonableness and effectiveness of equipment modifications must also be validated.04 Processing Process Validation and Post-Processing ManagementThe initial printed products must undergo necessary post-processing, such as eliminating thermal stress, surface roughness treatment, and removal of powder residues. These post-processing steps are essential for ensuring the reasonable mechanical properties and biocompatibility of the products. Currently, the standard developed by the National Institute for Food and Drug Control, “Cleaning and Cleaning Effect Verification Methods for Metal Powders in Medical Additive Manufacturing Powder Bed Fusion Processes,” is in the approval stage, focusing on the technical content of “common cleaning processes for residual metal powders” and “cleaning effect verification methods.” Manufacturers can implement cleaning processes according to these regulations and demonstrate compliance with cleaning standards.05 Finished Product Quality Control and Risk Assessment of Product Application3D printed medical devices must not only meet performance requirements after manufacturing but also consider the potential impact on human health when interacting with the body. For example, regarding the evaluation of metal ion release from 3D printed titanium alloy implants, the National Institute for Food and Drug Control has developed the “Evaluation Methods for Metal Ion Release from 3D Printed Titanium Alloy Implants for Additive Manufacturing Medical Products,” which has been completed and submitted for approval. The standard specifies the morphology of the samples used for testing and the metal ions (Ti, Al, V, and impurity elements Fe) that need to be detected.Other aspects to focus on include: control of physical properties (mechanical properties and fatigue properties), chemical properties (chemical composition control, microstructure), and biocompatibility. Biocompatibility should be comprehensively evaluated according to the requirements of the GB/T16886 series of standards.
A Series of Policies Promote the Integration of 3D Printing Technology with the Real Economy
In February 2015, the Ministry of Industry and Information Technology, the National Development and Reform Commission, and the Ministry of Finance jointly issued the “National Additive Manufacturing Industry Development Promotion Plan (2015-2016),” proposing that by 2016, China should preliminarily establish a relatively complete additive manufacturing industrial system, maintaining overall technological levels in sync with international standards.
In May 2015, the State Council issued the “Made in China 2025” plan, clearly designating the additive manufacturing industry as a development focus to promote the research and application of 3D printing technology and equipment in China. As an important component of intelligent manufacturing, 3D printing technology has been mentioned in several plans under “Made in China 2025”. Relevant enterprises in the 3D printing field will also receive special listing system support from the state.
In December 2016, the Ministry of Industry and Information Technology approved the establishment of the National Additive Manufacturing Innovation Center, formed by five universities: Xi’an Jiaotong University, Beihang University, Northwestern Polytechnical University, Tsinghua University, and Huazhong University of Science and Technology, along with 13 key enterprises in equipment, materials, software, and R&D, to conduct research on common technologies, standard formulation, and industrialization of 3D printing. At the same time, the National Quality Supervision and Inspection Administration approved the establishment of the National Additive Manufacturing Product Quality Supervision and Inspection Center in Wuxi to carry out relevant product testing and certification services.
In November 2017, the Ministry of Industry and Information Technology and 12 other departments issued the “Additive Manufacturing Development Action Plan (2017-2020)”, clearly stating that by 2020, China’s additive manufacturing industry annual sales revenue would exceed 20 billion yuan, with an average annual growth rate of over 30%. The development of 3D printing technology requires improvements in key technological R&D and industrialization capabilities, as well as the promotion of innovative applications in key industries.
The action plan clarifies the direction for the development of medical 3D printing technology, enhancing the quality and process performance of dedicated additive manufacturing materials for medical use, improving material design and microstructure design technology for personalized medical devices, and enhancing the quality performance and reliability of additive manufacturing equipment and core components. Additionally, it aims to actively explore new models of “3D printing + medical” demonstration applications, addressing the needs for personalized medical devices, rehabilitation devices, implants, and soft tissue repair in the medical field, promoting the improvement of policies and regulations regarding classification, clinical testing, registration, and market access for personalized medical additive manufacturing products, and researching and determining medical service project charging standards and medical insurance payment standards for medical 3D printed products and services. Meanwhile, a complete additive manufacturing standard system, testing and certification system, and talent cultivation system will be established.
The Technical Specifications for Registration of 3D Printed Medical Devices Open Up Pathways for Market Access
The clinical use of 3D printed medical devices has always been restricted by regulatory policies, and no relevant standards for approval registration exist in various countries. Most 3D printed products primarily include clinical auxiliary products such as tumors, organ models, and surgical guides, which only require filing and are not strictly regulated under approval registration. In 2017, the US Food and Drug Administration (FDA) released the “Technical Guidance for 3D Printed Medical Devices” to standardize the production activities of related products, clarifying the additive manufacturing process for medical products and relevant testing operational norms, providing specific technical requirements for the basic processes of 3D printing methods, design, workflows, manufacturing processes, material control, post-processing, testing, and quality management, thereby providing a basis for the approval registration of 3D printed medical devices and opening pathways for product market access.
The Basic Process for 3D Printed Medical Devices
In February 2018, the National Medical Products Administration (CFDA) issued the draft for public comment on the “Technical Review Guidelines for Registration of Customized Additive Manufacturing Medical Devices,” clarifying the operational and documentation requirements related to registration approval, and proposing specific requirements for the usage, product performance, clinical trials, and quality management of 3D printing products. It particularly emphasizes the conditions and capabilities for medical-engineering interaction, requiring strict control over the production and verification processes of 3D printed medical devices, including printing equipment, processes, post-processing, raw materials, and final product testing, and confirming the qualifications and capabilities of personnel involved in design development, product delivery, and product usage to ensure the safe and effective clinical use of 3D printed products. Furthermore, it emphasizes establishing a database of patient health status throughout the product’s lifecycle to evaluate the durability of the devices and the traceability of medical accidents. The introduction of this approval registration specification signifies that the 3D printing industry in China’s medical field is about to have formal technical review guidelines, clearing obstacles for the registration, approval, and market entry of 3D printed medical devices.
Outlook
In summary, “standardization of 3D printed medical devices” can be divided into three concepts: 3D printing, medical devices, and standardization. 3D printing is the technology for manufacturing products, medical devices are the products, and standardization is the process of ensuring that products meet requirements. Only products that meet these requirements can be practically applied, thus realizing the significance of the products.
Currently, due to the systematic and extensive nature of standardization work, to continue promoting the standardization of 3D printed medical devices, it is necessary to advance many aspects of work simultaneously, including: 1) Promoting the industrialization process of China’s additive manufacturing technology; 2) Strengthening exchanges and cooperation between China and other countries and organizations in standardization work; 3) Providing constructive opinions to Chinese regulatory authorities for establishing relevant regulations from various parties in the field; 4) Offering technical support for formulating regulatory guidelines on special risk analysis, risk control, etc.; 5) Regulatory authorities further establishing standards for technology and methods, raw materials, equipment, and processes.
It can be seen that industry and standards are interdependent; industry cannot be divorced from the guidance of standards, nor can standards become disconnected from industry. Furthermore, production, education, research, inspection institutions, medical units, standardization organizations, and regulatory authorities are all important components of this field. Each party should achieve synergy and integration based on different divisions of labor, functional and resource advantages, to jointly promote the development of standardization work for additive manufacturing medical devices.
During the “2020 National Medical Device Safety Publicity Week” event, the Drug Administration has showcased the latest elements of quality control formed regarding the evaluation of additive manufacturing medical device products, including performance and characteristics, which can be broadly divided into three major categories based on products, manufacturing, and users, ensuring the quality of 3D printed medical devices in a relatively comprehensive and systematic manner to meet user needs.
These can serve as entry points to help medical device companies better understand the seemingly complex standardization work from scratch. There is an ancient Chinese saying, “Respond to change with constancy,” which reflects in standardization work that although products are personalized, workflows and operational methods can still be standardized, using standardized processes to regulate various personalized products. Understanding these concepts, coupled with continuous familiarity with regulatory laws and 3D printing technology, will enable enterprises to better innovate their products according to standardization requirements, truly utilizing new technologies to bring forth new products and meet approval requirements.
Extending product development into a longer process, from experimental research to production application, even in the laboratory, research on 3D printed medical devices should incorporate the awareness of industrialization and clinical translation as an important principle throughout the R&D process, and not merely remain in the research phase for the sake of publishing papers. Similarly, from research to industrial phases, the requirement for medical device companies is that when developing a 3D printed medical device product, obtaining approval and certification from regulatory authorities should not be the ultimate goal. Product certification is just the beginning of application; the effectiveness of the application is the ultimate pursuit of medical device products.
Regarding the future development of regulation and standardization of 3D printed medical devices, “quality” and “risk” will continue to be the two key keywords in this field’s exploration, while the primary task remains to establish a more comprehensive system of guidelines, standards, and regulatory frameworks. The construction of the standardization and regulatory system for 3D printed medical devices has been listed as one of the important tasks and plans during China’s 14th Five-Year Plan. These systems can continuously expand their coverage in a horizontal manner, covering more types of technologies and products, while also deepening vertically to extend and refine more details for specific products and technologies.
Source: Jiayu Testing Network
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