3D Printing Facility in Healthcare Institutions: An Effective Strategy to be Compliant with Medical Device Regulation EU 2017/745

With the onset of 3D printing, also known as Additive Manufacturing (AM), there has been a change in many sectors, notably healthcare, because this technology makes it possible to come up with solutions for each patient with unprecedented accuracy and versatility. It has to be noted that the introduction of technologies, including Computer-Aided Design and Manufacturing, has improved clinical outcomes related to surgical precision, the implementation of customized treatment plans, and particularly in the development of the personalization of medical devices and prosthetics.

Despite these benefits, the incorporation of 3D printing into healthcare systems faces a number of regulatory challenges, especially in Europe.

The regulatory framework for medical devices in Europe is based on the EU Medical Device Regulation 2017/745 [1], further detailed by other guidelines of the Medical Device Coordination Group (MDCG) [2], setting strict requirements on the security, effectiveness, and traceability of medical devices. However, to date, there is no defined and detailed strategy that would be specifically tailored to individual healthcare institutions involved in 3D printing of devices. One of the major barriers that have been identified in terms of the general adoption of 3D printing technologies into clinical practice is regulatory uncertainty. The ambiguity with which most healthcare organizations run under the exemption in Article 5(5) of the Medical Device Regulation-allowing manufacture of a device for internal use without fully meeting stringent regulatory requirements, which apply to companies manufacturing custommade devices.

Globally, there are similar issues: in the United States, the FDA applies its existing medical device regulations to 3D printing but has recognized the increasing need for specific guidelines in relation to point-of-care (PoC) manufacturing [3].

Recent attempts to develop frameworks for PoC 3D printing emphasize a balance between promoting innovation and ensuring patient safety. Other regions, such as France and Italy, have seen individual initiatives to address these issues, but no European hospitals are fully registered as custom made medical device manufacturers, as evidenced by datasets from the Italian Ministry of Health website, where manufacturers must register. In 2021, experts from the French Society of Stomatology, Maxillo-Facial Surgery, and Oral Surgery (SF-SCMFCO) issued guidelines for inhouse 3D printing in maxillo-facial surgery, claiming that compliance with MDR 2017/745 calls for hospitals to have comprehensive risk management plans in place, to use CE-marked products, and to provide extensive documentation of pre-clinical evaluations and clinical follow-ups [4]. All the steps of the 3D printing process, from design to post-processing, must meet these standards to ensure patient safety and device efficacy. Italy, in particular, has seen a very large increase in the number of healthcare 3D printing facilities, with leading institutions being 3D4MED in Pavia [5], Policlinico Gemelli in Rome [6], and 3DIL in Humanitas Research Hospital in Milan. Such facilities have proven the power of 3D printing in surgical planning, medical education, and customized solutions for specific patients. However, how each of these institutions provides evidence of compliance with laws and regulations remains unclear due to a lack of in-depth studies of their pathways toward regulatory adherence.

The aim of this study is to fill in these gaps by setting out a structured workflow and regulatory compliance strategy for health institutions adopting 3D printing technologies. The methodology is indeed set out through a detailed analysis of the MDR, MDCG documents, and ISO standards in order to classify devices, identify required documentation, and outline quality and risk management processes.

The range of applications for 3D printing in the health sector is wide, including Fused Deposition Modelling (FDM), Stereolithography (SLA), Selective Laser Sintering (SLS), PolyJet printing, and Bioprinting. All these technologies have different advantages, from inexpensive production of anatomical models to the production of highly detailed surgical guides and bioprinted tissues, suitable for regenerative medicine. Still, deployment in the health sector requires strict compliance with regulatory standards throughout the product life cycle, including design and material selection through post-processing and clinical testing.

In addition to exploring the regulatory impediments, this study presents the potential benefits three-dimensional printing could have on patient outcomes, surgical times, and medical research and education initiatives. The study was designed as a roadmap for healthcare organizations, with its comprehensive framework of regulations and illustrations of applications, to guide the adoption of 3D printing technologies in an efficient and effective manner.

The classification and regulation of 3D-printed medical devices in the European Union (EU) are governed by the Medical Device Regulation (MDR) EU 2017/745, which has been in full effect since May 26, 2021. This regulatory framework replaced the older directives, namely the Medical Device Directive (MDD) 93/42/EEC and the Active Implantable Medical Devices Directive (AIMDD) 90/385/EEC, with the primary aim of enhancing the safety, effectiveness, and quality of medical devices available on the EU market, setting out stringent requirements across the entire product lifecycle, from design and manufacturing to market surveillance.

Under the MDR, the intended use of the 3D-printed product is the primary determinant of its classification as a medical device. A medical device is defined in Article 2 as any instrument, apparatus, appliance, software, or related article intended by the manufacturer for human use in one or more of the following purposes:
A. Diagnosis, prevention, monitoring, treatment, or alleviation of disease.
B. Diagnosis, monitoring, treatment, or compensation for an injury or disability.
C. Supporting or sustaining life.
D. Disinfection of medical devices or providing information through in vitro diagnostics.

Medical devices are further classified based on their risk profile into Class I (low risk), Class IIa (moderate risk), Class IIb (mediumhigh risk), and Class III (high risk), which dictates the corresponding regulatory pathway and the level of scrutiny during the conformity assessment, assessing whether or not a notified body is required (usually only for class III devices). The classification process is outlined in MDR Annex VIII and considers factors such as the device’s invasiveness, duration of use, and the level of risk posed to the patient.

Another classification, in addition to risk class, is the division in categories, such as: Custom-Made, Patient- Matched, CE-Marked, Investigational, In-House, Mass-Produced and Adaptable. Among these categories, the ones of interest for the 3DIL, where this research has been conducted are Custom-Made, Patient-Matched, CE-Marked, Investigational, In-House, as they are the most suitable for a 3D printing facility.

Bringing a medical device to the market or using within a healthcare institution involves, as previously stated, a complex regulatory landscape where key elements play a central role to ensure the safety, effectiveness, and quality of the medical devices; These key elements are:
A. Quality Management System (QMS): A robust QMS ensures that devices are designed, manufactured, and monitored according to high standards. For this document the compliance with ISO 13485 [7] is critical, as it governs all processes from initial design, to risk assessment and post-market activities.
B. Risk Management System (RMS): RMS is central in the development of a medical device, and it is assessed in ISO 14971 [8], which outlines the framework for identifying, evaluating, and controlling risks throughout a device’s lifecycle, ensuring that manufacturers address both potential hazards and residual risks effectively.
C. Post-Market Surveillance (PMS): Monitoring device performance after its introduction in the market is a legal requirement; through PMS, in fact, manufacturers collect realworld data, identify safety concerns, and implement corrective actions when needed. This process includes creating periodic safety update reports (PSURs) for higher-risk devices.
D. Unique Device Identification (UDI): To enhance traceability, devices are labelled with a unique identifier, allowing this way for efficient recall management and ensures that all devices in use meet regulatory standards.
E. EUDAMED Registration: The European Database on Medical Devices (EUDAMED) serves as a central repository of information, facilitating transparency and oversight, ensuring traceability and compliance across EU Member States.

All these elements, combined with the analysis of the categories and the risk class of Medical Devices, are the base for the development of the Compliance Workflow and consequent Strategy.

Building on the previous sections, this section provides a handson approach for healthcare providers and manufacturers to achieve compliance with the Medical Device Regulation (MDR).

Given the regulatory requirement elements and definitions described in the Methods section, the information regarding Medical Devices categories can be reassumed in the Compliance Workflow in Figure 1. In fact, successfully introducing a medical device-especially innovative 3D-printed products-requires a structured workflow that adheres to regulatory demands.

Figure 1: Compliance workflow.

In the developed workflow, for each category is shown a set of documents necessary for the compliance, whether they need Unique Device Identification (UDI) and/or registration in the European Database on Medical Devices (EUDAMED), and their eventual market placement condition.

Hereinafter a brief description of the possible paths illustrated in the Compliance Workflow, according to the medical device category:
A. Investigational device, which is a device used in clinical trials, where performance and safety data are collected. Require completion of documents with the clinical investigation plan, investigator’s brochure and ethical approval application. Although UDI is not required, registration on EUDAMED is still necessary to ensure transparency and traceability, even considering that their usage is limited to the clinical investigation and cannot be extended to the market.
B. In-house devices: are devices used only in the healthcare institution that produced them, without being placed on the market. They require a complete technical documentation including the manufacturing process and a public declaration of conformity attesting that the general safety, quality and performance requirements are met, as well as documentation to prove that no alternative CE marked devices exist on the market. These devices designed and used under the sole responsibility of the manufacturer are exempt from CE marking, UDI and EUDAMED registration.
C. CE Marked devices are devices that comply with the European health, safety and environmental protection requirements. The technical documentation shall be prepared in accordance with Annexes II and III of the MDR and shall include an EU declaration of conformity. These devices require UDI and registration on EUDAMED, and can be freely placed on the market without production limits
D. Patient matched devices are devices designed to fit the patient’s anatomy, using images or other anatomical references. They must be produced by validated processes and in any case the manufacturer is fully responsible for the safety, performance and compliance of the device. They do not have their own specific path but can fall into the one of investigational, in house or CE marked, respecting all the required documents and the market placement requirements.
E. Custom made devices are devices designed to meet the specific needs of an individual patient, on a doctor’s prescription. The required documentation includes details of the device, technical specifications, a public declaration of conformity as well as registration on EUDAMED. Documentation must demonstrate also that no device on the market bearing the CE mark would produce the same outcome. This category of devices requires the manufacturer to declare a priori the number of devices to be produced during the year and to register on the website of the Italian Ministry of Health.

For the purposes of strategy development, it is important to note that the foundation condition to produce any other documentation for any device category, is the development of a Quality Management System with related Risk Management System and Post-Market Surveillance Plan.

The creation of a complete Quality Management System is the basis for this process, as it serves as the foundation for compliance with ISO 13485. In addition to the Quality Management System, compliance with all these requires integration of several other necessary systems and processes, including Risk Management Systems (RMS), Post-Market Surveillance (PMS), clinical investigation plans, and separate workflows for in- house and custom-made devices.

Based on ISO 13485, the QMS forms the foundation: it ensures that the strict regulatory requirements are followed through every step of design, development, and production. Parallel to this, RMS identifies, assesses, and mitigates the risks in the device lifecycle by being closely integrated with QMS to proactively solve problems before they can fester. PMS then rounds out these processes by having the device performance actually in the market, allowing gathering of real-life performance data to assure safety and efficacy over time.

The preparation of regulatory and ethical principles demands careful preparation for medical devices in the process of clinical trial. This includes developing supporting documents: Clinical Investigation Plan (CIP), Investigator Brochures, and Informed Consent Forms. Equally, the exemption route placed for in-house patient- matched devices under Article 5(5) of the Medical Device Regulation establishes a practical initial framework for manufacture and use within healthcare facilities before full certification is achieved. While for custom-made devices, the strategy requires careful alignment with patient-specific needs and regulatory standards, including detailed documentation and compliance measures.

The plan provides a holistic framework by harmonizing these systems: QMS, RMS, PMS, clinical investigations, in-house device usage, and custom-made device protocols. This framework does not only achieve initial compliance but continues to enhance device quality and patient safety in light of new data and changes in regulations.

Figure 2 offers a month-by-month roadmap for implementing the QMS and related processes. This phased approach ensures a realistic, systematic progression from initial planning to full compliance, while integrating all critical elements from the start.

Figure 2:Compliance strategy.

A. Months 1-2-Initial Preparation and Gap Analysis: begins by understanding ISO 13485 requirements, conducting a gap analysis to identify where current practices fall short. Early staff training ensures everyone understands their role in the new system. Here preliminary work also starts on clinical investigations and custom-made devices to set the stage for future activities
B. Months 3-4-Documenting the QMS and Associated Processes: create the Quality Manual, Standard Operating Procedures (SOPs), and Work Instructions; meanwhile develop the Risk Management and PMS plans, as well as clinical investigation protocols. These documents form the operational backbone of the strategy.
C. Months 5-6-Implementing QMS, RMS, and PMS: put the written procedures into practice. Conduct internal audits to ensure that the QMS works as intended; the RMS and PMS plans come alive as means to ensure continual risk assessment and performance monitoring after devices have reached the marketplace.
D. Months 5-8-Clinical Investigation Submission: prepare and submit all necessary documents for clinical trials to both regulatory authorities and ethics committees. Alignment of clinical investigations through the QMS means these studies are performed with more ethics, efficiency, and with compliance to MDR requirements.
E. Month 7 onward-Refining systems and initiating in-house device production-once the QMS has matured, start in-house device production under Article 5(5) exemptions. This early start fosters practical experience, providing valuable feedback for ongoing improvements in quality and compliance.
F. Months 7-8-Select the Certification Body and Apply for Certification-Choose an accredited certification body and formally apply for ISO 13485 certification. This is a major milestone, turning from internal preparation to external validation.
G. Months 9-10-Stage 1 Audit (Documentation Review) and Clinical Trial Initiation: auditors review QMS documentation to determine readiness for the on-site audit. Concurrently, initiate clinical trials under approved protocols to ensure real-world data collection supports PMS and RMS activities
H. Months 11-12-Stage 2 Audit (On-Site) and Ongoing Clinical Monitoring: the certification body assesses the QMS in action. Concurrent clinical monitoring activities ensure data integrity and patient safety while providing real-time assessments of device efficacy and facilitating continuing improvement.
I. Months 13-14-Addressing Non-Conformities: if auditors identify gaps, implement corrective actions. This demonstrates commitment to improvement and ensures the QMS meets ISO 13485 standards fully.
J. Month 15 onward-Certification issuance and continued vigilance-ISO 13485 certification confirms the QMS. Following this certification, continue active clinical investigations, PMS activities, and RMS refinements to ensure the devices are safe, effective, and comply with the established regulations.
K. Month 16-19- Custom-Made Device Registration: once the QMS and supporting systems are established, focus on meeting custom-made device requirements by preparing technical documentation and registering with the Italian Ministry of Health’s dedicated portal.

Given the complexity and detail required, many organizations gain by enlisting the services of regulatory consulting firms whereby experts lead manufacturers through the intricacies of ISO 13485 implementation, helping with gap analyses, SOP development and internal audits. These professionals can additionally enhance interactions with certification authorities, streamline the preparations for clinical investigations, and guarantee continuous adherence to the continuously changing regulatory landscape. Such consultants may represent a prudent investment as they expedite the process leading to successful certification and market entry.

The strategy given served as a foundational guideline for health professionals to orient themselves in offering 3D printed products in the market, specifically since the integration of 3D printing laboratories into healthcare organizations has drastically grown over the past years, and the necessity to standardize a common methodology in this field for it to effectively comply with the regulation.

A critical point of the plan is to demonstrate that while obtaining ISO 13485 certification is a long-term goal, there are other ways that allow healthcare providers to start operating in the meantime with respect to the manufacturing and use of in-house devices under the Article 5(5) exemption of the Medical Device Regulation (MDR). This approach allows for flexibility so that institutions can offer immediate benefits while putting in place a firm foundation for wider regulatory compliance and future expansion. Beginning the process with internal devices lets institutions harness the technology to enhance patient care and internal processes even before full certification is reached.

These distinctions among the classes of medical devices within the regulatory framework, including in-house, custommade, and investigational devices, may seem very complicated, but this complexity is an avenue manufacturer can use to develop approaches that fit their specific needs and available resources. In fact, institutions may decide to keep their focus on one category only or work with several at the same time. The best and most strategically sound approach is to create a framework that inquiries about all categories of devices, thus allowing for flexibility and growth. In this manner, the healthcare provider would be wellequipped to adjust and evolve into manufacturing products with the CE mark in due time, for instance, by expanding into startup firms. This development represents a natural evolution and an opportunity to enhance revenue while simultaneously elevating patient care. Those efficiencies represent some of the benefits of bringing 3D printing technologies directly inside healthcare organizations. By manufacturing devices precisely tailored to fit individual patient anatomies, those organizations not only avoid human error and reduce surgery times but also significantly raise the overall level of care delivered.

Prospective developments can further raise the benefits of such a facility. Implementation of the approach put forward in this discussion would create an absolute standard for compliance and operational excellence.

Moreover, the measuring of costs involved in compliance and weighing those against the economic value of the facility would generate great insight as to its sustainability; the developing of accurate pricing models for 3D- printed products and exploring the feasibility of turning the lab into a profit-making venture also would further raise its impact.

A further development will be the practical application of the proposed strategy by means of a study which investigates the implications of situating the laboratory in a separate legal entity or outsourcing production but maintaining the legal entity within the control of the Hospital. Such an analysis might include the motivating factors for an institution to focus its efforts on the manufacture of In-House devices versus Custom Made products or Investigational activities, depending on their legal status.

This marriage between 3D printing facilities with healthcare brings the newest in manufacturing technology to improve, directly and indirectly, the quality of care of a patient, reducing production time in surgical precision and ultimately the results of better care and health outcomes. An integral part of the commitment through a clear strategy means sustainability and enduring value creation, both for the institution and patients.

1. (2017) European Parliament and the Council of the European Union. Medical Device Regulation (EU) 2017/745. Official Journal of the European Union, Volume 117.
2. Europan Union. Guidance - MDCG endorsed documents and other guidance. Public Health.
3. Beitler BG, Abraham PF, Glennon AR, Tommasini SM, Lattanza LL, et al. (2022) Interpretation of regulatory factors for 3d printing at hospitals and medical centers, or at the point of care. 3D Printing in Medicine 8: 7.
4. Khonsari RH, Adam J, Benassarou M, Bertin H, Billotet B, et al. (2021) In-house 3D printing: Why, when, and how? Overview of the national French good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery. Journal of Stomatology, Oral and Maxillofacial Surgery 122(4): 458-461.
5. IRCCS Policlinico San Matteo. 3D4MED Homepage. 3D4MED.
6. Fondazione Policlinico Universitario Agostino Gemelli IRCCS. A 'tailor-made' wrist, made with a 3D printer, saves a new mother's right hand. Gemelli Polyclinic.
7. International Organization for Standardization ISO 13485 (2016) Medical devices-Quality management systems- Requirements for regulatory purposes. Geneva, Switzerland.
8. ISO 14971 (2019) Medical devices - Application of risk management to medical devices. Geneva, Switzerland.