3Dresyns conclusions about 3D Printing Medical Devices at the Point of Care
3Dresyns considers that manufacturers of a medical devices, and not their suppliers, are responsible under the law for the safety and quality, and for any health problems caused by the lack of quality of their products.
In the case of 3D printing with photopolymer 3D resins, quality problems can potentially cause severe health problems for consumers, since any 3D printed medical device, including dental and orthodontic appliances, can release uncured monomers and other extractables as long as they have not previously been fully polymerized and/or removed before use.
The delegation of production to third parties can result in certain worrying ambiguity related to responsibility allocation, and uncertainty related to quality and safety assurance for consumers, specially when it comes to holding legal liability for any possible lack of quality of medical device.
3Dresyns is concerned about the risk of unclear allocation of legal liability between Health Care Facility HCF (including dentists and orthodontists) and the recently conceived 3D Printing Medical Device Production System MDPS and the risk of malpractice and realistic consumer health concerns of proposals that do not guarantee the quality and safety of consumers, as it is the case of the proposed 3D printing scenario by the FDA where the HCF acts as the "user" and not as the "manufacturer" of 3D printed medical devices, where the manufacturer (MDPS) assumes full responsibilities for FDA regulatory requirements and manufacturing of devices printed by the HCF using the MDPS.
Similarly, it is of great concern that "certified" 3D resins pretending to be medical devices as supplied, without having included in their certifications the printer, the printing and postprocessing equipment settings and specifications, etc are being used as certifications of medical devices by printer users instead of certifying their "in house" 3D printed medical devices.
Raw materials, including 3D resins, for additive or subtractive manufacture, as with any other manufacturing raw materials, are not medical devices. This clearly contradicts real life since for decades the use of reactive dental resins for restorations in the repair of teeth or the use of monomers, such as methyl methacrylate (MMA), have been marketed as medical devices for making thermally catalysed dentures, despite being dangerous as supplied (check the toxicity of MMA before polymerization). The same practices have been used with 3D resins used for printing dental and orthodontic devices since also have been wrongly considered ‘materials’ regulated as being medical devices in some jurisdictions.
In our opinion the use of fully cured and cleansed polymer materials used in subtractive 3D printing technologies are not so prone to cause potential consumer health problems as thermally or photo reactive 3D resins used in additive 3D printing technologies, since leaving the reponsibility of fully curing and cleansing 3D printed photo curable reactive 3D resins to printer users without being legally liable of the output, relying on their 3D resin supplier certifications can leave consumer health in high risk, since the polymer conversion and uncured monomer content trapped inside 3D printed medical devices is out of control as dependent on the skills of printer users, beyond the control of 3D resin manufacturers.
This scenario is prone to cause poor safety and quality problems of 3D printed medical devices since the use of certifications of raw material suppliers instead of medical devices certifications by printer users, the real and legally liable for the safety and quality of their in house produced medical devices creates ambiguity related to responsibility allocation, and uncertainty related to quality and safety assurance for consumers, specially when it comes to holding legal liability for any possible lack of quality of medical device.
The legal and realistic responsibilities of the 3D resin suppliers are clearly explained in this 3Dresyns review:
On the other hand, subtractive 3D printing technologies where for example a non reactive, fully polymerised disk is shaped by milling to 3D print dentures or crown and bridges, does not suppose significant risk if the disks are safe and certified beforehand since the subtractive tecnologies do not involve any physical modifications nor any chemical reactions as it is the case when using additive 3D printing technologies with photo reactive 3D resins, since leaving the responsibility of fully polymerizing and cleansing the 3D resins to HCFs without clear legal liability of their 3D printed medical devices may leave consumers are risk.
FDA has published a paper related to 3D printing at the Point of Care: Discussion Paper: 3D Printing Medical Devices at the Point of Care.
The 3Dresyns team has summarised and reduced the size of this document as follows and has reached to conclusions related to the use of 3D printed medical devices made with photoreactive 3D resins at the Point of Care (PoC).
3D printing at the PoC may serve an important public health purpose, and may provide for rapid and agile production of devices. This technology has the potential to help a Health Care Facility (HCF) quickly respond to patient needs, bring personalized care to patients in a timely manner, and lead to new innovations in patient care and treatment.
FDA recognizes that HCFs may not have the same level of experience or familiarity with FDA’s regulatory framework for medical devices as traditional manufacturers. An HCF should, however, ensure that any medical devices 3D printed at the PoC will be high-quality, perform as intended, and will not expose patients to unreasonable risk of illness or injury. There are different ways in which an HCF could engage in 3D printing at the PoC, with important questions and considerations associated with each potential situation.
FDA has developed an initial outline for a regulatory approach for devices manufactured using 3D printing at the PoC:• Assuring devices 3D printed at the PoC are safe and effective
• Assuring appropriate control of devices 3D printed at the PoC
• Clarifying the responsible entity
• PoC training and capabilities
This discussion paper discusses these challenges and presents a potential approach for regulatory oversight of 3D printing devices at the PoC.
3D Printing Medical Device Production System (MDPS) is a collection of the raw materials, software and digital files, main production equipment and post-processing (if applicable) equipment intended to be used by a healthcare provider or healthcare facility, to produce a specific type of medical device at the point of care, for treating or diagnosing their patients, or preventing or mitigating disease, or to affect a structure or function of the body. An MDPS includes the medical device it is intended to produce.
What FDA requirements are relevant for device manufacturers?
Medical device manufacturers in the United States are subject to the regulatory controls and required by FD&C Act , among other obligations, to register with FDA and list the devices they manufacture, prepare, propagate, compound, assemble, or process.
Manufacturers of finished devices, including entities who 3D print devices, are also responsible for compliance with the Quality System (QS) Regulation under 21 CFR Part 820 unless expressly exempted. The QS Regulation governs the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use. In some cases, manufacturers must obtain marketing authorization through an FDA submission prior to legally marketing their device in the United States.
How are devices regulated in the United States?
The FD&C Act includes a comprehensive, risk-based framework for how FDA regulates devices in the United States. Devices are categorized into three different classes: class I (general controls), class II (special controls), and class III (premarket approval).
How does the Center for Devices and Radiological Health (CDRH) regulate 3D printing?
FDA does not regulate all 3D printing activities, but generally does regulate such activities when they produce medical devices. FDA generally regulates the methods used in, and the facilities and controls used for manufacturing devices, when such devices are subject to the QS Regulation. 3D printing systems could be commercially distributed with the specific intended use to produce specific type(s) of medical devices at the PoC, referred to as MDPS. The regulatory requirements for the 3D printed medical devices using the MDPS would generally govern the responsibilities of the entities manufacturing and commercially distributing the 3D printing MDPS for use at the PoC.
How do the capabilities of a PoC 3D printing facility factor into device safety and effectiveness?
PoC 3D printing facilities may have a wide range of 3D printing equipment and experience, which means that PoC 3D printing facilities may have differing abilities to manufacture devices. When devices are manufactured at the PoC, it may be possible for a PoC 3D printing facility to leverage existing processes within their HCF. Because devices vary in complexity and risk, an individual HCF PoC 3D printing facility may be capable of 3D printing some devices but not others. Other devices may not be appropriate to manufacture at the PoC based on available technology and expertise.
Approach for Discussion
FDA is considering the following concepts in developing a potential approach for 3D printing devices at the PoC: employ a risk-based approach, device specification should not change based on location of manufacture, capabilities available at a PoC HCF can help mitigate production risks,entities should understand their responsibilities, and leverage existing controls.
Risks includes both the risks involved in 3D printing the device (for example, the complexity of printing, the materials used, the post-processing needed), and the risks related to the use of the device. The sources and types of risks should be carefully considered for all devices.
The FDA discusses three potential 3D printing scenarios:
1. HCF using a 3D printing MDPS, where the MDPS manufacturer assumes responsibilities for FDA regulatory requirements and manufacturing of devices printed by the HCF using the MDPS
- In this situation, the PoC 3D printing facility within the HCF uses an MDPS to 3D print devices covered by the MDPS. Generally, in a situation like this, the responsibility for FDA compliance lies with the manufacturer of the MDPS, and the PoC 3D printing facility within the HCF is the user of the MDPS.
2. Traditional Manufacturer on or near the HCF site
- In this situation, the HCF does not engage in any 3D printing activities being the Traditional Manufacturer responsible for compliance with FDA’s regulatory requirements.
3. HCF assuming all Traditional Manufacturer responsibilities
- In this situation, the PoC 3D printing facility within the HCF would not use an MDPS, and would not work with a Traditional Manufacturer to 3D print devices. Rather, the HCF has chosen to engage in the activities of a Traditional Manufacturer in their PoC 3D printing facility. In this situation, the HCF would be responsible for complying with FDA regulatory requirements applicable to device manufacturers.
Several Traditional Manufacturers have already started working with HCFs to discuss new models that use 3D printing capabilities at the PoC. Standards development organizations are also working on test methods, best practices, and guides. Medical societies can also develop clinical guidelines and criteria to help clinicians decide when and how to make or use 3D printed devices. Clinical and engineering training programs will also be important to adoption of 3D printing of medical devices at the PoC. These programs could help bring the same confidence to 3D printing of devices at the PoC that exists with devices currently marketed by Traditional Manufacturers.
Training programs, including certification and licensing programs, could eventually could be useful when 3D printing medical devices. In addition, there may be a certification that the PoC could obtain to assess the capabilities of a facility with respect to 3D printing design, manufacturing, post-processing, and quality control. HCFs with a specific certification level may be better suited to 3D printing at the PoC. Many manufacturing facilities can be certified to conform to quality standards, such as ISO 13485: 2016 Medical devices — Quality management systems — Requirements for regulatory purposes and FDA could consider an approach to quality system regulation that takes conformity to this ISO standard into account. Similarly, many HCFs already obtain accreditation from hospital certifying bodies, clinical practice standards groups, and state regulators. FDA recognizes that 3D printing technology is developing rapidly and a solution designed for today’s technology may not be applicable in future years. A durable solution will be built on a foundation of strong science, sensible clinical guidelines, and an appropriate regulatory approach that balances innovation with regulatory oversight. Such a solution can be created through stakeholder engagement, discussion, and consensus-building. 7.
FDA recognizes that 3D printing at the PoC contributes to the development of innovative devices and the importance of providing assurance of device safety and effectiveness.
Industry, professional organizations, and clinical societies have already started to develop new guidelines for 3D printing at the PoC. Expansion of 3D printing capabilities at HCFs could lead to an increased use of 3D printing technology during non-emergency situations. This discussion paper describes factors and scenarios that FDA is considering as the Agency further explores appropriate regulatory approaches for PoC 3D printing of devices, including considerations of timely patient access to 3D printed devices that have a reasonable assurance of safety and effectiveness.
3D printing is a versatile technology for advancing state of the art devices and treatments. The technology has typically been used by Traditional Manufacturers who must comply with the FD&C Act and its implementing regulations.
3D printing can generally be divided into five stages:
- The device design
- The software workflow
- Material control stage before manufacturing
- Post-processing stage. This frequently includes steps to remove the device from the build platform. This may also include processes for: a. Cleaning of 3D printing residues (e.g., uncured or unsintered raw material); b. Annealing or heat treating; c. Post-printing machining to obtain final dimensions or features; d. Biocompatibility assessment; and e. Terminal sterilization and cleaning
- Validation after post-processing, the final finished device is ready for testing during the process validation and acceptance activities stage. For many cleared devices, most characterization is done before production begins. Production processes are then established, maintained, and monitored so that the manufacturer verifies the design output meets their specifications. This is called a validated process. Design parameters are often checked after each build by inspection and/or testing. These tests are important to ensure that the device continues to meet its specifications.
International Medical Device Regulators Forum IMDRF has published "Personalized Medical Devices - Regulatory Pathways"
The 3Dresyns team has summarised and reduced the size of this document as follows and has reached to conclusions related to the use of 3D printed medical devices made with photoreactive 3D resins at the Point of Care (PoC). 3Dresyns opinions have been included in the text as blockquotes
Additive Manufacturing AM and 3D printing technologies are already being used for manufacturing personalized medical devices, including at the PoC, by health professionals, such as dentits, rather than by traditional manufacturers.
This has raised questions about the suitability of these manufacturing methods for the production of safe personalized medical devices, particularly with respect to the validation of their design and production methods; and the sufficiency of the quality control over any and all components, equipment, and raw materials used for production purposes.
Accordingly, a new concept is introduced—the medical device production system (MDPS). Additionally, some considerations and guidance are provided herein on:
- raw materials used for manufacture; and
- materials that are medical devices in their own right
Medical device production systems
If control over a manufacturing process, such as additive or subtractive manufacturing, outside of a regulated manufacturing facility is needed, jurisdictions may consider defining and regulating a ‘medical device production system’ on the basis of the device the system is intended to produce. The intended device includes the intended use for the device, which is validated by the manufacturer of the medical device production system.
A Medical Device Production System (MDPS) is manufactured by a regulated manufacturer for the purpose of producing personalized medical devices by end users, usually health professionals, and usually at the point of care.
We define it here as: A medical device production system (MDPS) is a collection of the raw materials, software and digital files, and main production and post-processing (if applicable) equipment intended to be used by a healthcare provider, or healthcare facility, to produce a specific type of medical device at the point of care, for treating their patients.
- The MDPS includes the medical device it is intended to produce and the intended use for the device validated in accordance with safety and performance requirements in the relevant regulatory jurisdiction.
- The MDPS may require the use of ancillary equipment, human factors considerations, technical capability requirements, or other specified input and design limit controls;
however, all components must be validated as a production process to consistently produce the intended medical device with the use of the supplied instructions. For the purposes of the Global Harmonization Task Force GHTF/IMDRF model, the MDPS is in keeping with the concept of a kit or system, that is, a group of products that together achieve a stated intended use —and as such, can be considered a medical device in its own right.
Consequently, all applicable elements of the medical devices framework then apply to it. In this case, and if appropriate to the applicable jurisdiction, the ‘medical device production system’ is not intended to be regulated as a production tool for universal manufacture of medical devices as it would be if it were used for production in a regulated manufacturing facility. Jurisdictions may choose to introduce limits on the types of devices accepted for manufacture by an MDPS, such as limiting them to low-risk products only; and they may also choose to impose credentialing requirements for the use of an MDPS. The GHTF/IMDRF definition of ‘manufacturer’ applies to the manufacturer of an MDPS. This allows for multiple OEMs and outsourcing to component manufacturers while one legal manufacturer takes responsibility for the entire system, and all final medical devices produced by the system.
The manufacturer of an MDPS is regulated in a similar manner to the manufacturer of an adaptable medical device. The responsibility for medical device safety and performance is with the manufacturer of the MDPS, along with the other responsibilities placed on the manufacturer in the jurisdiction in which the MDPS is supplied. The manufacturer of an MDPS may require the intended user to: make use of ancillary equipment, accommodate human factors considerations, ensure that technical capability requirements are met, adhere to other specified input and design limit controls, and participate in a regular maintenance and service program. As with all other medical devices, the manufacturer of an MDPS must identify and document any necessary requirements regarding use of the MDPS. These might include, for instance, environment controls; staff training and certification; conduction of verification testing; and maintenance of records. Manufacturers should also establish methods for ensuring that the necessary controls are implemented and that they remain effective over the lifetime of the MDPS.
Note: it remains the manufacturer’s responsibility to ensure safety and performance of the MDPS together with all final devices produced by the MDPS. If the healthcare institution or professional uses the MDPS to produce a device outside the original manufacturer’s intended use of the MDPS, it would take on the responsibilities for that new intended use. This would be considered off-label use. However, if the healthcare professional or healthcare institution additionally markets or promotes the new intended use then the healthcare professional or healthcare institution would be considered to be a manufacturer in his, her, or its own right and, consequently, all the requirements on manufacturers would then apply to him, her or it.
Raw materials for manufacture
Raw material for additive or subtractive manufacture, as with any other manufacturing raw material, is not a medical device as it is not directly used for treating a patient. This is because regulating the raw material for a 3D-printer or CAD/CAM system (for example) will not ensure that the final devices the system produces will comply with applicable safety and performance requirements. Additive and subtractive manufacture involves more than assembling or adapting a device for a particular patient; it is a complex multifactorial process that has an impact on the finished device’s compliance with the essential principles. Consequently, instructions for use provided by the manufacturer of a raw material for additive or subtractive manufacture cannot adequately specify sufficient means of control over all of the variables in an additive or subtractive manufacturing process.
Materials that are medical devices
According to the GHTF definition of medical device, a ‘material’ can be a medical device in its own right. An example of a ‘material’ regulated as a medical device in some jurisdictions is dental resin materials used for restorations in the repair of teeth. A dentist assembles and/or adapts the resin material for an individual patient, as intended by the manufacturer of the resin, in accordance with the instructions for mixing, forming, curing, etc. the resin. The assurance that the final assembled or adapted resin medical device will perform as intended comes from the validated instructions provided by the manufacturer. This means that the resin manufacturer will have tested the safety and performance of samples of its device, when adapted or assembled according to its instructions. The manufacturer makes certain specifications for the use of its product, such as the mixing constituents, the mixing ratio, the type and size of defect to which the resin should be applied and how long it needs to cure. When the dentist follows these instructions, the dental resin restoration will perform as intended by the manufacturer of the resin. It is important to note that the material regulated as a medical device is only to be used for the specific intended use identified and not for unlimited intended uses for other medical devices that have not been validated for safety and performance.
3Dresyns opinion about the text shown in green and red color in the previous paragraghs: Raw materials, including 3D resins, for additive or subtractive manufacture, as with any other manufacturing raw materials, are not a medical devices. This clearly contradicts with real life since for decades the use of reactive dental resins for restorations in the repair of teeth or the use of monomers, such as methyl methacrylate (MMA), have been marketed as medical devices for making thermally catalysed dentures, despite being dangerous as supplied (check the toxicity of MMA before polymerization). The same practices have been used with 3D resins used for printing dental and orthodontic devices since similarl have been wrongly considered ‘materials’ regulated as medical devices in some jurisdictions.
Now we repeat ourselves some of the conclusions mentioned initially:
In our opinion the use of fully cured and cleansed polymer materials used in subtractive 3D printing technologies are not prone to cause potential consumer health problems as thermally or photo reactive 3D resins used in additive 3D printing technologies, since leaving the reponsibility of fully curing and cleansing 3D printed photo curable reactive 3D resins to printer users without being legally liable of the output, relying on their 3D resin supplier certifications can leave consumer health in high risk, since the polymer conversion and uncured monomer content trapped inside 3D printed medical devices is out of control as dependent on the skills of printer users, beyond the control of 3D resin manufacturers. This scenario is prone to cause poor safety and quality problems of 3D printed medical devices since the use of certifications of raw material suppliers instead of medical devices certifications by printer users, the real and legally liable for the safety and quality of their in house produced medical devices creates ambiguity related to responsibility allocation, and uncertainty related to quality and safety assurance for consumers, specially when it comes to holding legal liability for any possible lack of quality of medical device.
Considerations for point-of-care manufacture of personalized medical devices Introduction Healthcare institutions or healthcare professionals may be involved in manufacturing of personalized medical devices for use in treating their patients. Medical device manufacturing usually occurs under appropriate quality management systems, and in regulated manufacturing facilities. Under the GHTF model, it is recognized that regulatory oversight of medical device manufacturers is an important factor in ensuring safety and performance of medical devices. For this reason, there should also be oversight of manufacturing that is occurring in alternative locations such as at the point of care. Traditionally, point-of-care manufacturing has been limited in scope; however, advances in technology have enabled the manufacture of more complex, higher-risk personalized medical devices by healthcare professionals (on a routine basis) without the usual requirements and oversight that traditional manufacturers are typically subject to. Oversight of healthcare institutions and healthcare professionals varies in different jurisdictions around the world, from full regulation of them as regulated entities (as traditional manufacturers), through to pathways that allow for exemption under certain criteria (for example, when personalized medical devices are manufactured at recognized healthcare institutions or by recognized healthcare professionals). The following sub-sections in this Appendix include recommendations for three possible approaches that regulators might choose to implement for regulatory oversight of manufacturers of personalized medical devices at the point-of-care. These are:
1. Manufacturing under special arrangements
2. Medical Device Production Systems
3. Fully regulated manufacturing (as per the GHTF/IMDRF model)
1. Manufacturing under special arrangements
Some jurisdictions apply different regulatory frameworks (such as exemptions or special provisions) for medical device manufacturing undertaken in healthcare institutions, or by healthcare professionals, as compared to manufacturing undertaken by traditional manufacturers. The different frameworks tend to be limited to medical devices intended to address indispensable clinical needs within specific institutions or their network of subsidiary or partner institutions. Any exemptions for manufacturing within a healthcare institute should not apply to establishments primarily claiming to pursue health interests or healthy lifestyles, such as gyms, spas, wellness and fitness centers, or to establishments focused on beauty treatments such as cosmetic clinics.
Protection of safety and performance When healthcare institutions and professionals design and/or manufacture a personalized medical device under special arrangements, including at the point-of-care, it is recommended that they be required to protect patient safety, and ensure appropriate performance of the medical device, by meeting certain imposed requirements that include the following: a) the manufacture and use of the devices to be undertaken under an appropriate quality management system; b) the healthcare institution or professional to be required to have on file, and to provide information upon request, on the use of devices it has manufactured to its competent authority. The information should include a justification of the indispensable clinical needs warranting manufacture of the device and details of their manufacture, including appropriate quality management validation documentation, device designs or modifications, and the intended use; c) the healthcare institution or professional to be required to make available to the patient receiving the device the following information: i. the name and address of the manufacturing healthcare institution or professional; ii. the details necessary to identify the device; iii. a declaration that the device meets general safety principles and, where applicable, information on which principles have not been fully met together with a reasoned justification thereof; d) the healthcare institution or professional to be required to draw up documentation under its quality management system that makesit possible to have an understanding of the manufacturing facility; the manufacturing process; and the design and data providing confidence that the device will function as intended, including the intended purpose, and that is sufficiently detailed to enable the regulatory authority to ascertain that the general safety and performance requirements have been met; e) the healthcare institution or professional to be required to take all necessary measures to ensure that all devices it manufactures are manufactured in accordance with the documentation referred to in point (d); and f) the healthcare institution or professional to be required to review experience gained from clinical use of all devices it manufactures, report any adverse events to the regulatory authority, and take all necessary corrective and preventive actions. g) the healthcare institution will allow the regulatory authority to inspect the manufacturing processes when appropriate. Regulators who apply special frameworks for the manufacture of medical devices within a healthcare institute, or by healthcare professionals, should consider including regulatory oversight commensurate with that of the equivalent frameworks in place for traditional manufacturers. For instance, a hospital may be required to operate under a quality management system certified by a competent 3rd party, and be required to meet, and be assessed against, appropriate safety and other technical standards that are equivalent to the essential principles of safety and performance.
2. Using Medical Device Production Systems
A healthcare institution, or healthcare professional, that relies upon a Medical Device Production System (MDPS) approach for producing medical devices is not considered to be the manufacturer under the Global Harmonization Task Force GHTF definition. However, the user still has some responsibilities to ensure that the devices produced by the MDPS meet applicable safety, performance, and local jurisdictional requirements. These responsibilities may be specified by the manufacturer of the MDPS and/or by the local jurisdictional authority. The responsibilities placed upon the user of the MDPS will vary depending on the complexity and type of medical devices produced, and may include: following manufacturer’s instructions for the use of the system, including using materials, components, software, or other equipment as specified by the manufacturer; keeping records; controlling the production environment (including contamination control); ensuring that infrastructure (including of networks, cybersecurity) is in place as per the manufacturer’s requirements; completing post-processing activities, such as annealing and heat-treating operations; undertaking end-user verification and validation activities, including any associated testing, of the final medical device; cleaning; sterilizing; reporting performance of the MDPS to the manufacturer; applying identification marking (such as labelling) to the final device for identification by the patient or user; post-market reporting as per jurisdictional requirements; and making arrangements with the manufacturer of the MDPS with regards to adverse-events, complaints, and investigations.
3. Fully regulated manufacturing (as per the GHTF/IMDRF model)
The regulator treats healthcare institutions and healthcare professionals that/who undertake manufacturing the same way they treat traditional manufacturers. These ‘point-of-care manufacturers’ need to ensure their medical devices are correctly classified, and need to follow the usual regulatory requirements to obtain pre-market approval, according to the risk classification, in the jurisdiction in which the devices are supplied. Manufacturers are required to meet both pre- and post-market regulatory requirements in the jurisdiction where their medical devices are supplied; these might include, for example, implementation of appropriate quality management systems generation of clinical evidence; compliance with safety and performance standards; design; testing; manufacturing standards; undertake supplier control (including outsourcing of different elements of manufacture); the provision of labels and information; registration; and post-market surveillance, corrective action, and adverse-event reporting.