About Certification of biomedical devices and food and pharma packagin

3D printed medical devices fall within the scope of specific EU product legislation, the EU Medical Device Regulation MDR 2017/745. Therefore, manufacturers of medical devices must ensure that their 3D printed products meet the requirements of the applicable EU legislation, carry out the necessary conformity assessment procedures, compose a technical file, draft the EU declaration of conformity, and affix the CE marking, before placing them on the EU market.

3D resins are raw materials, not finished medical devices

Photopolymer 3D resins are liquid photo reactive (photo curable) raw materials, which photopolymerise or react with light in the printers, normally layer by layer, to cure and become printed solid materials with specific shapes and functionalities to comply with the quality requirements of a broad range of biomedical devices and packaging, including dental, orthodontic, hearing, implant, prosthesis, food, pharmaceutical devices, etc.

Biocompatibility certifications of photo reactive liquid photopolymers "3D resins" considering them as medical and packaging devices are considered as "placing on the market unsafe non-conforming products or products to which the CE marking has been affixed falsely or in a misleading manner". For more info read: CE marking and Health & Safety concerns of "certified" 3Dresins

EU legislation forbids to affix the CE marking (and any sort of medical device certification) to products (raw materials) for which EU specifications do not exist or do not require the affixing of CE marking, as clearly highlighted in the relevant EU regulation on product requirements and market surveillance

CE marking and certifications of 3D resins, "pretending" to consider them medical devices are forbidden, non legally valid, non relevant, misleading, do not make any sense, nor provide any warranty, nor safety, nor biocompatibility assurance for medical device manufacturers and final users.

Most photopolymer 3D resins are cytotoxic before and even after printing unless they are custom designed in tune with appropriate equipment, printing, and processing workflows to ensure their full cure, cleansing, and safety.

Biomedical device, food, and pharmaceutical packaging manufacturers need to design high quality medical devices and packaging products with compliant raw materials "3D resins", equipment, workflows, processes, and protocols to achieve the required biocompatibility for each class of biomedical device or packaging system.

Biocompatible resins and devices need to be designed properly with safe ultra low leachable / extractable ingredients, to ensure that once properly manufactured (printed, postcured and post processed) are free of leachables, extractables, contaminants, residuals, reaction byproducts, and any potential unreacted monomers, before commercialization and usage.

Toxicity of biocompatible 3D resins before & after printing

Discover these recent published findings about the toxicity of Formlabs Dental 3D resins even after printing and postprocessing:

Fig. 2

As clearly highlighted in the last mentioned scientific paper published by the Northwestern University (Chicago, USA), Formlabs’ Dental SG and LT Clear printed in Form 2 SLA 3D printer were toxic, despite being certified as biomedical devices.

This publication "The Biological Effects of 3D Resins Used in Orthodontics: A Systematic Review" concluded that although these resins are considered biocompatible, they exhibit reproductive toxicity in mouse oocytes after direct and indirect exposure. The tested resins were Formlabs Dental SG resins (DSG) and Dental LT Clear (DLT), classified as biocompatible for medical use and currently used in dental surgical guides and oral retainers.

Conclusions: Within the scope of this review, it was noted that studies evaluating the biological effects of 3D resins in orthodontics are mostly conducted in vitro. Although mixed results are described, 3D printed aligners may present higher levels of cytotoxicity and genotoxicity when compared to thermoplastic resins, particularly those that have not been subjected to a final surface treatment. As such, clinical studies analyzing saliva, blood, or even urine samples must be carried out in the future to determine the levels of monomers released in humans upon the use of these devices.

In this publication: Evaluation of dimensional accuracy and degree of polymerization of stereolithography photopolymer resin under different postpolymerization conditions: An in vitro study the degree of polymerization of a Clear Formlabs 3D resin was evaluated following Formlabs printing and post processing protocol. Several specimens were cleaned with isopropanol in the Form Wash unit (Formlabs) for 15 minutes to remove excess resin and poscured with Formlabs light box Form Cure at 15 and 30 minutes and at 40, 60, and 80 ºC. The results are shown in the following table:

The degree of polymerization for all the post processing conditions is in between 70 and 90%, which confirms that the % of residual uncured monomer is between 10 and 30%. The % of residual uncured monomer is extremely high, consequently it can leach out from the prints and be absorbed, causing potential cytoxicity, and potential health problems. These findings confirm the importance of using 3Dresyns monomer free 3D resins.

Similarly to the previously reported findings, the resin of Graphy for direct printing of aligners also may raise concerns on potential health hazards as reported in this paper published in the European Journal of Orthodontics: Leaching from a 3D-printed aligner:

"Although efficiently polymerized and BPA free, the great variability in the amount of UDMA monomer leached from the examined samples may raise concerns on potential health hazards after repeated intraoral exposure"

Unfortunately, in both reported cases, the equipment, instructions for use, and protocols recommended by the mentioned 3D resin manufacturers were reported to be followed without any cutting corners.

3Dresyns statement:

The biocompatibility failure of the mentioned commercial resins might have happened to any biocompatible resin, even to the most biocompatible resins as long as they would not had been properly printed and post processed.

Conclusions

Biocompatibility and safety failure can be due to an inadequate resin design from its conception (eg by using toxic raw materials), or due to inadequate printing, postcuring, and post processing equipment and practices, leaving the prints with leachables and extractables, unreacted free monomers, residuals, and reaction byproducts.

On one hand, 3D resin suppliers are responsible for using as safe as possible raw materials, while on the other hand 3D printed medical device manufacturers are responsible of designing and implementing appropriate workflows to ensure that their medical devices are safe and free of leachables and extractables before commercialization.

Photopolymer 3D resins are liquid photo reactive raw materials, not certified medical devices, which photopolymerise or react with light in the printers, normally layer by layer, to become printed solid photopolymer materials with specific shapes.

Biocompatible 3D printed medical devices need to be manufactured properly without leachables and extractables after appropriate design, printing, postcuring, and post processing workflows to ensure maximum quality and safety for final users.

Medical device manufacturers, including dental and orthodontic clinics are legally responsible for their produced and traded medical devices since biocompatibility and safety depend on the compliancy of the chosen raw materials after appropriate usage (3D resins and auxiliaries), but also on the quality of the medical device as result of the overall medical device design and manufacture, including the used software, hardware, printing, postcuring, and post processing design, protocols, workflow, and overall quality control system, since medical device manufacturers (not their raw material suppliers) are legally responsible for the final quality of their manufactured and traded medical devices.

Passing the hot potato to the raw materials (3D resin) suppliers is unethical since medical device manufacturers are legally responsible for assuring the safety of their products and that leachables, extractables, unreacted monomers, residuals, reaction byproducts, and contaminants are eliminated before commercialization.

3Dresyns statement: "3D resin suppliers cannot ensure, nor grant any warranty, as a blank cheque, of certifiability since the quality and safety of any manufactured biomedical device it is beyond its competence and control. Nevertheless, 3D resin manufacturers are responsible for making resins compliant with the quality requirements of the claimed standards, for aiding manufacturers in getting the required certifications for making biomedical devices"

Analysis and split of 3D resin and medical device manufacturer responsibilities for biocompatibility:

3D resin suppliers are responsible for designing and producing resins compliant with the safety and quality required by the regulatory for the medical device class and sort they have been designed for:

3D resins need to be designed with as safe as possible ingredients, with the lowest possible leachability risk after appropriate curing, printing, postcuring, and post processing, to reduce the risk of causing cytotoxicity and potential health hazards
3D resin suppliers cannot be liable nor responsible for leachables and extractables when inappropriate curing, printing, postcuring, and post processing equipment, protocols and controls are used by medical device manufacturers in their premises and under their own responsibility as final medical device manufacturers

Medical device manufacturers are responsible for designing and producing certified medical devices compliant and in accordance to the applicable regulations for which they should obtaine their own certification for producing the specific sort and class of the produced 3D printed medical devices (and/or packaging):

medical devices need to be designed with safe low leachable biocompatible raw materials "3D resins", after appropriate curing, printing, postcuring, and post processing, to avoid the risk of causing cytotoxicity and potential health hazards
manufacturers need to use compliant 3D resins (not certified 3D resins), printers, post processing equipment, quality control* instrumentation, and should validate their implementation and protocolization in their production workflow for ensuring the production of safe biocompatible medical devices

manufacturers are responsible for the final quality, including the overall performance and safety of their produced and traded medical devices, and for their compliancy and certification with the relevant and applicable regulatory standards

*Note: quality control by device manufacturers should include the analysis, elimination and control of any potential leachables, extractables, and contaminants before use by final customers

3D resins are photoreactive raw materials, not medical devices

3D resins are raw materials, not certified medical devices. Certification of 3D resins as being medical devices, besides misleading may cause potential health and safety concerns, since certified products cannot be updated when reclassification of their constituents considers them dangerous to humans and to environment. 3D resin suppliers which misleadingly certify their resins as medical devices, create confussion and false sense of quality assurance. It is considered a misleading marketing practice as clearly highlighted in the EU regulation on product requirements and market surveillance where indicates that it is forbidden to affix the CE marking (including certification) to products for which EU specifications do not exist or do not require the affixing of CE marking (or certification): "placing on the market unsafe non-conforming products to which the CE marking has been affixed falsely or in a misleading manner.”

For more infor read:

Quality and safety assurance

Quality and safety depends on the polymer conversion, which depends on the chosen 3D resin, printer, printing, postcuring, and post processing design, equipment and their specifications, as well as on the composition, safety of all the raw materials and auxiliaries used for making medical devices, which affect and determine the risks for health of the residuals, byproducts, impurities, and contaminants, susceptible of leaching out, unless their extraction of the printed device is ensured before commercialization.

Conclusions

Medical device manufacturers are responsible for:

using compliant 3D resins for the intended use, not misleading certified resins pretending to be and replace medical device certifications
using reliable calibrated and well maintained equipment, printers, postcuring, post processing and quality control equipment
integrating and validating them with Good Manufacturing Practices GMP, with consistent and reliable validated manufacturing
implementing well designed, integrated, and implemented printing, cleaning, postcuring, post processing, and quality control workflows and protocols
ensuring the manufacturing of 3D printed medical devices with maximum safety and quality, which production process must be validated to consistently produce the intended medical device

Learn more about biocompatibility of 3D resins:

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About Certification of biomedical devices and food and pharma packaging