About Certification of biomedical devices and food packaging

3D resins are raw materials, not finished medical devices

Biocompatibility certifications (including biomedical devices (including dental, hearing, implants, food and pharmaceutical devices and packaging) of photoreactive liquid photopolymers "3D resins" considering them as medical devices (or eg food or pharmaceutical grade packaging) is 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, since 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 (and 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.

Photopolymer 3D resins are liquid photo reactive raw materials, which photopolymerise or react with light in the printers, normally layer by layer, to cure or become printed solid materials with a specific shape.

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 postprocessed) are free of leachables, extractables, contaminants, residuals, reaction byproducts, and any potential unreacted monomers, before commercialization and use.

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 postprocessing 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 postprocessing 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, genotoxicity, 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 equipments, instructions for use, and protocols recommended by the mentioned 3D resin manufacturers were reported to be followed without any corner cuttings.

3Dresyns statement:

The biocompatibility failure of the mentioned commercial resins might have happened to any biocompatible resin, even to the most biocompatible resins if and when they would not had been properly printed and postprocessed.

Reasons for biocompatibility failure

Biocompatibility and safety failure can be due to an inadequate resin design from its conception, and/or due to an inadequate postcuring and postprocessing, leaving the medical device (or packaging) full of leachables and extractables, unreacted monomers, residuals, and reaction byproducts.

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 of 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 and in accordance to the applicable regulations for which they have been designed:

3D resins need to be designed with as safe as possible ingredients, with the lowest possible leachability risk after appropriate curing, printing, postcuring and postprocessing, to avoid 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 postprocessing equipment, protocols and controls are used by medical device manufacturers in their premises and under their resposibility as final manufacturers

Medical device suppliers are responsible for designing and producing medical devices compliant and in accordance to the applicable regulations for which they have or should have obtained their own certification (for producing the specific sort and class of the produced medical devices and packaging):

medical devices need to be designed with safe low leachable biocompatible raw materials "resins", after appropriate curing, printing, postcuring and postprocessing, to avoid the risk of causing cytotoxicity and potential health hazards

Medical device manufacturers are responsible for:

the appropriateness of the chosen resin, printer, post processing equipment, quality control* instrumentation, and their implementation and protocolization in their production workflow for ensuring the production of safe biocompatible medical devices
the final quality, including the overall performance and safety of their produced and traded medical devices, and compliancy with the relevant and applicable regulatory standards

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

Quality and safety depends on the polymer conversion, which depends on printer, printing, postcuring and postprocessing equipment and specifications, as well as on the composition, safety, and concentration 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 and sterilisation are ensured before commercialization.

Conclusions

Non-properly designed and produced biocompatible resins, despite undertaking appropriate cleaning, postcuring and postprocessing are prone to fail the biocompatibility testing (
Properly designed and produced biocompatible resins with the appropriate cleaning, postcuring and postprocessing can pass the biocompatibility testing, but may also fail the biocompatibility testing with inappropriate equipment, cleaning, postcuring, postprocessing, and controlling of the safety and quality of medical devices
Medical device manufacturers are responsible for using appropriate printing and post processing equipments, implementing the right printing, cleaning, postcuring, and postprocessing protocols, as well as for producing with appropriate quality controls to ensure maximum safety and quality of their products

Learn more about biocompatibility of 3D resins: