The present article describes the aspects related to material characterization, removing manufacturing material residues, and sterilization.
Table of Contents
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to technical considerations for additive manufactured medical devices. The document highlights the most important aspects related to medical devices manufactured with the use of 3D-printing (additive manufacturing, or AM) technologies based on their specific nature. The guidance is intended to provide additional clarifications regarding the applicable regulatory framework, as well as recommendations to be considered by medical device manufacturers and other parties involved to achieve and sustain compliance thereto. The authority mentions that provisions of the guidance are non-binding due to their legal nature, and are not intended to introduce new rules or requirements to be followed. At the same time, an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance.
Material Characterization
When addressing the matters associated with the use of additive manufacturing technologies, the Agency pays special attention to the aspects related to the materials used since they could significantly impact the safety and quality of the final product due to the specific nature of the manufacturing process. The authority emphasizes the importance of identifying any materials used in the process, and rigorous assessment of each of them. The manufacturers are requested to provide exhaustive information about the materials used including, if applicable, Certificates of Analysis and/or Materials Safety Data Sheets (MSDS), as well as the Chemical Abstract Service (CAS) number. Apart from this, manufacturers are obliged to duly document the composition of a final medical device.
Another important aspect is related to the manufacturing process, during which the initial material could be subject to changes numerous times that could impact its characteristics. To evaluate the significance of such impact, a rigorous assessment should be performed. The scope of such an assessment should cover, inter alia, biocompatibility-related matters as prescribed in the respective guidance on the use of International Standard ISO-10993 “Biological Evaluation of Medical Devices Part 1: Evaluation and Testing within a Risk Management Process”. The Agency expects the manufacturer to provide detailed information about any chemical changes in the materials used. Based on this information, the manufacturer should also provide testing reports demonstrating that such changes would not adversely impact the safety and performance of a medical device, nor would expose patients to additional risks.
Should the device composition include metal or ceramic, the manufacturer is also expected to provide information about the microstructure (grain size, orientation, and phase composition). In case the manufacturing process is associated with certain changes to the structure, the impact of such changes to the overall safety and performance should be assessed as well.
In case the device is composed of polymers, the manufacturer should ensure consistency in the manufacturing process, as this impacts the characteristics of the final device. It is important to ensure that the manufacturing process itself does not harm the material used.
If the material used is absorbable, the manufacturer should undertake in vitro degradation testing using the finished product to evaluate the impact caused to the material and its degradation profile.
Post-manufacturing Processes
The guidance also covers some of the post-manufacturing processes, such as removing manufacturing material residues and sterilization.
Additive manufacturing technologies could be used to produce medical devices with complex geometries, which provide flexibility that far exceeds the abilities of traditional manufacturing technologies. At the same time, this also makes the procedures associated with removing manufacturing material residues and sterilization much more difficult. For instance, due to the complexity of geometries, a medical device could have elements with limited or even no access. Apart from this, the use of additive manufacturing technologies sometimes results in the creation of porous structures that have their specific characteristics as well. Hence, medical device manufacturers using additive manufacturing technologies should take all the steps to ensure the complexity of geometries would not impact adversely the safety and effectiveness of the product due to the inability of the manufacturer to complete post-manufacturing processes. For this purpose, manufacturers should develop and validate the efficient processes for the reduction of the manufacturing material residue to the acceptable level.
For the guidance, manufacturing material means any material or substance used in or used to facilitate the manufacturing process, a concomitant constituent, or a byproduct constituent produced during the manufacturing process, which is present in or on the final finished device as a residue or impurity not by design or intent of the manufacturer. The process used to remove residual manufacturing material should be described in detail and be efficient enough to ensure the safety and effectiveness of the final finished device. The authority mentions that in certain cases the effectiveness of such a process could be validated only by the virtue of destructive testing, as this is the only way to reach and assess parts of the device the access to which is limited due to the complexity of the geometries.
If the material used could adversely impact the safety of the finished device, the manufacturer is obliged to take all the steps to ensure the effectiveness of the procedures performed to remove such material to the extent at which it would not result in additional risks. Moreover, the Agency mentions that since most healthcare institutions using medical devices do not have the necessary equipment and qualified personnel to remove residual manufacturing materials, the medical device manufacturer shall ensure the device is supplied in a cleaned condition with no further actions required. It is also important to consider that cleaning becomes much more difficult in the case of porous materials used.
Based on the above, the authority expects medical device manufacturers to include an overview or summary of the manufacturing residue removal process and information (e.g., testing procedure and data) in [the] premarket submission to demonstrate that [the] device is cleaned of manufacturing residues before being provided to the end-user.
When determining the extent to which manufacturing material residue should be removed, the manufacturer should take into consideration the aspects related to the manufacturing process itself, characteristics of the materials used, the intended use of a medical device, and other important matters.
In summary, the present FDA guidance outlines the key points to be considered concerning materials used in the additive manufacturing process in the context of the overall safety and effectiveness of a medical device. The authority pays special attention to the aspects related to the removal of manufacturing material residues to prevent them from adversely impacting the safety and effectiveness of a final finished device.
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