Draft Guidance Document - Licensing Requirements for Implantable Medical Devices Manufactured by 3D Printing
This guidance document is being distributed for comment purposes only.
Draft date: 2018/10/08
Health Canada is responsible for helping Canadians maintain and improve their health. It ensures that high-quality health services are accessible, and works to reduce health risks.
Également disponible en français sous le titre :
Exigences d'homologation pour les instruments médicaux implantables fabriqués par impression 3D
©Her Majesty the Queen in Right of Canada, as represented by the Minister of Health, 2018
Publication date: November 2018
This publication may be reproduced for personal or internal use only without permission provided the source is fully acknowledged.
Guidance documents are meant to provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. Guidance documents also provide assistance to staff on how Health Canada mandates and objectives should be implemented in a manner that is fair, consistent, and effective.
Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. Alternate approaches should be discussed in advance with the relevant programme area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.
As a corollary to the above, it is equally important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, in order to allow the Department to adequately assess the safety, effectiveness, or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justifiable and that decisions are clearly documented.
This document should be read in conjunction with the accompanying notice and the relevant sections of other applicable Guidance documents.
Table of contents
- 1. Introduction
- 2. Guidance for implementation
- 2.1 Information applicable to 3D-printed implantable medical device licence applications
- 2.2 Safety and effectiveness requirements
- 2.3 Device labels, package labelling and documentation
- Appendix A - Glossary
- Terminology related to printing processes as defined in ISO/ASTM 52900:2015
- Appendix B - References
The guidance document is intended to aid manufacturers and regulatory representatives in preparing medical device licence applications for 3D-printed medical devices. As with all Class III and IV medical devices, devices produced by additive manufacturing, or 3D printing, are subject to the Medical Devices Regulations (Regulations) and require a review of submitted evidence of safety and effectiveness before a licence can be issued.
This guidance document should be read in conjunction with the Guidance Document on supporting evidence to be provided for new and amended licence applications for Class III and Class IV medical devices, not including In Vitro Diagnostic Devices (IVDDs).
1.2 Scope and application
The document provides guidance for manufacturers regarding the evidence to support pre-market Class III and Class IV licence applications for implantable medical devices manufactured by 3D printing processes under ISO 13485. Considerations related to the design and manufacturing processes, material controls, device testing, and labelling of 3D-printed devices are included in this guidance document. However, not all considerations will be applicable to every device type.
The content described in this guidance document is to be submitted for review in addition to the general data elements listed in paragraphs 32(3) and (4) of the Regulations.The guidance document will not provide guidance on third-party software, custom-made devices, patient-specific anatomical models, devices manufactured at point-of-care, and devices with biological components.
1.3 Policy objectives
To ensure that manufacturers have the necessary information to complete a medical device licence application for an implantable device manufactured by 3D printing pursuant to the Regulations.
1.4 Policy statements
All Class III and Class IV medical devices require a review of submitted evidence of safety and effectiveness before a licence can be issued.
The same data requirements apply to 3D-printed devices as those for conventional devices in terms of their characterization, and evidence of safety and effectiveness, including physical and mechanical bench testing, biocompatibility testing, software and clinical evidence. However, additional requirements may apply to 3D-printed devices.
In keeping with international standards, the guidance document adopts definitions developed by the International Medical Device Regulators Forum (IMDRF) with respect to Definitions for Personalized Medical Devices.
Hospitals that manufacture 3D-printed implantable medical devices for distribution beyond their institution qualify as a manufacturer, and should comply with the same obligations as other medical device manufacturers.
Health Canada is committed to supporting the integration of 3D-printed technologies into health care systems in Canada, and providing Canadians with the highest possible quality of care.
The federal government is actively working and collaborating with international counterparts to keep pace with the research and development of 3D printing. Canada's licensing approach for implantable medical devices manufactured by 3D printing is well aligned with international best practices.
Due to the fast-changing technological environment, Health Canada will continue to adapt its policy approach to 3D-printing as issues on the topic evolve. This guidance document therefore represents the first phase of 3D printing policy in Canada.
2. Guidance for implementation
2.1 Information applicable to 3D-printed implantable medical device licence applications
2.1.1 Device description
The device description should include the starting material (with reference to any applicable material standards) and a description of the 3D printing method (e.g., laser sintering, direct metal laser sintering, powder bed fusion etc.). An overview of the manufacturing process should be provided. Any additives or processing agents mixed with the starting material should be clearly identified.
The device description should state whether the entire device or only a component of the device is 3D-printed.
In cases where the device is patient-specific 1 rather than manufactured to standard size, manufacturers should describe:
- key design parameters
- parameters of the device that may be altered to be patient-specific, if not the entire device
- critical features, including the range and boundaries of dimension (i.e., location and thickness of porous features)
Further characterization of the starting material may include parameters measured prior polymerization/fusion including but not limited to:
If the material is in solid phase: particle size and size distribution for powders or filament diameter and diametric tolerances for filaments, composition and purity (for alloys), mix ratio (for composites)
If the material is in liquid phase: viscosity or viscoelasticity, pH, ionic strength, and pot life
If the material is a polymer or monomer mixture: composition, purity, water content, and chemical structure molecular formula
In some cases, the starting material may be approved for a specific intended use (i.e., for the fabrication of dental restoratives and prosthetic devices by healthcare professionals). Evidence should be provided to show that the material is suitable in terms of physical and chemical properties, for the specific indications for use.
2.1.2 Licence amendments
If the application is to modify a licensed device, a description of the modification is required (e.g., changes in design, performance, indications, etc.). A comparison of the subject device with the proposed modifications and the previously licensed device should be provided in a table format.
Examples of device modifications related to 3D printing may include, but are not limited to:
- a 3D-printed component that is being added to an approved device (i.e., porous surface coating)
- a 3D-printed component that is to be used with an approved device (i.e., dental superstructures/abutments/implants)
An amendment application may also be required if potential effects on safety and effectiveness of the finished device are identified. These may include:
- changes in material (i.e., supplier, incoming material specification, ratio of recycled powder)
- software changes (i.e., change or update of build preparation software)
- Changes to the printer or printing process which may effect the finished device
2.1.3 Design philosophy
The design philosophy should describe the advantages of using 3D printing as a manufacturing process (i.e., patient-matched devices, devices with complex geometry and/or non-standard sizing) compared to conventional manufacturing methods.
2.1.4 Marketing history/regulatory status
If the market history for the 3D-printed device is not yet available or limited, a summary of the market history for a previously authorized device can be provided if relevant/applicable. The market history for any comparable 3D-printed components may also be provided (i.e., if the same 3D-printed porous coating is used on multiple devices) if relevant/applicable.
2.2 Safety and effectiveness requirements
2.2.1 List of standards
In addition to providing a list and a declaration of conformity to any applicable standards, the manufacturer should indicate whether or not the device complies with any standards specific to 3D-printing.
2.2.2 Preclinical studies
This section should include additional information regarding process and performance validation for 3D-printed devices. Validations may be required and/or apply to each of the following components: printer, starting material, test coupon, and finished device.
If not provided under the device description, this section should also include a summary of the complete manufacturing process, including device design, software workflow, printing and post-processing steps. A description of all quality control measures in place for each manufacturing step should be included in the manufacturing overview.
126.96.36.199 Considerations related to validation of the printing process
With respect to the printer, the following evidence should be provided:
- A summary of the cleaning and maintenance processes for the printer.
- Validation of the consistency of the printer performance, including analysis of worst case parameters and recommended in-process parameters (i.e., build-space conditions, power of energy delivery systems, test coupon evaluation).
- Validation of the printer and material combination with consideration of build direction(s), build location(s), variations between various sizes/designs, to determine the degree to which the build orientation and location may affect the mechanical properties of the finished device.
- If multiple build paths are used, each build path should be documented and validated.
- If multiple devices and/or components are printed simultaneously in the same build location, quality assurance should consider repeatability and consistency within a cycle and across lots.
- With respect to patient-specific devices, evidence to support the accuracy of device reproduction from patient images is required.
With respect to the starting material, the following evidence should be provided:
- Chemical composition of the starting material to verify if the material meets specifications for impurities (as applicable, including certificates of analysis).
- A description of any additional materials added to the starting material and/or to the printer during the manufacturing process (i.e. machine oil, lubricants, additives) or cleaning process (reagents, chemicals). Any residual levels of additional materials should be compared to those of devices manufactured via conventional methods, if applicable.
- Validation of the powder removal process, if applicable,to support the capacity of the cleaning process to remove loose powder particles.
- Validation of the powder recycling, if applicable, with consideration of potential effects on melting properties and bonding between layers.
The use of test coupons as a representative sample of the material and/or finished device may be included in the validation of the printer and print process to identify worst case conditions with respect to orientation and location in the build space; test coupons may also be suitable for in-process monitoring of worst case conditions. This approach may also be considered for validation of multiple printers or changes in printers or printer location.
188.8.131.52 Considerations related to device performance
The use of test coupons may also be appropriate for validation of finished device performance where the manufacturer can demonstrate that the test coupon:
- is sufficiently representative of the subject device in terms of critical design parameters (i.e., orientation, geometry, thickness, critical dimensions, smooth edges) and,
- has undergone identical post-printing processing and sterilization as the final finished device.
Preclinical performance testing should be conducted on the final, finished device subjected to all post-processing, cleaning and sterilization steps. For each test, a detailed summary is required and should include a description of the test objective, samples tested, analysis of the worst case configuration of the test samples with respect to dimensions and features (holes, supports, porous areas), acceptance criteria with justification, adherence to recognized standards (where applicable), test results and a discussion/analysis of the results in terms of the test objective. For patient-specific devices, performance testing should consider the worst case configuration based on the critical boundaries of design, size, and geometry of the finished device.
The performance validation of the finished device should be equivalent to that of conventionally manufactured components, with respect to applicable mechanical performance and strength tests and may include:
- tensile strength (ultimate tensile strength, yield strength, maximal elongation)
- flexural strength
- dynamic fatigue strength
- shear strength/adhesion for a coating
In some cases, comparison of the mechanical performance of the 3D-printed device to that of conventionally manufactured previously licensed device may be appropriate and should be provided in the test report.
2.2.3 Shelf life studies for the product
Shelf life considerations related to 3D-printed devices include:
- effects on long term material stability (with respect to inter-layer bonding and homogeneity across build layers)
- shelf life of recycled powder
- possible time-dependent changes to patient anatomy for patient-specific devices
2.2.4 Software verification and validation
The manufacturer should provide an overview of the software-related workflow from medical image acquisition (if applicable) to segmentation and design manipulation for the final print preparation including a summary of all risk control considerations and measures associated with all software components and applications that are used in the device development and printing process. These considerations may include, but are not limited to:
- verification of adequate medical image quality, if applicable
- validation of automated software process steps, including segmentation, if applicable
- verification of file format compatibility, integrity, and conversions between process steps
- patient identification information, considering patient privacy and confidentiality, and
- maintenance of final device files and printer logs for later retrieval
2.2.5 Biocompatibility tests
Evidence of biocompatibility from non 3D-printed previously licensed devices or materials is not generally considered sufficient to support biocompatibility of 3D-printed devices due to differences in the manufacturing process (even with adherence to recognized material standards specific to 3D printing).
Biocompatibility testing should be conducted on the final, finished device as per the requirements of ISO 10993-1:2009 (refer to Appendix B).
Biocompatibility testing should also address the use of any additives (i.e., chemicals, machine oils, lubricants, reagents, solutions) during the manufacturing process.
For multiple 3D-printed devices in a single application, with identical manufacturing/cleaning/sterilization processes, testing should be conducted on the worst case device.
2.2.6 Animal studies
Animal studies may be required for a 3D-printed device with a novel design, material, or intended use.
2.2.7 Clinical studies
Device-specific clinical data may be required for a 3D-printed device with a novel design, material, or intended use.
Where long term clinical data for 3D-printed device may not be available, the clinical experience of a comparable non 3D-printed device may be considered during the evaluation of safety and effectiveness of the 3D-printed device. However, the requirement for device-specific clinical data is determined on a case-by-case basis.
Manufacturers may request a pre-submission meeting with Health Canada for more in-depth advice or guidance on their licence application.
2.2.8 Considerations related to the post-processing and sterilization
This section considers both the cleaning and sterilization processes related to 3D-printed devices, where "cleaning" generally refers to the removal of excess starting material (where applicable) and/or manufacturing material residues.
Validation of the cleaning and sterilization processes should consider the worst case scenario in terms of surface area, porosity and voids in the finished device. Cleaning and sterilization challenges should be addressed in the validation and may include:
- complex geometry: engineered porosity, honeycomb structures, internal channels/voids/cavities
- increased surface area and/or limited internal access
- destructive testing may be required to support validation of devices with complex structures
- adequate removal of supportive structures such as overhangs, protruding features, internal features (voids, channels), thin features prone to warping
With respect to sterilization validation, evidence should be provided to show how:
- bioburden was minimized throughout the 3D printing processes
- the sterilization process may affect the material characteristics and device performance (i.e., one-piece solid cast device vs. 3D printed porous device)
- the sterilization method is appropriate for the device material
For patient-specific devices, sterilization validation should consider the worst case configuration based on the critical boundaries of design, size, and geometry of the finished device.
Any changes from methods of sterilization validation as outlined in the requirements of recognized standards should be described and justified in the sterilization validation.
2.3 Device labels, package labelling and documentation
For patient-specific devices, the manufacturing process may include multiple transfers of patient images and device design files between the manufacturer and health care professional. Adequate labelling for device identification and design version control should be provided, while considering patient privacy and confidentiality.
Labelling of patient-specific devices may include:
- the patient's name or
- a patient identifier and
- anatomical location for implantation
For 3D-printed devices that are patient-matched, Health Canada recommends additional labelling information since clinical staff, device manufacturers, or a designated third party might modify the design of a patient-specific device. Each patient-matched 3D-printed device should be marked or have accompanying healthcare practitioner labelling included in the packaging to identify the following characteristics:
- patient identifier
- use (e.g., left distal femoral surgical guide) and
- final design iteration or version used to produce the device
The expiration date for a patient-matched device may be based on the patient imaging date or the design finalization date rather than the standard methods of determining device shelf life (refer to section 2.3.3 of this guidance document). Because it is possible that the patient may have experienced events between the time of imaging and surgery (e.g., additional trauma), which could impact performance of the device, manufacturers of patient-matched devices should include a precaution in their labelling stating that the patient should be assessed for potential anatomical changes prior to the procedure.
Specific instructions for image-acquisition protocols (i.e., supported imaging modalities, scanning parameters, image reconstruction parameters, file types, patient positioning, gating requirements, etc.) should be clearly outlined on the Instructions for Use.
Appendix A - Glossary
3D printing (3DP) 2:
Also referred to as "Additive Manufacturing" (AM) and defined as "a process that builds an object by iteratively building 2-dimensional (2D) layers and joining each to the layer below, allowing device manufacturers to rapidly alter designs without the need for retooling and to create complex devices built as a single piece."
Additive manufacturing (AM) 3 :
Process of joining materials to make parts from 3D model data, usually layer upon layer, as opposed to subtractive manufacturing and formative manufacturing methodologies.
Specific printing methods and processes are provided in the terminology list below, and commonly include laser sintering, stereolithography, powder bed fusion, digital light processing, extrusion or fused deposition modelling, binder and material jetting.
Patient-matched medical device (or Patient-specific medical device) 4:
A medical device that meets the following requirements:
- it is matched to a patient's anatomy within a specified design envelope using techniques such as scaling of the device based on anatomic references, or by using the full anatomic features from patient imaging; and
- it is typically produced in a batch through a process that is capable of being validated and reproduced; and
- it is designed and produced under the responsibility of a manufacturer even though the design may be developed in consultation with an authorized healthcare professional.
Note 1: A written request from an authorized healthcare professional may be present; but is not mandatory.
Note 2: The number and type of design inputs in consultation with a healthcare professional may vary depending on the medical devices to be manufactured.
Note 3: The design must remain within the validated parameters of the specified design envelope.
Terminology related to printing processes as defined in ISO/ASTM 52900:2015
Additive manufacturing process in which a liquid bonding agent is selectively deposited to join powder materials.
Powder bed fusion:
Additive manufacturing process in which thermal energy selectively fuses regions of a powder bed.
Directed energy deposition:
Additive manufacturing process in which focused thermal energy is used to fuse materials by melting as they are being deposited.
Additive manufacturing process in which material is selectively dispensed through a nozzle or orifice.
Additive manufacturing process in which droplets of build material are selectively deposited.
Enclosed location within the additive manufacturing system where the parts are fabricated.
Single process cycle in which one or more components are built up in layers in the process chamber of the additive manufacturing system.
Location where it is possible for parts to be fabricated, typically within the build chamber or on a build platform.
Area where material is added, normally on the last deposited layer which becomes the foundation upon which the next layer is formed.
Total usable volume available in the machine for building parts.
3D digitizing, method of acquiring the shape and size of an object as a 3-dimensional representation by recording x,y,z coordinates on the object's surface and through software the collection of points is converted into digital data.
Additive Manufacturing File Format (AMF):
File format for communicating additive manufacturing model data including a description of the 3D surface geometry with native support for colour, materials, lattices, textures, constellations and metadata.
Powder bed fusion process used to produce objects from powdered materials using one or more lasers to selectively fuse or melt the particles at the surface, layer upon layer, in an enclosed chamber.
One or more, process steps taken after the completion of an additive manufacturing build cycle in order to achieve the desired properties in the final product.
Powder used as feedstock which could be used powder, virgin powder or a blend of the two.
Part bed, build area in an additive manufacturing system in which feedstock is deposited and selectively fused by means of a heat source or bonded by means of an adhesive to build up parts.
Powder that has been supplied as feedstock to an AM machine during at least one previous build cycle.
Unused powder from a single powder lot.
All parts produced in one build cycle or sequential series of build cycles using the same feedstock batch and process conditions.
Appendix B - References
- Guidance Document on supporting evidence to be provided for new and amended licence applications for Class III and Class IV medical devices, not including In Vitro Diagnostic Devices (IVDDs)
- Guidance for the Interpretation of Sections 28 to 31: Licence Application Type
- IMDRF Proposed Document International Medical Device Regulators Forum, Definitions for Personalized Medical Devices
- US FDA's 2017 Guidance Document for Industry and FDA Staff, Technical Considerations for Additive Manufactured Medical Devices, (https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM499809.pdf)
- ISO 10993-1:2009 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process, ISO 10993-1:2009/Cor.1:2010SO 10993-1:2009
Throughout this guidance document the terms patient-specific devices and patient-matched devices are used interchangeably.
US FDA's 2017 Guidance Document for Industry and FDA Staff, Technical Considerations for Additive Manufactured Medical Devices
ISO/ASTM 52900:2015 Standard Terminology for Additive Manufacturing - General Principles-Terminology
IMDRF Proposed Document International Medical Device Regulators Forum, Definitions for Personalized Medical Devices
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