The State Food and Drug Administration's Equipment Review Center recently issued a notice (No. 13, 2022) on seven key technical review points, including the key technical review points of medical electronic linear accelerator, including the Key Technical Review Points of 3D Printing Intervertebral Fusion Cage.
The following is the full text of Key Points for Technical Review of 3D Printing Intervertebral Fusion Cage. 'Read the original text' at the bottom left corner of the text can be downloaded as an attachment in Word.
Annex 4
Key points of technical review of 3D printing intervertebral fusion cage
The main points of this review are intended to guide the registration applicant to prepare and write the registration and application data of 3D printing intervertebral fusion cage products, and also provide reference for the technical review department to review the registration and application data.
The main points of this review are the general requirements for 3D printing intervertebral fusion cage products. The registration applicant shall determine whether the contents are applicable according to the specific characteristics of the product. If not, it is necessary to specify the reasons and corresponding scientific basis, and enrich and refine the contents of the registration application materials according to the specific characteristics of the product.
1、 Scope of application
This review point is applicable to the registration of 3D printing intervertebral fusion cage products. 3D printing intervertebral fusion cage products are usually manufactured by TC4 or TC4 ELI titanium alloy powder laser or electron beam fusion and other additive manufacturing processes. This product does not include the requirements for specially designed products such as self-stabilizing, stretchable, split combination and other intervertebral fusion cages, but the applicable parts can refer to the corresponding technical content in the basic requirements of this review.
According to the current Classification Catalogue of Medical Devices, the product classification code is 13-03-04, and the management category is three.
2、 Basic requirements
The research data of 3D printing intervertebral fusion cage can be submitted in accordance with the requirements of the relevant guiding principles such as the Guiding Principles for the Technical Review of the Registration of Intervertebral Fusion Cage and the Guiding Principles for the Technical Review of the Registration of 3D Printing Artificial Vertebra.
3、 Risk management
According to YY/T 0316-2016 'Application of Medical Device Risk Management to Medical Devices', fully identify the safety characteristics of each link in the product life cycle of 3D printing interbody fusion cage product, including biological hazards (sources), environmental hazards (sources), hazards (sources) related to the implantation process Conduct a comprehensive risk analysis of the product from the aspects of hazards (sources) caused by functional failure and fatigue, and detail the risk control measures taken.
Provide the risk management report formed by the comprehensive review of the risk management activities of the 3D printed interbody fusion cage before its launch. This report aims to explain and promise that the risk management plan has been properly implemented, and after verification, it is determined that the comprehensive residual risk is acceptable, and there are appropriate methods to obtain the relevant information of the product design, manufacturing, post-delivery circulation and clinical application.
The risk management report shall include risk analysis, risk evaluation, risk control and other relevant data of product risk management, at least including the list of product safety characteristics, the list of foreseeable hazards and hazard analysis of the product (description of hazards, sequence of foreseeable events, i.e. hazard cause analysis), the relationship between the hazard situation and possible damage, risk evaluation, risk control measures and the summary of residual risk evaluation.
4、 Product research
3D printing of intervertebral fusion cage research data should focus on the following requirements:
（1） Physical and chemical properties of products
The raw material quality control requirements of 3D printing intervertebral fusion cage, the minimum structural unit of the porous part, the physical and chemical properties research and defect control, and the metal ion release research of the product can refer to the requirements of the Guiding Principles for the Technical Review of the Registration of 3D Printing Artificial Vertebra and the Guiding Principles for the Technical Review of the Registration of 3D Printing Acetabular Cup Products to submit the research data.
（2） Mechanical properties of products
1. Dynamic and static mechanical test of 3D printing intervertebral fusion cage
It is recommended to carry out dynamic and static mechanical performance test according to YY/T 0959 standard. The cervical fusion cage provides dynamic and static mechanical test reports including compression, shear and torsion, and the thoracolumbar fusion cage provides dynamic and static mechanical test reports including compression and shear. The test report shall include the test sample information, equipment model, tooling material, loading mode, disc height, actual test pictures, static test load-displacement curve and dynamic test load-cycle curve of each sample, data processing, sample failure mode and other relevant information. Please consider the size of the bone graft area (if applicable), the size of the side opening window (if applicable), the inclination, length, width and height of the fusion cage of different models and specifications, and select the worst case of the cervical spine and the thoracolumbar spine fusion cage for the above tests, and provide the selection basis. Please provide the acceptable basis for the mechanical performance test results of cervical and thoracolumbar fusion cage products in clinical application, and describe the differences in mechanical properties between the declared products and the same products, as well as the differences in failure forms, such as the fracture form of porous structure, powder precipitation, etc., which need to be analyzed and demonstrated for acceptability.
2. Static axial compression settlement test of 3D printing intervertebral fusion cage
It is recommended to evaluate the settlement tendency of 3D printing intervertebral fusion cage under static axial compression load according to the test method specified in YY/T 0960.
3. Impact resistance of 3D printing intervertebral fusion cage
Considering that when the 3D printing interbody fusion cage is inserted into the intervertebral space, knocking may cause fracture failure of the porous structure of the fusion cage and the joint of the porous structure and the solid, it is recommended to provide the impact resistance research data of the product in combination with the structural design of the interbody fusion cage (porous structure and solid structure), the mechanical coordination design of the holder and the fusion cage, and the resistance of different design of the implanted intervertebral space.
4. 3D printing intervertebral fusion cage anti-detachment performance
Considering that the 3D printing intervertebral fusion cage has the risk of prolapse without bone ingrowth at the initial stage of implantation, it is suggested to provide the research data of the anti-prolapse performance of the 3D printing intervertebral fusion cage in combination with the anti-prolapse structure design of the surface of the intervertebral fusion cage.
（3） Research on biological characteristics
The biocompatibility evaluation of the product should be combined with the corrosion resistance of the product and the metal ion precipitation behavior, Carry out risk assessment according to the system method block diagram in GB/T 16886.1-2011 Biological Evaluation of Medical Devices - Part 1: Evaluation and Test in the Process of Risk Management and the review points in the Notice of the State Food and Drug Administration on Printing and Distributing the Guidelines for Biological Evaluation and Review of Medical Devices (GSYJX [2007] No. 345), and carry out biological tests according to GB/T 16886 series standards when necessary.
（4） Pyrogen and bacterial endotoxin
Considering that there may be residual powder and bacterial corpses in the porous structure of 3D printing intervertebral fusion cage, it is necessary to verify the pyrogen and bacterial endotoxin.
（5） MRI compatibility test
If the applicant has verified the MRI compatibility of the declared product, the MRI test equipment, magnetic field strength, SAR and other test parameters as well as the temperature rise, displacement force and artifact evaluation results shall be listed according to the research report. If the applicant has not verified the MRI compatibility of the declared product, it should be emphasized that the product has not been tested and evaluated for temperature rise, displacement and artifacts under the magnetic resonance (MRI) environment. The relevant contents shall be indicated in the warning of the manual to indicate the existing risks.
（6） Cleaning and sterilization study
The worst case shall be selected for the validation of cleaning process and sterilization process according to the product characteristics. For example, the material residue shall be considered in the validation of cleaning process, and the factors affecting the microbial load such as surface area, porosity, pore size, etc. shall be considered in the validation of sterilization process. Demonstrate the effectiveness of the cleaning verification method, and use destructive test to verify the cleaning method if necessary. Considering the complexity of additive manufacturing process, the cleaning process validation of its porous structure should be completed by the applicant.
（7） Stability study
For validation of validity period of 3D printing intervertebral fusion cage, please refer to the Guidelines for Registration and Application of Shelf Life of Passive Implantable Medical Devices.
（8） Animal test
The effect of the porous structure of the 3D printed interbody fusion cage product on the effect of bone growth, focusing on the evaluation of new bone formation, interface bonding, bone growth depth, bone growth time, and local tissue reaction after implantation. If it is impossible to demonstrate the equivalence with the porous structure characteristics of the products already on the market, the effect of the porous structure on bone growth can be proved through animal experiments. If it is necessary to carry out animal experimental research, it should be carried out in accordance with the Guiding Principles for the Technical Review of Animal Experimental Research of Medical Devices (Part I: Decision Principles and Part II: Experimental Design and Implementation Quality Assurance), and follow the 3R principle; Attention should be paid to the scientificity and rationality of animal model establishment, as well as the significance for clinical reference.
5、 Clinical research
At present, this product is not exempt from clinical evaluation as stipulated in the Regulations on the Supervision and Administration of Medical Devices. The applicant should select an appropriate clinical evaluation path and submit clinical evaluation data according to the requirements of the Technical Guidelines for Clinical Evaluation of Medical Devices. Clinical evaluation can prove the safety and effectiveness of medical devices by conducting clinical trials, or by analyzing and evaluating the clinical literature and clinical data of the same variety of medical devices according to the product characteristics, clinical risks, existing clinical data, etc.
（1） Evaluation path of medical devices of the same variety
See the requirements for analysis and evaluation of data obtained from clinical trials or clinical use of the same variety of medical devices in the Technical Guidelines for Clinical Evaluation of Medical Devices for details.
（2） Clinical trial evaluation path
For the selection of clinical trials, please refer to the relevant contents of the guiding principles such as the Guiding Principles for Technical Review of Intervertebral Fusion Cage Registration, the Guiding Principles for Clinical Evaluation of Medical Devices, and the Guiding Principles for Clinical Trial Design of Medical Devices, and submit complete clinical trial data.
If the applicant has overseas clinical trial data, he/she can submit relevant clinical trial data according to the requirements of the Technical Guidelines for Receiving Overseas Clinical Trial Data of Medical Devices.
6、 Instructions
The product manual shall comply with the requirements of the Regulations on the Management of Instructions and Labels of Medical Devices, as well as the requirements of relevant national and industrial standards, such as YY/T 0466.1-2016 Symbols for Medical Devices Used for Labeling, Marking and Providing Information - Part 1: General Requirements.
7、 Others
The relevant requirements for the production and manufacturing of 3D printing intervertebral fusion cage products can refer to the requirements of the Guiding Principles for the Technical Review of the Registration of 3D Printing Artificial Vertebra and the Guiding Principles for the Technical Review of the Registration of 3D Printing Acetabular Cup Products. The production process of 3D printing intervertebral fusion cage products is detailed, and the production process flow chart is provided. Control the production and verification process of medical devices manufactured with additives, such as design software, printing equipment, printing process, post-treatment process, cleaning process, etc.
Appendix 1
Relevant standards applicable to the product
Including but not limited to the following standards:
GB/T 228.1 Metallic Materials Tensile Testing Part 1 Room Temperature Test Method
GB/T 10610 Geometrical Product Specifications (GPS) Rules and Methods for Evaluating Surface Texture by Surface Texture Profile Method
GB/T 5168 α-β Test method for macrostructure and macrostructure of titanium alloys
GB/T 4698 (all parts) Chemical analysis methods of sponge titanium, titanium and titanium alloys
GB/T 13810 Titanium and titanium alloy processed materials for surgical implants
GB/T 33582 General Principles for Finite Element Mechanical Analysis of Mechanical Products
YY/T 0316 Application of Medical Device Risk Management to Medical Devices
YY/T 1427 Test solution and conditions for static and dynamic corrosion test of implantable materials for surgical implants and medical devices
YY/T 1552 Surgical Implants Measurement Method of Open Circuit Potential for Evaluation of Long-term Corrosion Behavior of Metallic Implants and Medical Devices
GB/T 14233.1 Test Methods for Medical Infusion, Blood Transfusion and Injection Apparatus Part 1: Chemical Analysis Methods
GB/T 14233.2 Test Methods for Medical Infusion, Blood Transfusion and Injection Apparatus Part 2: Biological Test Methods
GB/T 16886.1 Biological Evaluation of Medical Devices Part 1: Evaluation and Test in the Process of Risk Management
GB/T 35021 Additive Manufacturing Process Classification and Raw Materials
GB/T 35351 Additive Manufacturing Terminology
GB/T 36984 Method for X-ray CT examination of porous metal materials for surgical implants
YY 0341.2 Passive surgical implants - Bone joint and spine implants - Part 2: Special requirements for spine implants
YY/T 1502 spinal implant interbody fusion cage
YY/T 0343 Liquid Penetrant Inspection of Surgical Metal Implants
YY/T 0640 General Requirements for Passive Surgical Implants
YY/T 0466.1 Symbols for medical device labeling, marking and providing information Part 1: General requirements
YY/T 0959 Test Method for Mechanical Properties of Spinal Implant Intervertebral Fusion Cage
YY/T 0960 Test Method for Static Axial Compression Settlement of Spinal Implant Intervertebral Fusion Cage
GB 18278 series standards
GB 18279 series standards
GB 18280 series standards
WS310.2 Hospital Disinfection Supply Center Part 2: Technical Operation Specifications for Cleaning, Disinfection and Sterilization
ASTM F2077 Test Methods for Intervertebral Body Fusion Devices
ASTM F2267 Standard Test Method for Measuring Load Induced Subsidence of Intervertebral Body Fusion Device Under Static Axial Compression
ASTM F2119 Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants
ASTM F2182 Standard Test Method for Measurement of Radio Frequency Induced Heating Near Passive Implants During Magnetic Resonance Imaging
ASTM F2213 Standard Test Method for Measurement of Magnetically Induced Torque on Medical Devices in the Magnetic Resonance Environment
ISO 17296-2 Additive manufacturing -- General principles -- Part 2: Overview of process categories and feedstock
ISO 17296-3 Additive manufacturing -- General principles -- Part 3: Main characteristics and corresponding test methods
ISO 17296-4 Additive manufacturing -- General principles -- Part 4: Overview of data processing
ISO 19227 Implants for surgery -- Cleanliness of orthopedic implants -- General requirements
ASTM F3335 Standard Guide for Assessing the Removal of Additive Manufacturing Residues in Medical Devices Fabricated by Powder Bed Fusion ASTM F3122 Standard Guide for Evaluating Mechanical Properties of Metal Materials Made via additive manufacturing process
ISO/ASTM 52921 Standard terminology for additive manufacturing -- Coordinate systems and test methodologies
ISO/ASTM52915 Specification for additive manufacturing file format (AMF) Version 1.2
ISO/ASTM 52901 Additive manufacturing -- General principles -- Requirements for purchased AM parts
ISO/ASTM 52900 Additive manufacturing -- General principles – Terminology
ISO/ASTM 52910 Additive manufacturing -- Design -- Requirements, guidelines and recommendations
ASTM F2924 Standard Specification for Additive Manufacturing Titanium-6 Aluminum-4 Vanadium with Powder Bed Fusion
ASTM F3001 Standard Specification for Additive Manufacturing Titanium-6 Aluminum-4 Vanadium ELI (Extra Low Interstitial) with Powder Bed Fusion
ASTM F3049 Standard Guide for Characterizing Properties of Metal Powders Used for Additive Manufacturing Processes
Appendix 2
Guiding principles applicable to the product
Guiding Principles for Division of Medical Device Registration Units
Guiding Principles for Technical Review of Intervertebral Fusion Cage Registration
Guidelines for Registration and Application Data of Shelf Life of Passive Implantable Medical Devices (2017 Revision)
Guiding Principles for Registration and Review of Medical Device Animal Experimental Research Part I: Decision Principles (Revised in 2021)
Guiding Principles for Registration and Review of Animal Experimental Research of Medical Devices Part 2: Quality Assurance of Experimental Design and Implementation
Technical Guidelines for Clinical Evaluation of Medical Devices
Code for Quality Management of Clinical Trials of Medical Devices
Technical Guidelines for Receiving Overseas Clinical Trial Data of Medical Devices
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