GB/T 16886.19-2011 English PDF (GBT16886.19-2011)
GB/T 16886.19-2011 English PDF (GBT16886.19-2011)
GB/T 16886.19-2011: Biological evaluation of medical devices -- Part 19: Physio-chemical, morphological and topographical characterization of materials
Biological evaluation of medical devices.Part 19. Physico-chemical, morphological and topographical characterization of materials ICS 11.040.01
National Standards of People's Republic of China
Medical device biology evaluation
Part 19. Physical chemistry, morphology and
Part 19. Physico-chemical, morphologicalandtopographical
(ISO /T S10993-19.2006, IDT)
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China China National Standardization Administration issued
GB/T 16886 "Biological Evaluation of Medical Devices" consists of the following components. --- Part 1. Evaluation and testing in the risk management process;
--- Part 2. Animal welfare requirements;
--- Part 3. Genotoxicity, carcinogenicity and reproductive toxicity test; --- Part 4. Test options for interaction with blood;
---Part 5. In vitro cytotoxicity test;
--- Part 6. Post-implantation local reaction test;
---Part 7. Ethylene oxide sterilization residue;
--- Part 8. Guidelines for the selection and quantification of reference materials for biological testing; ---Part 9. Qualitative and quantitative frameworks for potential degradation products; --- Part 10. Stimulation and delayed type hypersensitivity test;
--- Part 11. Systemic toxicity test;
---Part 12. Sample preparation and reference samples;
--- Part 13. Qualitative and quantitative determination of polymer degradation products; --- Part 14. Qualitative and quantitative determination of ceramic degradation products; ---Part 15. Qualitative and quantitative determination of metal and alloy degradation products; ---Part 16. Design of toxicokinetics of degradation products and solubles; --- Part 17. The establishment of a limitable amount of leachables;
---Part 18. Chemical characterization of materials;
---Part 19. Physical chemistry, morphological and surface characterization of materials; --- Part 20. Principles and methods for immunological toxicology testing of medical devices. This part is the 19th part of GB/T 16886.
This part is drafted in accordance with the rules given in GB/T 1.1-2009. This section uses the translation method equivalent to ISO /T S10993-19.2006 "Medical Device Biology Evaluation Part 19. Material Physics Chemical, Morphological and Surface Characterization.
The documents of our country that have a consistent correspondence with the international documents referenced in this part are as follows. GB/T 16886.1-2011 Biological evaluation of medical devices - Part 1. Evaluation and testing (ISO 10993-1.2009, IDT) GB/T 16886.18-2011 Biological evaluation of medical devices - Part 18. Chemical characterization of materials (ISO 10993-18.2005, IDT)
This part is proposed by the State Food and Drug Administration.
This part is under the jurisdiction of the National Technical Committee for Standardization of Medical Device Biology Evaluation (SAC/TC248). This section drafted by. State Food and Drug Administration Jinan Medical Device Quality Supervision and Inspection Center. The main drafters of this section. Pan Huaxian, Wan Min, Yu Shaohua, Liu Bin, Liu Chenghu. introduction
YY/T 0316 states that toxicological risk analysis should consider the characteristics of the material. GB/T 16886.1 provides a structural assessment procedure framework for biological safety assessment, which is described in Chapter 3 of the standard. The materials used to make the device should first be considered suitable for the intended purpose, that is, attention should be paid to the characterization and properties of the material, including chemistry, toxicology, Physics, electrical, morphological and mechanical properties. This type of information is necessary prior to any biological evaluation. The physicochemical, morphological and surface characterization of the materials used in finished medical devices is a biological evaluation of the device and its materials. Importantly, this type of information can be used to.
a) Assessment of the overall biological evaluation of medical devices (GB/T 16886); b) Screening of new materials and/or processing of medical devices suitable for clinical applications. The compositional properties of the materials used in manufacturing are generally controlled by the material supplier, but other characteristics are mainly subject to the satisfaction of the finished medical device. Requirements and the impact of the manufacturing process used by the medical device manufacturer. Medical device biology evaluation
Part 19. Physical chemistry, morphology and
This part of GB/T 16886 gives the physical, chemical, morphological and surface properties (PMT) judgments for finished medical device materials. Various parameters and test methods with evaluation. This assessment is limited to biological evaluation and the intended use of medical devices (clinical applications and Time-related performance, even if such performance coincides with clinical effectiveness. This part of GB/T 16886 does not describe the characterization of degradation products Or quantitative determination, this part has been specified in Part 9, Part 13, Part 14, and Part 15 of GB/T 16886, Chemical characterization of the material can be found in GB/T 16886.18. The GB/T 16886 standard does not apply to medical devices and materials that are not in direct or indirect contact with the human body (see ISO 10993-1). 2 Normative references
The following documents are indispensable for the application of this document. For dated references, only the dated version applies to this article. Pieces. For undated references, the latest edition (including all amendments) applies to this document. ISO 10993-1 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management (Biologicalevalua- tionofmedicaldevices-Part 1.Evaluationandtestingwithinariskmanagementprocess) ISO 10993-18 Biological evaluation of medical devices - Part 18. Chemical characterization of materials (Biologicalevaluationofmedical devices-Part 18.Chemical characterizationofmaterials)
3 Terms and definitions
The following terms and definitions defined by ISO 10993-1 and ISO 10993-18 apply to this document. 3.1
Physical and chemical properties of (material).
Morphology, contours and microstructure of (material).
Surface characteristic topographical
Surface characteristics of (material).
4 symbols and abbreviations
This section uses the following abbreviations.
---PMT. physical chemistry, morphology and surface properties
Chapter 7 uses the abbreviations listed in Table 1.
Table 1 Methodology abbreviations
Abbreviation analysis method
AES Auger electron spectroscopy, including scanning tunnels
AFM/SPM Atomic Force Microscopy/Scanning Probe Microscopy, including surface roughness and phase contrast microscopy BET Brunauer-Emmett-Teler porosity determination
CLSM laser confocal scanning microscopy
DMTA dynamic mechanical thermal analysis
DSC differential scanning calorimetry
ESC balance solvent content
EWC equilibrium water content
EDX-SEM X-ray electron spectroscopy - scanning electron microscopy
FTIR Fourier transform infrared (spectrum), including microscopy, imaging, and diffuse reflectance FTIR-ATR Fourier Transform Infrared (Spectral) - Attenuated Total Reflection (Multiple Internal Reflection) IR infrared (spectrum)
OM optical microscopy, including polarized light and phase contrast microscopy QCM Quartz Crystal Microbalance (or other microbalance technology)
SEM/T EM scanning electron microscopy/transmission electron microscopy
SPR surface plasmon resonance
TOF/SIMS time-of-flight mass spectrometry
TMA thermomechanical analysis
XPS/ESCA X-ray photoelectron spectroscopy/electron spectroscopy for chemical analysis 5 basic principles
When assessing the biosafety and clinical effectiveness of a device, as in the chemical characterization of materials (see ISO 10993-18), the manufacture of medical devices Consideration of material PMT characterization is a necessary step, and both characterizations are also important in determining the following equivalence. a) the intended materials and clinically established materials, or
b) Prototype and final instruments.
The correlation between PMT characterization of materials used in devices and their biocompatibility and clinical effectiveness is still a developing collar. Domains, but there are some examples of these associations that can be further understood. 1) by using certain surface characteristics of the porous material of the orthopedic implant surface, the tissue can be ingrowth from the surface of the implant, This allows the implant to be better integrated with the surrounding tissue. 2) Stents and mesh materials with specific PMT properties are used as implants for implanting soft tissue or hard tissue, which can promote some The beneficial infiltration of cells contributes to the tissue repair process (Dexteretal. ). 3) The surface PMT characterization of the material used for the catheter has a large influence on the adhesion of bacteria and proteins on the inner and outer surfaces, which in turn affects To the risk of infection and occlusion.
4) Changes in the microstructure of the surface of the material, such as fine grooves or other patterns on the surface, may affect some cells on the surface of the material. Direction of adhesion and migration (Alaertsetal. ; Dewezetal. ). 5) Some medical devices, such as orthopedic implants and vascular implants, may affect biological properties such as tissue Remodeling.
Note. The shape and geometry of medical devices and their components, such as the aspect ratio, thickness, and morphology associated with blood flow, are thought to influence biological responses. Specific equipment The information can be seen in the corresponding product standard.
This section provides examples of PMT characterization parameters and methods that can be used for medical device materials. Medical device manufacturers should choose the appropriate parameters and methods and explain the reasons for the choice. Manufacturers should document the use of medical devices and The level of characterization of the constituent materials is compatible with the clinical application of the device. The degree of characterization should reflect the nature and timing of clinical exposure and can be used for device biological safety risk assessment. PMT characterization should also be suitable Reflects the materials used and their physical form, such as solids, liquids, gels, polymers, metals, ceramics, composites or biogenic materials. This kind Characterization often requires close collaboration between materials experts, analytical test experts, and risk assessment experts. 6 characterization procedure
The analytical method chosen should give the information needed for the evaluation. Before developing a new method, consider existing standards, monographs, and scientific theories. Search for applicable test methods in the literature or other relevant scientific literature. It may be necessary to use the methods in the literature and confirm before use. If it is not possible to determine the appropriate method, it is advisable to develop suitable new methods. The analytical methods used should be validated, demonstrated and reported in accordance with Chapters 7 and 8. The confirmation method of the analytical method is to determine the party The performance characterization of the method meets the requirements of the intended analytical use. When confirming the suitability of the analytical method, it also involves the following analytical characteristics. Accuracy, precision, specificity, detection limits, limit of quantitation, linearity, range, durability, robustness, and system suitability. In each step of the characterization process, it is advisable to determine the adequacy of the acquired data, which can be used as a basis for risk analysis. This The procedure should take into account each of the materials in the finished device. Note. It may be possible to obtain a suitable analytical method from the supplier. In the absence of raw material data, it is recommended to conduct a literature method study. Choosing the most appropriate analytical method for the relevant material can help. 6.2 Qualitative information
This type of information describes the material/device and its intended use. It is recommended that the PMT characterization of the finished device be described in the form of a document. Characterization of each material used in the device (see ISO 10993-1). The qualitative data level given should reflect the invasive procedure according to the medical device Information on the categories determined by degree and clinical contact time, as well as material properties. Where appropriate, qualitative descriptions should include details of production lots, suppliers, and technical specifications for each material. Medical device manufacturers should obtain qualitative and quantitative characterization information about the final product, such information from raw material suppliers, Obtained in the literature or in additional tests. The PMT properties of the material should be in accordance with applicable material standards or as specified by the manufacturer. In this Adequate data should be collected to identify all hazards (potential risks) and possible benefits due to material properties. Developed in the product In the process, as the amount of information continues to increase, this assessment will be further improved. 6.3 Material equivalence
As part of the evaluation of material suitability, these data should be compared to determine that the material has the same clinical exposure/ Whether the materials used in the instruments used and used in the same manufacturing and sterilization process are equivalent, for example, on products used for intact skin Determine the material equivalent of the safety application. Appendix A gives a more detailed guide to determining material equivalence, and Appendix B gives the application of nanoparticles. Information on special materials for particles (any size ≤ 100 nm).
6.4 Quantitative information
Quantitative material characterization should be established when qualitative characterization data alone does not provide sufficient data for material suitability evaluation. Data, documenting and applicability and risk assessment.
6.5 Quantitative assessment
Adequate quantitative characterization information should be obtained to be able to assess the suitability of all materials in the finished device for the intended use of the material. This information is also part of a comprehensive biological evaluation of medical devices. Such quantitative characterization information can be used to determine the intended application with the clinic Comparison of safety and effectiveness of materials and/or finished medical devices, and for those who have found that they are not required in such applications Characterized materials/products are compared. This comprehensive evaluation is outside the scope of this part of ISO 10993 and can be combined with the ISO 10993 standard. The information given in his section applies ISO 14971.
7 Characterization parameters and methods
The formation of qualitative and quantitative PMT characterization data for suitability/risk assessment is described in Chapter 6, and Table 2 is a summary. Material characterization parameters and examples of methods that can be used to determine qualitative and/or quantitative data. The table gives the phase corresponding to the parameters (such as surface characteristics) Standards and/or references. Not all parameters or related methods are applicable to each material and should be selected to suit the specific material or Characterization parameters of the finished medical device. Due to the diversity of medical devices, it is generally believed that the identified material parameters are not related to all/some of the devices. Mechanical applications are all relevant. As described in 6.2, it is necessary to consider the degree and timing of clinical exposure during the intended application of the device. The degree of characterization.
Analysts and materials experts should determine which parameters to consult with the manufacturer's material use applicability assessor (risk assessor) The number is related to the evaluation of the material or medical device, and the characterization data of all relevant parameters should be considered by the manufacturer's risk assessor. Note. For natural macromolecules, the most basic is to first identify the source of the organism (species) and the variety/line. YY/T 0771/ISO 22442 series standard gauge Establishing the safe use of non-human tissues and their derivatives in the manufacture of medical devices, YY/T 0616/EN455-3 specifies protein residues in natural latex. Assessment of related risks.
Natural macromolecules used in medical devices include, but are not limited to, proteins, glycoproteins, polysaccharides, and ceramics, including, for example, gelatin, gelatin Pro, elastin, fibrin, albumin, alginate, cellulose, heparin, chitosan, processed bone, coral and natural rubber. These materials can It can be processed, purified and modified to varying degrees. Many of these materials are involved in the relevant sections of the Pharmacopoeia, and the ASTM F04 series The characterization of these materials is also given in the quasi-middle. Table 2 Examples of characterization parameters and methods for polymers, metals, alloys, ceramics and natural polymer materials Examples of analytical parameter examples (not limited to this) Qualitative determination quantitative measurement standards or references Porosity
General characteristics OM
Gas adsorption (BET)
Porosity mercury intrusion assay
ISO 18754 
ISO 18757 
Table 2 (continued)
Examples of analytical parameter examples (not limited to this) Qualitative determination quantitative measurement standards or references morphology
Crystallinity X-ray diffraction
Hard/soft surface OM
Hasegawa and Hashimoto 
Hydrophobic wettability (contact angle) × ×
Hydrophilic wettability (contact angle) × ×
Protein adsorption QCM or SPR
Protein exclusion QCM or SPR
---General human cells
---Human blood cells
---Human specific cells
---Special class bacteria
---General human cells
---Human blood cells
---Human specific cells
---Special class bacteria
Ebara and Okahata 
Jenney and Anderson