GB/T 16886.18-2011 English PDF (GBT16886.18-2011)
GB/T 16886.18-2011 English PDF (GBT16886.18-2011)
GB/T 16886.18-2011: Biological evaluation of medical devices -- Part 18: Chemical characterization of materials
Biological evaluation of medical devices.Part 18. Chemical characterization of materials ICS 11.040.01
National Standards of People's Republic of China
Medical device biology evaluation
Part 18. Chemical characterization of materials
Part 18.Chemical characterizationofmaterials
(ISO 10993-18.2005, 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 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 18th 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 10993-18.2005 "Medical Device Biology Evaluation Part 18. Material Chemistry Table Expropriation. The documents of our country that have a consistent correspondence with the international documents referenced in this part are as follows. GB/T 16886.17-2005 Biological evaluation of medical devices - Part 17. Establishment of leaching allowances (ISO 10993-17. 2002, 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. Luo Hongyu, Qin Dongli, Yu Shaohua, Sun Guangyu, Liu Chenghu. introduction
ISO 10993-1 provides an evaluation process framework for biosafety evaluation. ISO 10993-1.2003, Chapter 3, in the choice When manufacturing materials for a device, the primary consideration is that the material should be suitable for the purpose of the device, ie, the characterization and performance of the material, including Learning, toxicology, physics, electricity, morphology and mechanical properties. It is necessary to obtain this information before conducting a biological evaluation. YY/T 0316 also states that toxicological risk analysis should consider the chemical nature of the material. The requirements specified in this section are used to derive the following information that will help predict the biological response of the material. ---The chemical composition of the materials used in the production process, including processing aids and residues, such as trace chemicals, cleaning agents, disinfectants and Test reagents, acidic and corrosive substances.
--- Characterization of the materials used in the production of medical devices, and the final form on the device. --- Identification of the composition of medical device materials.
--- The possibility of medical device materials releasing substances or decomposition products during the production process. --- Changes in the production process or insufficient control during the production process leads to changes in the material structure. The compositional properties of materials used in the manufacture of medical devices are mainly controlled by the material supplier, but other characteristics are mainly subject to the finished medical device. The requirements to be met and the impact of the manufacturing process used by the medical device manufacturer. Medical device biology evaluation
Part 18. Chemical characterization of materials
This part of GB/T 16886 describes the qualitative and quantitative framework for material identification and its chemical composition. The chemical characterization information obtained can be obtained. Used for some important applications, such as.
--- As part of the overall biosafety evaluation of medical devices (ISO 10993-1 and ISO 14971). --- By measuring the level of leachables in medical devices to assess compliance with the allowable limits for the substance based on health risk assessment Quantity (ISO 10993-17).
--- Determine the equivalence of the proposed material and the clinically established material. --- Determine the equivalence of the final device and the prototype device, and check the relevance of the prototype device data used to support the final device evaluation. --- Screening for new materials for the intended clinical application of medical devices. This part of GB/T 16886 does not cover the qualitative and quantitative determination of degradation products. See ISO 10993-9 for details on this. ISO 10993-13, ISO 10993-14 and ISO 10993-15.
The GB/T 16886 standard applies to materials or instruments that come into direct or indirect contact with the human body. (See ISO 4993-1.2003, 4.2.1) This part of GB/T 16886 is intended to be applied to material suppliers and medical device manufacturers for biosafety evaluation. 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 10993-1.2003 Biological evaluation of medical devices - Part 1. Evaluation and testing (Biologicalevaluationof medicaldevices-Part 1.Evaluationandtesting)
ISO 10993-17 Biological evaluation of medical devices - Part 17. Establishment of leaching allowances (Biological evaluationofmedicaldevices-Part 17.Establishmentofalowablelimitsforleachablesubstances) YY/T 0316-2008 Medical Device Risk Management for Medical Devices (ISO 14971.2007, IDT) 3 Terms and definitions
The following terms and definitions defined by ISO 10993-1 apply to this document. 3.1
A person or company that produces and/or supplies raw materials for the manufacture of medical devices. 3.2
Natural or legal person responsible for the design, production, packaging and identification of the device before it enters the market under its own name, regardless of Whether these operations are done by themselves or by a third party in their name. 3.3
A part made of a basic raw material is not a medical device itself, but an integral part of a medical device. 3.4
An individual or company that processes or manufactures a basic raw material, such as a length of bar, tube or film. 3.5
Identification of materials and characterization and quantification of chemicals present in materials or finished medical devices. 3.6
Limit extraction exhaustiveextraction
Subsequent leaching to the extract is less than the 10% detectable amount of the first extract. Note. Leaching is a complex process that is affected by time, temperature, surface area to volume ratio, leaching medium, and material phase equilibrium. Material phase equilibrium decision The relative amounts of the amorphous phase and the crystalline phase are present. For the amorphous phase, the glass transition temperature (Tg) determines the polymer chain mobility and the diffusion rate in the phase, usually It is believed that the diffusion rate of the temperature above Tg is higher than the diffusion rate of the temperature below Tg, and the diffusion rate is the lowest in the crystalline phase. The leaching conditions should not change the phase equilibrium of the material, and the phase change may affect the amount and type of the extract. If full leaching is used, the high temperature or its The effect of his conditions on the kinetics of the extraction and the consistency of the extract. For example, pay attention to the following situations when using high temperatures. a) an increase in the temperature of the energy can lead to an increase in the cross-linking of the polymer, thereby reducing the total amount of free monomers eluted by the polymer; b) that elevated temperatures can produce degradation products that are not typical of the finished device under conditions of use; c) An increase in temperature can result in the absence of a typical dissolution of the finished device. 3.7
Simulated leaching simulatedextraction
Means a leaching method using a suitable medium and simulating the use of the product to evaluate potential for the patient or user during routine application of the device risk.
Note. See note to 3.6.
4 symbols and abbreviations
Chapter 7 uses the following abbreviations.
Table 1 Methodology abbreviations
Abbreviation analysis method
DMTA dynamic mechanical thermal analysis
DSC differential scanning calorimetry
EDX-SEM X-ray electron spectroscopy---scanning electron microscopy
FTIR Fourier transform infrared (spectrum)
GC gas chromatography
MS mass spectrometry a
GPC gel permeation chromatography
HPLC high performance liquid chromatography
ICP inductively coupled plasma emission spectroscopy
Table 1 (continued)
Abbreviation analysis method
IR infrared (spectrum)
NMR nuclear magnetic resonance (spectrum)
UV ultraviolet (spectrum)
XPS X-ray photoelectron spectroscopy
XRF X-ray fluorescence
2DPAGE two-dimensional polyacrylamide gel electrophoresis
a Mass spectrometry is usually combined with chromatographic techniques such as GC-MS, LC-MS and MS-MS. 5 General principles
Chemical characterization of materials used in the manufacture of medical devices is the first step in the evaluation of the biosafety process of devices, as well as the following Equivalence is also important.
a) the proposed materials and clinically established materials, and
b) Prototype and final instruments.
Appendix A of this section reviews the chemical characterization steps described in this section and their relationship to risk analysis. Qualitative data should be obtained to describe the chemical composition of the material, and quantitative data should be obtained when biological safety is involved. For some materials Material and component information can be obtained directly from the material specification. Materials like polymers may have a more complex composition, the details of which are detailed Detailed information should be obtained from the supplier of the material. In the absence of such information, appropriate analytical techniques should be used to analyze the material to obtain the components. data.
The intrinsic toxicity of each component can be investigated by identifying the components used in the medical device manufacturing materials. Expected data obtained Can be used by medical device manufacturers as part of the overall biosafety evaluation of medical devices, so it is important to introduce controls to prevent materials The material supplier changes the composition of the material supplied under a specific trade name, or changes the supply contract without first notifying the medical device manufacturer. Manufacturers should evaluate the impact of any notified changes on the biosafety of the product. Any material component or additive used in the manufacture of medical devices is potentially bioavailable and therefore necessary to obtain The finished product confirms the bioavailability of these components under actual conditions of use to assess the risks posed. This can be done by material dip The test is carried out for evaluation. Appropriate extraction conditions (simulated leaching) ensure that any components that may be released during use of the finished product will Will be released into the leaching medium. Qualitative and/or quantitative analysis of the obtained extract can be used for medical device biology Safety evaluation.
The range of chemical characterization required should reflect the nature and timing of clinical exposure and should be based on the toxicological risk assessor The data required for biological safety assessment is determined and reflects the physical form of the materials used, such as liquids, gels, polymers, Metal, ceramic, composite or biosourced materials.
Successful completion of the chemical characterization presented in this section requires close collaboration between materials scientists, chemical analysis and toxicological risk assessors. In this partnership, material scientists and chemical analysts provide the necessary qualitative and quantitative data, and risk assessors use these Data to determine the safety of the device.
6 Characterization steps
The generation of chemical characterization data is a step-by-step process that is closely linked to the risk assessment loop. A five-step process is given in Appendix A. Figure. The chemical characterization requirements and guidelines for each step are specified in 6.2 to 6.6. Analytical analysis should be given to give the information needed for toxicological evaluation Method, if the applicable method cannot be determined, a suitable new method should be developed. Before developing a new method, it is advisable to consult existing standards and special Discuss, scientific papers or other relevant scientific literature to see if there are current applicable test methods. The methods found in the literature may be used before use. Need to be modified and confirmed.
The analytical methods used should be validated, validated and reported (see Chapter 8). The confirmation of the analytical method is to determine that the characteristics of the analytical method are met. A process that is expected to analyze the application requirements. Analytical methods should be validated against the following analytical characteristics. ---Accuracy;
--- Detection limit;
---The limit of quantitation;
--- System adaptability.
The sufficiency of the resulting data for risk analysis should be judged at each step of the characterization process. This step is in addition to considering the final In addition to the chemical characterization requirements of the device, it is also appropriate to consider each material used in the medical device. Note 1. Steps 2 and 4 correspond to 6.3 and 6.5 respectively, which are part of the risk assessment process and are not included in this section. Given in these two steps The information shows an important interrelationship between chemical characterization and risk assessment. Note 2. Suppliers may be able to provide appropriate analytical methods. In the absence of raw component data, literature studies are recommended to determine the nature of the feedstock and any additives. Quality, which helps to select the most suitable analytical method for the test material. This part of the standard applies if the material or device is in direct or indirect contact with the human body. (See ISO 4993-1.2003, 4.2.1) 6.2 Step 1 - Qualitative information
Describe the material/instrument and its intended purpose. A documented qualitative description of the finished device component is required, including the device Additives and processing residues for each material used (see ISO 10993-1.2003, 3.3 and 4 and Appendix B). Provided/required Qualitative data levels should reflect the classification of medical devices in terms of degree of invasiveness, clinical exposure time, and material properties, and should be Argument.
Where appropriate, qualitative descriptions should include details such as lot number, supplier and material specifications for each material, using standardized materials such as ISO When 5832-1), it should meet the corresponding requirements according to its intended use. It is best for medical device manufacturers to obtain qualitative and quantitative component information from raw material suppliers, any processing additives (such as mold release agents). Qualitative information should also be obtained from the relevant personnel in the manufacturing process, including the processor and component manufacturer. The composition of the material should conform to the relevant material Material standards, or should be specified by the manufacturer. Sufficient information should be obtained at this stage to identify all toxic risks caused by the chemical composition of the material. Harm and conduct risk assessment (see 4.3 in YY/T 0316-2003).
6.3 Step 2 - Material Equivalence
Sufficient qualitative information should be obtained to compare these data to determine if the material is in contact with a clinical Same as, and the materials used to produce the same equipment as the sterilization process are equivalent, for example, to established safety applications on products for intact skin. The material is equivalent.
Note. See Appendix C for examples of toxicological equivalence.
6.4 Step 3 - Quantitative Information
When qualitative analysis alone does not provide sufficient data to complete a toxicological risk analysis, quantitative chemical components should be identified and documented (See B.6) and then conduct a risk assessment. Specifically, a quantitative chemical component refers to each chemical that is identified in the material. The amount.
6.5 Step 4 - Quantitative Risk Assessment
Adequate quantitative information should be obtained in conjunction with existing toxicological information (see ISO 10993-17 and 4.1 of YY/T 0316-2008) To conduct a risk assessment.
6.6 Step 5 - Estimate the chemical exposure to the chemical
Depending on the expected clinical exposure, any amount of chemical should be determined if toxicologically relevant residues are present. The extent of exposure and the estimated total amount of exposure. The extraction conditions used should be documented and demonstrated. Note 1. The degree of leaching depends on the nature of the human contact and the degree of contact. If the contact time is long and the degree of intrusion is high, it may be necessary to provide a leaching solution. Analytical method of information on dynamics.
Sensitive, specific methods should be used to analyze the extract and analyze the quantitative levels of the chemical. Note 2. In some cases, in addition to the test, a mathematical model can be used to determine the leachables. 7 Chemical characterization parameters and methods
Chapters 6 and A of this section give the steps for generating qualitative and quantitative chemical characterization data...