GB/T 16886.10-2017 English PDF (GBT16886.10-2017)
GB/T 16886.10-2017 English PDF (GBT16886.10-2017)
GB/T 16886.10-2017: Biological evaluation of medical devices -- Part 10: Tests for irritation and skin sensitization
Biological evaluation of medical devices-Part 10. Tests for irritation and skin sensitization ICS 11.100.20
National Standards of People's Republic of China
Replace GB/T 16886.10-2005
Medical device biology evaluation
Part 10. Stimulation and skin sensitization test
(ISO 10993-10.2010, 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 skin sensitization test;
--- Part 11. Systemic toxicity test;
--- Part 12. Sample preparation and reference materials;
--- Part 13. Qualitative and quantitative determination of degradation products of polymer medical devices; --- 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 toxicokinetic studies of degradation products and leachables; --- Part 17. The establishment of a leachable allowable limit;
---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 10th part of GB/T 16886.
Other aspects of biological testing will have other parts of the standard. This part is drafted in accordance with the rules given in GB/T 1.1-2009. This part replaces GB/T 16886.10-2005 "Medical Device Biological Evaluation Part 10 Stimulation and delayed type hypersensitivity test Inspection, compared with GB/T 16886.10-2005, the main technical changes are as follows. --- Modified the standard name;
---Modified terms and definitions (Chapter 3, Chapter 3 of the.2005 edition); --- Cancellation of "material identification" (see 5.4 of.2005 edition); --- The intradermal reaction test was adjusted from the appendix to the text (see 6.4, Appendix B of the.2005 edition); --- Human skin irritation test method is adjusted from the text to the appendix (see Appendix C,.2005 edition 6.4); --- Skin sensitization test increases the local lymph node test in mice (see 7.2); --- Increased in vitro skin irritation test (see Appendix D);
--- Added method for preparing polymer test material extract (see Appendix E). This section uses the translation method equivalent to ISO 10993-10.2010 "Medical Device Biology Evaluation Part 10. Stimulation and Skin Sensitive test.
The documents of our country that have a consistent correspondence with the international documents referenced in this part are as follows. GB/T 16886.2-2011 Biological evaluation of medical devices - Part 2. Animal welfare requirements (ISO 10993-2..2006, IDT) GB/T 16886.9-2017 Biological evaluation of medical devices - Part 9. Qualitative and quantitative framework for potential degradation products (ISO 10993-9.2009, IDT)
GB/T 16886.12-2017 Biological evaluation of medical devices - Part 12. Sample preparation and reference materials (ISO 10993-12. 2012, IDT)
GB/T 16886.13-2017 Biological evaluation of medical devices - Part 13. Qualitative analysis of degradation products of polymer medical devices Quantification (ISO 10993-13.2010, IDT)
GB/T 16886.14-2003 Biological evaluation of medical devices - Part 14. Qualification and quantification of ceramic degradation products (ISO 10993-14.2001, IDT)
GB/T 16886.15-2003 Biological evaluation of medical devices - Part 15. Qualification and quantification of degradation products of metals and alloys (ISO 10993-15.2000, 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; Shenzhen Medical Device Testing Center. The main drafters of this section. Wang Wei, Cao Ping, Fan Chunguang, Liu Wei, Xu Wei District. The previous versions of the standards replaced by this section are.
This part of GB/T 16886 is used to assess the exposure hazards that may be caused by chemicals released from medical devices, including Skin and mucous membrane irritation, eye irritation or skin sensitization. Certain materials contained in medical devices have been tested and their potential skin, mucous membrane irritation or sensitization has been confirmed. other Some untested materials and their chemical composition may have adverse effects when in contact with human tissue. Therefore, the manufacturer is responsible Evaluate the potential adverse effects of the device before it is placed on the market. Traditionally, small animal experiments have to be carried out before human trials to help predict human response. Recently, it has also been added as an auxiliary or Optional in vitro and human trials. Although much effort has been made in this area and some progress has been made, the results show The previously designed in vitro tests have not been satisfactory, so it has not been possible to eliminate the in vivo test. When appropriate, this section encourages in vitro pre-testing The method was used as a screening test before animal testing. In order to reduce the number of animals used, this section proposes a step-by-step evaluation method, which is tested at each stage. The results are reviewed and analyzed. Animal testing is generally required prior to human testing. These studies should be conducted in accordance with good laboratory quality management practices and in compliance with animal welfare regulations. Suggested in the right circumstances Statistical analysis of the data.
This section is used by trained and experienced professionals who are able to interpret the standard requirements and consider all aspects of the device. The factors, including the intended use of the device, the current knowledge of the medical device given by the review of the scientific literature and prior clinical experience, Determine the evaluation results of each medical device.
The tests included in this section are important tools for the development of safety products and are tested by trained personnel and explain the test results. This section is based on a number of standards and guidelines, including OECD guidelines, the United States Pharmacopoeia and the European Pharmacopoeia. This section can be used as a basic text. Used to select and implement tests that evaluate stimuli and skin sensitization reactions associated with the safety of medical materials and devices. Medical device biology evaluation
Part 10. Stimulation and skin sensitization test
This part of GB/T 16886 describes the evaluation steps for potential stimulation and skin sensitization of medical devices and their constituent materials. This section includes.
a) pre-stimulation considerations, including bio-simulation experiments and in vitro methods for skin contact; b) detailed in vivo (stimulation and sensitization) test procedures;
c) Key factors for interpretation of the results.
Appendix A gives specific material preparation instructions related to the above tests. Appendix B gives the skin removal unit for medical devices. Several special stimulation tests outside the position.
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. GB/T 16886.1-2011 Biological evaluation of medical devices - Part 1. Evaluation and testing in the process of risk management (ISO 10993- 1.2009, IDT)
ISO 10993-2 Medical Device Biology Evaluation Part 2. Animal welfare requirements (Biologicalevaluationofmedical devices-Part 2.Animalwelfarerequirements)
ISO 10993-9 Biological evaluation of medical devices - Part 9. Qualitative and quantitative framework for potential degradation products (Biologicaleval- uationofmedicaldevices-Part 9. Frameworkforidentificationandquantificationofpotentialdegra- Dationproducts)
ISO 10993-12 Biological evaluation of medical devices - Part 12. Sample preparation and reference samples (Biologicalevaluationof medicaldevices-Part 12. Samplepreparationandreferencematerials)
ISO 10993-13 Biological evaluation of medical devices - Part 13. Qualification and quantification of degradation products of polymer medical devices (Bi- OLOGICALevaluationof medicaldevices-Part 13.Identificationandquantificationofdegradation Productsfrompolymericmedicaldevices)
ISO 10993-14 Biological evaluation of medical devices - Part 14. Qualification and quantification of ceramic degradation products (Biologicalevalua- tionofmedicaldevices-Part 14.Identificationandquantificationofdegradationproductsfromceram- Ics)
ISO 10993-15 Biological evaluation of medical devices - Part 15. Qualification and quantification of metal and alloy degradation products (Biological evaluationofmedicaldevices-Part 15.Identificationandquantificationofdegradationproductsfrom Metalsandaloys)
ISO 10993-18 Biological evaluation of medical devices - Part 18. Chemical characterization of materials (Biologicalevaluationofmedical devices-Part 18.Chemical characterizationofmaterials)
ISO 14155-1 Clinical investigation of medical devices for human body Part 1. General requirements (ClinicalInvestigation ofMed- icalDevicesforHumanSubjects-Part 1.GeneralRequirement)
ISO 14155-2 Clinical studies of medical devices for humans - Part 2. Clinical research medicaldevicesforhumansubjects-Part 2.Clinicalinvestigationplants)
3 Terms and definitions
The following terms and definitions as defined in GB/T 16886.1-2011 apply to this document. 3.1
A substance or material that causes a specific type of hypersensitivity reaction after repeated exposure. 3.2
The leaching medium without the test material was placed in the same vessel as the test material and subjected to the same leaching conditions as the test material. Note. The purpose of the blank control is to evaluate the possible interference effects of the leaching vessel, the leaching medium and the leaching process. 3.3
The process after the induction phase, at which the individual's subsequent exposure to the immunological response of the inducing material is examined. 3.4
The amount of test sample (eg, mass, volume) expressed in terms of unit weight or surface area. Note. These two terms are usually used interchangeably (used more commonly). 3.5
Redness of the skin or mucous membranes.
Scarring or discolored skin.
A liquid or suspension obtained after contact of a test material or control material with a solvent under controlled conditions. 3.8
A process that results in an individual's re-establishment of an immunologically active state of a particular material. 3.9
a substance that causes irritation.
A local, non-specific inflammatory response caused by one, multiple, or continuous contact with a substance/material. Note. Skin irritation is a reversible reaction characterized by local erythema (redness) in the skin. 3.11
Irreversible changes due to injury or disease directly lead to cell death. Note. It should be noted that tissue repair can lead to complete functional recovery or scar formation. 3.12
Negative control negativecontrol
Appropriate negative, non-reactive or most reproducible in the test system to demonstrate the suitability of the test procedure when tested in accordance with the prescribed procedure A sufficiently characterized material or substance that is small in response. Note. In practice, negative controls include blanks, media/solvents, and reference materials. 3.13
Swelling caused by abnormal penetration of liquid into the tissue.
Appropriate positives or reactions that reproduce the suitability of the test procedure in the test system when evaluated according to the specified test method A well characterized material or substance that is sexually responsive. 3.15
Skin corrosion skincorrosion
The irreversible damage of the skin after application of a test sample is manifested by significant necrosis from the epidermis to the dermis. Example. Skin ulcers caused by the action of a mixture/chemical/test sample (see 3.19). 3.16
Skin sensitization skinsensitization
Allergic contact dermatitis
Immune-mediated skin response to a substance.
Note. This reaction is characterized by itching, erythema, edema, papules, large (small) blisters, or such syndromes in the human body. Other species may behave differently, only There are erythema and edema.
Test material testmaterial
Sampling materials, instruments, parts of a device or components thereof for biological or chemical testing. 3.18
Test sample testsample
A material, device, part of a device, component, leachate or part of a leachate for biological or chemical testing or evaluation. 3.19
It is characterized by open ulceration of superficial tissue defects.
A liquid used to wet, dilute, suspend, leach, or dissolve test materials/materials. 4 Basic Principles - Step by Step Evaluation
Existing test methods for testing stimuli and sensitization are specifically designed to measure potential skin irritation and mucosal irritation as well as skin sensitization These tests generally do not predict other types of adverse effects. Intradermal injection test for implanted medical devices or externally connected medical devices It is closer to the actual application, so it is used to test the stimulating effect and should be tested intradermally as described in 6.4. This section requires a step-by-step evaluation method that should include one or more of the following. a) in accordance with the basic principles of ISO 10993-9, ISO 10993-13, ISO 10993-14, ISO 10993-15 and ISO 10993-18, Characterizing the test material involves chemical characterization and analysis of the test sample; b) Literature search, including evaluation of the chemical and physical properties of the test materials, any product components and related structures of chemicals and materials Potential stimulation and sensitization information;
c) In accordance with ISO 10993-2, it should be considered that in vitro testing takes precedence over in vivo testing, if the new in vitro method is scientifically recognized and reasonable And practicality, can replace the in vivo test. There are in vitro alternative methods for the evaluation of chemical skin irritation and corrosion, currently In vitro testing of sensitizers that have not been internationally recognized and accepted; d) In vivo animal testing. In order to ensure the reproducibility and sensitivity of the test, the testing laboratory should include in each stimulation and sensitization test. A positive control was tested to verify the test system and confirm a positive response. However, for the guinea pig sensitization test, when the test system is When the sex is confirmed for 6 months or longer, it is not necessary to include a positive control in each test, but at regular intervals. (not more than 6 months) to conduct a positive control test;
Note 1. The current sensitization can only be determined by in vivo tests, using mouse local lymph node test (LLNA), guinea pig closure test or porpoise Rat Maximum Dose Test (GPMT). LLNA is currently the preferred method for determining the potential sensitization of a single chemical, see references , , .
Note 2. In vivo animal testing is applicable when the test material cannot be characterized or the information obtained in stages a), b) and c) cannot be assessed for risk. Note 3. For the guinea pig sensitization test, 10 animals are generally used for the positive control every 6 months. Positive in more frequent times than every 6 months When the control substance is tested, fewer guinea pigs may be used, and at least 5 test animals should be used for the positive substance and 5 control animals. e) Non-invasive human trials/clinical trials. if the material has been shown to be non-irritating, non-sensitizing or non-toxic to the animal, consider the human body Skin irritation studies.
Before the other evaluation results in a)~d) are known, the ISO 14155-1 and ISO 14155-2 and ethical guidelines should not be followed. Bed test.
5 pre-test considerations
It is important to emphasize that pre-test considerations are very important and can lead to conclusions that do not require stimulation and/or sensitization testing. The requirements given in Chapter 5 of GB/T 16886.1-2011 and the following clauses apply. Non-sterile samples should only be studied by local testing because the possibility of microbial contamination of the test sample interferes with the interpretation of the final test. Intradermal testing may be demonstrated for test samples that do not guarantee sterility but are still considered to be non-contaminating. 5.2 Material Type
5.2.1 Basic considerations
Other chemical components that may be used as processing aids (such as lubricants or mold release agents) during the manufacture and assembly of medical devices should be considered. apart from In addition to the chemical composition of raw materials and manufacturing processing aids, assembly of binders/solvent residues and sterilization residues or reactions due to sterilization processes Sex products may be present in the final product, and whether these ingredients pose a health hazard (risk) depends on the leakage or degradation properties of the final product. Consider the potential stimulatory/sensitizing activity of these ingredients. 5.2.2 Ceramics, metals and alloys
These materials are generally simpler in terms of chemical composition than polymers and biologically derived materials. 5.2.3 Polymer
Such materials are generally more complex in chemical composition than in 5.2.2, and may have several reactive products/impurities/additives, and The degree of completeness of the polymerization may vary.
5.2.4 Biologically derived materials
Such materials are particularly complex in their composition and often contain processing residues such as crosslinkers and antibiotics. Between biological material samples The ingredients may be incon...