Introduction to sensitization test of medical device biocompatibility company
Medical device biocompatibility company sensitization test
"CCIC Huatongwei" supports the submission of medical devices for inspection
Mail box： roy.yi@szhtw.com.cn
Sensitization test, the tissue damage or physiological dysfunction that occurs when the sensitized body is exposed to the same antigen or hapten again.
Chemicals with sensitizing effects enter the body through a certain route and combine with tissue proteins to form a complete antigen, which stimulates immunocompetent cells to produce sensitized lymphocytes or humoral antibodies; after a sensitization period of 1 to 2 weeks, the immune response in the body can be fully developed and formed A certain number of sensitized lymphocytes or specific antibodies. When exposed (stimulated) again, the body will have an increased susceptibility to the chemical, which manifests itself in a certain abnormal form
Sensitization test for compatibility testing of medical devices
The difference between sensitization test and irritation test
Stimulation test is a local inflammatory response, while sensitization is a response of the systemic immune system, which is a cellular immune response
Common test methods
1. Guinea pig maximum dose method (GPMT)
2. Closed application method (Buehler test)
3. Local lymph node test method (LLNA)
Among them, the guinea pig maximum dose method (GPMT) and the closed application method (Buehler test) are the two most commonly used methods with the highest use rate in biosafety evaluation.
Guinea pig maximum dose test is the most sensitive method, and it is widely used in European countries;
The closed application test is suitable for local products, and this method is commonly used in the United States.
The local lymph node test (LLNA) was accepted by the Economic and Cooperative Development Organization as the only alternative to the current guinea pig test. This method has also improved animal protection and is also approved for the detection of chemical allergenic activity.
Common test standards:
1. Biological evaluation of medical devices Part 10: Irritation and delayed-type hypersensitivity test ISO 10993-10:2010
2. Biological evaluation of medical devices Part 10: Irritation and skin sensitization test GB/T 16886.10-2017
Test steps
Sensitization Test-Guinea Pig Maximum Dose Method (GPMT)
Test principle: The maximum dose test of a single chemical substance is used in guinea pigs to evaluate the potential of the material to cause skin sensitization in guinea pigs under the test conditions.
1. Prepare the animals
30 guinea pigs, male or female, 300g~500g.
2. Pre-test
Pre-test purpose: To determine the concentration of the test sample used in the main test.
Determine the concentration of the test sample used in the main test
The highest concentration selected for the local induction phase of the main test should only cause mild erythema and no other harmful effects
The highest concentration selected for the challenge phase of the main experiment should not cause the animals to produce erythema
3. Main test
3.1 Animal grouping
At least 10 animals should be used for each test sample, and at least 5 animals should be used for the control group.
If all the 10 test animals and 5 control animals are negative, then the test may not show a positive reaction.
However, if there is any suspected reaction, it should be re-stimulated. If there is still a suspected reaction, the test should be repeated. At least 20 test animals and 10 control animals should be used.
3.2 Intradermal induction phase -> local induction phase -> excitation phase
Evaluation of the results
Animal observation
Observe the skin conditions of the stimulated parts of the animals in the test group and the control group at 24h and 48h after removing the patch. It is especially recommended to observe the skin reactions under natural or full-spectrum light. According to the Magnusson and Kligman grading standards, the skin erythema and edema reaction at each excitation site and each observation time were described and graded.
Result evaluation
The animal score of the control group is less than 1, and the score of the test group is ≥1, which indicates sensitization
The animal score of the control group is ≥1, and the reaction of the experimental group exceeds the most severe reaction in the control group, which is considered to be sensitized
If the number of animals in the test group reacted more than the control group animals, but the response intensity did not exceed that of the control group, it may be necessary to perform a second challenge 1 to 2 weeks after the first challenge to clarify the response
Biocompatibility testing