B. Sensitization
There are two types of sensitization tests that are generally submitted in support of IDE and marketing applications: the Guinea Pig Maximization Test and the Local Lymph Node Assay. In addition, the Buehler method can be used for topical devices only (i.e., those in contact with skin), per ISO 10993-10.
Guinea Pig Maximization Test (GPMT)
For this test, male and/or female healthy young adult animals are used. If female animals are used, the animals should be nulliparous and non-pregnant, as pregnancy reduces the ability of a female animal to detect a sensitization response.
Assays with positive controls using the same source and strain of animals only should be performed regularly (at least once every six months, or if longer, concurrent with the test assays) to ensure the reproducibility and sensitivity of the test procedure. These test reports should include positive control data from concurrent testing or from positive control testing within three months (before or after) of the device testing using the same methods and source and strain of animal. We also recommend that your positive control testing include a minimum of five animals to demonstrate a reproducible and appropriately positive response in the test system. If a periodic positive control fails, all GPMT data generated after the last valid positive GPMT response should be considered invalid because there is no assurance that the test system is working appropriately. However, repeating positive control testing to justify a failed positive control test would not be sufficient. If root cause analysis confirms the loss of sensitivity of the animal herd to the positive control, repeating device testing using a new animal herd is recommended for any GPMT data collected between the successful and failed periodic positive control testing. If a primary irritation study is not included in the sensitization protocol, adverse findings at the end of the study may be due to irritation or sensitization, and additional irritation studies to determine the causality may be required. …show more content…
Local Lymph Node Assay (LLNA)
The use of LLNA tests is for medical devices on a case-by-case basis for medical device extract/residuals that are composed of chemical mixtures. LLNA tests may be appropriate in the following circumstances:
• The LLNA can be used for testing metal compounds (with the exception of nickel and nickel-containing metals) unless there are unique physicochemical properties associated with these materials (e.g., nanomaterials) that may interfere with the ability of the LLNA to detect sensitizing materials.
• The LLNA can be used for testing device materials in aqueous solutions unless there are unique physicochemical properties associated with these materials (e.g., nanomaterials) that may interfere with the ability of the LLNA to detect sensitizing chemicals. When testing device materials in aqueous solutions, it is essential to use an appropriate vehicle to maintain the test extract in contact with the skin (e.g., 1% Pluronic L92) so that adequate exposure can be achieved, as demonstrated by positive control results. LLNA …show more content…
For borderline positive responses between an SI of 1.8 and 2.5 there is a potential for false positive results that could limit the usefulness of this type of LLNA test. In addition, the LLNA: DA is not appropriate for testing device materials that affect ATP levels (e.g., chemicals that function as ATP inhibitors) or those that affect the accurate measurement of intracellular ATP (e.g., presence of ATP degrading enzymes, presence of extracellular ATP in the lymph
There are two types of sensitization tests that are generally submitted in support of IDE and marketing applications: the Guinea Pig Maximization Test and the Local Lymph Node Assay. In addition, the Buehler method can be used for topical devices only (i.e., those in contact with skin), per ISO 10993-10.
Guinea Pig Maximization Test (GPMT)
For this test, male and/or female healthy young adult animals are used. If female animals are used, the animals should be nulliparous and non-pregnant, as pregnancy reduces the ability of a female animal to detect a sensitization response.
Assays with positive controls using the same source and strain of animals only should be performed regularly (at least once every six months, or if longer, concurrent with the test assays) to ensure the reproducibility and sensitivity of the test procedure. These test reports should include positive control data from concurrent testing or from positive control testing within three months (before or after) of the device testing using the same methods and source and strain of animal. We also recommend that your positive control testing include a minimum of five animals to demonstrate a reproducible and appropriately positive response in the test system. If a periodic positive control fails, all GPMT data generated after the last valid positive GPMT response should be considered invalid because there is no assurance that the test system is working appropriately. However, repeating positive control testing to justify a failed positive control test would not be sufficient. If root cause analysis confirms the loss of sensitivity of the animal herd to the positive control, repeating device testing using a new animal herd is recommended for any GPMT data collected between the successful and failed periodic positive control testing. If a primary irritation study is not included in the sensitization protocol, adverse findings at the end of the study may be due to irritation or sensitization, and additional irritation studies to determine the causality may be required. …show more content…
Local Lymph Node Assay (LLNA)
The use of LLNA tests is for medical devices on a case-by-case basis for medical device extract/residuals that are composed of chemical mixtures. LLNA tests may be appropriate in the following circumstances:
• The LLNA can be used for testing metal compounds (with the exception of nickel and nickel-containing metals) unless there are unique physicochemical properties associated with these materials (e.g., nanomaterials) that may interfere with the ability of the LLNA to detect sensitizing materials.
• The LLNA can be used for testing device materials in aqueous solutions unless there are unique physicochemical properties associated with these materials (e.g., nanomaterials) that may interfere with the ability of the LLNA to detect sensitizing chemicals. When testing device materials in aqueous solutions, it is essential to use an appropriate vehicle to maintain the test extract in contact with the skin (e.g., 1% Pluronic L92) so that adequate exposure can be achieved, as demonstrated by positive control results. LLNA …show more content…
For borderline positive responses between an SI of 1.8 and 2.5 there is a potential for false positive results that could limit the usefulness of this type of LLNA test. In addition, the LLNA: DA is not appropriate for testing device materials that affect ATP levels (e.g., chemicals that function as ATP inhibitors) or those that affect the accurate measurement of intracellular ATP (e.g., presence of ATP degrading enzymes, presence of extracellular ATP in the lymph