Medical devices and their component materials may leach compounds or have surface characteristics that may produce undesirable effects when used clinically. The selection and evaluation of materials and devices intended for use in humans requires a structured program of assessment to establish biocompatibility and safety. Current regulations, whether in accordance with the U.S. Food and Drug Administration (FDA), the International Organization for Standardization (ISO), require that manufacturers conduct adequate safety testing of their finished devices through pre-clinical and clinical phases as part of the regulatory clearance process.
The guidelines provide a general testing framework to aid manufacturers in the assessment of device biocompatibility. The number and type of specific safety tests required to assess product safety and compliance are dependent on the individual characteristics of the device, its component materials, and its intended clinical use.
Within the general safety testing framework, it remains the responsibility of the device manufacturer to select and justify the specific tests most appropriate for the establishment of product safety and compliance with ISO and FDA requirements. It is recommended that testing be performed to comply with GLP regulations.
Choosing the correct path for biocompatibility testing has become more complex than ever. Having knowledgeable experts on your team to help develop complete submission packages is crucial to successfully moving your product to market.
Cytotoxicity – ISO 10993-5
A cytotoxicity test determines whether a product or compound will have any toxic effect due to leachables on living cells. Generally used as a screening tool for raw materials or component products before they are put into the design of a medical device.
Sensitization – ISO 10993-10
Tests for sensitivity to any part of a device during exposure to the body for any length of time. Exposure can create allergic or other sensitive reactions.
Irritation/Intracutaneous – ISO 10993-10
Determines how irritable a product or compound is to the body. Studies should be made in combination with how the product or compound will be used and effected areas should be tested to determine the effect over time.
Acute Systemic Toxicity – ISO 10993-11
Identifies the effect of being exposed to a product or compound within 24 hours. Acute toxicity occurs after a single exposure or repeated exposures to the test subject. SubAcute symptoms appear within 14 to 28 days of delivery.
Subchronic Toxicity – ISO 10993-11
Studies that continue for 90 days or for up to 10% of a test subject’s life span are considered Subchronic. Studies that continue for longer than 10% of a test subjects life span are considered chronic.
Genotoxicity – ISO 10993-3
Genotoxicity, tests for gene mutations, changes in chromosomes, DNA and gene toxicities caused by products or compounds.
Implantation – ISO 10993-6
Studies the effects of products or compounds on living tissue. Exaggerated amounts of material should be used. It may be important to calculate the maximum amount of material that would be typically used and then implant multiples of that amount in an experiment.
Hemocompatibility – ISO 10993-4
Tests the effects of blood contacting the product or compounds on blood or blood components, directly or indirectly during routine use.
Chronic Toxicity – ISO 10993-11
Chronic toxicity studies can require that animal subjects be exposed to varying doses of test agents over an extended period of time.
Carcinogenicity – ISO 10993-3
This test should be performed only if there is data from other sources suggesting possible difficulties. This test is performed over the majority of the test subject’s life. It looks for tumorigenicity as well as chronic toxicity.
Reproductive/Developmental – ISO 10993-3
This study should only be performed when it is believed that the reproduction system will be affected by the product of compound. It tests the effects of the product or compound on the reproductive system, development of the embryo, as well as pre and postnatal development.
Turn Around Time
|ISO 10993 Part 5||Cytotoxicity||CY-GLP-01||3 – 4 Weeks||Cytotoxicity Test – MEM Elution – ISO|
|ISO 10993 Part 5||Cytotoxicity||CY-GLP-02||2 – 3 Weeks||Cytotoxicity Test – MEM Agar Diffusion – ISO|
|ISO 10993 Part 5||Cytotoxicity||CY-GLP-03||3 – 4 Weeks||Cytotoxicity Test -Neutral Red Uptake 1 concentration-ISO|
|ISO 10993 Part 5||Cytotoxicity||CY-GLP-04||3 – 4 Weeks||MTT Cytotoxicity Test – ISO|
|ISO 10993 Part 10||Sensitization||SEN-GLP-01||6 – 8 Weeks||Kligman Maximization/2 Extracts/35 animals/ concurrent (+) Controls-ISO|
|ISO 10993 Part 10||Sensitization||SEN-GLP-02||8 – 9 Weeks||Buehler Sensitization-ISO|
|ISO 10993 Part 10||Sensitization||SEN-GLP-03||3 – 4 Weeks||Murine Local Lymph Node Assay (LLNA)-2 extracts-ISO|
|ISO 10993 Part 10||Irritation||IR-GLP-01||3 – 4 Weeks||Intracutaneous Injection Assay-2 extracts-ISO-Polar and Non-Polar Extracts Included|
|ISO 10993 Part 10||Irritation||IR-GLP-02||3 – 4 Weeks||Primary Skin Irritation|
|ISO 10993 Part 10||Irritation||IR-GLP-03||5 – 6 Weeks||Primary Dermal Irritation-2 Ext-ISO|
|ISO 10993 Part 10||Irritation||IR-GLP-04||7 – 8 Weeks||Primary Buccal (Mucosal) Irritation-ISO-Polar and Non-Polar Extracts Included|
|ISO 10993 Part 10||Irritation||IR-GLP-05||7 – 8 Weeks||Irritation-Vaginal-2 EXT|
|ISO 10993 Part 10||Irritation||IR-GLP-06||7 – 8 Weeks||Irritation-Vaginal-Direct|
|ISO 10993 Part 11||Systemic Toxicity||STOX-GLP-01||4 – 5 Weeks||Systemic Injection Test-ISO- Polar and Non-Polar Extracts Included|
|ISO 10993 Part 11||Systemic Toxicity||STOX-GLP-01||4 – 5 Weeks||Acute Oral Toxicity, 2 Extracts -ISO-Polar and Non-Polar Extracts Included|
|ISO 10993 Part 11||Subchronic Systemic Toxicity||STOX-GLP-02||16 – 17 Weeks||28 Day Abridged Sub Chronic Tox in Rats-IP-ISO|
|ISO 10993 Part 11||Rabbit Pyrogen/Material Mediated||RP-GLP-01||4 – 5 Weeks||Rabbit Pyrogen-Material Mediated-ISO|
|ISO 10993 Part 3||Genotoxicity||GEN-GLP-01||4 – 6 Weeks||Ames Assay/Salmonella and one E. Coli -2 extracts-ISO|
|ISO 10993 Part 3||Genotoxicity||GEN-GLP-02||4 – 6 Weeks||Ames Assay/Salmonella and one E. Coli -2 extracts with Confirmation-ISO|
|ISO 10993 Part 3||Genotoxicity||GEN-GLP-03||8 – 9 Weeks||Rodent Bone Marrow Micronucleus Assay-2 Extracts/Solutions-ISO|
|ISO 10993 Part 3||Genotoxicity||GEN-GLP-04||8 – 10 Weeks||Mouse Lymphoma Forward Mutation Assay-2 Extracts-ISO|
|ISO 10993 Part 6||Muscle Implantation||IM-GLP-2||7 – 8 Weeks||Implant/Muscle/2 Weeks-ISO|
|ISO 10993 Part 6||Muscle Implantation||IM-GLP-4||10 – 11 Weeks||Implant/Muscle/4 Weeks-ISO|
|ISO 10993 Part 6||Muscle Implantation||IM-GLP-8||14 – 15 Weeks||Implant/Muscle/8 Weeks-ISO|
|ISO 10993 Part 6||Muscle Implantation||IM-GLP-13||19 – 20 Weeks||Implant/Muscle/13 Weeks-ISO|
|ISO 10993 Part 6||Subcutaneous Implantation||SQ-GLP-2||7 – 8 Weeks||Implant/SubQ/2 Weeks-ISO|
|ISO 10993 Part 6||Subcutaneous Implantation||SQ-GLP-4||10 – 11 Weeks||Implant/SubQ/4 Weeks-ISO|
|ISO 10993 Part 6||Subcutaneous Implantation||SQ-GLP-8||14 – 15 Weeks||Implant/SubQ/8 Weeks-ISO|
|ISO 10993 Part 6||Subcutaneous Implantation||SQ-GLP-13||19 – 20 Weeks||Implant/SubQ/13 Weeks-ISO|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-01||4 – 5 Weeks||Complement Activation-C3a & SC5b-p per ISO|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-02||3- 4 Weeks||Prothrombin time (PT)-Direct|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-03||3- 4 Weeks||Unactivated Partial Thromboplastin Time (Direct)-ISO|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-04||3- 4 Weeks||Hemolysis Complete (Direct and Indirect)-ASTM|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-05||3- 4 Weeks||In Vitro Hemocompatibility (Direct)-ISO|
|ISO 10993 Part 4||Hemocompatibility||HEM-GLP-06||6 – 7 Weeks||Dog Thromboresistance/2 Animals|