Biological compatibility/safety evaluations are conducted on biomaterials, medical devices, and related products to identify potential risks for the use of medical devices in humans. Biocompatibility testing ranges from the screening of new materials to product release testing, audit testing, and pre-market safety evaluations to meet current FDA guidance and ISO 10993 standards.

Genotoxicity

Bacterial Reverse Mutation Test (Ames Test)
ISO 10993-3
The bacterial reverse mutation test evaluates the mutagenic potential of a test article by using Salmonella typhimurium and Escherichia coli strains to detect point mutations, which includes the substitution, addition or deletion of one or a few DNA base pairs, in the presence and absence of metabolic activation (S9).

Cytotoxicity

Test by Direct Contact (MEM Elution)
ISO 10993-5, ISO 10993-12

This assay tests for biocompatibility. The test article is extracted with DMEM media supplemented with 5% fetal bovine serum and tested on monolayer L929 mouse fibroblast cells based on the current ISO 10993‐5 standard. This protocol is a qualitative test to determine the potential of a test article to produce cytotoxicity.

Test by Indirect Contact (Agar Overlay)
ISO 10993-5
This assay tests for cytotoxicity by indirect contact. This assay is not appropriate for leachables that cannot diffuse through the agar or may react with agar. The test article is laid on an agar layer poured above a monolayer of L929 mouse fibroblast cells based on the current ISO 10993-5 standard. This protocol is a qualitative test to determine the potential of a test article to produce cytotoxicity.
Neutral Red Uptake (NRU) Cytotoxicity Test
ISO 10993-5
This assay tests for the cytotoxic potential of a test article when applied to a monolayer of epidermal keratinocytes or fibroblasts in culture.
MTT Cytotoxicity Test
MB Protocol
To determine the proliferative or cytotoxic potential of a test article when applied to epidermal keratinocytes or fibroblasts in culture. Can use MTT reduction or Neutral Red Uptake.

Implantation

Implantation in Subcutaneous Tissue
ISO 10993-6

For more information about our 10993-6 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Implantation in Muscle
ISO 10993-6

For more information about our 10993-6 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Sensitization

In Vitro Assays

Human Cell Line Activation Test (h-CLAT)
ISO 10993-10
The h‐CLAT is an in vitro method that quantifies changes in cell surface markers on a human cell line following 24 hours exposure to test chemical, as measured by flow cytometry. The relative fluorescence intensity of CD54+ and CD86+ expression when compared to solvent control are calculated and used in a prediction model to support the discrimination between sensitizers and non‐sensitizers.
KeratinoSens™ (Non-GLP/GLP)
ISO 10993-10
Upon exposure to skin sensitizers, the KeratinoSensTM Test measures activation of Keap1-Nrf2-antioxidant/electrophile response element (ARE). These tests use an immortalized, adherent, human keratinocyte cell line (HaCaT) that was transfected with a plasmid to monitor luciferase gene induction.
IL-18 RhE In Vitro Sensitization Assay (IVSA)
Custom Protocol Format
The IVSA is an in vitro test that quantifies interleukin-18 (IL-18) release from keratinocytes following test article (TA) administration to reconstructed human epithelial (RhE) tissue. IL-18 is quantified via a commercial ELISA kit. IL-18 release from TA-treated tissues is compared that of vehicle-treated controls. Solids, extracts, mixtures, insoluble chemicals and soluble chemicals are eligible for evaluation via the IVSA. Results are used to support the discrimination between sensitisers and non-sensitisers, and can be used for potency ranking.
Direct Peptide Reactivity Assay (DPRA)
Custom Protocol Format
The DPRA is an in chemico method that quantifies cysteine‐ or lysine‐containing peptide depletion following 24 hours incubation with the test article (TA). Relative peptide concentration is measured by HPLC and UV detection. Cysteine and lysine peptide percent depletion values are then calculated and used in a prediction model which allows assignment of the TA into one of four reactivity classes which enables the discrimination between sensitizers and sonosensitizers.

Additional Assays

Local Lymph Node Assay (LLNA)
ISO 10993-10

The local Lymph Node Assay (LLNA) is an alternative in vivo study to the Guinea Pig Sensitization Test, used for determining sensitization potential of materials. Following exposure to a sensitizing test substance, lymphocyte proliferation occurs in the local lymph node. The LLNA measures increased proliferation of lymphocytes in the auricular lymph nodes (which drain the site of exposure; ears). Proliferation is assessed by determining the incorporation of the thymidine analog, bromodeoxyuridine (BrdU), into the DNA of lymph node cells using flow cytometric method.

Guinea Pig Maximization Test (GPMT)
ISO 10993-10
The Guinea Pig Maximization Test (GPMT) uses a combined intradermal and topical induction regime to assess a test article’s ability to dermally sensitize the test subjects.  A challenge of the highest non-irritating concentration is used to elicit potential effects.
Closed-patch Test (Buehler Test)
ISO 10993-10
The Buehler Assay uses a three– or nine-induction regime to assess a test article’s ability to dermally sensitize the test subjects. A challenge of the highest non-irritating concentration is used to elicit potential effects.

Systemic Toxicity Studies

Acute Systemic Toxicity
ISO 10993-11

For more information about our 10993-11 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Pyrogenicity

Pyrogenicity Test in Rabbits
ISO 10993-11, USP 151

For more information about our 10993-6 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Irritation Studies

In Vitro Assays

In Vitro Reconstructed Human Epidermis Model (SIT)
ISO 10993-23
The SIT utilizes three-dimensional reconstructed human epidermis (RhE) tissues. The RhE tissues are composed of primary human cells, which have been cultured to form a stratified, highly differentiated squamous epithelium morphologically similar to that of human skin. Following exposure to a test article (TA) and incubation, tissue viability is measured via MTT reduction. The SIT assay will classify a liquid, powder or solid as either non-irritating or irritating. This assay is not designed to test gases and aerosols.

Additional Assays

Irritation Test by Skin Exposure
ISO 10993-23

For more information about our 10993-23 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Irritation Test by Intracutaneous (Intradermal) Administration
ISO 10993-23

For more information about our 10993-6 Assays, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

Special Irritation Tests
ISO 10993-23
For more information about our 10993-23 Special Irritation Tests, please contact our Client Services Team at clientservices@mbresearch.com or call 215-536-4110.

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