Biocompatibility

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.

Quick Jump:

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 an enzyme-linked immunosorbent assay (ELISA).

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

The acute systemic toxicity test is used to assess whether leachables from medical devices can cause harmful effects when introduced into the body. In this test, extracts of the material are administered to animals—commonly mice or rats—via relevant systemic routes such as intravenous, intraperitoneal, or oral. The animals are observed over a 72-hour period for signs of toxicity, including behavioral changes, weight loss, or mortality. The results help determine if the material poses an acute risk to patient health when used as intended. 

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

Pyrogen testing is performed to detect pyrogenic or fever responses following exposure to a medical device, bio-material, or their extracts.  Pyrogenic responses may be material-mediated, endotoxin-meditated, or mediated by other substances.  The febrile response is detected by a rise in body temperature following intravenous injection.

For more information about our 10993-11 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

The irritation test by skin exposure (topical) evaluates the potential of medical device materials to cause skin irritation through direct contact. In this method, test materials or their extracts are applied topically. The application site is observed over a 72-hour period for signs of erythema (redness) and edema (swelling). The reactions are scored and assessed to determine whether the material induces a dermal irritation response. This test ensures the safety of materials intended for direct skin contact in medical applications.

 

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

This study is designed to assess the potential of medical devices to cause localized irritation when introduced into the skin. In this test, extracts of the device material are injected into the dermis of test animals and the injection sites are observed over a 72-hour period for signs of erythema (redness) and edema (swelling). The severity of the reactions is scored and averaged to determine if the material induces a significant irritant response.

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

Special Irritation Tests are designed for specific exposure scenarios beyond standard intracutaneous or topical testing. These tests help ensure that medical devices are safe for contact with various mucosal tissues, depending on their intended use.

  1. Ocular Irritation Test: Assesses the potential of a material or extract to cause irritation when applied to the eye. The test evaluates redness, swelling, and discharge in the conjunctiva, cornea, and iris.
  2. Oral Mucosal Irritation Test: Used for materials intended for intraoral use. The material or extract is applied to the oral mucosa and tissues are examined for signs of irritation or inflammation.
  3. Vaginal Irritation Test: Designed for devices used in vaginal applications. The test material is introduced into the relevant site and tissues are assessed for irritation or histopathological changes.

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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