Medical Device Biocompatibility Testing – ISO 10993

Biocompatibility is, by definition, a measurement of how compatible a device or material is with a biological system. The ISO 10993-1: 2018 standard defines biocompatibility as the “ability of a medical device or material to perform with an appropriate host response in a specific application”.

The purpose of performing biocompatibility testing is to determine the fitness of a device for human use, and to see whether use of the device can have any potentially harmful physiological effects. As stated by the International Organization of Standards (ISO): “The primary aim of this part of ISO 10993 is the protection of humans from potential risks arising from the use of medical devices.” (ISO 10993-1:2018). Before performing biocompatibility testing, it is important for the manufacturer to gain a better understanding of the device materials, device manufacturing, sterilization and other processes. The ISO 10993-1:2018 standard emphasizes chemical characterization before proceeding to in vitro and in vivo biocompatibility testing.

The general process of biocompatibility testing can be broken up into three steps: planning, testing and evaluating the data. In the planning stage data on the materials used to manufacture the device should be collected. A biological evaluation plan (BEP) should also be developed which will determine the type of testing that is required. See PBL’s Biocompatibility Planning Tool (BioPT) for more information on how to determine which tests are needed. Testing typically starts with in vitro screening by performing cytotoxicity testing. Extractable leachable testing, or chemical characterization, is also usually conducted before the in vivo testing. Cytotoxicity, chemical characterization and in vivo biocompatibility testing is described below.

Cytotoxicity In Vitro – ISO 10993-5

Cytotoxicity is a biocompatibility test performed on mammalian cells in culture. There are three in vitro cytotoxicity tests that PBL performs: MEM Elution, Agarose Overlay, and Direct Contact. Cytotoxicity testing evaluates the toxicity or materials and chemicals by exposing cultured cells to the sample directly or by preparing an extract from the sample and exposing the cells to the extract. Please visit our Cytotoxicity Testing Page for more details.

Device Extractables and Leachables – ISO 10993-18

Typically, chemical characterization and analysis of a device’s components, also known as device extractables and leachables testing, is conducted prior to any biological testing. This involves extracting leachable materials from the device or components at an elevated temperature and analyzing the extracts using a variety of instrumentation. A toxicological risk assessment is conducted on the leachable extracts for potentially harmful or toxic chemicals. This aspect of biocompatibility follows ISO 10993-18, Chemical characterization of materials, and has become increasingly important over the last several years. For more information please visit our Chemical Characterization Page for more details.

Hemolysis Testing – ASTM F756

We conduct hemolysis tests, via direct and extract methods, to evaluate the adverse effects of medical devices, leachables, and biomaterials on rabbit blood. This assay is well suited to evaluate the hemocompatibility of medical devices and biomaterials according to the international standard ISO 10993-4:2017 and ASTM F756.

In Vivo Biocompatibility Testing

Once in vitro testing has been completed, in vivo biological testing is performed, with the extent of type of testing to be performed based upon the device’s intended use. In vivo testing can range from skin irritation testing, to sensitization testing, implantation testing and systemic toxicity testing. Turnaround time for tests can range from three weeks to greater than several months, depending on the specific test data needed. Subchronic or chronic systemic toxicity studies can last even longer.

General Information – Preclinical CRO

Pacific BioLabs is a bay area preclinical CRO that has been assisting medical device companies with FDA IDE and 510k, as well as international regulatory submissions for several decades. PBL has been performing biocompatibility testing for over 37 years and our experienced personnel have performed testing on thousands of devices of various materials, configurations and applications making Pacific BioLabs one of the most experience biocompatibility testing laboratories. We offer testing performed according to ISO 10993, compliant with all major regulatory bodies. Our animal programs are AAALAC accredited, and we carry ISO 17025 accreditation.

Available Biocompatibility ISO 10993 Testing Services

Chemical Characterization (ISO 10993-17 and 10993-18 )
Cytotoxicity
- USP/ISO Agarose Overlay Test
- USP/ISO MEM Elution Test
- USP/ISO Direct Contact Test
Irritation/Intracutaneous Reactivity
- USP/ISO Intracutaneous Reactivity Test
- ISO Mucosal Irritation Test (vaginal, rectal)
- ISO/OECD Ocular Irritation Test
- Intraocular Toxicity
- ISO/OECD/FSHA Dermal Irritation Test
Hemolysis Testing – Direct and Extract Method
Sensitization
- ISO/OECD Maximization Test for Delayed-Type Hypersensitivity
- ISO/EPA/OECD Closed Patch (Buehler) Test
Systemic Toxicity
ISO Acute Systemic Toxicity Test
Pyrogen Tests
- USP/CFR Pyrogen Test
- ISO/USP Rabbit Pyrogen Test – Material Mediated Test
- 14-Day Subacute Systemic Toxicity Testing
- 28-Day Subchronic Systemic Toxicity Testing
Implantation Testing
- ISO Subcutaneous Implantation
- ISO Intramuscular Implantation
- Intraperitoneal Implantation
USP Plastic Tests (USP Class I-VI) for Materials
- USP Systemic Injection Test
- USP Intracutaneous Test
- USP Implant Test
- USP Safety Test