Medical Device Biocompatibility Testing – ISO 10993

Biocompatibility is, by definition, a measurement of how compatible a device 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 four in vitro cytotoxicity tests that PBL performs, MEM Elution, Agarose Overlay, Direct Contact, and the MTT assay. 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 Leachables and Extractables – ISO 10993-18

Typically, chemical characterization and analysis of a device’s components, also known as device leachables and extractables 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.

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 cytotoxicity 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 toxicologists 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 17025:2017 accreditation.

Available Biocompatibility ISO 10993 Testing Services

  • Chemical Characterization (ISO 10993-18 and 10993-17)
  • Cytotoxicity
    • USP/ISO Agarose Overlay Test
    • USP/ISO MEM Elution Test
    • USP/ISO Direct Contact Test
    • ISO MTT Assay (quantitative)
  • Hemocompatibility
    • JP Hemolysis Test
    • ASTM Hemolysis Test
  • Irritation / Intracutaneous Reactivity
    • USP / ISO Intracutaneous Reactivity Test
    • ISO Mucosal Irritation Test (vaginal, rectal, oral, penile)
    • ISO / FSHA / OECD / EPA Ocular Irritation Test
    • Intraocular Toxicity
    • ISO / EPA / OECD / FSHA Dermal Irritation
  • Sensitization
    • ISO / EPA Closed Patch (Buehler) Test
    • ISO Maximization Test for Delayed-Type Hypersensitivity
  • Systemic Toxicity – ISO Acute Systemic Toxicity Test
  • Pyrogen Tests
    • USP / CFR Pyrogen Test
    • ISO Rabbit Pyrogen Test – Material Mediated
    • EP Pyrogen Test
  • Implantation Testing
    • USP Intramuscular Implantation
    • ISO Subcutaneous Implantation
    • ISO Intramuscular Implantation
  • USP Plastic Tests (USP Class I-VI)
    • USP I-VI
    • USP Systemic Injection Test
    • USP Intracutaneous Test
    • USP Implant Test
    • USP Safety Test
  • USP Safety Tests for Biologics
    • USP Safety Test

Read More About ISO 10993 and Biocompatibility Testing

PBL Learning Center – Assessing Biocompatibility

PBL Learning Center – Introduction to Biocompatibility Testing

PBL Learning Center – Biocompatibility Planning Tool (BioPT)

PBL Learning Center – Biological Test Methods

PBL Learning Center – Materials Characterization and Analytical Testing of Biomaterials

PBL Blog – Learn About the Types of Biocompatibility Tests

PBL Blog – The Key Concepts of Biocompatibility Testing

PBL Blog – Toxicologists Weigh in on Biocompatibility

PBL Blog – Material and Chemical Characterization of Devices: Part 1, an Overview

PBL Blog – Detailed Methods for Performing Extractables Testing of Materials

PBL Blog – A Note on Chemical Characterization

PBL Blog – FTIR – A Helpful Tool to Determine Chemical Composition

 

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