Biocompatibility Testing - ISO 10993 Standard

Biocompatibility is a measurement of how compatible a device is with a biological system (not generating any local or systemic responses from a living system or tissue). In the simplest sense, a biocompatible material or device does not harm the patient. From a regulatory view, it is a series of tests that are used to determine the toxicity resulting from contact of the parts of medical devices or combination products with the body. A medical device may consist of materials that are biocompatible, although the device itself requires biocompatibility testing and all testing is performed on the final product.

ISO Standard for Biocompatibility Testing

• Common biocompatibility testing, such as those described by ISO 10993, is conducted prior to clinical evaluation of the device or clearance to market the product. This testing involves analysis of the device if non-toxic and non-allergic as per ISO 10993 standard. The purpose of this testing is to determine the fitness of a device for human use, and to check whether the device can have any harmful physiological effects.

•  Implementation of ISO10993 varies, based on the risk associated with the use of the product. Many of the biological screens that comprise the remaining parts of ISO 10993 are designed to estimate specific aspects of biocompatibility, and therefore are not required for all medical devices.

ISO

ISO was established to determine a uniform worldwide standards and it is a non-governmental network of national standards institutes and acting as a bridge between the private and public sectors. International Organization for Standardization is abbreviated ISO from the Greek word “isos” meaning equal.

ISO-10993 Standard

(ISO 10993-1) Risk management process

• (ISO 10993-2) Animal welfare requirements

• (ISO 10993-3) Tests for genotoxicity, carcinogenicity and reproductive toxicity

1. Genotoxicity- Gene or point mutations ,small deletions, mitotic recombination or microscopically visible chromosome changes

2. Carcinogenicity- Ability of a carcinogen to produce invasive cancer cells from normal cells.

3. Reproductive toxicity- It includes adverse effects on sexual function and fertility in adult (males and females) as well as adverse effects on offspring

• (ISO 10993-4) – Test for medical devices that interact with blood, Hemocompatibility – Tests evaluate the effects of medical devices or materials that are in contact / indirect contact with blood on blood components

• (ISO 10993-5) – Test for in vitro Cytotoxicity–to evaluate cell damage caused by materials either by direct interaction or by leachable 

• (ISO 10993-6) – Tests for evaluating the local effects of implant material on living tissue

• (ISO 10993-7) – Ethylene oxide sterilization residuals – It refers to a materials ability to induce specific delayed type hypersensitivity in the body’s initial exposure (Haptens, Langerhans cells and T-cell lymphocytes ,Lymphokines)

• (ISO 10993-8) – For biological tests selection and qualification of reference materials

• (ISO 10993-9) – Framework for identification and quantification of potential degradation products

• (ISO 10993-11) – Tests for acute systemic toxicity ,Sub acute/sub chronic

• (ISO 10993-12) – For Sample preparation and reference materials

• (ISO 10993-13) – Test for Identifying and quantifying degraded products from polymeric medical devices

• (ISO 10993-14) – Identifying and quantifying degraded products from ceramics

• (ISO 10993-15) – Identifying and quantifying degraded products from metals and alloys

• (ISO 10993-16) – Design of Toxicokinetic study for degradation products and leachable

• (ISO 10993-17) – Specifies the determination of allowable limits for substances leachable from medical devices

• (ISO 10993-18) – Chemical characterization test for materials

• (ISO 10993-19) – This test is for evaluating Physico-chemical, topographical and morphological characterization of materials

• (ISO 10993-20) – Immunotoxicology testing of medical devices

ISO 10993 testing is not required for all medical devices, including the following

• Lab on a chip devices

• Micro total chemical analysis systems used in laboratory instrumentation

• Clinical Point of care systems OR hand held devices that do not interact or penetrate the skin

• Micro-Electro-Mechanical Systems devices used in medical imaging machines

Characterization Methods

Identification of materials constituents

• Changes of the material overtime

• Changes with exposure to different environment

• Lot –to –Lot Consistency for manufacturing purposes

Methods

• Infrared spectral analysis (IR)

• Thermal analysis

• Density analysis

• Molecular Weight distribution

• Mechanical properties

• Surface properties