Biocompatibility Testing for Medical Device

Overview of Biocompatibility

Biocompatibility refers to the interaction between a medical device with human tissues and physiological systems during the treatment process.

An evaluation of biocompatibility is an integral part of the overall safety assessment of a Medical Device during regulatory submission to US FDA and EU CE Marking. Biocompatibility of devices is investigated using analytical chemistry, in vitro tests, and animal models.

The biocompatibility of a device depends on following factors,

  • Chemical and Physical nature of the materials used in the construction of device
  • Type of patient tissue and area of exposure
  • Duration of human contact

International Organization for Standardization (ISO) and FDA recommends to follow ISO 10993-1: XXXX( guidelines for Biological Evaluation of Medical Devices)
Download Biocompatibility Chart 
Download List of Harmonized Standards

The following are the important biocompatibility testing to be followed by medical device manufactures according to ISO 10993-1 (Biological evaluation of medical devices, Part 1: Evaluation and testing within a risk management process)

Genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic.

Standard Reference : ISO 10993-3 (Tests for genotoxicity, carcinogenicity and reproductive toxicity)
Testing Duration  = 4 Months
Approximate Investment Cost : 2500 – 5000 USD based on the protocol.

The interaction of devices or biomaterials with blood is an immediate and serious concern during safety assessment. The effects of the biomaterial may be broadly classified into cellular and humoral effects.

Standard Reference : ISO 10993-4 (Selection of Tests for Interactions with Blood, suggests areas of hemocompatibility that should be tested, including thrombosis, coagulation, platelets and platelet function, hematology, and immunology)
Testing Duration  = 5 Months
Approximate Investment Cost : 3500 – 5000 USD based on the protocol.

The cytotoxicity test is one of the biological evaluation and screening tests that use tissue cells in vitro to observe the cell growth, reproduction and morphological effects by medical devices. The in vitro tests for cytotoxicity assess the response of cells in culture to direct contact with devices or to their extracts.

Standard Reference : ISO 10993-5 (Tests for In Vitro Cytotoxicity)
Testing Duration  = 3 Months
Approximate Investment Cost : 500 – 800 USD based on the protocol

The local effects of an implantable device or a material on tissue are assessed by implantation procedures that introduce the material or device, or a representative portion, into tissue.

Standard Reference : ISO 10993-6  (Tests for local effects after implantation)
Testing Duration  = 4 Months
Approximate Investment Cost : 6500 – 9500 USD based on the protocol

ETO Residue estimation
Standard Reference : ISO 10993-7 (Ethylene oxide sterilization residuals)
Testing Duration  = 15 Days
Approximate Investment Cost : 100 – 300 USD based on the protocol

Sensitization test evaluates the potential of a material or product to cause a sensitizing effect or allergenic reaction in a patient over an extended period of exposure of medical device. Sensitization or hypersensitivity is tested by exposing an animal’s skin to the material, or taking extracts from the device/material and injecting and/or topically applying them, and looking for adverse reactions. The results are noted by observing redness and swelling.

Standard Reference : ISO 10993-10 (Tests for Irritation and Sensitization recommends either of these tests)
Testing Duration  = 4 Months
Approximate Investment Cost : 800 – 1300 USD based on the protocol

Irritation   ( Skin /Ocular / Mucosal)
The Irritation test determines if a medical device with which a patient would have contact is an irritant. It measures the reaction to a single, repeated, or continual exposure from medical device that may produce skin, mucosal, or ocular irritation. Irritation is a local tissue response characterized by the usual signs of inflammation, redness, and swelling, and could be accompanied by heat and pain. 

Standard Reference : ISO 10993-10 (Tests for Irritation and Sensitization)  & ISO 10993-12 (Sample preparation and reference materials)
Testing Duration  = 4 Months
Approximate Investment Cost : 800 – 1300 USD based on the protocol

Systemic Toxicity
Acute systemic toxicity testing is conducted to predict the effects of acute exposure of medical device in human. In the animal test, acute exposure is defined as exposure to a substance for less than 24 hours and the main routes of exposure are oral, dermal, and inhalation. If appropriate, data from acute systemic toxicity tests are used to develop warning labels, protective packaging, occupational personal protective equipment requirements, and environmental release limits.

Standard Reference : ISO 10993-11 (Tests for Systemic Toxicity)
Testing Duration  = 4 Months
Approximate Investment Cost : 2000 – 3000 USD based on the protocol

Pyrogenicity test determine the potential presence of pyrogens in extracts of solid materials in order to limit to an acceptable level the risks of febrile reaction following usage of Medical device in the patient. Bacterial endotoxin contamination is most commonly associated with such an adverse effect.

Standard Reference : ISO 10993-11 (recommends testing the pyrogenicity potential of extractable substances derived from material leaching)
Testing Duration  = 4 Months
Approximate Investment Cost : 200 – 400 USD based on the protocol

Biocompatibility Chemical Characterization
Now a days it is more common that notified bodies reviewers request chemical characterization data during the review process.  Several sections of the ISO 10993 standard cover aspects of material and chemical characterization studies are the following

Standard Reference: ISO 10993-9 (Framework for identification and quantification of potential degradation products)
Standard Reference: ISO 10993-13 (Identification and quantification of degradation products from polymeric medical devices)
Standard Reference: ISO 10993-14 (Identification and quantification of degradation products from ceramics)
Standard Reference: ISO 10993-15 (Identification and quantification of degradation products from metals and alloys)
Standard Reference: ISO 10993-16 (Toxicokinetic study design for degradation products and leachable)
Standard Reference: ISO 10993-17 (Establishment of allowable limits for leachable substances)
Standard Reference: ISO 10993-18 (Chemical characterization of materials)
Standard Reference: ISO 10993-19 (Physio-chemical, morphological and topographical characterization of materials)

To investigate the biocompatibility of a medical device material used in the construction and nature of releasing leachable matters to identify preclude subsequent toxicology problems with finished devices. regulatory bodies ask for analytical characterization of device materials and potential leachable per ISO 10993-17 and ISO 10993-18 testing. 

CE Applicants are increasingly aware of the possibility that they might be asked by the reviewer to provide this data. However, the current standards in this area are still fairly vague, as it’s a newer concept than the more tried and true area of biocompatibility testing.

Biological Evaluation Procedure and Plan

Our Laboratories in Israel, Germany, Hongkong and India are AAALAC, NABL, ISO 9001, DSIR, US FDA, IBSC approved.
We provide protocols before initiation of actual testing.

We take up the responsibility of answering to FDA / EU Notified Body queries. No laboratory does it!!!. Our prices are very economic.

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