ISO 10993-1:2018


Biocompatibility Testing for Medical Device


Overview of Biocompatibility Testing

Interaction of medical device with human tissues and physiological systems during the treatment process is commonly called Bio-compatibility.

Bio-compatibility assessment for Non-Active and active medical devices safety with human tissues and physiological system is important for US FDA 510k and CE Marking regulatory submissions. Biocompatibility testing of devices is investigated using analytical chemistry, in vitro tests, and animal models.


Biocompatibility Testing for Medical 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).

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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

Genotoxicity is a routine protocol that has to be performed to detect the effect of medical device in causing genetic mutation, chromosomal aberrations and or toxicity of genetic material. It is also performed to determine the mutagenic and clastogenic materials or compounds that may be carcinogens. The medical device genotoxicity is analysed through in-vitro and in-vivo methods using the appropriate ISO standards as mentioned below..

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.

Hemolysis

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.

Cytotoxicity

The ability of the medical device or the material to inhibit cell proliferation in cell lines is determined through in-vitro cytotoxicity test. The parameters such as cell growth, cell proliferation and morphological effects of the cells are determined in this test.

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

Implantation

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

Sensitization test are conducted for a medical device to detect its hypersensitivity potential or allergic symptoms on the human skin. The medical device or the material extracts are injected or topically applied on the test system and are observed for erythema and edema at appropriate intervals for detecting the sensitizing and allergic potency of the test item (extracts).

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)

Irritation tests are performed to determine the medical device potency to cause irritation in dermal, ocular and mucosal sites. The irritational effects are measured by the localized inflammatory response caused due to single, repeated or continual exposure of the extracts from the medial device. The symptoms such as pain, edema, erythema are observed in this test.

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 is done to evaluate the medical device effect in short term exposure. The extracts are administered one time through oral, dermal and inhalation means within 24 hours and various clinical signs and symptoms are observed for a period of 14 days. Any significant change in clinical signs and symptoms are noted and the systemic effects are observed in detail through gross pathology and blood parameters. The test also aids in determining the lethal dose (LD50) of the extracts from the medical device.

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

Pyrogenicity

The medical device potential to cause fever is determined through the Pyrogenicity test. The common pyrogen in medical device or the pharmaceutical product is the bacterial endotoxins. The contamination of the medical device or the pharmaceutical product leads to the presence of pyrogens in them. Hence the test is necessary to perform through in-vitro or in-vivo method to confirm it is non-pyrogenic before releasing the medical device or the product into the market.

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

Chemical characterization of the medical device is a crucial part of biocompatibility evaluation. Manufactures should provide the composition of the medical device and its toxicity profile to prove its safety in clinical use.

The chemical characterization shall be performed through various techniques like NMR, FTIR, MS, GC-MS etc., The ISO 10993-18 standard is adopted to evaluate the leachable profile of the materials used in manufacturing of the medical device. The results obtained in chemical characterization outlines the exact structural and functional property of the medical device. It also aids in planning the further in-vitro and in-vivo evaluation of the medical device.

Standard Reference: ISO 10993-9 (Identification & quantification of potential degradation products)
Standard Reference: ISO 10993-13 (Identification & quantification of degradation products from polymeric medical devices)
Standard Reference: ISO 10993-14 (Identification & quantification of degradation products from ceramics)
Standard Reference: ISO 10993-15 (Identification & quantification of degradation products from metals and alloys)
Standard Reference: ISO 10993-16 (Toxicokinetic study design for degradation products & 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 & 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 Certificate / EU Notified Body queries. No laboratory does it!!!. Our prices are very economic.

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