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ISO 10993: Biological Evaluation of Medical Devices

by David Milstein on June 10, 2013

Medical devices are defined as health or medical instruments used in the treatment, mitigation, diagnosis or prevention of a disease or abnormal physical condition.  This general description covers a wide range of products, from items as simple as a tongue depressor, to as complicated as prosthetic limbs and implantable drug delivery pumps.  As consumers and patients, we interact with medical devices on an almost daily basis, and the safety of their use is a concern.  Medical devices that are either applied to the surface of the skin or implanted in the body, must be tested to ensure that the do not cause painful irritation due to the chemicals and plastics used.

To this end, the Organization for International Standardization (ISO) developed a series of test requirements to assess the potential of relevant medical devices and their constituents to cause irritation.  This series of tests is summarized in the ISO 10993 guidelines.  Briefly, the most common of these tests are cytotoxicity, ocular irritation, dermal irritation, skin sensitization and intracutaneous irritation, all of which are offered by Nucro-Technics.

Cytotoxicity testing evaluates the potential for medical devices to damage cells with an in-vitro assay.  An extraction is performed on the medical device in question, and the constituents are placed in a media that promotes cell growth.  Then, this media is separated into 5 groups, each of which is diluted to a different degree.  Cells from a human cell line are then introduced to these 5 different dose strengths and allowed to incubate for 24-48 hours.  After this time, the media is observed under a microscope to determine if the constituents of the medical device in question have led to an abnormal rate of cell death.  For comparison, standard materials known to be cytotoxic and non-cytotoxic are extracted into media and mixed with cells as controls for the experimental procedure.  The findings are typically rated on a scale of 0-4, with a rating of 2 or higher being considered cytotoxic.  This is an important first step in determining the safety of a medical device that does not rely on in vivo models, and can be performed cost-effectively.  This test has a turn-around time of two weeks.

Next, depending on the route of administration of the medical device, either ocular or dermal irritation studies are performed.  In these tests, an extraction is performed with saline, and the constituents of the extraction are applied to the skin of an animal for a set period of time, between two weeks and one month. The area is then observed for signs of irritation.  As a control, a separate patch with a known irritant is applied to another location on the skin of the animal, and can be used for comparison.  Both tests have a turn-around time of two weeks.

Although some compounds are known to cause irritation, others simply sensitize the skin, making it possible for previously non-irritating compounds to cause irritation.  To test for this property, an extraction is performed, similar to irritation testing, and then patches are applied to the skin of an animal.  This test differs from the irritation testing in that the application of this patch does not cause irritation directly.  After the patch is removed, a known irritant is applied to the same area, however, the concentration of this irritant is below the minimum value known to cause irritation.  If this sub-threshold application still causes irritation, then the medical device can be considered a skin sensitizer.  Nucro-Technics is capable of performing both the Buehler and Maximization variants of this test, and the turn-around time for each is one month.

For medical devices implanted underneath the skin, intracutaneous testing is a requirement.  In this testing, extractions are performed using both polar (i.e. saline) and non-polar (i.e. oil) vehicles.  Animals then receive four injections: as controls, each of the two vehicles are injected alone, and for the test, each of the two vehicles with extracted constituents are applied as well.  These four areas are then compared for signs of intracutaneous irritation.  The turn-around time for this testing is one week.

While some medical devices call for special considerations and tests, such as testing for vaginal irritation in the case of some contraceptive devices, the tests described above will be sufficient for most medical devices that require ISO 10993 testing.

For more information on any of these ISO 10993 toxicology tests that Nucro-Technics offers, please visit our Genetic Toxicology and the Toxicology pages.  For any information not covered, to receive a quotation, or to schedule a test, please contact NUCRO-TECHNICS.

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