An extract of the device or biomaterial is prepared in up to four (4) standard USP extraction solutions and is injected intracutaneously into rabbits to assess the irritancy of extractable compounds that may exist in the biomaterial. The animals are observed for dermal reactions over a 72-hour period. If the animals exposed to the test article extract do not show significant signs of irritation above those observed in the concurrent test control groups, the test article passes the test. Gross photography may be requested. Additional fees apply.

Test material coming in direct or indirect contact with mucosal tissue can be assessed as to its irritation potential by repeated instillation of an extract into rabbit vaginas. Acute irritation is evaluated by gross observation and histopathology of the vaginal mucosa and submucosa. Usually an application is performed on each of five days unless longer treatment is indicated due to the use of the device.

Three rabbits receive a 0.1 ml dose of a polar (normal saline) or nonpolar (cottonseed oil) extract of the test material into one eye of each rabbit. After a 24-hour exposure, the eye is flushed and the conjunctiva, cornea and iris are evaluated for up to 72 hours for acute irritation or injury. Test materials should be prescreened using the Cytotoxicity Agarose Diffusion Test.

A 0.15 ml dose of test material extract is injected with a fine-gauge needle into the anterior chamber of one eye. At the same time, a vehicle control is injected in the same manner into the opposing eye. Over the 3-day exposure of the test, the reaction to the injected substance is evaluated using a slit-lamp microscope and the degree of reaction is scored using a standard scoring system. The test material passes the test if the test article extract does not produce irritation to a significantly greater degree than the control material. Test materials should be prescreened using a cytotoxicity test.

This test is performed to assess the potential for topical irritation from acute exposure or use of the device material. The material is applied to intact skin of three (3) rabbits and left in contact for 4 to 24 hours. An estimate of irritation, erythema (redness) and edema (swelling) is made during the next 72 hours. Histopathologic evaluation and photomicrographs (gross and histologic) will also be provided at the request of the sponsor. Additional fees apply.

Note: Sponsor specifies contact duration (4 hours to 24 hours) on test request form.

The test articles are prepared in a sterile solution, which is injected intravenously into three (3) rabbits to assess pyrogenicity. The animals are observed over a 3-hour period for an increase in body temperature. If the animals exposed to the solution do not show significant increase in body temperature, the test article passes the test. If any single animal of the three has a temperature increase above the acceptable range, the test can be continued with 5 additional animals at client’s request. (See below.)

An extract of the test article is prepared in a sterile saline solution and injected intravenously into three (3) rabbits to assess pyrogenicity. The animals are observed over a 3-hour period for an increase in body temperature. If the animals exposed to the test article extract do not show significant increase in body temperature, the test article passes the test. If any single animal of the three has a temperature increase above the acceptable range, the test can be continued with 5 additional animals at client’s request. (See below.)

See USP Rabbit Pyrogen and ISO Rabbit Pyrogen – Materials Mediated tests above. Continuation of testing is at client's request. Additional fees apply.

Guinea pigs are exposed to the extract twice within a two-week period (Inductions I and II). The animals are re-exposed (challenged) 10-14 days after Induction II by placing fresh extract in contact with previously unexposed skin. Over a 72-hour period, the animals are observed for signs of a delayed allergic response when compared to a control group. If the test results are equivocal, a re-challenge can be conducted within 7-10 days of the initial challenge.

Guinea pigs are patched with the test material three times per week for three weeks during the Induction Phase. After a two-week recovery period, the animals are topically challenged with similar patches of the test material to assess for delayed contact sensitization.

Multiple extracts of a device are prepared with standard polar and/or nonpolar vehicles and injected into 6 male and 6 female mice over a 14-day period. Two similar control groups are also injected with control vehicle. The animals are observed during the 14-day period for signs of toxicity and are subjected to a gross observation at study termination. The test article passes if the test parameters (weight, survival, clinical observation and gross necropsy) are not significantly different from the concurrent control animal parameters. Other parameters, such as hematology, clinical chemistry and histopathology, may also be evaluated. Additional fees apply. [For test codes, see test listings below.]

Tests 800530 and 800532 are recommended for medical devices categorized as "prolonged contact" (24 hours to 30 days).

Tests 800531 and 800533 are recommended for medical devices categorized as "permanent contact" (more than 30 days).

An extract of the device or biomaterial is prepared in up to four (4) standard USP extraction solutions and injected into mice (10 per extract) to assess the toxicity of extractable compounds that may exist in the biomaterial. The animals are observed over a 72-hour period. If the animals exposed to the test article extract do not show signs of toxicity greater than the concurrent control groups, the test article passes the test.

This assay is designed to serve as a safety evaluation for lot release. A single unit or device is extracted with sterile saline solution and injected intravenously into five mice to assess the acute toxicity of the device. The animals are observed over a 48-hour period. If the animals survive the injection with no signs of toxicity, the device passes the test.

EXTRACT
Normal Saline

Specify one set of extraction conditions: 
121°C/1hour,     70°C/24 hours,    50°C/72 hours,     37°C/72 hours

SAMPLE REQUIREMENTS
One (1) device to represent the lot under test.