Hemocompatibility Testing: The Standard FDA Doesn't Want to Endorse

FDA Won’t Endorse AAMI ISO 10993 Standard; Committee and Agency Meet to Rewrite Guidance

Over the years it has been difficult for medical device manufacturers who make devices coming in contact with the human body’s circulatory system to test for safety due to the FDA's nonendorsement of AAMI ISO 10993-4, the standard for hemocompatibility testing.

As it currently stands, 10993-4 provides a chart—Table 1—of medical device examples. Manufacturers compare their device to one on the chart and then conduct the appropriate hemocompatibility test. FDA doesn’t agree with the chart, but provides no guidance for testing.

The rest of the world widely accepts the standard, but FDA has never endorsedit, instead requesting manufacturers use various tests or trends to show hemocompatibility safety of their devices.

One trend is Hemolysis testing—a test that must be performed on any device coming in contact with blood. The test looks for bursting red blood cells. The test is conducted by placing a device sample in blood to see if there are toxic reactions that impact the red blood cell. If there are none then the sample is perceived to be safe.

A second test—Complement Activation—is part of ISO 10993-4, but in the standard the test only applies to devices with large surface areas that come in contact with blood. FDA is now requiring this for all devices that contact the circulatory system.

The test looks at two pathways to an immune system reaction called classical and alternative represented by two proteins—C3A and SC5b-9. The test looks to see if the medical device activates the two pathways, which is what you don’t want.

The most controversial test, and the only animal test of the three, is In Vivo Thrombosis. It is an expensive test and is not always reproducible. The test requires a sample medical device, along with another similar device known to be safe (predicate device), to be placed in animals to test its reaction.

The in vivo thrombosis test is especially controversial since the results are not always accurate and there is a major push and trend in Europe to discontinue all animal testing.

Realizing the complexities and difficulties coming from a lack of guidance, the AAMI ISO Standard Committee met in Milan, Italy to discuss ways to create new guidance for hemocompatibility testing that would basically work for everyone, including guidance the FDA could readily endorse. The FDA itself participated in the committee meeting indicating a strong desire of the agency to develop acceptable guidance. They will also help in the rewrite of the standard.

The hope is to make the standard more effective in result predictions instead of just for safety purposes. The goal is to get it to the point where tests are not used unnecessarily, but rather use acceptable protocols written directly into the standard. The rewrite will define exactly when to use the protocols.
 

Thor Rollins is a biocompatibility specialist, RM(NRCM) for Nelson Laboratories (Salt Lake City, UT)

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Nelson Labs to Participate on Rewrite of AAMI ISO 10993: New Guidance for Hemocompatibility Testing