The Big Three: Tests Every Manufacturer Needs to Know

There are myriad tests that medical device manufacturers need to be prepared to conduct on their creations in order to pass regulation requirements before they are released to the marketplace. None more important than the Cytoxicity, Sensitization, and Irritation tests—the Big Three as I like to call them.

They are the Big Three because they must be conducted on every device before they can be submitted to the U.S. Food and Drug Administration (FDA). There is no way you can get around doing the three tests. Other tests may or may not need to be conducted.

By understanding these three tests, you can be better prepared for submission to the FDA and better prepared to write justifications when the tests indicate a failure. Here is a description of each of the tests:

Cytoxicity testing is a very basic, very simple in-vitro test that can begin at any time. Due to its low cost, it also can be done many times throughout the process. It is a test at the cellular level and measures the impact your device has on drawing toxins out of the device.

Sensitization testing is done in-vivo and looks for delayed hypersensitivity or Type 4 sensitivity. The test determines if your device causes a reaction with repeated exposure. The test looks for a reaction by the immune system. The test takes longer and requires careful planning to avoid additional costs and wasted time.

Irritation testing is similar to sensitization testing, but it tests Type 1 sensitivity—an immediate reaction to your device. The test allows you to know if the device creates an immediate chemical reaction when it comes in contact with a patient’s body.

It’s important to have a clear understanding of these tests in order to look for things that aren’t sensitizers, cytoxic or irritants from the very beginning of the manufacturing process. With just a little background manufacturers can:

1. Know the importance of each test and why they have to be done. It helps to know what each test is looking for and the acceptance standard for each;
2. Get an idea of the potential dangers in each test and what impact your device may have on the test; and
3. Know what the reaction to the patient may be based on the results of a failed test. Is it something you can justify? Do you need to reevaluate the materials and processes you are using to get it to pass? Can a risk assessment on the toxicity of the device be made or does the toxicity need to be eliminated?

If your medical device passes all three tests, the FDA process can go very quickly. But, if it is a complicated device, or there are certain test failures that need to be justified, then the reviewing process can be longer or even bog down.

it is critical to understand and implement these tests in order to develop products that pass clinical and regulatory muster—it allows you to see the impact. If a failure is flagged, it gives you the time and the tools to make intelligent decisions about what to do with the device—whether it is to make adjustments to pass or to make justifications for the failure.
 
About the Author
Thor Rollins is a certified microbiologist, RM (NRCM) with the National Registry of Certified Microbiologists and has been with Nelson Laboratories, Inc. since 2002. Currently, he is the In-vivo Biocompatibility Subcontracting Section Leader, and from 2002-2006, he was the study director over cytotoxicity. He specializes in the in-vitro and in-vivo biocompatibility tests and actively speaks on the topics through Nelson Labs external seminars, webinars and tradeshows.
He is a participating member on all AAMI 10993 ISO committees and plays an active role along with the FDA and regulatory committees developing standards, and discussing and voting on changes to those standards. As one of a select group of experts in the industry, Thor’s participation on the committees offers him insight on industry changes and helps prepare Nelson Labs and its clients for changes in testing. Thor studied engineering at Colorado School of Mines and received his B.S. in biology with an emphasis in cell biology and genetics from Idaho State University.