There are three basic tests every medical device must be subjected to: cytotoxicity, sensitization, and irritation. Each test screens for the presence of toxic, leachable materials. Based upon the category of the device, as many as five additional different testing categories may also be required.
Occasionally, a product will fail a test. However, this does not mean the end of the line for that device. We can help you determine the cause of a failure and what steps to take next. A failed result may be due to a single component. In order to understand this, we recommend component testing of any failed product. The MEM elution test is an inexpensive and reliable way to identify potential component issues. By identifying potential component issues early in the process, companies can save money by preventing costly retests or delays on the more expensive and time consuming tests.
If raw materials are ruled out as a cause for failure, the next area to investigate is the manufacturing process where additional leachables may be added to the product. Some of the most common problems are inks or adhesives which have not cured completely and residual detergents on the device. Residues can also be added during the sterilization process.
If the raw materials and the manufacturing process are not the cause, a decision must be made whether or not the amount of toxicity is justifiable based on the benefits of the device. A failed test is certainly not the best scenario for submission, but it need not be the end of the road. Biocompatibility testing must evaluate all test results, as a whole, and the relationship to the device, its use, benefits, and risk. A failed test result is more likely to be accepted if higher level tests (e.g., tests which more directly simulate the products use such as functional implant studies) show normal results, and a well supported, risk assessment-based justification can be written.
To support such a justification, test results can be compared with results of similar devices which are already on the market (i.e. predicate testing). In addition, dilutions of the device extract can also be prepared and tested to determine an endpoint for the toxicity. This end point determination provides you with a more quantitative perspective as to the concentration of the leachate.
Of course, the key to a successful biocompatibility testing experience is working with a laboratory that will closely partner with you about all of the details of your testing. Frequent updates and regular communication can help you save time and money and avoid the pitfalls that so many companies experience. It is also essential to have an open and communicative relationship with your regulatory reviewer. Early buy in on your testing scheme seems to always bode well when it is time for final review.
Nelson Laboratories is dedicated to helping customers determine the right biocompatibility test plan, and partnering with our customers throughout the testing process.