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What biocompatibility tests can be performed on an adhesive to be considered for use in a medical device application?

It is important to not only be aware of the location of the adhesive, sealant, or encapsulant within the medical device but also the nature of the medical device in question. As a rule of thumb, in choosing such compounds, the adhesive must exhibit non-leaching characteristics. Biocompatibility is of utmost importance when there is skin or body contact involved, while in some non-contact type applications, this biocompatibility requirement may not be as stringent for the adhesive. In terms of biocompatibility testing for adhesives, there are two widely used standards, the USP class VI, which involves in vivo biocompatibility testing, and ISO 10993-5, which involves in vitro cytotoxicity testing. In applications, wherein the adhesive might come in contact with the skin, the ISO 10993-5 test is a good gauge to ensure compliance for the medical device in question.


Biocompatibility Testing

In the ISO 10993-5 test, the biological reactivity of mammalian cell cultures is monitored through in vitro testing. This is often used as an important measure in gauging the cytotoxicity of a product. To pass USP Class VI requirements for biocompatibility, 3 main tests need to be performed. These include the Systemic Injection, the intracutaneous injection, and finally implantation. After such testing, there are observations made for signs of toxicity and skin reactivity post treatment. Also, there are observations made macroscopically to ensure that there are no signs of infection. The ISO 10993-5 test on the other hand involves non-cytotoxic deterministic procedures. The USP Class VI test is conducted by producing an extract of the product in sodium chloride, alcohol, polyethylene glycol, and vegetable oil. These are also injected in specimens, so that the biological response to the extracts can be observed.


Acute Systemic Toxicity (Systemic Injection) TestThe Acute Systemic Toxicity (Systemic Injection) Test measures the toxicity and irritation when a sample of the compound is administered orally, applied to the skin, and inhaled.


Intracutaneous TestThe Intracutaneous Test measures toxicity and localized irritation (between the skin) when the sample is in contact with the tissue in question.


Implantation TestThe Implantation Test measures toxicity, infection, and irritation of an intramuscular implantation of the compound into a test specimen over several days.


All of these are pass / fail tests, which means an adhesive either passes USP class VI standards, or doesn’t. The USP Class VI is therefore considered one of the most stringent and useful specification for adhesives in medical device applications. It is a great guideline for medical equipment manufacturers, for qualification of the eventual device. It must also be noted that the extraction testing for adhesives can be performed at different temperatures and different time periods. The three most common temperatures and times are 50°C for 72 hours, 70°C for 24 hours, or 121°C for 1 hour.