USP 88 class VI vs ISO 10993

In its origin, USP <88> was developed as a series of tests packaged together in various iterations to become what is known as a Class Test. These classifications range from Class I through Class VI and as the classification increases, so does the number of extraction vehicles and number of tests required. These individual tests include intracutaneous irritation, acute systemic toxicity and implantation and the four possible vehicles used are USP 0.9% Saline for Injection, Vegetable Oil (cottonseed or sesame seed), Ethanol and Polyethylene Glycol 400. At its inception, a Class VI would be performed to label a plastic product with the VI-70 to indicate it had passed a class test with extracts at 70 degrees. USP <88> was originally written to consider plastics, but it has expanded over the years to be applied to many other material types. A Class VI tested material can be sold to medical device companies with a certain level of comfort about material safety. Medical device and drug companies many times put into their spec sheets that a material or individual component in their final device designs or manufacturing lines must be Class VI material. Then the final finished product is ISO 10993 tested for biocompatibility if applicable. Material vendors though many times sell their resins, tubing, filters etc. to many different end users although they may custom formulate materials also.
This variety of end users may have different internal quality standards and some may simply require a USP <88> Class VI to be performed while others may want ISO 10993 testing. While it’s a boon for the biocompatibility labs to first perform a USP <88> Class I-VI and then later ISO 10993 tests when different end users request it, it’s an obvious burden on the material vendors. It is possible to combine the requirements of the two testing guidances into a single test that could support a wider range of end user requirements. ISO 10993 contains within it an equivalent test for each of the USP Class VI individual components, but all details are not the same. What the USP/ISO Class VI could do is to take the worst case conditions for the intracutaneous irritation and acute systemic toxicity tests from each version of the tests and then have two separate implant tests performed.
The table below goes through each of the tests and lists the differences between the two methods.
It should be noted, but not to be bogged down in details, that USP <88> also allows for the irritation test to be performed in guinea pigs and the implantation test to be performed in rats. These options are not used in any frequency but are available.
In the end, this combined version of the Class VI may allow for material vendors to satisfy most of their client quality requirements. Vendors may still be requested for additional testing of materials such as USP <87>, USP <661>, ISO 10993-10 sensitization, ISO 10993-5 cytotoxicity or ISO 10993-11 pyrogenicity.
Now, I know there may be some manufacturers out there wondering if they can submit USP <88> testing in lieu of ISO 10993 testing and the answer is an emphatic no! Also, just because all of the materials used to make a device are USP <88> Class VI certified it does not mean manufacturers are exempt from 10993-1 evaluation. When different material components are combined to form finished products that are then sterilized, there are a lot of chemical interactions going on which can form byproducts. Analytical chemists and sterilization specialists can talk your ear off on this and I promise you’ll learn a few new things after talking with them. Class VI tests are an important tool in your toolbox, but you’ll need all your tools to build your framework, biological evaluation and
final toxicological risk assessments.
Moving forward, there are current discussions about USP <87> and <88> that they become more of a risk based evaluation of raw materials or manufacturing components closer to a ISO 10993-1 approach. A meeting was held at USP regarding this topic and while changes aren’t imminent, they are on the horizon.。