The End of USP Class VI

732USP Class VI dates back to the 1960s and was originally developed as part of a six-tier classification system for plastics. The testing evaluates materials through a series of in vivo studies based on worst-case exposure assumptions. Over time, Class VI, the most stringent of the six classifications, became deeply embedded in the medical device supply chain. It was familiar, easy to reference, and widely viewed as a conservative benchmark for material safety.  If a material met Class VI, it was often assumed to be “safe enough.”  The challenge is that USP Class VI alone was not designed to answer the question that matters most for medical devices: Is this material safe in this specific application?  

Relying on Class VI alone does not take into account how a component is actually used in practice, how long it is in contact with the patient, what type of tissue it interacts with, or the clinical context of the finished device. For example, a tubing set used for short-term fluid transfer carries a very different biological risk profile than an implantable component, even if both are made from the same base material. That distinction matters, because USP Class VI is fundamentally a material-level screening test, not a device-level biocompatibility assessment. 

There are a few clear reasons behind this change, and they align with what many of our customers are already experiencing.  First, the industry continues to prioritize risk-based evaluation, including an increased emphasis on chemical characterization and toxicological risk assessment. Standards like ISO 10993 focus on intended use, contact duration, and patient exposure. That is a more meaningful way to assess safety than a one-size-fits-all material classification.

Second, USP Class VI relies heavily on animal testing based on generalized worst-case assumptions rather than application-specific clinical risk. As the industry continues to prioritize sustainability, ethical testing practices, and the reduction of unnecessary animal studies, there has been increasing pressure to use more scientifically justified testing strategies.

Finally, regulatory expectations have already evolved. Global regulators, including the FDA and international notified bodies, primarily expect biocompatibility evaluations to be conducted within the framework of ISO 10993 as part of an overall biological risk assessment. In practice, USP Class VI alone has not been considered sufficient to support most medical device submissions.

USP <88> has historically defined the in vivo testing requirements behind USP Class designations, including USP Class VI. With the upcoming USP<88> revisions, several important changes are being introduced:

• USP Class designations, including Class VI, are being eliminated
• USP <88> will be limited to systemic injection testing
• Intracutaneous and implantation tests are being removed from USP <88> 

At the same time, USP <87> is being updated.  Under the revised framework:

• Cytotoxicity testing remains
• Additional biological endpoints, including irritation and genotoxicity, are being incorporated into the overall evaluation approach
• Lower-sensitivity methods, such as agar diffusion cytotoxicity testing, are being phased out in favor of more sensitive and clinically relevant methods

Future claims of full compliance to USP <87> will require a broader biological assessment, including genotoxicity and irritation evaluations, rather than relying solely on cytotoxicity testing as in the past.

These updates bring USP methods closer in alignment with modern, risk-based biocompatibility approaches, but they do not replace ISO 10993 as the primary framework for evaluating medical device biological safety.

For component manufacturers and their customers, this change is less about losing losing a benchmark and more about getting more precise about what actually drives biological safety.

Going forward, you should expect conversations to shift from:

• “Is this material USP Class VI?”

to:

• “How is this component used in the final device?”
• “What type and duration of patient contact should be considered?”
• “What are the relevant biological risks for this specific application?”
• "What are the risk considerations for this device according to ISO 10993-1?"

USP <88> will still have a place, but primarily in pharmaceutical packaging and certain combination product applications. For most medical device components, it will no longer be the primary framework used to demonstrate biological safety, and USP Class VI designation and testing will be eliminated under the revised USP <88> framework.

The discontinuation of USP Class VI does not lower the bar for safety. It raises it in a more meaningful way.

For medical device and component manufacturers, this is an opportunity to:

• Eliminate redundant or non-informative testing
• Reduce unnecessary animal use
• Build stronger, application-specific justifications for material selection

Most importantly, it improves how we communicate about safety with each other and with regulators. The companies that adapt quickly will not just stay compliant. They will be better positioned to support faster development, clearer customer conversations, and ultimately better patient outcomes. If you are evaluating how this impacts your materials, specifications, or customer requirements, it is worth taking a closer look now. The shift is already happening.