Breaking the Mold: The Biotech Industry Says Goodbye to USP <88> Class VI Plastics

The biotech industry is undergoing a significant transformation as it moves away from outdated material classifications and embraces new regulatory frameworks. The elimination of USP <88> Class VI plastics marks a critical shift, impacting manufacturers, consulting design firms, and end users who must adapt to evolving standards. With the introduction of USP <665> and expanded in-vitro testing under USP <87>, the industry is transitioning toward more relevant, scientifically sound testing methodologies. These changes not only enhance patient safety but also reduce the associated animal testing and increase animal-welfare. 

The September 2024 ASME BPE Meeting: A Turning Point

In September 2024, the Polymeric Materials (PM) group met in Albuquerque, New Mexico, for the American Society of Mechanical Engineers Bioprocessing Equipment (ASME BPE) meeting. The group is responsible for authoring proposed revisions to the ASME BPE standard in alignment with the upcoming changes to USP <87>, <88>, and the newly introduced USP <665>. At the same time, BioPhorum released an industry position paper titled Bioreactivity Testing in Single-Use System Biomanufacturing, reinforcing the need for change. The room was abuzz; gone were the classifications of plastics in USP <88>, meaning the deletion of USP Class VI terminology. These updates signify a move towards more relevant testing criteria and improved regulatory alignment.

Understanding USP Class VI and Its Role in Biotech

USP Class VI is one of six designations under USP <88>, which provides guidance for in-vivo biological reactivity testing of plastics and other polymers. These tests have been traditionally used to evaluate the suitability of materials intended for drug products, drug containers, medical devices, implants, and packaging systems. In-vivo testing, in this context, refers to animal implantation tests. This testing approach has sparked ethical concerns and raised questions about its continued relevance in modern biotech manufacturing.

Despite its origins outside of biotech manufacturing, USP Class VI plastics became widely adopted across the industry. The ASME BPE integrated USP Class VI compliance into its standards, making it a best practice for manufacturers. This, in turn, contributed to the widespread reliance on USP Class VI plastics in single-use technologies in the absence of specific regulatory guidance. Outside of single-use plastics, these materials can be found in components like tri-clamp gaskets, instrument o-rings, diaphragm valves, and door seals for autoclaves, washers, downflow booths, and pass-throughs.

What Are USP <87> and USP <665>?

The transition away from USP <88> is facilitated by two key standards: USP <87> and USP <665>.

• USP <87>  is meant for use in the same applications as <88>, except it focuses on in-vitro biological reactivity testing, using cell culture methods to assess material safety. This approach offers an alternative to in-vivo animal testing while maintaining rigorous safety standards.

• USP <665> is the first USP standard to directly address drug substance and drug product manufacturing. It introduces chemical suitability testing, which includes extractables profiling and toxicological assessments. Extractables profiling evaluates the potential release of chemical compounds from materials under specific conditions, ensuring their suitability for use in pharmaceutical and biopharmaceutical applications.

Why Move Away from USP <88>?

For years, the biotech industry relied on USP <88> in the absence of dedicated regulatory standards for drug product and biopharmaceutical manufacturing. However, over time the correlation between USP <88> testing and patient safety has been questioned. With rising concerns over animal welfare and the need for more scientifically sound testing methods, the necessity for an updated approach became clear.

With these considerations in mind, USP <88> has been largely phased out, with only one test remaining. USP <87> has been expanded to offer more in-vitro testing options, while USP <665> provides a more comprehensive framework for chemical characterization testing. These updates shift the industry towards a risk-based approach that emphasizes extractables profiling and in-vitro biological testing.

What Comes Next?

The changes to USP <665>, <88>, and <87> are already published and will officially take effect on May 1, 2026. This leaves a little more than a year for companies to prepare for compliance.

ASME BPE is expected to issue updated industry guidance in its 2026 edition. Some of these proposed changes will be shared during my presentation at ISPE MAST, where we will explore their impact on manufacturers, design firms, and end users

As the industry prepares for these changes, manufacturers will need to update their literature to remove references to Class VI plastics. A key question remains: How will we determine standardized testing requirements for common components? For example, do tri-clamp gaskets and single-use tubing require the same extractables testing?

Design firms will also need to revise their legacy piping and instrumentation specifications, and end users must update their global engineering specifications and User Requirements Specifications to reflect the new standards. The industry’s shift to a risk-based approach will require ongoing collaboration to ensure all components are tested appropriately and safely.

For a deeper dive into how these changes will impact manufacturers, consulting firms, and end users, join Cory Perelman at ISPE's 2025 Mid-Atlantic Science & Technology (MAST) Showcase, where he will break down the evolving standards and what they mean for the industry.