Learn About the Future of USP Plastics in Biotech
The United States Pharmacopeia (USP) has long set standards for the use of plastics in medical devices for implantation and packaging. The biotech industry has adopted these standards so efficiently that it is ingrained in every product containing a plastic exposed to a biotech process.
Significant changes will soon be coming to the USP standards which will ripple into the biotech industry. Cory Perelman will discuss USP standards updates on plastics in an upcoming webinar on Tuesday, 7 October. This webinar will focus on explaining the past, present, and future, to enable biotech industry personnel of any experience, be it their first day on the job or a seasoned veteran, to help raise awareness and lessen the impact of these changes.
The Regulatory Ladder
Understanding the relationship between the US Food and Drug Administration (US FDA), USP, American Society of Mechanical Engineers: Bioprocessing Equipment (ASME BPE), and other industry groups of interest can be complicated, but it does not need to be. Learning these relationships can help biotech industry personnel understand past USP regulations in the biotech industry and how we ended up here, as well as how these same regulatory and standards-focused organizations can be implemental to the future.
What can drive industry-wide regulatory changes for such a large scope? This is where the regulatory ladder comes into play. Industry may call for change directly, as industry groups of interest such as ISPE publish guidance documents. These groups of interest may also put pressure on organizations such as ASME BPE and USP to update their standards.
In addition, change can come from the top down, as the US FDA or USP creates a set of rules or laws for the industry, and then ASME BPE may write the standard, and the groups of interest may publish best practice guides to meet the standards.
In the case of plastics, both origins of change are applicable.
Understanding USP Class VI and Its Role in Biotech
ASME BPE requires polymeric materials exposed to process fluids (or with high probabilities of exposure) to comply with USP directives <87> and <88>.
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. 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 with its standards, making it the 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.
The changes to USP <88> now remove the entire Table 1., Classification of Plastics, and leaves only one test – systemic injection test. Industry guidance now says to avoid USP <88> testing.
The transition away from USP <88> is facilitated by two key standards: USP <87> and USP <665>.
What Is USP <87> and How Is It Changing
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 testing while maintaining rigorous safety standards. USP <87> testing is often required in addition to <88> testing, but the current USP <87> guidelines have fewer tests than <88>, and is arguably less robust.
In the absence of USP <88>, USP <87> updates include more varieties of tests in lieu of USP <88> test deletions. This makes USP <87> a robust biological reactivity testing directive to use in place of <88>.
What is USP <665>?
USP <665> is the first USP standard to directly address drug substances and drug product manufacturing directly, instead of needing to be “adopted” by a standard such as ASME BPE. 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 biotech multiuse and single use applications.
A key differentiator of USP <665> from USP <88> and <87> is that it is not for biological reactivity tests. USP <665> is a chemical suitability test for the intended use of the product.
The other major differentiator is that USP <88> and <87> maintain relevance in this industry due to standards like ASME BPE and industry groups that publish its use as best practice. USP <665>, as it is for drug substances and drug product manufacturing, adherence might be enforced by the US FDA, regardless of what the standards and groups of interest determine.
Why Move Away from USP <88>?
For years, the biotech industry relied on USP <88> in the absence of dedicated regulatory standards for drug products 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. USP <665> will be effective 1 May 2026, while the updates to <88> and <87> will be effective 1 December 2026. This leaves a little more than a year for companies to prepare for compliance. A timeline for visualization has been provided.
Figure 1: Timeline for Preparing for USP Changes
ASME BPE is expected to issue updated industry guidance in its 2026 edition. Some of these proposed changes will be shared during the webinar, which will also explore the impact on manufacturers, design firms, and end users.
As 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.
