Industry Response to USP <87> & <88> Biological Reactivity Updates: A Risk-Based Approach for Single-use in BioPharma Applications

<jats:p>The biopharmaceutical industry is transitioning toward modern, risk-based frameworks for evaluating biocompatibility and applying biological reactivity testing of single-use systems (SUS) with major revisions planned to USP &lt;87&gt; and USP &lt;88&gt;. Set to take effect in December 2026, the revisions are being introduced to: • Reduce reliance on animal testing by shifting from in vivo methods in USP &lt;88&gt; to more ethical in vitro approaches in USP &lt;87&gt; • Align with modern risk-based and regulatory standards, such as ISO 10993, which address concerns like cytotoxicity and extractables • Streamline testing by eliminating outdated and lengthy animal testing in favor of faster, more targeted in vitro assessments. We have been focusing on this area since 2024. In our latest efforts, we wanted to better understand the impact of these updated standards and have published our new paper. It reinforces the idea that the future of SUS qualification lies in scientifically justified, risk-based evaluation rather than inherited compendial expectations. Covering topics such as biological reactivity standards and USP/ISO tests, and risk-based approaches to biocompatibility assessment, it makes a recommendation for future biological reactivity claims. This paper follows our Industry response to USP &lt;87&gt;/&lt;88&gt; updates: Implications for single-use systems published in 2025, which addressed issues such as the removal of the USP &lt;88&gt; Class I–VI system and the introduction of risk-based approaches and in vitro methods, such as neutral red uptake and reconstructed human epidermis. This was itself a follow-up to a 2024 paper titled Bioreactivity testing in single-use system biomanufacturing: industry position paper. These papers all enable easier navigation of the updated USP &lt;87&gt; and &lt;88&gt; standards from both single-use suppliers’ and end users’ perspectives, which will accelerate innovation and regulatory alignment across the biopharmaceutical industry.</jats:p>