Understanding USP <665>: What It Means for Single-Use Systems, Extractables and Leachables, and Why Is It Raising Questions?
The introduction of USP <665> has sparked extensive discussion across the pharmaceutical and biopharmaceutical industry, particularly among organizations relying on single-use technologies. While concerns initially focused on the potential need for additional extractables and leachables (E&L) studies and the associated costs, the conversation has gradually evolved toward understanding the true purpose and practical implications of the new framework.
In this expert insight, Monika Deptuła, Extractable & Leachables Principal Expert, explores what USP <665> means for manufacturers today, addresses some of the most common misconceptions surrounding the guideline, and explains how organizations can approach implementation through a science- and risk-based lens. Drawing on both industry experience and our contribution to BioPhorum guidance, she discusses how companies can leverage existing E&L knowledge, avoid unnecessary testing, and build effective risk assessment strategies for single-use systems.
What about USP <665> today?
The introduction of USP <665, effective from May 1, 2026, has triggered noticeable concern across the pharmaceutical and biopharmaceutical industries. The discussion is largely driven by the potential need for additional E&L studies, along with the significant cost implications, particularly in facilities that rely heavily on single-use systems and polymeric materials.
USP <665> introduces a standardized framework for extractables testing, defining specific extraction study conditions and linking the scope of testing directly to a risk-based E&L assessment. It also recommends analytical techniques that may differ from those commonly used in current practice.
Extractables studies themselves are not new. They have long been a core component of material qualification for single-use systems. However, what has changed is the level of structure in defining testing conditions, analytical expectations, and the interpretation of results.
And this is exactly where the real challenge begins.
At first, the industry response was marked by uncertainty. Questions around alignment with existing E&L data, potential additional testing burden, and the practical meaning of the new requirements appeared everywhere. There was also ongoing discussion about how USP <665> should be interpreted in real-world applications.
One issue kept coming up repeatedly in industry conversations: the regulatory status of this guideline. Over time, however, the picture became clearer.
“Much of the concern around USP <665> stems from the assumption that it will inevitably require extensive new testing. However, successful implementation is not about generating data for the sake of compliance, but about understanding risk, critically evaluating existing E&L knowledge, and determining where additional evidence is scientifically justified. Compliance is most effective when driven by science, not by fear.”
Understanding the Purpose of USP <665>
USP <665> is not mandatory unless explicitly referenced in General Notices, a monograph, or another applicable USP chapter.
This clarification, also supported by a key contributor to USP <665>, helped shift the industry perspective. The intention behind the guideline is to:
- Standardize extractables testing approaches
- Define minimum expectations for E&L studies
- Enable risk-based decision making
- Allow the use of existing extractables and leachables data provided it is scientifically justified within the process context
With this understanding, the focus moves away from fear-driven compliance and toward strategic implementation of E&L risk assessment. From a practical standpoint, a structured response is essential.
At our organization, we approached USP <665> proactively by:
- Conducting a comprehensive review of existing extractables and leachables (E&L) documentation
- Assessing alignment of existing E&L documentation with USP <665> expectation
- Aligning data with risk-based E&L assessment principles
- Monitoring industry trends and regulatory discussions
- Actively contributing to BioPhorum Operations Group (BPOG) guidance
Today, USP <665> can be viewed not as a regulatory disruption, but rather as a harmonization framework for Extractables and Leachables . While the document establishes an important foundation, additional industry experience, clarification, and further alignment with related standards will be important to support its consistent and practical implementation.
With the right strategy, companies working with single-use systems can:
- Avoid unnecessary duplication of extractables studies
- Effectively leverage existing E&L data packages
- Strengthen risk-based decision-making processes
- Maintain compliance while controlling costs
- Accelerate implementation and reduce risk by leveraging the expertise of a CDMO partner experienced in E&L strategy and single-use technologies
Want to go deeper?
The implementation challenges and practical considerations discussed here reflect some of the broader industry conversations around USP <665> and E&L risk assessment.
As contributors to BioPhorum guidance, including the publication “Navigating USP <665> and Other Extractables and Leachables Standards: Industry Strategies for Single-Use Risk Assessment and Implementation”, we have had the opportunity to support these industry-wide discussions.
For the full BioPhorum guidance, including risk assessment approaches, implementation considerations, and practical recommendations for single-use systems, explore the publication here:
If you’re interested in another topic shaping the future of pharmaceutical manufacturing, explore our latest article on AI risk management in pharma, developed alongside our contribution to BioPhorum’s guidance on practical approaches to AI risk assessment and implementation.
Monika Deptuła
Extractable & Leachables Principal Expert
With nearly 26 years of experience in the pharmaceutical industry, Monika has built extensive expertise across analytical sciences, product development, quality control, MS&T, and E&L assessments. At Rezon Bio, she leads E&L risk assessments for single-use materials and systems in biopharmaceutical manufacturing and is responsible for developing E&L strategies, overseeing extractables and leachables studies in collaboration with external laboratories, and partnering with toxicologists to evaluate study results. Her work supports product quality, patient safety, and successful regulatory submissions. Her previous experience includes 14 years at Polpharma S.A. and more than 12 years focused on biologics, MS&T, and single-use technologies throughout biopharmaceutical processes. Monika holds an MSc in Biotechnology from Gdańsk University of Technology. Recognized for her pragmatic, science-based approach, she combines deep technical expertise with a strong understanding of regulatory expectations, helping organizations address complex E&L challenges throughout product development and commercialization.
This post is for informational and educational purposes only and does not constitute legal, professional or regulatory advice of any kind. Please consult a compliance expert or legal counsel for guidance specific to your organization’s processes.
