A New Approach to Supporting Quality of Biologics

The United States Pharmacopeia (USP) is proposing a new approach for its work to support the quality and availability of selected biologic medicines. Building on decades of experience in setting public standards for protein therapeutics, from insulins to growth hormones, USP is now advancing an evolved approach tailored to the complexity of biologics.

At the center of this evolution is the launch of emerging standards for biologics on USP’s Emerging Standards Platform. This platform enables an agile, iterative approach to shaping a potential standard and has grown in scope from focusing on analytical methods for small-molecule medicines to proposals for digital standards and now includes product-specific methods of analysis for biologics. This platform allows concepts in early development to be shared with the community prior to any compendial consideration in order to solicit feedback and stimulate a dialogue that contributes to its evolution.

The initial release includes methods for the analysis of Bevacizumab, Epoetin, Interferon beta 1-a, and Rituximab, spanning both glycosylated proteins and monoclonal antibodies. Together, these are intended to engage stakeholders and facilitate collaboration.

GEN sat down with Diane McCarthy, PhD, USP vice president of biologics, to discuss why USP published these tools, how industry can use these emerging standards, and what lies ahead.

GEN:  Last month, USP published “Emerging Standards for Bevacizumab, Epoetin,Interferon beta 1-a, and Rituximab.” What are these emerging standards?

Diane McCarthy: Emerging standards are concepts that USP shares with the scientific community to bring awareness and stimulate early discussion around a specific molecule, method, or attribute. Scientific experts may test or apply these emerging standards, submit comments, or propose additional test methods to be added. Emerging standards are developed outside of the normal compendial process to enable early stakeholder feedback. If an emerging standard evolves to the point of entering the official USP Documentary Standards process, it would go through USP’s formal notice and comment procedures through publication in the Pharmacopeial Forum.

The format of these emerging standards is different from current compendial standards and is intended to accommodate the natural heterogeneity of biologics that arise due to production in living cells and different manufacturing processes. The emerging standard focuses on quality attributes—such as biological activity, glycosylation, charge variants, and size variants—and establishing suitable test methods while providing greater flexibility in terms of analytical methods and acceptance criteria.

These emerging standards are also paired with reference standards that are intended to support system suitability testing and assay performance monitoring. These materials can help manufacturers ensure consistency in their analytical methods and generate reliable, consistent data over time.

Finally, it’s important to emphasize that emerging standards continue USP’s tradition of welcoming constructive feedback to advance the development of standards and tools that support the quality of medicines.

GEN: Why is USP publishing these emerging standards for biologics now?

McCarthy: USP’s release comes at a defining moment. Policymakers are seeking ways to broaden patient access to quality, affordable biological medicines, including biosimilars. The urgency of this work is underscored by what has been described as the “biosimilars void.”¹ Over the next decade, approximately 118 biologic drugs are expected to lose patent protection, yet only 12 currently have biosimilars in development. This gap represents a potential $230+ billion market opportunity for biosimilar competition in the U.S. alone and highlights a significant missed opportunity to reduce costs and expand patient access to more affordable biologic therapies.

Adding biologics to the emerging standard platform also advances a USP Convention resolution—adopted by 450+ organizations across 50+ countries—to expand availability of and access to quality-assured biologics products.

By taking this step to publish emerging standards, USP is responding to stakeholder requests and joining pharmacopeias around the world as they expand their portfolios of standards to support biologics. The publication of these emerging standards for comment reflects USP’s commitment to advancing public health worldwide through science-based, publicly accessible quality tools developed in a transparent and collaborative manner.

GEN:  How does USP envision the industry and regulatory authorities using an Emerging Standard?

McCarthy: These emerging standards are aligned with the evolving paradigm for biosimilar development, where analytical characterization plays a central role. Increasingly, regulators are recognizing that comparative analytical assessments, supported by pharmacokinetic and immunogenicity data, may be sufficient to demonstrate biosimilarity, reducing reliance on large, costly clinical studies.

We see several ways industry can leverage these emerging standards.

First, they provide a strong starting point for method development. Sponsors can use these publicly available analytical approaches in combination with reference products and in-house standards to assess product quality attributes and design robust analytical strategies early in development.

Second, the accompanying reference standards support system suitability testing and assay control. This is particularly important for helping ensure method performance, enabling data trending, and reducing variability across laboratories and over time.

Third, these emerging standards promote greater alignment between manufacturers and regulators. One of the challenges we’ve heard consistently from global regulators is the wide variability in analytical approaches submitted in biologics applications. By providing common tools and methods, we can help streamline review processes and improve regulatory predictability.

GEN: How are emerging standards different from official USP standards?

McCarthy: There are several important distinctions.

First, in contrast to current official USP standards, emerging standards are potential standards in their initial development phase and may never become official.

Second, emerging standards focus on quality attributes rather than prescribing market specifications. Instead of embedding fixed product specifications as in traditional monographs, they emphasize the critical attributes that define product quality, recognizing that specifications may be process-dependent. Manufacturers are expected to work with relevant regulatory authorities to define product-specific specifications.

Third, they are designed with flexibility in mind. Emerging standards provide multiple analytical methods to assess a given quality attribute and allow for the use of scientifically justified alternatives, including, where appropriate, compendial methods from other pharmacopeias. This approach supports innovation, keeps pace with evolving technologies, and can help improve the efficiency of development and manufacturing.

However, the emerging standards also leverage existing USP standards that help establish quality across an entire product class or multiple types of products. For example, emerging standards may cite cross-cutting standards such as USP General Chapter <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies or <509> Residual DNA Testing, as well as chapters related to assessment of microbial contamination and other broadly applicable compendial tests.

GEN:  You’ve highlighted that these are open for comment. What type of feedback are you seeking?

McCarthy: At a high level, we want feedback on the utility of the overall approach. At a technical level, we are interested in feedback on the methods themselves. Are they appropriate, sufficiently detailed, and representative of current best practices? Are there alternative methods that should be included? One of the key features of the emerging standards platform is the ability for stakeholders to submit their own methods for consideration.

We are also looking for feedback on gaps, whether additional quality attributes or orthogonal techniques should be incorporated, and on usability, including how easy the emerging standards are to interpret and apply.

GEN:  As USP looks forward, what will be the next steps for these emerging standards, as well as other potential biologics standards?

McCarthy: Now that we have published the first four emerging standards for comment, our immediate focus is on engagement. We will collect more stakeholder feedback during the comment period and use that to refine and potentially republish updated versions of these emerging standards.

In parallel, we will continue expanding the portfolio of emerging standards to additional biologics—particularly high-impact therapeutic proteins and monoclonal antibodies, while incorporating lessons learned from this initial release.

We also continue to build out our reference standards pipeline, ensuring a reliable supply and robust characterization to support these methods. Regulators have made it clear that product-specific reference standards are critical for establishing system suitability and controlling assay performance over time, and that remains a key focus.

Longer term, if we have sufficient stakeholder and regulatory support, we may consider evolving those emerging standards that show broad utility into official USP documentary standards, including monographs.

Ultimately, this initiative is about enabling global alignment on biologics quality, supporting efficient development, manufacturing, and regulatory review to increase the availability of biologic and biosimilar therapies for patients around the world.

Reference

1. IQVIA “Assessing the Biosimilar Void in the U.S.” Institute Report. Feb 3, 2025

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