Overcoming Analytical Bottlenecks in Advanced Therapies Development
How can new analytics reduce development delays and accelerate patient access to advanced therapies?
The rapid growth of advanced therapies is placing increasing pressure on bioanalytical characterization workflows. As pipelines shift toward larger and more complex biomolecules, traditional bioanalysis methods have struggled to deliver the speed, sensitivity, and resolution needed to support efficient process development and regulatory approval.
In response, analytical science companies are developing technologies that enable faster, more detailed characterization of complex biomolecules. By addressing long-standing analytical bottlenecks, these approaches aim to improve efficiency and data quality across biopharma development, while supporting regulatory expectations for increasingly complex therapies.
Technology Networks spoke with David Curtin, vice president and general manager, Biologics Business, Waters Corporation, to discuss the analytical challenges shaping advanced therapy development and the scientific drivers behind the development of the Xevo™ CDMS System.
In this interview, Curtin explains the limitations of conventional mass spectrometry for mega-mass biomolecules, how charge detection mass spectrometry (CDMS) could streamline characterization workflows for modalities such as adeno-associated viruses (AAVs), and why faster, lower-volume analyses may play an important role in improving access to rare disease treatments.
What are the most critical analytical challenges currently slowing the development and approval of advanced therapies?
David Curtin (DC):
Over the past 15 years, the drug development landscape has dramatically shifted towards biologics. Large molecule applications are seeing rapid growth, with biologics and complex modalities now representing roughly half of the global pharmaceutical pipeline.
Because these advanced therapies are both new and highly complex, the industry has not yet optimized the analytical tools needed for real-time characterization during process development. As a result, current methods are incredibly time and cost-intensive. Recognizing cost as the number one bottleneck for patient access, this creates a significant challenge.
As scientists continue to pioneer life-saving treatments, their progress is slowed by analytical tools that lack the resolution, sensitivity, and compliance-readiness needed to bring these treatments from the lab to market. By delaying the development and approval process, this technology gap directly impacts the patient, driving up costs and limiting access to critical medicines.
AM:
DC:
At Waters, I oversee a team of talented employees who develop tools and techniques to characterize next-generation modalities. Our mission is to equip scientists with the tools they need to move breakthrough therapies from the lab to the patient’s bedside faster, with greater efficacy.
In 2022, this mission led us to Indiana University, where distinguished professors, Martin F. Jarrold and David Clemmer, had been developing CDMS technology that had the potential to transform and accelerate advanced therapy development: the electrostatic linear ion trap (ELIT). This novel technology enabled the direct measurement of individual ions through simultaneous measurement of mass-to-charge ratio and charge, allowing scientists to characterize molecules that were previously unmeasurable.
However, in its academic form, the ELIT had limited reach beyond the university setting. With a shared vision of accelerating the path to impact, Waters partnered with Jarrold and Clemmer to commercialize and expand access to the groundbreaking technology.
Today, the ELIT is at the heart of the Waters Xevo CDMS, driving the characterization and analysis of large molecules. With this advancement, we address an industry-wide unmet need for an efficient characterization method that accelerates the therapeutic development and approval process. By bringing this technology to market, we hope to deliver meaningful impact by enabling more patients to benefit from advanced therapies and beginning to close current access gaps.
AM:
DC:
The first-of-its-kind Xevo CDMS sets a new standard for the industry, delivering unmatched measurement and characterization for the broadest range of mega-mass molecules central to next-generation therapeutics and structural biology.
The Xevo CDMS unlocks direct, individual-particle mass measurements for molecules up to 100+ megadaltons (MDa), surfacing previously inaccessible information about the characteristics of large molecules. In addition, Xevo CDMS offers fast, accurate analysis of gene therapy samples, paving the way for real-time characterization in process development. This efficiency can be demonstrated in the analysis of AAVs—a popular gene therapy viral vector. During production, manufacturers must determine whether particles are empty, partially filled, or fully loaded—an indicator of the therapy’s safety and effectiveness.
Currently, this process takes approximately four hours, requires a huge quantity of sample, and depends on the support of a highly trained expert. With the Xevo CDMS, this analysis can be achieved in less than 10 minutes, using 100 times less sample volume, conserving scarce and expensive resources for therapy development.
By simplifying and accelerating the development process, Xevo CDMS helps ensure that advanced therapies are produced efficiently, at a lower cost, and with the highest standards of safety—ultimately making them more accessible for patients in need.
AM:
DC:
The Xevo CDMS has demonstrated transformational value for our partners working in the chronic and rare disease space.
One example comes from our collaborators at Lexeo Therapeutics, who are developing gene therapies for conditions with substantial unmet need, including Alzheimer’s disease and cardiovascular disorders. The Xevo CDMS has enabled the precise analysis of AAV capsids in just minutes, delivering accurate, reproducible results that accelerate development.
According to the World Health Organization, rare diseases affect more than 300 million people worldwide, yet over 95% still lack effective treatments. With Xevo CDMS, we aim to help partners like Lexeo Therapeutics fine-tune their production processes more efficiently, so that they can deliver high-quality life-saving therapies to patients sooner.
AM:
DC:
Our commitment to building an industry-leading technology portfolio is reflected in our ongoing innovation and growth strategy. Breakthrough platforms, like Xevo CDMS, are giving scientists unprecedented clarity into highly heterogeneous large molecules.
Our acquisition of Wyatt Technologies (light scattering) and Halo Laboratories (particle analysis) strengthens our ability to assess critical quality attributes in emerging modalities. Together, these advancements will revolutionize the characterization of gene therapies and other emerging modalities, solving critical unmet needs and accelerating patient access.
Our combination with the BD Biosciences and Diagnostic Solutions businesses further expands our analytical capabilities, bringing together complementary strengths that progress us towards developing the laboratory of the future for biologics.
The US Food and Drug Administration is placing greater emphasis on analytical techniques in the review and approval pathways of generic medicines and biosimilars. Waters technologies will play a critical role in expanding access to high-quality medicines for millions of people.
Waters is able to help our customers navigate the path to bringing analytical techniques that characterize their complex molecules to market. Advanced modalities will get there one day, and it’s only by being present at the beginning of a molecule’s journey that we’re able to provide the tools that enable this change.
The introduction to this interview includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.
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