The US Pharmacopeia (USP) has recognized mass photometry as a critical orthogonal method for characterizing adeno-associated virus (AAV) capsids – an important step toward harmonizing analytics in gene therapy manufacturing.

This recognition marks a significant milestone for developers and manufacturers of viral vectors, offering a new level of analytical consistency as the industry scales up gene therapy production.

Addressing a longstanding analytical challenge

AAV vectors remain central to the delivery of genetic payloads in many approved and pipeline gene therapies. However, the ability to distinguish between empty, full, and partially filled capsids has historically been a source of variation and concern across labs and regulatory filings.

USP’s new reference standards for AAV8 full and empty capsids aim to address this by providing validated materials and test guidelines. The inclusion of mass photometry alongside established techniques such as analytical ultracentrifugation (AUC), size-exclusion chromatography with multi-angle light scattering (SEC-MALS), and charge detection mass spectrometry (CD-MS) adds credibility to the method’s growing adoption.

“Until now, there has been a lack of harmonized methods and physical standards for full/empty AAV quantitation,” USP stated in its accompanying documentation.

Mass photometry in the spotlight

Developed by UK-based Refeyn, the SamuxMP mass photometer was used in the multi-laboratory study supporting the new USP standards. Its ability to deliver quick, low-sample-volume measurements has made it increasingly attractive for both development-stage analytics and in-process monitoring.

Notably, mass photometry is capable of identifying partially filled and overfilled capsids- a key limitation of some other methods.

“Mass photometry is being accepted as a valuable part of the AAV analytics toolbox,” said Gabriella Kiss, market development director at Refeyn.

Global regulatory momentum

USP’s move follows a similar recognition by the British Pharmacopeia in 2024, which endorsed mass photometry in its guidance for characterizing recombinant AAV (rAAV) products. In particular, it described the method as a “viable option for at-line process monitoring.”

Together, these endorsements represent a shift in how emerging technologies are incorporated into regulatory frameworks for advanced therapy medicinal products (ATMPs).

Toward harmonization and quality assurance

The broader goal is clear: method harmonization across analytical platforms, enabling gene therapy developers—especially those working with CDMOs—to generate consistent, regulator-ready data from preclinical stages through to commercial release.

A recent webinar co-hosted by scientists from USP and Pharmaron Biologics emphasized the need for best practices in viral vector testing and provided further validation for mass photometry’s use in optimizing AAV capsid content.

The webinar, still available on Refeyn’s website, explores how orthogonal techniques can reduce uncertainty, increase confidence in results, and facilitate robust quality control in gene therapy programs.

Implications for the Industry

For CDMOs and biopharma companies navigating a fast-evolving regulatory landscape for gene therapy, USP’s formal backing of mass photometry offers a new route to compliance, efficiency, and precision in viral vector analytics.

As the gene therapy field matures and scrutiny intensifies around product quality, embracing validated orthogonal methods like mass photometry may become more than best practice—it may become essential.