Rethinking Release Testing: Building the Analytical Infrastructure for the Next Generation of Advanced Therapies

The science of advanced therapies has moved rapidly. Manufacturing needs to move just as fast. Yet even as manufacturing timelines accelerate, one of the most time intensive stages can occur after manufacturing is complete: release testing.

Traditional analytical workflows can take days or weeks to generate the results needed for a release decision, in some cases representing more than 50% of overall manufacturing time. For therapies with highly compressed production timelines, particularly personalized and autologous therapies, analytical turnaround has become a critical manufacturing bottleneck. Every additional day waiting for analytical results can extend manufacturing timelines, increase operational burden, and delay treatment.

Adding another assay to an already complicated release workflow is unlikely to solve the underlying problem. In our experience, the bottleneck is increasingly not the assay itself, but what happens between generating the data and making the release decision. That means rethinking analytics as an integrated part of manufacturing, rather than simply a final checkpoint, could meaningfully improve efficiencies and shorten timelines for these critical therapies.

Reimagining Release Testing Through Rapid Analytics

Speed should never come at the expense of rigor.

The goal is straightforward: build analytical workflows that generate reliable, actionable data faster without compromising GMP requirements. At ElevateBio, we are exploring how next-generation sequencing (NGS), rapid analytics, automation, and integrated data workflows can make analytical data more readily available and connect testing more directly to manufacturing decisions.

For us, that means looking at the entire path from sample preparation through data generation, analysis, reporting, and ultimately the release decision – not just the speed of an individual assay.

ElevateBio’s sequencing capabilities can generate certain assay results in as little as four days, compared with traditional release timelines that can extend to weeks. But speed is only part of the equation. If multiple analytical needs can be addressed through a more streamlined workflow, manufacturers may also be able to reduce handoffs, conserve limited product material, and simplify the path to release.

Reducing manual handoffs and simplifying analysis and reporting could also make these workflows easier to scale as manufacturing volumes increase.

Bringing Sequencing into the GMP Release Conversation

NGS has historically been used more extensively for characterization and development than routine GMP release testing. But its potential for high sensitivity and broad detection makes it an increasingly compelling approach to faster, more informative safety testing. These capabilities could enable a more comprehensive approach to detecting and characterizing potential risks, including those that may be difficult to capture using traditional testing methods.

Unlike conventional approaches that may simply determine whether contamination is present, sequencing can potentially identify what is present, creating a more actionable starting point for investigation and decision making.

At ElevateBio, we are developing an integrated NGS-based rapid analytics method for cell therapy release testing designed to detect a broad range of contaminants within a single, streamlined analytical workflow. The intent is to connect sample preparation, sequencing, and bioinformatics in one workflow, generating more information while reducing disconnected analytical steps.

We are not trying to bypass established safety expectations. We are trying to meet them in a way that better fits the timelines and complexity of modern cell therapy manufacturing. That will require rigorous method development, validation, and evidence from real manufacturing workflows.

In developing this approach, we have found that shortening the assay is only one part of the challenge. The handoffs between sample preparation, sequencing, bioinformatics, review, and reporting can also have a meaningful impact on overall turnaround time.

That distinction is important to us: faster testing only matters if the resulting data is trusted enough to support a release decision.

Faster, More Sensitive, and More Actionable

For prospective partners, the question is not simply: “How fast is the test?” The better question is: Does the technology improve the release process as a whole?

When we evaluate a new analytical approach, we come back to three questions.

• Speed. How quickly can an analytical result be generated, and how quickly can that result be translated into a release decision? For autologous therapies in particular, every day of analytical turnaround matters.
• Performance. How sensitive, accurate, and comprehensive is the method? Faster results have limited value if they compromise the ability to detect relevant contaminants or appropriately characterize results.
• Simplicity. Can an integrated workflow reduce secondary testing, manual analysis, sample requirements, or additional investigative steps?

In our view, the strongest solution has to address all three. Faster results are valuable, but only when they come with the performance and operational simplicity needed for routine use.

Building Toward Regulatory Confidence

Technical performance alone will not transform release testing.

A technology can perform well analytically and still fail to make an impact in GMP manufacturing. The method has to be fit for purpose, appropriately controlled, and supported by evidence that demonstrates that the method is reliable and fit for purpose.

That requires strong evidence that the method can reliably detect relevant contaminants, perform consistently, and deliver accurate and comprehensive results. It also requires demonstrating that the full workflow, from sample preparation through analysis and reporting, can operate reliably within a GMP quality system.

ElevateBio is approaching NGS-based rapid analytics with that broader perspective, integrating analytical development with manufacturing and process development as it works to advance NGS-based safety testing for GMP.

Our data package demonstrates analytical performance, reproducibility, and reliable workflow integration. The next step is to build on that evidence through regulatory engagement and continued evaluation in the context of GMP manufacturing. Moving from a promising development technology to a routine GMP release method will require demonstrating that the approach performs reliably not only in the laboratory, but within a controlled manufacturing environment.

From Rapid Analytics to Real Time Release

Rapid analytics is an important near-term opportunity, but it may ultimately enable a fundamentally different manufacturing model.

If analytical data becomes available sooner and is connected directly to manufacturing decisions, it could eventually support earlier release decisions and, for some applications, real-time or near-real-time release.

That is not an immediate outcome, and significant scientific, quality, technological, and regulatory work remains. But the potential is clear: analytics can become part of the manufacturing process rather than something that happens after it.

A New Role for Analytics in Advanced Therapies

Advanced therapies are only as accessible as the manufacturing systems that support them. As these therapies become more sophisticated, release testing can become a critical bottleneck if analytical workflows cannot keep pace.

The goal is to make analytical data available when it is most useful – early enough to inform manufacturing decisions, and clear enough to support confident release decisions.

At ElevateBio, we see analytical turnaround as part of the manufacturing challenge, not a separate testing issue. The future of advanced therapy manufacturing will depend not only on how quickly we can make a therapy, but also on how quickly we can generate and interpret the data needed to release it.