From days to hours: the closest you can get to real-time sterility testing for Cell & Gene Therapies
Cell & Gene Therapy (C>) products are transforming the therapeutic landscape, offering curative potential for conditions previously deemed untreatable. However, the same characteristics that make these therapies powerful also introduce unique Quality Control (QC) challenges; one of the most prominent being sterility testing. Traditional compendial sterility methods require several days, far exceeding the short shelf life of most cell‑based therapies. As a result, sterility testing has become a critical bottleneck in the timely release of these life‑saving products.
Recent advances in analytical microbiology are changing this paradigm. Ultra‑rapid sterility testing now offers the possibility to compress workflows from days to hours, aligning QC timelines with the clinical and manufacturing realities of C>.
Among these advancements, the new CELL‑BURST patented technology represents a significant breakthrough as the first true same‑day sterility testing method designed specifically for cell‑based products.
Why Traditional Sterility Testing Falls Short for C>
Most cell-based therapies, CAR T-cell therapy being a prime example, often have an extremely limited viability window once manufactured. In many cases, their shelf life is counted in hours rather than days, and production volumes are inherently small, leaving little room for large sampling volumes, repeat testing, or extended incubation methods.
However, this is not always strictly due to intrinsic product instability. In some situations, these therapies are effectively “short-lived” because they are required urgently for the patient, meaning the treatment must be administered very quickly even if the drug itself does not inherently have a short shelf life.
At the same time, manufacturers face increasing expectations around data integrity, automation, traceability, and scalability. The industry needs sterility methods that are not only faster, but also robust, validated, and compatible with regulatory requirements such as EP 2.6.27 and USP <72> for cell‑based products.
CELL‑BURST: Same‑Day Sterility Testing Without Compromise
CELL‑BURST introduces a new workflow that couples solid‑phase cytometry, as used in the established SCANRDI® platform, with a patented cell‑lysis protocol that meets pharmacopeia and industry standards for regulated markets. CELL-BURST renders dense, cell‑based matrices fully filterable. This approach preserves the integrity of microorganisms while removing the cellular background that historically prevented filtration‑based methods from being applied to C> products.
How the Method Works
The CELL‑BURST workflow follows three fundamental steps:
Filtration
After destroying mammalian cells, the sample is filtered through a membrane that retains microorganisms while eliminating the product matrix.Enzymatic Fluorescent Labeling
Microorganisms are labeled using a fluorogenic dye activated only by living cells. This ensures selective detection of viable contaminants.Solid‑Phase Cytometry
A laser scans the membrane surface to detect and enumerate fluorescent microorganisms.
Results are displayed in a 21 CFR Part 11–compliant audit-ready software environment.
Because solid‑phase cytometry relies on direct labeling rather than growth, sterility results can be delivered within a single working shift without having to neutralize the sample.
Ensuring Sensitivity, Specificity, and Equivalency
A comprehensive validation program was conducted using JURKAT cells as the primary model, supplemented by several additional cell types to ensure broad applicability. The study evaluated:
- Limit of Detection (LOD)
- Specificity
- Suitability with multiple matrices
- Robustness and ruggedness
- Equivalency to BACT/ALERT® and compendial sterility tests.
Nine microbial strains were used for LOD and equivalency assessments. Equivalency was demonstrated* through:
Both statistical criteria confirmed that CELL‑BURST performs on par with established reference methods.
A specificity study involving 13 additional strains further demonstrated that the presence of mammalian cells, even after controlled lysis, does not impair microbial detection.
A Turning Point for C> Quality Control
By enabling same‑day sterility results with minimal sample volumes, CELL‑BURST allows manufacturers to:
- Accelerate product release timelines
- Preserve precious therapeutic batches
- Strengthen QC data integrity
- Adopt a method already recognized across the pharmaceutical industry
Ultimately, ultra‑rapid sterility testing helps ensure that patients receive critical therapies faster, without compromising safety or compliance.
* The presented data is extracted from bioMérieux’s Primary Validation Report, available on demand.
