OVERCOMING THE CHALLENGES IN STERILITY TESTING OF CELL AND GENE THERAPIES
Sterility testing remains a major bottleneck in the release of cell and gene therapies and other advanced therapy medicinal products (ATMPs). Traditional sterility testing methods require up to 14 days. While alternative rapid microbiological methods are gaining regulatory acceptance, combining rapid and reliable results with ease of use has remained a challenge.
The Symcel calScreener+ and caloTrace Sterility Testing Systems are designed to overcome this challenge, combining growth-based testing, non-destructive direct inoculation, volume flexibility, continuous monitoring and rapid time to results.
Faster and More Confident Sterility Testing
The Symcel sterility testing systems are based on isothermal microcalorimetry (IMC), a high-sensitivity rapid microbiological method (RMM) that measures the metabolic heat released by viable microorganisms. They enable sterility testing that combines the benefits and safety of growth-based detection with 1 CFU sensitivity, continuous monitoring and rapid time to negative results.
Compared to the compendial 14-day sterility method and respiration-based CO₂ methods, which typically require 7 days, the Symcel systems offer considerably faster results. All USP compendial microorganisms can be detected within 36 hours and additional Ph. Eur. microorganisms, including slow-growing C. acnes, within 48 hours, enabling product release within 3 days.
This means faster results no longer require compromising on safety or reliability, allowing you to overcome challenges associated with testing complex product matrices, simplify manufacturing processes and slash your time to market.
Strategic R&D collaboration with Johnson & Johnson
Sterility testing is the most time-consuming step in releasing cell therapies. Current methods can take 7–14 days, delaying access to critical treatments. This collaboration aims to deliver a validated, GMP-compliant test that cuts release time to under 3 days—improving manufacturing efficiency with faster access for patients.
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Growth-based microbial detection with results in 3 days
The high sensitivity of IMC allows many microorganisms to be detected in just a few hours, while continuous real-time monitoring eliminates the need to wait for the full test cycle to finish — contamination is automatically flagged as soon as it is detected.
- Majority of bacteria detected in less than 24 hours
- Yeast and molds detected in 36 hours
- C. acnes, assay rate limiting organism, detected in as little as 48 hours
Minimized risk of false results, even in complex backgrounds
The calScreener+ and caloTrace growth-based systems measure continuously and, since they work phenotypically, detect only viable microorganisms. They offer exceptional sensitivity, with a limit of detection (LOD) down to 1 CFU, and minimise the risk of false results caused by debris, residual genetic material, or components of the cellular product.
Where other growth-based sterility methods rely on a chain of indirect measurements, the isothermal microcalorimetry-based systems offer a more direct measure of microbial activity.
STERILITY TESTING OF COMPLEX CELL THERAPY PRODUCT MATRICES
One major challenge in testing Advanced Therapy Medicinal Products (ATMPs) is the complexity of their product matrices, which can inhibit microbial growth or mask detection signals. This often requires extensive pre-processing steps that can introduce additional variability and potentially affect the accuracy of the test results. Biocalorimetry enables direct inoculation and reliable detection of contamination—even in highly complex sample matrices. This makes the Symcel sterility test optimal for cell and gene therapy products.
- No filtering
- No sample concentration
- No extraction
EASIER CONTAMINATION INVESTIGATION
Root cause analysis is critical if contamination is detected. The calScreener+ and caloTrace measurements are non-destructive and require no sample manipulation steps or interfering reagents. If a sample is found positive, inoculated samples can immediately be analyzed further using standard methods.
- No reagents
- No dyes
- No lysing
PRESERVE MORE PRODUCT FOR THE PATIENT
Traditional sterility testing methods require sample volumes that many advanced therapy products simply can’t spare. In contrast, the Symcel systems require only a minimal volume, enabling reliable testing even when product availability is critically low.
3-DAY CAR-T THERAPY STERILITY TESTING
Several evaluations on a wide range of complex advanced therapy matrices, including high-concentration CAR-T products, have demonstrated detection of USP <71> compendial microorganisms and additional Ph. Eur. species, including C. acnes, at <10 CFU/vial within 50 hours.
This supports reducing the sterility testing timeline for product release, including safety margin, from the 14 day compendial test to under 3 days.
ADVANCING STERILITY TESTING OF BIOLOGICS AND VACCINES
Earlier release of biologic pharmaceuticals and vaccines can reduce production costs, ease logistical challenges, and ultimately save lives. The caloTrace® platform is being developed to support a broad range of pharmaceutical applications, and as part of a grant awarded by the Coalition for Epidemic Preparedness Innovations (CEPI), Symcel is developing a rapid sterility testing method aimed at enabling release testing of vaccines in under three days.
VALIDATION & REGULATORY
The Symcel Rapid Microbial Method (RMM) systems follow the US and EU standards USP <1223> and <1071>, PDA TR 33, EP 5.1.6 and EP 2.6.27. Primary validation package is conducted on method limit of detection (LOD), comparability, specificity, ruggedness and robustness, with data package availability before conducting method validation. Measurement performance of calScreener+ compared to the compendial USP <71> sterility test has been evaluated on a broad panel of microorganisms.
Contact us at sterility@symcel.com for more information and to conduct feasibility studies on your samples.
