Study highlights broad microbial specificity of IMC growth-based sterility testing
The pharmaceutical industry currently relies on the USP <71> and Ph. Eur. 2.6.1 sterility test, a method that requires a 14-day incubation period to allow for the visual detection of microbial growth. This reliance on detecting visual turbidity of the growth medium to identify microbial growth creates a significant challenge for products that themselves can cause turbidity, such as cell and gene therapy products, and creates a logistical bottleneck for short-shelf-life therapeutics due to the 14-day incubation period.
A study titled "Evaluation of a novel isothermal microcalorimetry-based sterility test", published on February 11, 2026, by Indra Sioen and Tom Coenye (Laboratory of Pharmaceutical Microbiology, Ghent University), evaluates sterility testing based on detection of the metabolic activity of microorganisms via isothermal microcalorimetry (IMC) compared to the compendial USP sterility test. The study included broad specificity testing, with a panel of 16 different microorganisms, including the six standard USP <71> compendial strains and ten field isolates.
Comparing the performance of calScreener+ to the USP<71> sterility test
The study utilized the calScreener+ system to monitor the metabolic activity generated by living microbial growth. By testing 16 different microbial strains, including facility isolates commonly found in manufacturing environments such as Staphylococcus epidermidis and Cutibacterium acnes, the authors demonstrated that metabolic activity can be detected long before visible colonies form.
The IMC method achieved a 95.8% detection rate across all samples, whereas the traditional membrane filtration and visual inspection method reached 87.5%. This indicates that the thermal sensors can identify contamination that might otherwise go undetected.
For samples with higher contaminant levels, the IMC system reduced the time to detection to as little as 19.5 hours. Even at low inoculum levels below 10 colony-forming units, the system consistently provided faster detection than the compendial method.
Notoriously slow-growing organisms such as filamentous fungi (A. brasiliensis, A. versicolor, and P. chrysogenum), as well as C. acnes were all detected within 3 days at 5 CFU.
Broad and sensitive growth-based microbial detection combined with faster time to results
The study conclusions highlight the promise of IMC to accelerate batch release while detecting low-level contamination. Detection times were consistently shorter compared to the compendial USP sterility test, and IMC had a lower false negative rate.
The study demonstrates broad detection capabilities across a wide range of microorganisms. Unlike rapid methods based on predefined targets or optical secondary effects, biocalorimetry through IMC detects microorganisms through their metabolism, a universal biological signal. If contaminating microorganisms are alive and metabolically active, they can be detected by the IMC sterility test.
The findings in the study demonstrate the potential of isothermal microcalorimetry to replace the compendial USP <71> sterility test, combining its broad specificity and the reliability of being growth-based with automated continuous detection and faster time to results. Combined with the benefits of direct product inoculation and non-destructive measurement without manipulation steps or interfering reagents, the IMC system can maintain the advantages of the traditional method while gaining speed, sensitivity, and automation.
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