Evaluation of a novel isothermal microcalorimetry-based sterility test

Abstract Parenteral drugs must meet strict release criteria to ensure patient safety upon administration. Sterility is a critical requirement, and is typically assessed using the compendial U.S. Pharmacopoeia (USP) sterility test. However, with the growing demand to reduce batch release times, the test’s 14-day incubation period is becoming a concern, emphasizing the need for more rapid alternatives. Here, we compared the performance of the calScreener+ isothermal microcalorimetry (IMC) device (Symcel) to that of the compendial USP sterility test, using a panel of sixteen microorganisms (six USP reference strains and ten field isolates) in two inoculum sizes (100 and 5 CFU). The IMC-based method detected a higher number of positive samples compared to the compendial method (95.8% vs 87.5%; p < 0.05). Furthermore, IMC was consistently faster, reducing mean detection times from 43 hours to 19 hours at 100 CFU and from 46 hours to 28 hours at 5 CFU (p < 0.001). In conclusion, the calScreener+ IMC device shows promise as a rapid and sensitive alternative to the compendial sterility test, with the potential to speed up batch releases without compromising patient safety. Competing Interest Statement The authors have declared no competing interest.