Validation of the Bactec system for sterility testing of advanced therapy medicinal product suspensions in Ringer’s Lactate

Ensuring sterility is a key quality requirement in the manufacturing of cell-based medicinal products. This study evaluated the capability of the BACTEC automated microbial detection system to identify viable microorganisms in adipose-derived stem cell-based products suspended in Ringer's Lactate. The validation process comprised four stages: i) sterility testing of uninoculated media to assess reagent quality; ii) growth promotion test to confirm medium performance; iii) suitability testing for compatibility with the sample matrix; iv) confirmation using pharmacopeial methods. All inocula met the European Pharmacopoeia recommendations. Validation was defined as the demonstration that the BACTEC system provides results equivalent to the pharmacopeial sterility test in terms of sensitivity, reliability, and detection time. Evaluated parameters included accuracy, repeatability, and detection limit, following European Pharmacopoeia requirements for alternative microbiological methods. The system successfully detected microbial contamination for all reference strains with a detection limit of 5 CFU and repeatability > 95 %. All microorganisms showed growth within 24-72 h, well inside the 7-day acceptance criterion. Quantitative comparison with the pharmacopeial method demonstrated full concordance (Cohen's κ = 1.0) and a strong correlation of detection times (r = 0.92, p < 0.001). These results confirm that the BACTEC system is a validated and reliable alternative to the pharmacopeial sterility test, providing faster detection without loss of analytical accuracy. The validation supports its applicability for sterility assurance of cell-based materials and integration into quality management during the manufacture of advanced therapy medicinal products.