Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products

Parveen, Seema; Kaur, Simleen; David, Selwyn A. Wilson; Kenney, James L.; McCormick, William; Gupta, Rajesh K.

doi:10.1016/j.vaccine.2011.08.055

Cited by 63 publications

(42 citation statements)

References 20 publications

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“…Eur./ USP compliant method (Hocquet et al 2014;Parveen et al 2011;Khuu et al 2004Khuu et al , 2006. The results of these validations supported the general use of automated culture systems for sterility testing of celltherapy products.…”

Section: Discussionmentioning

confidence: 53%

Validation of shortened 2-day sterility testing of mesenchymal stem cell-based therapeutic preparation on an automated culture system

et al. 2015

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Cell therapy products represent a new trend of treatment in the field of immunotherapy and regenerative medicine. Their biological nature and multistep preparation procedure require the application of complex release criteria and quality control. Microbial contamination of cell therapy products is a potential source of morbidity in recipients. The automated blood culture systems are widely used for the detection of microorganisms in cell therapy products. However the standard 2-week cultivation period is too long for some cell-based treatments and alternative methods have to be devised. We tried to verify whether a shortened cultivation of the supernatant from the mesenchymal stem cell (MSC) culture obtained 2 days before the cell harvest could sufficiently detect microbial growth and allow the release of MSC for clinical application. We compared the standard Ph. Eur. cultivation method and the automated blood culture system BACTEC (Becton Dickinson). The time to detection (TTD) and the detection limit were analyzed for three bacterial and two fungal strains. The Staphylococcus aureus and Pseudomonas aeruginosa were recognized within 24 h with both methods (detection limit ~10 CFU). The time required for the detection of Bacillus subtilis was shorter with the automated method (TTD 10.3 vs. 60 h for 10-100 CFU). The BACTEC system reached significantly shorter times to the detection of Candida albicans and Aspergillus brasiliensis growth compared to the classical method (15.5 vs. 48 and 31.5 vs. 48 h, respectively; 10-100 CFU). The positivity was demonstrated within 48 h in all bottles, regardless of the size of the inoculum. This study validated the automated cultivation system as a method able to detect all tested microorganisms within a 48-h period with a detection limit of ~10 CFU. Only in case of B. subtilis, the lowest inoculum (~10 CFU) was not recognized. The 2-day cultivation technique is then capable of confirming the microbiological safety of MSC and allows their timely release for clinical application.

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Section: Discussionmentioning

confidence: 53%

Validation of shortened 2-day sterility testing of mesenchymal stem cell-based therapeutic preparation on an automated culture system

et al. 2015

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“…The sinus sections were placed into separate aerobic, anaerobic, and fungal broths, and incubated at 37°C for 1 week (29). Sabouraud dextrose broth (Teknova, Hollister, California) was used for fungal identification.…”

Section: Methodsmentioning

confidence: 99%

Supercritical Carbon Dioxide–Based Sterilization of Decellularized Heart Valves

Hennessy

Jana

Tefft

et al. 2017

JACC: Basic to Translational Science

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Objective The goal of this research project encompasses finding the most efficient and effective method of decellularized tissue sterilization. Background Aortic tissue grafts have been utilized to repair damaged or diseased valves. Although, the tissues for grafting are collected aseptically, it does not eradicate the risk of contamination nor disease transfer. Thus, sterilization of grafts is mandatory. Several techniques have been applied to sterilize grafts; however, each technique shows drawbacks. In this study, we compared several sterilization techniques: supercritical carbon dioxide, electrolyzed water, gamma radiation, ethanol-peracetic acid, and hydrogen peroxide for impact on the sterility and mechanical integrity of porcine decellularized aortic valves. Methods Valve sterility was characterized by histology, microbe culture, and electron microscopy. Uniaxial tensile testing was conducted on the valve cusps along their circumferential orientation to study these sterilization techniques on their integrity. Results Ethanol-peracetic acid and supercritical carbon dioxide treated valves were found to be sterile. The tensile strength of supercritical carbon dioxide treated valves (4.28 ± 0.22 MPa) was higher to those valves treated with electrolyzed water, gamma radiation, ethanol-peracetic acid and hydrogen peroxide (1.02 ± 0.15, 1.25 ± 0.25, 3.53 ± 0.41 and 0.37 ± 0.04 MPa, respectively). Conclusions Superior sterility and integrity were found in the decellularized porcine aortic valves with supercritical carbon dioxide sterilization. This sterilization technique may hold promise for other decellularized soft tissues. Summary Sterilization of grafts is essential. Supercritical carbon dioxide, electrolyzed water, gamma radiation, ethanol-peracetic acid, and hydrogen peroxide techniques were compared for impact on sterility and mechanical integrity of porcine decellularized aortic valves. Ethanol-peracetic acid and supercritical carbon dioxide treated valves were found to be sterile using histology, microbe culture and electron microscopy assays. The cusp tensile properties of supercritical carbon dioxide treated valves were higher compared to valves treated with other techniques. Superior sterility and integrity was found in the decellularized valves treated with supercritical carbon dioxide sterilization. This sterilization technique may hold promise for other decellularized soft tissues.

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“…A sterility test may be defined as a critical; the traditional method described in EP [15,41] for the sterility test takes 14 days, although other rapid methods have been published and supported in the last annex II of the GMP [42], which entail 7 days [43], the ''shelf-lives'' of cells do not exceed 48 h. Therefore, the final cell medicine must be released parametrically [44], being necessary to provide all additional quality controls described in QCP to ensure that the medicine is free of contaminating microorganisms at the time of release [45]. Through sterility tests prior to release, in the intermediate phases (MCB and WCB) and on the starting material and reagents, besides endotoxin and mycoplasma assays, Gram stain and management of the monitorization process in the final cellular medicine, the absence of viable and active microorganisms can be ensured [6].…”

Section: Discussionmentioning

confidence: 99%

Standard Requirement of a Microbiological Quality Control Program for the Manufacture of Human Mesenchymal Stem Cells for Clinical Use

Gálvez

Clares²,

Bermejo³

et al. 2014

Stem Cells and Development

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The manufacturing of human mesenchymal stem cells (hMSCs) as cell-based products for clinical use should be performed with appropriate controls that ensure its safety and quality. The use of hMSCs in cell therapy has increased considerably in the past few years. In line with this, the assessment and management of contamination risks by microbial agents that could affect the quality of cells and the safety of patients have to be considered. It is necessary to implant a quality control program (QCP) covering the entire procedure of the ex vivo expansion, from the source of cells, starting materials, and reagents, such as intermediate products, to the final cellular medicine. We defined a QCP to detect microbiological contamination during manufacturing of autologous hMSCs for clinical application. The methods used include sterility test, Gram stain, detection of mycoplasma, endotoxin assay, and microbiological monitoring in process according to the European Pharmacopoeia (Ph. Eur.) and each analytical technique was validated in accordance with three different cell cultures. Results showed no microbiological contamination in any phases of the cultures, meeting all the acceptance criteria for sterility test, detection of mycoplasma and endotoxin, and environmental and staff monitoring. Each analytical technique was validated demonstrating the sensitivity, limit of detection, and robustness of the method. The quality and safety of MSCs must be controlled to ensure their final use in patients. The evaluation of the proposed QCP revealed satisfactory results in order to standardize this procedure for clinical use of cells.

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Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products

Cited by 63 publications

References 20 publications

Validation of shortened 2-day sterility testing of mesenchymal stem cell-based therapeutic preparation on an automated culture system

Validation of shortened 2-day sterility testing of mesenchymal stem cell-based therapeutic preparation on an automated culture system

Supercritical Carbon Dioxide–Based Sterilization of Decellularized Heart Valves

Standard Requirement of a Microbiological Quality Control Program for the Manufacture of Human Mesenchymal Stem Cells for Clinical Use

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