Efficacy and toxicity of biocides used in handling sterile pharmaceuticals

Abstract

This thesis has sought to investigate disinfection agents and procedures which may provide sanitisation against bacterial spores. A hard-surface disinfection test method was designed to ascertain which combinations of biocide and application method were most effective against bacterial spores. A combination of spraying and wiping was the most effective method of disinfection against Bacillus spores, with wiping found to play a key role in spore removal. The most efficacious of the biocides investigated was the 6% hydrogen peroxide. Vaporised Hydrogen Peroxide (VHP) gassing was more effective than traditional disinfection. In addition to efficacy, the toxic potential of the biocides to human airway epithelial cells in vitro was evaluated. Toxicity against human bronchial and nasal epithelial cells was assessed by determining cell viability, inflammatory status, protein oxidation and epithelial cell layer integrity. In addition the cell death mechanism following biocide exposure was investigated. There was a decrease in viable cells following exposure to all biocides when applied at practical concentrations. Almost all of the biocides tested elicited a pro-inflammatory response from the cells as measured by IL-8 production. All biocides increased protein oxidation as measured by thiol and carbonyl levels. Measurement of transepithelial electrical resistance and paracellular permeability indicated biocide-dependent decrease in epithelial cell barrier function. The cellular response was biased towards necrotic rather than apoptotic death. The use of biocides, although efficacious to some effects against Bacillus spores, will require careful monitoring for adverse health effects on personnel.