National Institute for Biological Standards and Control, UK
Thea Sesardic has completed her Ph.D from University of Westminster, London in Medical Microbiology and postdoctoral studies from Royal Postgraduate Medical School, London. With over thirty year experience in biomedical research and twenty four year experience on regulatory science at NIBSC, a part of UK MHRA regulatory agency, she is now head of the toxin laboratory. She is expert adviser to WHO, British Pharmacopoeia, EDQM European Pharmacopoeia, USP and appointed member of the EURL ECVAM Scientific Advisory Committee (ESAC), with more than 150 published papers in reputed journals on a broad range of topics.
Bioassays play a central role in evaluation of biological products and those derived from bacterial toxins often rely exclusively on in vivo models for assurance of safety and potency. This is because many in vitro methods are often not suitable to provide assurance of the clinically relevant biological property. This is particularly relevant for products where active components have multiple mechanism of action to an extent that physiochemical methods alone are insufficient to permit evaluation of biological activity. This is, for example, relevant for therapeutic Botulinum toxins for injection, or for safety evaluation of tetanus toxoid vaccines. Likewise, effective antibodies against these toxins need to demonstrate ability to neutralize the toxin action in relevant bioassay models. Bioassays are also required when the production process is complex and biological activity is dependent on many conditions during production, purification and formulation. Bioassays based on cells offer an advantage to all other in vitro alternative models as they offer the potential for the complete animal replacement. Such bioassays can detect all of the key hallmarks of toxicity of bacterial toxins which generally include binding, translocation, internalization and intracellular activity. The creation of new standard bioassays that are reproducible, sensitive, fast and fully functional will have great impact on public health and economy. Whereas cell based assays are already at advanced stage of validation for diphtheria and pertussis toxins, availability of neurons derived from pluripotent stem cells has made significant contribution in the field for neurotoxins such as botulinum and tetanus.