Abstract
This case study examines the automation and process change options available to emerging discovery/development stage pharmaceutical companies when considering implementing sophisticated high-throughput screens. Generally there are both financial and personnel constraints that have to be addressed when implementing state-of-the-art screening technology in smaller companies which generally are not as significant as in large pharmaceutical companies. When NPS Pharmaceuticals considered installing a Molecular Devices FLIPR™ for high-throughput cell based screening it became clear that, to make the best decision, the whole screening process at NPS Pharmaceuticals from screen development and validation, tissue culture, compound distribution, data handling and screening had to be re-examined to see what automation options were possible and which, if any, made sense to implement. Large scale automated systems were not considered due to their cost and the lack of in-house engineering infrastructure to support such systems. The current trend towards workstation based laboratory automation suggested that a minimalist approach to laboratory automation, coupled with improved understanding of the physical process of screening, would yield the best approach. Better understanding of the work flow within the Biomolecular Screening team enabled the group to optimize the process and decide what support equipment was needed. To install the FLIPR™, train users, set up the tissue culture protocols for cell supply, establish high-throughput screening database protocols, integrate compound distribution and re-supply and validate the pharmacology on four cell based screens took the team 3 months. The integration of the screening team at the primary, secondary and tertiary screening stages of the target discovery project teams at NPS has enabled us to incorporate minimal automation into the Biomolecular Screening Group whilst retaining an enriching work environment. This is reflected in our current consistent throughput of 64 96-well microplates per day on the FLIPR™, a figure that is comparable with that achieved within most major pharmaceutical companies. This case study suggests that process optimization coupled with modern stand alone automated workstations can achieve significant throughput in a resource constrained environment. Significantly greater throughput could be achieved by coupling the process improvement techniques described above with 384-well microplate technology.