Automation of drug discovery-based quality control workflows using Biomek liquid handlers

Development of various therapeutics such as recombinant proteins, vaccines and plasma-based therapies continues to produce safe and effective treatments. However, much of the therapeutic development process relies on cell culture processes that are susceptible to cross-contamination with various pathogens including viruses and bacteria. If such contamination occurs, it can lead to a heavy financial burden related to the cost of recovery, slowdowns in product development, and a potential endangerment of patient life. To avoid this, routine quality control (QC) testing for potential contaminants is necessary at every stage of product development.

Among documented pathogens in which QC analysis of pathogenic particles is necessary for regulatory approval are viruses (e.g., Mouse Minute Virus - MMV), Bacteria endotoxins (BET) and mycoplasma. While various methods for determining the presence/absence of these pathogens exists, automating them can increase testing efficiency to easily identify and remove contaminated drug products and increase production of safe and effective treatments. Moreover, emerging cell and gene therapies, gene editing techniques, and plasma-based therapeutics create an increased reliance on cell-based assays for drug development, suggesting an increase in demand for efficient protocols to detect potential contaminations.

A Biomek i7 hybrid liquid handler was used to develop automated methods for viral, Mycoplasma, and bacteria endotoxin tests. Data was also generated manually, and comparisons were made for both manual and automated data sets to establish testing efficiency, data similarities and determine throughput capacity. The kits used in the automation of the workflows included the ViralSEQ MMV Real-Time kit (ThermoFisher), MycoProbe mycoplasma detection kit (R&D systems), Limulus Amebocyte Lysate (LAL) kinetic endotoxin kit and Pyrogen endotoxin kit (Lonza). Data from the automated assays were reproducible across days with low percent coefficient of variance (%CV) and were comparable to manually produced datasets. The automated protocols can be adapted to plate-based miniaturization assays ranging from 6-well to 384-well formats and are better suited for high-throughput applications to match demand for large-scale product development.