An Madin-Darby canine kidney (MDCK) cell line, 9B9-1E4, was cloned by limit dilution from a heterologous cell population and chosen as a potential production cell substrate for cell culture-based influenza vaccine manufacture. Since MDCK cells are transformed cells of canine origin, extensive characterization, including evaluation of tumorigenicity and oncogenicity, was performed to ensure the safety of this cell line for vaccine production. Injection of intact MDCK cells into adult and newborn athymic nude mice did not lead to progressive tumor formation in two separate tumorigenicity studies. In addition, neither MDCK cell lysate nor cellular DNA induced tumors in newborn rodents (athymic nude mice, hamsters and rats) in six oncogenicity studies. Observations from these studies demonstrate the low tumorigenic and oncogenic potential of the MDCK cell clone 9B9-1E4. These observations coupled with other characterization study results strongly suggest a high safety assurance level can be achieved through cell cloning and selection of low tumorigenic and oncogenic cells for influenza vaccine production.
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