title: Issues associated with residual cell-substrate DNA in viral vaccines.
abstract: The presence of some residual cellular DNA derived from the production-cell substrate in viral vaccines is inevitable. Whether this DNA represents a safety concern, particularly if the cell substrate is derived from a tumor or is tumorigenic, is unknown. DNA has two biological activities that need to be considered. First, DNA can be oncogenic; second, DNA can be infectious. As part of our studies to assess the risk of residual cell-substrate DNA in viral vaccines, we have established assays that can quantify the biological activities of DNA. From data obtained using these assays, we have estimated the risk of an oncogenic or an infectious event from DNA. Because these estimates were derived from the most sensitive assays identified so far, they likely represent worst-case estimates. In addition, methods that inactivate the biological activities of DNA can be assessed and estimations of risk reduction by these treatments can be made. In this paper, we discuss our approaches to address potential safety issues associated with residual cellular DNA from neoplastic cell substrates in viral vaccines, summarize the development of assays to quantify the oncogenic and infectivity activities of DNA, and discuss methods to reduce the biological activities of DNA.
authors.affiliation: Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drugs Administration, Bethesda, MD 20892, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng-Fowler
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lewis
authors.forename: Keith
authors.initials: K
authors.lastname: Peden
mesh_terms: D000465:Algorithms; D004247:DNA / Q000502:physiology*; D014765:Viral Vaccines
chemical_list: D014765:Viral Vaccines; D004247:DNA