title: A Bayesian Approach to Residual Host Cell DNA Safety Assessment.
abstract: Biological medicinal products inevitably contain residual DNA from host cells. Therefore, there is a theoretical possibility that cellular DNA in a medicinal product may cause oncogenic or infective events. Over the past decades, quantification of such risk has been the subject of intense scientific and regulatory interest. While several methods have been proposed in the literature, they are primarily concerned with point estimation of the oncogenic and infective risk. In this article, we propose a full Bayesian procedure to assess the safety risk. Safety risk is redefined as the posterior probability for the safety factor to be above an acceptable limit. The formulation of the problem in the Bayesian framework makes it possible to incorporate the uncertainties of key parameters into the safety risk assessment. It also allows for taking full use of prior knowledge of the risk associated with residual DNA and the understanding of DNA removal process. As a result, the method not only provides a more accurate estimation of oncogenicity or infectivity risk but also a probabilistic interpretation of the risk estimation.
  Medicines produced from biological sources like cells can contain DNA. It is not clear what health risk the DNA can pose to the product recipients, but often it can be designed to minimize the risk by reducing the levels of DNA during manufacture. This article characterizes residual DNA risk in terms of probability, and a Bayesian approach to assessing the health risk is proposed.
authors.affiliation: MedImmune LLC, Gaithersburg, MD yangh@medimmune.com.
authors.forename: Harry
authors.initials: H
authors.lastname: Yang
authors.affiliation: MedImmune LLC, Gaithersburg, MD.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001499:Bayes Theorem; D001688:Biological Products / Q000032:analysis* / Q000592:standards; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004247:DNA / Q000032:analysis*; D006801:Humans; D009857:Oncogenes; D018570:Risk Assessment
chemical_list: D001688:Biological Products; D004247:DNA
keywords: Acceptable limit; Bayesian analysis; Infectivity; Oncogenicity; Residual DNA; Risk-based assessment