RT Journal Article
SR Electronic
T1 A Bayesian Approach to Residual Host Cell DNA Safety Assessment
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2015.006296
DO 10.5731/pdajpst.2015.006296
A1 Yang, Harry
A1 Zhang, Jianchun
YR 2016
UL http://journal.pda.org/content/early/2016/01/14/pdajpst.2015.006296.abstract
AB 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 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 understanding of DNA removal processes. As a result, the method not only provides a more accurate estimate of oncogenicity and infectivity risk but also a probabilistic interpretation of the risk estimate.