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 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.
- Received November 3, 2015.
- Accepted January 5, 2016.
- Copyright © 2016, Parenteral Drug Association
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.