Establishing acceptable limits of residual DNA.

Biological products can contain residual DNA from host cell substrates. It is therefore possible that such residual DNA could encode or harbor oncogenes and infectious agents, and transmit to product recipients, leading to possible oncogenic or infective events. The World Health Organization and U.S. Food and Drug Administration guidelines recommend that 10 ng/dose and 200 base pairs be the limits of content and size of residual DNA in the final product dose. This paper discusses establishment of acceptable limits of residual DNA using a risk-based approach that may differ from the current regulatory specifications. Methods currently in use for DNA safety assessment are also reviewed and compared. LAY ABSTRACT: Medicines produced from biological sources like cells can contain DNA. It is not clear what health risk the DNA can pose in the product recipients, but often manufacturing can be designed to minimize the risk by reducing the levels of DNA. This article describes new methods for calculating the health risks.