A statistical approach to determining criticality of residual host cell DNA

J Biopharm Stat. 2015;25(2):234-46. doi: 10.1080/10543406.2014.972514.


We propose a method for determining the criticality of residual host cell DNA, which is characterized through two attributes, namely the size and amount of residual DNA in biopharmaceutical product. By applying a mechanistic modeling approach to the problem, we establish the linkage between residual DNA and product safety measured in terms of immunogenicity, oncogenicity, and infectivity. Such a link makes it possible to establish acceptable ranges of residual DNA size and amount. Application of the method is illustrated through two real-life examples related to a vaccine manufactured in Madin Darby Canine Kidney cell line and a monoclonal antibody using Chinese hamster ovary (CHO) cell line as host cells.

Keywords: Critical quality attribute; Infectivity; Oncogenicity; Quality by design; Residual host cell DNA; Risk assessment.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / genetics
  • Biopharmaceutics / standards
  • Biopharmaceutics / statistics & numerical data*
  • CHO Cells
  • Chemistry, Pharmaceutical
  • Consumer Product Safety
  • Cricetulus
  • DNA / analysis*
  • Data Interpretation, Statistical
  • Dogs
  • Drug Contamination / statistics & numerical data*
  • Guidelines as Topic
  • Humans
  • Influenza Vaccines / biosynthesis
  • Influenza Vaccines / genetics
  • Influenza Vaccines / standards
  • Madin Darby Canine Kidney Cells
  • Models, Statistical*
  • Quality Control
  • Risk Assessment
  • Technology, Pharmaceutical / methods
  • Technology, Pharmaceutical / standards
  • Technology, Pharmaceutical / statistics & numerical data*


  • Antibodies, Monoclonal
  • Influenza Vaccines
  • DNA