This white paper by Phil Kuhlman, Biopharmaceutical Technical Specialist at RSSL, discusses an approach to monitoring the levels of residual DNA derived from the production host for the drug including consideration of practical control of contamination as well as the MHRA’s guidance on performing PCR analysis
The expression of biological products using recombinant DNA technology has enabled the use of peptides and proteins for therapeutic use. One of the main concerns with this expression technology especially in immortal cell lines is the possibility of transference of the immortal trait to the end user of the medication. Thereby, potentially inducing cancer.
The World Health Organisation (WHO), has released guidance requiring the monitoring throughout the manufacturing process of HCDNA to demonstrate reduction to safe levels, either by process validation or lot release testing.
The WHO go on to dictate that the levels of residual host cell DNA that should not exceed 10 ng/dose for parenteral administered drugs.
The WHO guidance for the potential risk of residual host cell DNA suggests these factors should be considered:
The detection and quantification of residual host cell DNA is possible at very low levels using both fluorescence probes that bind to nucleic acid as well as more targeted analysis using polymerase chain reaction (PCR). Depending on the specific drug manufacturing process there are two main routes for dealing with residual host cell DNA control and monitoring.