Residual DNA quantification in clinical batches of BBG2Na, a recombinant subunit vaccine against human respiratory syncytial virus

BBG2Na, a well-defined recombinant protein produced in Escherichia coli, is a promising human respiratory syncytial virus subunit vaccine candidate. T his study describes the quantification of residual DNA in large scale batch es used in phase I to III clinical trials. Two different analytical methods were developed and applied on five different final bulks of Drug Substance and their associated in process control samples, namely a chemiluminescent hybridisation assay and the total DNA Threshold(TM) System assay. These tw o complementary methods demonstrated the clearance of residual DNA during t he downstream purification process. The amount of residual DNA found in the final bulks was below 20 pg of DNA per 300 mug BBG2Na, the highest tested clinical dose of antigen. This is very low level of residual DNA for a reco mbinant subunit vaccine produced in a bacteria and contribute to make for B BG2Na a well-characterised biopharmaceutical. This study also provides data concerning the validation of the hybridisation dot blot assay and the tota l DNA Threshold(TM) assay. (C) 2001 The International Association for Biolo gicals.