Process contaminants in biopharmaceuticals: Host cell DNA & protein
Biopharmaceuticals such as therapeutic antibodies and recombinant proteins are produced in genetically engineered host cells. Effective removal of host cell contaminants from the production cell lines is required by regulatory agencies to ensure product safety. In general, levels up to 10 ng residual host cell DNA per dose, depending on the host cell type and the route of administration, and 100 ppm for residual host cell protein are acceptable.
To quantify host cell DNA, quantitative real-time PCR offers superior sensitivity with a limit of quantification in the subpicogram range. Existing PCR systems cover a wide variety of host cell types like E. coli, P. pastoris, CHO or human expression systems. Proper performance of the whole analytical procedure, including sample preparation, DNA extraction and PCR analysis is thoroughly verified for each sample matrix before routine testing. If higher specificity of detection is required (e. g. specific detection of the genetically engineered production cell line), Eurofins offers assay development and validation of methods according to customer specifications.
To quantify host cell protein, the ELISA method offers the highest sensitivity and reproducibility. For early phase products, commercially available generic ELISA kits may be used. However, for the testing of late phase or marketed products, an ELISA using antibody raised against process-specific host cell proteins is more desirable. As in all residual testing, sample matrix effects need to be carefully assessed using dilution linearity and spiking studies to ensure the validity of the testing results.
Several laboratories within the Eurofins Group have extensive expertise in method development and GMP testing of process contaminants. For more information, please visit: