Host cell contaminant protein assay development for recombinant biopharmaceuticals.

The efficiency and consistency of a biopharmaceutical purification process determines drug quality, including which specific types and concentrations of residual host cell or process contaminants may remain. Commercial reagents and generic analytical methods are available for quantitating most of these contaminants. However, no generic assay is available for quantitation of the specific contaminant host cell proteins (HCPs) which are unique to a novel purification process. Because of this, proprietary reagents and assays must be developed for the quantitation of process-specific HCPs in each biopharmaceutical drug. The need to develop proprietary reagents which are both sensitive to, and specific for, potentially complex mixtures of unique contaminant proteins has defined what is acceptable methodology for development of quantitative HCP assays. Within the biopharmaceutical industry this need is most often satisfied by the development of multi-analyte HCP immunoassays based upon the null cell mock purification model. Confidence in the quantitative nature of a given HCP assay, and the validity of analytical measurement obtained by the assay, is dependent upon empirical demonstration of the unique stoichiometry of the HCP assay reagents. In conjunction with other analytical and validation methods, an HCP immunoassay may be thought of as a necessary quantitative tool for the optimization and validation of biopharmaceutical purification process efficiency and consistency, rather than as an end in itself.