When our client suddenly experienced significant changes in the Host Cell Protein (HCP) levels of identical drug samples, ELISA-MS coverage analysis and quantitative LC-MS revealed that the changes were due to the recent implementation of a new HCP ELISA kit standard. The client is now developing a custom ELISA standard that better fits the HCPs in their drug substance.
Following the introduction of a new HCP ELISA kit version, our client, an EU-based biotechnology company manufacturing vaccines and cancer immunotherapies, observed a sudden 20-fold decrease in HCP levels measured on an identical drug substance sample.
The client contracted Alphalyse to investigate the reason for this sudden change. As part of the analysis, we performed an ELISA-MS™-based coverage analysis on the kit itself, as well as an LC-MS evaluation of the suitability of the HCP ELISA standard.
A combination of ELISA-MS coverage analysis and quantitative HCP-MS found that the new kit standard contained disproportionately high amounts of 5 HCPs found in the drug sample:
In addition, the ELISA kit antibodies were overly sensitive to these exact 5 HCPs.
This made the ELISA calibration slope shift, resulting in a misinterpretation of the total amount of HCPs in the drug sample.
The client has subsequently contracted Alphalyse to characterize a new custom-developed ELISA standard to evaluate if it is a better fit for the HCPs in their drug substance.