posted on 2020-06-05, 17:03authored byJiao Ma, Greg W. Kilby
There is a growing industry and regulatory
need to detect host
cell protein (HCP) impurities in the production of protein biopharmaceuticals,
as certain HCPs can impact product stability, safety, and efficacy,
even at low levels. In some cases, regulatory agencies require the
identification and the quantification of HCPs in drug products (DPs)
for risk assessment, and this is an active and growing topic of conversation
in the industry and amongst regulators. In this study, we developed
a sensitive, robust, and reproducible workflow for HCP detection and
quantification in a significantly shorter turnaround time than that
previously reported using an Evosep ONE LC system coupled to an Orbitrap
Fusion Lumos mass spectrometer. Because of its fast turnaround time,
this HCP workflow can be integrated into process development for the
high-throughput (60 samples analyzed per day) identification of HCPs.
The ability to rapidly measure HCPs and follow their clearance throughout
the downstream process can be used to pinpoint sources of HCP contamination,
which can be used to optimize biopharmaceutical production to minimize
HCP levels. Analysis of the NIST monoclonal antibody reference material
using the rapid HCP profiling workflow detected the largest number
of HCPs reported to date, underscoring an improvement in performance
along with an increased throughput. The HCP workflow can be readily
implemented and adapted for different purposes to guide biopharmaceutical
process development and enable better risk assessment of HCPs in drug
substances and DPs.