Host cell proteins (HCPs) have become particularly notorious among process-related impurities. Purification workflows generally yield highly pure drug substances, and the biopharmaceutical industry has a strong track record of ensuring patient safety. However, some HCPs are known to coelute with therapeutic proteins into drug substances. If such “hitchhiker” proteins are not removed, then they can diminish product quality and even harm patients — and until the past decade or so, drug manufacturers have not had general access to analytical technologies that could provide sufficiently detailed information about what impurities were in their process streams and in what quantities. Thus, as this eBook shows, much work remains for the biopharmaceutical industry regarding high-risk HCPs. Scientists not only need to identify problematic proteins, but also must gain a mechanistic understanding of their origins, adapt downstream processes to ensure impurity removal, and validate the analytical methods by which HCPs are detected.

First, BPI’s managing editor summarizes HCP-focused presentations from the 2023 BioProcess International (BPI) Conference and Exhibition in Boston, MA. Those presenters sought to destabilize traditional conceptions of process-related impurities by exploring how aggregates could mediate HCP coelution with product proteins during protein-A chromatography. In turn, the presenters shed light on the need for further investigation into the origins of problematic HCP subsets and the mechanisms by which they can persist into drug substances. Then, scientists from the United States Pharmacopeia (USP) explore evolving technologies for HCP detection. The writers call attention to the growing importance of liquid chromatography with mass spectroscopy (LC-MS) to HCP analytics amid industry calls for detailed information about what particular HCPs are present in a sample. Such assays, the writers explain, require effective reference standards such as peptides labeled with stable isotopes. In the final chapter, scientists from eBook sponsor Cygnus Technologies focus on analytical methods for establishing the accuracy of HCP assays such as enzyme-linked immunosorbent assays (ELISAs) based on polyclonal anti-HCP antibodies. Traditional methods for ensuring sufficient antibody coverage are inadequate, the contributors contend, and more accurate and sensitive technologies now enable biologics manufacturers to gather valuable HCP information for regulatory submissions.

Read this eBook to learn about emerging approaches to HCP identification — and about the kinds of questions that come with improved understanding of HCP behavior.

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