Host cell proteins (HCP) constitute a major group of impurities for biologic drugs produced using cell culture technology. Even at nanogram per milligram concentrations of HCP to drug substance (DS), HCPs can elicit undesired immune response, interfere with drug safety and efficacy, or impact DS stability. A broadly-reactive HCP ELISA should be used during the purification processes to ensure removal of HCPs and to demonstrate process consistency and final DS purity. Regulatory authorities are requesting biopharmaceutical companies employ orthogonal methods to demonstrate antibody coverage to individual HCPs and provide a comprehensive assay qualification package to ensure the HCP ELISA used by a sponsor is fit for this purpose.
Antibody Affinity Extraction (AAE), a novel method developed by Cygnus Technologies, is used to determine antibody coverage and reactivity to those HCPs that co-purify with DS. AAE is more predictive of the anti-HCP antibody performance in the HCP ELISA and facilitates identification of individual downstream HCPs.
ELISA is the gold standard for monitoring HCP levels but it does not provide information about what HCPs are present in the DS. Identification of HCPs by mass spectrometry (MS) is a powerful orthogonal method to ELISA. However, one of the limitations of MS is that IgG drug substances often mask HCPs by a factor of 10^4 – 10^6. To improve MS sensitivity, AAE can be used as a sample preparation method to enrich HCPs and eliminate most of the DS in a sample.
In this webinar, we will present data showing HCP identification by MS before and after AAE. In addition, we will discuss the integration of orthogonal methods for comprehensive HCP analysis that provide data throughout DS purification to inform process development teams of how to modify their purification processes to improve DS purity.
- Enrichment of HCPs by AAE and identification by MS is a powerful orthogonal method to ELISA
- Biopharmaceutical companies that integrate MS with ELISA data provide comprehensive quality control data for regulatory agencies
Jared Isaac PhD MBA
Senior Scientist, Research and Development
Jared Isaac, PhD MBA has over 6 years of industry experience in oncology, molecular diagnostic, medical device, and biopharmaceutical markets. Dr. Isaac is currently leading Cygnus Technologies’ mass spectrometry service for identification and quantification of biopharmaceutical process impurities. Dr. Isaac partners Cygnus Technologies with Biopharmaceutical companies to ensure biological drugs are safe and effective.
Prior to joining Cygnus Technologies, Dr. Isaac worked for Thermo Fisher Scientific for over 5 years as a Scientist, Scientist III, and Staff Scientist developing molecular diagnostic products for the clinical market using qualitative and quantitative mass spectrometry proteomics methods and technologies. Dr. Isaac earned his MBA from Western Michigan University in 2014, PhD in Biomedical Research from the University of Cincinnati in 2012, BS in Biochemistry from Lee University in 2005, and AS in Chemistry from Southern State Community College in 2003.
Cost: No Cost!