In response to current regulatory guidance a Mass Spectrometry (MS) based Host Cell Protein (HCP) detection approach with faster, more accurate and wider-ranging detection is essential. In order to meet the newly prevailing demands Protagen Protein Services (PPS) recently invested in more far-reaching MS capabilities: The new high-performing mass spectrometer ThermoFisher Q Exactive™ HF-X started operational service last month and brings PPS to the next level of reproducible, accurate and sensitive analyses of majorly complex samples for different aspects of translational research and biopharma applications.

Heilbronn/Dortmund January 2019: The study of biomolecules for potential use as therapeutic agents requires the analysis of highly complex samples. This includes full characterization of complex biotherapeutics as well as comprehensive proteome profiling and quantitation. Developers of biosimilars and new biological entities demand in-depth analysis, high-end data quality and analytical precision without compromising on robustness or speed.

The new high-performing MS device not only allows to detect a higher number of proteins and peptides but also delivers much higher accuracy than previous models. The extended capabilities offer an up to eight times improved signal to noise ratio for intact, native monoclonal antibody mass determination. A higher scan rate simultaneously enables the detection of multiple attributes (MAM) for peptide based analysis like PTM characterization or glycoprofiling as well as it reaches a new level in characterizing protein impurities such as HCPs.

Residual host cell proteins (HCPs) are ppm-level contaminants in biotherapeutics that may elicit an unpredictable immune response in patients and need to be monitored meticulously. The new high-performing instrument gives access to a more accurate approach that detects a wider population of HCPs than traditional ELISA technologies. “Due to our long-term experience, our intuitive specialized bioinformatics and to our newly acquired high-end MS technologies we are now able to offer advanced MS as a technique for the comprehensive analysis of HCPs in our clients’ products”, says Dr. Heiner Falkenberg, MS Team Leader at PPS. In DSP characterization the detectable HCPs in one mAb product were increased by a factor of about 4 (49 versus 12 HCPs) by using the newest technology. “The perspective that high-end MS technologies offer”, adds Falkenberg, “has been inspiring regulatory groups worldwide, who by now often recommend MS as an orthogonal approach to HCP-ELISA.”

In contrast to HCP-ELISA, which relies on the presence of polyclonal antibodies for positive HCP detection, the amplified qualities of high-performing mass spectrometers such as the ThermoFisher Q Exactive™ HF-X offer the advantage of detecting HCPs in a de novo manner, without specialized polyclonal antibody reagents or product-/process-specific method development. At PPS, we apply our profound MS expertise within a clearly defined staged approach including

  • qualitative analysis aiming at the identification of low abundant HCPs in the drug substance,
  • quantitation of low abundant HCPs relative to purification-process samples, and
  • absolute quantitation of HCPs against heavy labeled marker peptides.

“We remain committed to positioning ourselves at the forefront, constantly looking for innovations and thus bringing the best technical and analytical service to our clients”, emphasizes Dr. Heiner Falkenberg. “We are improving HCP assessments significantly by means of the more decisive analytical technique of MS and we look forward to serving our clients with our extended options in HCP detection.”

Besides the new Mass Spectrometry (MS) based HCP detection approach method it is outmost important also to analyze the protein research object with other indicating methods. Learn more from our broad analytical spectrum at www.protagenproteinservices.com.