Genmab mAb HCP Control Strategy

Part II: Experiences from an “off-ELISA” road

April 2024, by Margarita Sabater

Get a detailed overview of how Genmab uses LC-MS to assess process changes, demonstrate HCP clearance, and document process consistency:

  • Process development aided by LC-MS: HCP identification analysis of in-process samples and the bulk mAb product to aid process development and a comparison study of two harvest filter setups to evaluate their efficiency.
  • Investigation of problematic HCPs and demonstration of consistent HCP clearance at commercial scale: LC-MS analysis of in-process samples and bulk mAb product from 4 PPQ runs showed consistent removal of HCPs, including problematic HCPs, such as Phospholipase B-like and Carboxypeptidase.
  • Feedback from regulatory authorities including EU, Japan, USA, Canada, and UK: Licensing applications in 25 countries with submission data using commercial ELISA kit and coverage analysis by ELISA-MS and LC-MS characterization.

Furthermore, Margarita discusses with Ejvind Mørtz, COO at Alphalyse:

  • When should we use mass spec analysis in development?
  • What do you do when you detect potentially problematic HCPs?
  • What is the future of HCP analytics for mAbs development and perspectives for an MS-only strategy?

Part 1: Experiences from an “off-gel” road

March 2024, by Søren Skov Jensen

Genmab presents the first elements of their holistic HCP Control Strategy:

  • Obtaining knowledge and understanding of the HCP levels in the mAb production process and identifying HCPs in the bulk mAb product using LC-MS. The analysis assessed samples from the Clarified Harvest, Chromatography 1 and Chromatography 2, and the bulk mAb product.


  • Selecting suitable anti-CHO HCP reagents. 
    Here, Genmab screened commercial ELISA reagents – 11 kits from 4 suppliers – using the ELISA-MS™ method to investigate which ELISA reagents provided the best coverage of the HCPs present in the process and the final bulk DS.


  • Further coverage analysis evaluation of the commercial ELISA kit that was found optimal for the process and best covered the HCPs present in the final bulk DS by multiple methods, including 2D fluorescence/Western blot, Immunoaffinity chromatography (IAC) and 2D DIGE, and ELISA-MS.

The webinar includes a discussion of perspectives for HCP analysis, the importance of USP chapter 1132.1, and the change to MS-based HCP strategies.

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