Assessing and monitoring the quality of therapeutic mAb products

Nov 25. 2019

Question:

Which analyses should be part of mAb characterization?

I need to ensure the quality and consistency of my mAbs. Which analyses should I conduct for proper mAb characterization?

Answer:

For several years, monoclonal antibodies (mAbs) have been the fastest-growing type of pharmaceutical molecules [1]:

More than half of all new drugs approved from 2015 to 2018 were mAbs [2].

Also, the number of approved mAb biosimilars increased substantially during the last few years.

Before approval for clinical administration, biosimilars must be characterized in detail like their originator products [2].

What I suggest

Characterization of mAbs can be pretty complex. It is not enough to check for the correct amino acid sequence – you must also analyze the structure of the N-glycans and the proper formation of disulfide bridges [2].

We suggest a comprehensive and robust mAb characterization program based on intact mass analysis and peptide mapping to get the complete picture.

A mAb characterization program often consists of the following steps:

Intact mass analysis

Before and after reduction
Before and after removal of N-glycans
As subunits after IdeS treatment

Peptide mapping

Application of single or multiple digests using proteases, such as Trypsin, Chymotrypsin, Asp-N, Glu-C, Lys-C, etc.
Digestion under reduced and non-reduced conditions

Data analysis

Detailed characterization based on the experimental data obtained by intact mass analysis and peptide mapping.
A high level of protein chemistry expertise is necessary for this process.

This workflow provides a reproducible, accurate, sensitive, and fast structural assessment.

The solution is particularly beneficial to the biopharmaceutical industry. Pharma companies thus use it to control mAb product quality and consistency, batch-to-batch comparability, and process modification.

For more information about characterization analysis, visit our page dedicated to antibody analysis.

References:

[1] Liu, J.K.H.: “The history of monoclonal antibody development – Progress, remaining challenges, and future innovations,” Annals of Medicine and Surgery, 2014

[2] Walsh, G.: “Biopharmaceutical benchmarks 2018”, Nature Biotechnology, 2018