Assessing and monitoring the quality of therapeutic mAb products

Question:

I need to ensure the quality and consistency of my mAbs. Which analyses should be conducted 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 drug approved from 2015 to 2018 were mAbs [2].

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

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

What I suggest

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

To get the full picture, we suggest a comprehensive and robust mAb characterization program based on intact mass analysis and peptide mapping.

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 digest 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 needed for this process.

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

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

For more information about characterization analysis, download this application note or visit our page dedicated to antibody analysis:

mAb Application Note >>>

Related blog posts:

• How to characterize antibody glycosylation by HILIC-MS
• What purity is required for de-novo sequencing of my antibody?
• Antibody de-novo Sequencing: How to get 100% sequence coverage
• Why disulfide bridges are critical quality attributes of biologics

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