Drug interference in immunogenicity assays depends on valency

Area of Science:

• Pharmacology
• Immunology
• Biotechnology

Background:

• Direct comparison of immunogenicity data for biological drugs is challenging due to assay interference.
• Drug interference in immunogenicity assays can vary significantly depending on the assay format and drug characteristics.

Purpose of the Study:

• To identify drug-related factors influencing drug interference in immunogenicity assays.
• To investigate the impact of drug valency on drug interference using antibody-derived biologicals.

Main Methods:

• Systematic investigation of drug valency's influence on drug interference.
• Utilized mono- and bivalent formats of adalimumab as a model system.
• Examined real-life examples: natalizumab (effectively monovalent IgG4) and certolizumab pegol (pegylated Fab fragment).

Main Results:

• Monovalent antibody-derived drugs exhibit less drug interference compared to bivalent antibodies.
• Drug interference was less pronounced for natalizumab and certolizumab pegol in antigen-binding tests.
• Demonstrated reduced interference for effectively monovalent drugs in specific assay formats.

Conclusions:

• Drug valency is a key factor influencing drug interference in immunogenicity testing.
• Monovalent biological drugs may offer advantages in immunogenicity assessment due to reduced interference.
• Consideration of drug valency is essential when comparing immunogenicity data across different biological therapeutics.