Synthetic and recombinant liraglutide show no significant difference in immunogenicity using novel PBMC-based testing | Research

The takeaway

A novel PBMC-based assay found no significant immunogenicity difference between synthetic (generic) and recombinant (branded) liraglutide, validating synthetic peptide drugs while establishing a new method for detecting innate immune response-modulating impurities.

Generic = branded for immunogenicity
No significant immunogenicity difference between synthetic and recombinant liraglutide using a novel PBMC assay—validating generic peptide drug safety

What the researchers found

No significant immunogenicity difference: synthetic vs recombinant liraglutide. Novel PBMC-based IIRMI detection method established. Fresh PBMCs from multiple volunteers. TLR/NOD ligand challenge testing. FDA tentative approval of generic June 2024.

Why it matters

As generic synthetic peptide drugs enter the market, ensuring equivalent immunogenicity is critical. This PBMC-based method detects unknown trace impurities that cell line-based systems might miss.

How the study worked

PBMC-based assays with fresh cells from different volunteers. Liraglutide ± TLR/NOD ligands. Comparison of recent and aged products. Cytokine/chemokine measurement.

What this study cannot tell us

In vitro assay. PBMC response may not predict in vivo immunogenicity. Limited number of volunteers. Only liraglutide tested. Long-term immunogenicity not assessed.

How to read the evidence

Novel methodology validation study. Important for regulatory science but limited to in vitro testing.

When this study was published

Published in 2025.

The bigger picture

This validates the broader trend toward synthetic peptide drug manufacturing. As more peptide generics enter the market, PBMC-based IIRMI testing could become a regulatory requirement.

Questions still open

Should PBMC-based IIRMI testing be required for all synthetic peptide generics?
Would the method detect impurities in other synthetic peptide drugs?
Does the finding apply to all manufacturing variations of liraglutide?

Common questions

Are generic GLP-1 drugs as safe as brand-name versions?

This study provides reassurance: synthetic (generic) liraglutide showed no significant immunogenicity difference from recombinant (brand-name) liraglutide. Even though they are made differently—chemical synthesis vs biological production—the immune response to both was equivalent.

What is IIRMI testing?

IIRMI (innate immune response-modulating impurities) testing checks whether trace contaminants in a drug activate the immune system inappropriately. This study developed a new method using fresh human blood cells that can detect unknown impurities better than previous cell line-based tests.

Read the original research

Assessment of innate immune response modulating impurities (IIRMI) in synthetic peptide drugs (liraglutide).

Biochemical and biophysical research communications, 771, 151967

View on PubMed ↗Publisher’s paper ↗

Citation

Tang, Yangming; Tang, Chao; Lu, Xiaojie; Xing, Xinhui. (2025). Assessment of innate immune response modulating impurities (IIRMI) in synthetic peptide drugs (liraglutide).. Biochemical and biophysical research communications, 771, 151967. https://doi.org/10.1016/j.bbrc.2025.151967