Immunogenicity and Peptides

The global market for therapeutic peptides is projected to continue to grow at a fast pace in the coming years in response to high demand for these products. The increasing complexity of chemical and recombinant peptide manufacturing processes may impact product quality attributes, including as related to immunogenicity risk.

(Peptides are short chains of amino acids, or small proteins, which our bodies naturally produce. They act as messengers, telling our cells what to do, and play vital roles in our skin health, immune system and helping to control our hormones.)

While it is well established that product-related factors, including impurities, can impact the immunogenicity of a biologic product, assessing the actual impact of a specific product quality attribute on immunogenicity is difficult. Despite significant advances in the analytical characterisation of complex peptide products, gaps still exist in the understanding of the significance of impurities to the overall peptide immunogenicity risk, and questions remain about what the best-suited control strategies are.

These gaps have the largest impact on the assessment of immunogenicity risk of follow-on therapeutic peptide products, when clinical data are not available to inform that risk. Current regulatory guidance on impurity qualification thresholds is sparse, and in vitro and in silico immunogenicity assessment methods for evaluating the immunogenicity risk of impurities present technical and methodological limitations.

Immunogenicity is the ability of a substance such as an antigen, vaccine, or, indeed a therapeutic product to provoke an immune response in the body. It refers to how well the immune system recognises a substance as foreign, triggering the production of antibodies or immune cells. There are twp sort of immunogenicity:

Wanted Immunogenicity: In vaccines, this is desirable, as it stimulates the immune system to create protective antibodies against viruses or bacteria

Unwanted Immunogenicity: In biologics or therapeutic drugs, this is undesired, as it causes the body to produce anti-drug antibodies (ADA) which can reduce a drug or therapeutic product"s effectiveness, cause allergic reactions, or lead to other adverse effects.

While it is established that product-related factors can impact the immunogenicity of a biologic product, assessing the actual impact of a specific product quality attribute on immunogenicity is difficult, whether in clinical trials or in the post-marketing setting. Quality data from clinical lots can be correlated with ADA information generated during clinical studies, but conclusions will be confounded by patient- and treatment-related factors.

Qualification thresholds for impurities provided in guidance applicable to peptide drug products, when available, are determined based on toxicity considerations or limited experience with products available commercially. Recommended qualification strategies involve toxicity studies as well as in vitro and in silico immunogenicity assessment (IVISIA) methods. The usefulness of these methods will increase as current technical and methodological limitations are addressed.

Considering the current challenges, there is value in prioritising impurity control strategies and drawing from available information on the immunogenicity risk of specific impurities (e.g., databases, literature). Lastly, the risk associated with a particular impurity is better understood in the context of the overall immunogenicity risk of the product, which an integrated summary of immunogenicity can help capture. Taken in combination, these approaches can help mitigate the risk associated with impurities until updated impurity qualification thresholds informed by immunogenicity risk are available.

Any properly sourced topical peptide is one thing - at worst, you can simply wash it off. Injecting peptides is a different matter. There are regulations regarding the production and use of peptides but these are in strict clinical conditions for very specific reasons (insulin, for example). Injecting any old peptide because of some trend pushed out on social media is a different kettle of fish, especially as those that you can presently access are for research only and as such have not been subjected to any form of approval (which really should give you a clue!)

You do not know what is in the product, you do not know what impurities may be in the product and being a recent trend, there is no evidence supporting or otherwise of any medium or long term effects, given a persons' medical history or condition (remember Thalidomide?) In the case of "research only" products which may be bought on the grey market, there is also no one to take to court if things go badly wrong.

Not (all) my own work. The above taken from:

Puig M, Shubow S. Immunogenicity of therapeutic peptide products: bridging the gaps regarding the role of product-related risk factors. Front Immunol. 2025 Jun 18;16:1608401. doi: 10.3389/fimmu.2025.1608401. PMID: 40607385; PMCID: PMC12213570.

Italics, above, are mine

Copyright © 2026 by the authors.

The above is taken from an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.