Abstract
AIMS: Polyethylene glycol (PEG) is used in many applications including drug development. Due to exposure to environmental products, there is a high prevalence of preexisting anti-PEG antibodies in the global human population. The presence of anti-PEG antibodies is a concern for potentially reducing the efficacy of therapeutics after administration and represents a risk of safety events after exposure to PEGylated drug products. We developed and validated a creative and sensitive method for the detection of anti-PEG antibodies in human serum to support clinical programs for PEGylated drugs. METHODS: In this method, biotin-PEG streptavidin beads were used to extract anti-PEG antibodies from human serum for analysis in an anti-PEG ELISA assay. The same serum sample was analyzed in an anti-drug antibody assay. RESULTS: The anti-PEG antibody assay was validated with a screening cut point of 1.41 normalized signal, confirmatory cut point of 32.2% inhibition, sensitivity of 7.81 ng/mL and sufficient reproducibility, selectivity, and drug tolerance in accordance with the FDA 2019 Immunogenicity guidance. CONCLUSION: This method of removal of anti-PEG antibodies enables the use of a single sample to detect anti-drug and anti-PEG antibodies to support drug development programs.