Immune response associated adverse events and hypersensitivity reactions are the major safety concerns related to enzyme replacement therapies. The immunogenicity against these therapeutic enzymes depends on structural similarities, manufacturing processes, formulation, and impurities etc. The drug developer has developed strategies to mitigate manufacturing related immunogenicity risk with improved processes such as optimization of the protein sequence, mammalian cell lines to express and purify recombinant human enzymes. Despite these efforts, the immunogenicity and anti-drug antibody generation against these therapeutic proteins are heterogeneous among the populations. In the same dose cohort, one subject may produce higher anti-drug antibodies titer with lesser efficacy. In contrast, another subject may have less or no anti-drug antibodies with no impact on drug efficacy. Identify and characterizing these individual factors would enable a better understanding of individual fact...