Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products

Gene therapy medicinal products (GTMPs) are currently undergoing intense industrial expansion and technological advancement. However, one issue facing development of most GTMPs is the generation of unwanted immune responses. Immunomodulatory strategies are also often applied in conjunction with GTMP administration to suppress or enhance these responses. This review focusses on the global regulatory requirements for immunogenicity assessments and immunomodulation in relation to GTMPs. The specific aims are to (1) identify the principal international guidelines; (2) identify areas of concordance and discrepancy between guidelines; (3) propose areas where guidelines could be harmonized; and (4) predict areas, which future guidance may address. Methodologies used included surveillance of literature, international guidelines, advocacy initiatives, and compilation of previous regulatory advice received. Overall, there is a clear absence of and need for GTMP-specific guidance on immunogenicity and immunomodulation. Several specific measures and areas for future regulatory harmonization and coverage are proposed.