A European Medicines Agency working group is recommending revisions to a guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins to account for differences between large complex and small, simple-structured proteins and other critical issues.
As development has proceeded on hundreds of biologics, the guidance on immunogenicity studies hasn’t kept pace. Specifically, the EMA must create clearer guidance for the presentation of immunogenicity data, and more requirements for data on antibody assays, the Biosimilar Medicinal Products Working Party says in a concept paper released Tuesday. BMWP seeks stakeholder input on those issues, as well as the following:
The role of in vitro and in vivo nonclinical studies;
Risk-based approach to immunogenicity;
Clinical data to on the correlations of induced antibodies to allergic and anaphylactic/anaphylactoid reactions, delayed immunological reactions, pharmacokinetics and lack of efficacy;
Comparative immunogenicity studies; and
Post-licensing immunological studies.
Clearer knowledge of the immunogenicity of reference products “may help to estimate the level of tolerance towards a particular protein. However, this needs care as the immunogenicity of the proposed biosimilar product may not be similar to the reference product,” the working group says.
BMWP notes that a rising number of questions concerning the sensitivity of such assays and the use of ligand-binding and cell-based assays to demonstrate neutralizing antibodies have surfaced during drug reviews. Risk analysis could help to estimate the extent of immunogenicity studies, as well as the length of follow-up pre- and post-licensing, the group says.
The goal in revising the guideline is not to increase the number of immunogenicity studies, but rather to improve the quality and clarity of studies for EMA reviewers, the paper says.
Comments on the concept paper are due June 30.
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