IQ Survey Results on Current Industry Practices-Part 1: Immunogenicity Risk Assessment

Abstract

An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guiding principle for an IRA includes a comprehensive evaluation of product- and patient-related factors that may influence the immunogenic potential of a biotherapeutic drug and a potential action plan. The Immunogenicity Working Group from the IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices for conducting IRAs and relevant aspects of bioanalysis. Survey results were provided by 19 IQ member companies participating in the Clinical Pharmacology Leadership Group (CPLG) and the Translational and ADME Sciences Leadership Group (TALG). Nearly all the respondents reported experience with monoclonal antibodies (mAb), with 10 other drug modalities including bioengineered protein therapeutics such as fusion and multi-domain proteins, peptides, oligonucleotides as well as gene and cell therapies. The survey results demonstrate that most companies have a defined IRA process, and there was a common understanding that the IRA may need to be revised as more information becomes available or the drug development strategy changes. Some differences found across the respondents are related to the time frame for implementation of IRA document, the types of preclinical data and computational methods used to assess risk, and how the IRA informs clinical plans and documentation practices. These results highlight that while there have been widespread insights gained with performing IRA for mAbs, more experience is needed to perform IRAs for the novel modalities.

Figure 1

Overall experience with different drug modalities from the 19 responding companies. Numbers above the bars in graph reflect the number of companies with experience for each modality.

Figure 2

Influence of geographic regions on content of IRA and intended application of IRA document to the responding company.

Figure 3

IRA team composition and the cross‐functional expertise participation.

Figure 4

Participant (n = 19) utilization of the in‐silico tools and in vitro assays used for immunogenicity risk assessment. DC, dendritic cell; IEDB, Immune Epitope Database; MAPPS, MHC‐II‐associated peptide proteomics.