Working Groups

Unwanted immune responses, both cellular and humoral, to therapeutics can have major safety, efficacy and/or commercial implications. Various pre-clinical evaluation tools (in silico, ex vivo and in vivo) are commonly used to assess immunogenicity risk, e.g. formation of ADA.

However, these tools are influenced by many factors such as the HLA or other genotypic diversities, specific CD4+ T cell frequency, assay sensitivity in general and also by the pharmacology of the drug itself, leading to false positives or negatives. Currently the field is lacking robust, consistent and, where feasible, standardized approaches and methods to better inform and mitigate risk.

The NCIRA working group of the EIP aims at providing evaluated positions on:

• limits of ex vivo and in vivo assays,
• best assay combinations to more robustly inform drug design, development, lead selection and risk assessment and utility of pre-clinical/non-clinical assays to inform critical quality attributes such as aggregation, glycosylation, deamidation, and other.

Subgroup members use NCIRA as a platform to share knowledge and increase understanding of the drivers of immunogenicity, including innate responses, antigen processing & presentation, T & B cell epitopes and immune regulation.

The focus of this working group is to align on the Immunogenicity Risk Assessment strategy performed in pharmaceutical and biotech companies and to publish the outcome as an aligned EIP position on this topic. In particular, the team aims to:

• exchange and align in more detail on how to assess
  • (Probability of) product-, process-, patient- and treatment-related risk factors
  • potential clinical consequences
  • overall risk level
• harmonize the analytical clinical strategy for low/middle/high risk projects and defining when to
  • analyze samples and when not (e.g., studies in healthy volunteers vs. patients)
  • have validated assays in place (incl. Nab assay)
  • implement additional analyses
• align on the update of assessments upon process changes

In addition, the team wants to emphasize and clarify the different focus, goal and benefits of IRA at different stages in development of the biotherapeutic and provide examples for assessments at different stages from different risk categories. Furthermore, the team wants to provide an overview on available literature on immunogenicity risk assessment.

The team is currently meeting every 2 weeks for 1 h.

As Immunogenicity risk Assessment is a multi-disciplinary evaluation, the team welcomes colleagues involved in immunogenicity risk assessment with background in Early Research, Non-clinical or Clinical Safety, Clinical Pharmacology, Clinical Development, CMC and Bioanalysis.

• The goal of the Working Group is for the members to exchange their company’s practices on immunogenicity assay related topics and work to publish industry best practices as recommended by EIP.
• The Working Group currently meets every 3 weeks for 1h.
• Currently, discussion topics include: all stages of humoral immunogenicity (or anti-drug antibody (ADA)) assays, including assay cross validation.

The Particle Characterisation Subcommittee (EIP-PCS) was established early 2008. The mission of the EIP-PCS is to discuss and exchange experience with protein characterisation and particle formation in relation with immunogenicity and safety, in order to increase our fundamental understanding of product-related causes of immunogenicity.

Aims of the EIP-PCS are:

• define common strategies and methodologies for particle detection and characterisation,
• evaluate current upcoming technologies,
• prepare aligned evaluations of new technologies,
• discuss and exchange experiences, needs and suitability of different methods for protein characterisation and the detection, quantification and characterisation of the presence of particles in biologics,
• have a common, scientific founded understanding about for particle detection and characterisation in biologics.