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 Immunogenicity Strategy Working Group meets monthly to discuss immunogenicity testing strategies in support of both non-clinical and clinical studies. The aim is to publish best practices as recommended by EIP.

Currently, strategies discussions include ADA sampling, optimised testing strategies, NAb assay strategy, alternative testing strategies (PK assay and/or PD markers); strategies for immunogenicity assessment of multi domain constructs are touched upon as well.

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.