The right safety – a case study

Safety is one of the two main reasons for drugs to fail in the clinic. Hence, the development of biological models to better understand the physiological role of the target in health and disease and its interaction with the drug will help to predict target-related safety risks. The development of novel human cellular systems and their application in early development phases thereby supports to shift the attrition to early phases, eliminating non-safe compounds and biologics early on. In addition, novel models such as organoids or organs-on-a-chip may open new avenues for in vitro safety predictions, possibly eliminating or reducing the need of animal testing in the future.

Immunogenicity testing is one of the major safety aspects that needs to be considered for biopharmaceutical (BP) development. The recent update of the FDA guidance document, recommending a risk-based approach to better understand immune responses elicited by therapeutic proteins, underlines the importance of this safety testing. Developing a cellular assay system that allows to test for immunogenicity of compounds is therefore a key requirement in the biologics drug discovery workflow. In 2017, Novo Nordisk presented a novel assay system to test for immunogenicity using irradiated PBMC as antigen-presenting population and CD4+ T cells from the same donor. In this assay setting, they were able to show in vitro immunogenicity to commercially available biopharmaceuticals that were known to elicit immune responses in the clinic. This example nicely demonstrates the capability of a biological model to help predict immunogenicity in vitro.

Integrated solutions to choose the right system for safety testing

A wide range of immune as well as other human primary cell types is available to build models for safety testing. Large donor panels allow to test your compound in donors from various genetic or phenotypic backgrounds. Cell culture media optimized for the respective cell type provide the basis for reproducible and robust assay results and are available as ready-to-use BulletKit^TM formats for all primary cell types. Our range of X-Vivo^TM serum-free media provide the optimal serum-free environment for blood and immune cells which may help to provide a biological model system free of artefacts caused by unknown or animal-origin components in the cell culture such as bovine serum.

1. FDA guidance document for industry, Jan. 2019, Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection 
2. Development of a novel T cell: PMBC assay to test drug candidates with low immunogenicity in the phase of early drug development. Published in PLOS One, May 31, 2017