Immunotoxicology assessment in the pharmaceutical industry

Area of Science:

• Toxicology
• Immunology
• Pharmaceutical Development

Background:

• Optimized inter-laboratory evaluation studies established predictive methods for detecting immune system toxicity.
• These methods form the basis for regulatory guidelines from the OECD, EPA, and FDA.
• A survey assessed the current status of immunotoxicity evaluation in the pharmaceutical industry.

Purpose of the Study:

• To report on ongoing immunotoxicity evaluation activities in major pharmaceutical companies.
• To describe Sanofi's strategy for applying immunotoxicity methods in preclinical development.
• To evaluate the predictive value of immunotoxicity assays using reference compounds and new molecular entities (NMEs).

Main Methods:

• Conducted a survey of pharmaceutical companies regarding their immunotoxicity assay practices.
• Evaluated 27 NMEs and four reference compounds (azathioprine, dexamethasone, cyclophosphamide, cyclosporin A) over 8 years.
• Utilized multiple animal species (rat, dog, monkey) and selected immunotoxicity assays.

Main Results:

• Described which assays are performed, compound selection criteria, and timing within drug development.
• Sanofi's experience with NMEs and reference standards is detailed.
• Immunotoxicity methods were integrated into drug development, yielding a low frequency of positive results.

Conclusions:

• Immunotoxicology parameters are a valuable adjunct for NME safety assessment.
• The evaluated methods were easily integrated into the drug development process.
• Immunotoxicity evaluation can be performed systematically or on a case-by-case basis.