The role of histopathology in the identification of immunotoxicity.
Recently finalized regulatory guidance documents concerned with the identification of immunotoxicity (CPMP: Note for Guidance on Repeated Dose Toxicity; FDA: Guidance for Industry, Immunotoxicology Evaluation of Investigational New Drugs; ICH S8) state that immunotoxicity testing should be performed on all new investigational drugs or medicinal products. In addition, all documents clearly identify gross and microscopic examination of lymphoid tissues as necessary and pivotal first steps in the assessment of new xenobiotics for immunotoxic potential. However, as is true for the evaluation of other organs systems, there are numerous approaches to the histopathologic examination of lymphoid tissues. To assist in a more uniform and consistent histopathologic assessment of the immune system, the Society of Toxicologic Pathology (STP), has recently prepared "best practice" recommendations concerning the collection, interpretation and reporting of organ weights, gross and microscopic observations, and other pathology data relevant to the immune system. The STP recommendations are intended to provide a scientifically sound and well-considered guidance document for routine pathology evaluation of the immune system. This presentation will consider the implications of this "best practice" document and place these recommendations in the context of normal animal tissue variability.
Haley
Patrick J
PJ
Global Safety Assessment, AstraZeneca Pharmaceuticals, Wilmington, Delaware 19850, USA. patrick.haley@astrazeneca.com