BSTP Review of 12 Case Studies Discussing the Challenges, Pathology, Immunogenicity, and Mechanisms of Inhaled Biologics.

The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this manuscript, the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Dog.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/inhand.

Epithelial Alteration Associated With Recovery From Laryngeal Squamous Metaplasia in Rats: Kinetics of Recovery From a Test Item-Related Change.

Squamous metaplasia is a nonspecific adaptive response to chronic irritation in the larynx and is often diagnosed as a test item-related change in rat inhalation studies. Investigating scientists are frequently asked to assess the adversity of laryngeal squamous metaplasia and to interpret its relevance to human risk. One factor in predicting relevance to human risk is the kinetics (degree and speed) of recovery following the cessation of exposure to the test item.

Evaluation of the rabbit nasal cavity in inhalation studies and a comparison with other common laboratory species and man.

The rabbit is occasionally used for inhalation and intranasal safety assessment studies, but there are no detailed descriptions of the anatomy or histology of the rabbit nose. To address this deficit, the nasal cavities of thirty-two control adult rabbits were sectioned and examined to provide mapping of the main epithelial types and histological structures present within the cavity and turbinates. Four levels of the nasal cavity were prepared and examined using anatomic landmarks.

Differences in neointima formation between impervious and porous polytetrafluoroethylene vascular patch material.

The aim of this study was to compare the neointima formation and blood loss of an impervious ePTFE with those of the porous ePTFE patch. Ten mongrel dogs were selected for the study. Both the impervious and porous ePTFE patches were implanted into the common iliac arteries in each dog.