The Role of the Toxicologic Pathologist in the Biopharmaceutical Industry

Tongeren, Susan van; Fagerland, Jane A.; Conner, Michael W.; Diegel, Kelly L.; Donnelly, Kevin B.; Grubor, Branka; Lopez-Martinez, Alric; Bolliger, Anne Provencher; Sharma, Alok; Tannehill-Gregg, Sarah H.; Turner, Patricia V.; Wancket, Lyn M.

doi:10.1177/1091581811413304

Cited by 27 publications

(25 citation statements)

References 51 publications

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“…As part of their increasing role in the biopharmaceutical industry (Ettlin 2013;van Tongeren et al 2011), toxicologic anatomic and clinical veterinary pathologists provide critical analyses during the preclinical phase. These analyses help sort out the possible cause/effect scenarios for the adverse drug reaction, including the possibility that it is mediated by ADA and an HSR.…”

Section: Ada In Monkeys On Preclinical Studies Of Therapeutic Proteinsmentioning

confidence: 99%

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.

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Section: Ada In Monkeys On Preclinical Studies Of Therapeutic Proteinsmentioning

confidence: 99%

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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“…The paradigm changes also require that toxicity investigations start early in the research phase (Kramer, Sagartz, and Morris 2007). The value added by toxicopathologists in discovery teams has been recognized (van Tongeren et al 2011), as anatomic and clinical pathology methods and know-how are needed for the following:…”

Section: Scientific and Technological Environmentmentioning

confidence: 99%

Toxicologic Pathology in the 21st Century

Ettlin¹

2012

Toxicol Pathol

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Toxicology is and will be heavily influenced by advances in many scientific disciplines. For toxicologic pathology, particularly relevant are the increasing array of molecular methods providing deeper insights into toxicity pathways, in vivo imaging techniques visualizing toxicodynamics and more powerful computers anticipated to allow (partly) automated morphological diagnoses. It appears unlikely that, in a foreseeable future, animal studies can be replaced by in silico and in vitro studies or longer term in vivo studies by investigations of biomarkers including toxicogenomics of shorter term studies, though the importance of such approaches will continue to increase. In addition to changes based on scientific progress, the work of toxicopathologists is and will be affected by social and financial factors, among them stagnating budgets, globalization, and outsourcing. The number of toxicopathologists in North America, Europe, and the Far East is not expected to grow. Many toxicopathologists will likely spend less time at the microscope but will be more heavily involved in early research activities, imaging, and as generalists with a broad biological understanding in evaluation and management of toxicity. Toxicologic pathology will remain important and is indispensable for validation of new methods, quality assurance of established methods, and for areas without good alternative methods.

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“…A c c e p t e d M a n u s c r i p t A great deal of knowledge on toxicity in humans has been obtained by post mortem molecular and anatomic analysis of cells, tissues and organs [159,160].…”

Section: Toxicity Assessment In Humansmentioning

confidence: 99%

Assessment of food toxicology

Gosslau

2016

Food Science and Human Wellness

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The Role of the Toxicologic Pathologist in the Biopharmaceutical Industry

Cited by 27 publications

References 51 publications

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

Toxicologic Pathology in the 21st Century

Assessment of food toxicology

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