title: Developmental immunotoxicity (DIT) testing of pharmaceuticals: current practices, state of the science, knowledge gaps, and recommendations.
abstract: The development and regulatory approval of immunomodulatory pharmaceuticals to treat many human diseases has increased significantly over the last two decades. As discussed by FDA and ICH guidelines, all human pharmaceuticals in development should be evaluated for potential adverse effects on the immune system. Developmental immunotoxicology (DIT) focuses on the concern that early-life (during pre-/post-natal development) exposure to agents which target the immune system may result in enhanced susceptibility to immune-related disease (e.g., infection, autoimmunity, and cancer, particularly leukemia) compared to adults, unique effects not observed in adults, or more persistent effects in comparison to those following adult exposure. This article provides a substantive review of the literature and presents detailed considerations for DIT testing strategies with a specific focus on pharmaceuticals and biopharmaceuticals. In this regard, differences between small molecule and large molecule therapeutics will be considered, along with recommendations for best practices in the assessment of DIT during drug development. In addition, gaps in the DIT knowledge base and current testing strategies are identified. Finally, a summary of an ILSI-HESI-ITC sponsored Workshop conducted in 2010, entitled 'Developmental Immunotoxicity Testing of Pharmaceuticals' will be presented. This Workshop consisted of participants from the pharmaceutical, biotechnology, academic, and regulatory sectors, where many of the issues relating to DIT outlined in this review were discussed, key points of consensus reached, and current gaps in the science identified.
authors.affiliation: Worldwide Research and Development, Pfizer Inc., Groton, CT, USA. mark.collinge@pfizer.com
authors.forename: Mark
authors.initials: M
authors.lastname: Collinge
authors.forename: Leigh Ann
authors.initials: LA
authors.lastname: Burns-Naas
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Chellman
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Kawabata
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Komocsar
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Piccotti
authors.forename: Jacintha
authors.initials: J
authors.lastname: Shenton
authors.forename: Daniel
authors.initials: D
authors.lastname: Wierda
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D004493:Education; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D006287:Health Planning Guidelines; D007107:Immune System / Q000187:drug effects* / Q000196:embryology; D007155:Immunologic Factors / Q000145:classification / Q000633:toxicity*; D018811:Maternal Exposure / Q000009:adverse effects*; D004364:Pharmaceutical Preparations / Q000145:classification; D018675:Toxicity Tests
chemical_list: D007155:Immunologic Factors; D004364:Pharmaceutical Preparations