title: New challenges and opportunities in nonclinical safety testing of biologics.
abstract: New challenges and opportunities in nonclinical safety testing of biologics were discussed at the 3rd European BioSafe Annual General Membership meeting in November 2013 in Berlin: (i)Approaches to refine use of non-human primates in non-clinical safety testing of biologics and current experience on the use of minipigs as alternative non-rodent species.(ii)Tissue distribution studies as a useful tool to support pharmacokinetic/pharmacodynamic (PKPD) assessment of biologics, in that they provide valuable mechanistic insights at drug levels at the site of action.(iii)Mechanisms of nonspecific toxicity of antibody drug conjugates (ADC) and ways to increase the safety margins.(iv)Although biologics toxicity typically manifests as exaggerated pharmacology there are some reported case studies on unexpected toxicity.(v)Specifics of non-clinical development approaches of noncanonical monoclonal antibodies (mAbs), like bispecifics and nanobodies.
authors.affiliation: Bayer Pharma AG, Berlin, Germany. Electronic address: andreas.baumann@bayer.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumann
authors.affiliation: Genentech, South San Francisco, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Flagella
authors.affiliation: CiToxLAB, Evreux, France.
authors.forename: Roy
authors.initials: R
authors.lastname: Forster
authors.affiliation: MedImmune, Cambridge, UK.
authors.forename: Lolke
authors.initials: L
authors.lastname: de Haan
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Kronenberg
authors.affiliation: Covagen AG, Zuerich, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Locher
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Richter
authors.affiliation: UCB Pharma, Braine-l'Alleud, Belgium.
authors.forename: Frank-Peter
authors.initials: FP
authors.lastname: Theil
authors.affiliation: Pfizer, La Jolla, USA.
authors.forename: Marque
authors.initials: M
authors.lastname: Todd
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics; D001688:Biological Products / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D023421:Models, Animal; D011323:Primates; D012449:Safety; D061905:Single-Domain Antibodies / Q000009:adverse effects; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution; D018675:Toxicity Tests
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D001688:Biological Products; D061905:Single-Domain Antibodies
keywords: Biologics; Bispecifics; Distribution; Minipigs; Non-clinical safety; PEGylated proteins; Pharmacokinetics