title: Nonclinical safety testing of biopharmaceuticals--Addressing current challenges of these novel and emerging therapies.
abstract: Non-clinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these often innovative and complex drugs. Hot Topics in this field were discussed recently at the 4th Annual European Biosafe General Membership meeting. In this feature article, the presentations and subsequent discussions from the main sessions are summarized. The topics covered include: (i) wanted versus unwanted immune activation, (ii) bi-specific protein scaffolds, (iii) use of Pharmacokinetic (PK)/Pharmacodynamic (PD) data to impact/optimize toxicology study design, (iv) cytokine release and challenges to human translation (v) safety testing of cell and gene therapies including chimeric antigen receptor T (CAR-T) cells and retroviral vectors and (vi) biopharmaceutical development strategies encompassing a range of diverse topics including optimizing entry of monoclonal antibodies (mAbs) into the brain, safety testing of therapeutic vaccines, non-clinical testing of biosimilars, infection in toxicology studies with immunomodulators and challenges to human risk assessment, maternal and infant anti-drug antibody (ADA) development and impact in non-human primate (NHP) developmental toxicity studies, and a summary of an NC3Rs workshop on the future vision for non-clinical safety assessment of biopharmaceuticals.
authors.affiliation: UCB Pharma, Slough, UK. Electronic address: frank.brennan@ucb.com.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Brennan
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumann
authors.affiliation: Abbvie GmbH, Ludwigshafen, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Blaich
authors.affiliation: Medimmune LLC, Cambridge, UK.
authors.forename: Lolke
authors.initials: L
authors.lastname: de Haan
authors.affiliation: Glaxo Smithkline Pharma, Stevenage, UK.
authors.forename: Rajni
authors.initials: R
authors.lastname: Fagg
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kiessling
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Kronenberg
authors.affiliation: Covagen, Zurich, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Locher
authors.affiliation: Novartis Pharma, Boston, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Milton
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Tibbitts
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Ulrich
authors.affiliation: Glaxo Smithkline Pharma, Stevenage, UK.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Weir
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D051379:Mice; D018570:Risk Assessment; D012449:Safety; D018675:Toxicity Tests / Q000379:methods
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: Biopharmaceuticals; Gene and cell therapies; Immunomodulation; Monoclonal antibodies; Non-clinical safety; Pharmacokinetics; Pharmcodynamics; Recombinant proteins; Vaccines