Nonclinical safety testing of biopharmaceuticals – Addressing current challenges of these novel and emerging therapies

• Published in: Regulatory toxicology and pharmacology Vol. 73; no. 1; pp. 265 - 275
• Main Authors: Brennan, Frank R., Baumann, Andreas, Blaich, Guenter, de Haan, Lolke, Fagg, Rajni, Kiessling, Andrea, Kronenberg, Sven, Locher, Mathias, Milton, Mark, Tibbitts, Jay, Ulrich, Peter, Weir, Lucinda
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2015
• Subjects: Animals; Biopharmaceuticals; Biosimilar Pharmaceuticals - adverse effects; Drug Evaluation, Preclinical - methods; Gene and cell therapies; Humans; Immunomodulation; Mice; Monoclonal antibodies; Non-clinical safety; Pharmacokinetics; Pharmcodynamics; Recombinant proteins; Risk Assessment; Safety; Toxicity Tests - methods; Vaccines; Pharmcodynamics; Immunomodulation; Monoclonal antibodies; Non-clinical safety; Gene and cell therapies; Vaccines; Biopharmaceuticals; Pharmacokinetics; Recombinant proteins
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2015.07.019

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. •Non-clinical safety of biologics discussed at Annual European Biosafe meeting.•Presentations, case studies and discussions from the main sessions summarized.•Monoclonal antibodies, cell and gene therapies, vaccines and biosimilars covered.•Topics included immune activation, cytokine release, PK/PD, immunogenicity.