Current challenges and opportunities in nonclinical safety testing of biologics.
Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use of PEGylated therapeutic proteins, selection of cynomolgus monkey as preclinical species, unexpected pharmacokinetics of biologics and the safety implications thereof are summarized. In addition, new developments in immunosafety testing of biologics, the use of transgenic mouse models and PK and safety implications of multispecific targeting approaches are discussed. Overall, the increasing complexity of new biologic modalities and formats warrants tailor-made nonclinical development strategies and experimental testing.
F. Hoffmann-La Roche, Basel, Switzerland. Electronic address: sven.kronenberg@roche.com.
Sven
S
Kronenberg
Andreas
A
Baumann
Lolke
L
de Haan
Heather J
HJ
Hinton
Jonathan
J
Moggs
Frank-Peter
FP
Theil
Ian
I
Wakefield
Thomas
T
Singer
D000818:Animals; D001688:Biological Products / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001691:Biological Therapy / Q000009:adverse effects* / Q000379:methods; D015195:Drug Design; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D011092:Polyethylene Glycols / Q000737:chemistry
D001688:Biological Products; D011092:Polyethylene Glycols