Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies.
An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.
Ponce
Rafael
R
ZymoGenetics, Inc., 1201 Eastlake Ave. E., Seattle, WA 98102, USA. rponce@amgen.com
Abad
Leslie
L
Amaravadi
Lakshmi
L
Gelzleichter
Thomas
T
Gore
Elizabeth
E
Green
James
J
Gupta
Shalini
S
Herzyk
Danuta
D
Hurst
Christopher
C
Ivens
Inge A
IA
Kawabata
Thomas
T
Maier
Curtis
C
Mounho
Barbara
B
Rup
Bonita
B
Shankar
Gopi
G
Smith
Holly
H
Thomas
Peter
P
Wierda
Dan
D
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001702:Biopharmaceutics / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity*; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods* / Q000706:statistics & numerical data
D011994:Recombinant Proteins