Immunogenicity of biologically-derived therapeutics: Assessment and interpretation of nonclinical safety studies

• Published in: Regulatory toxicology and pharmacology Vol. 54; no. 2; pp. 164 - 182
• Main Authors: Ponce, Rafael, Abad, Leslie, Amaravadi, Lakshmi, Gelzleichter, Thomas, Gore, Elizabeth, Green, James, Gupta, Shalini, Herzyk, Danuta, Hurst, Christopher, Ivens, Inge A., Kawabata, Thomas, Maier, Curtis, Mounho, Barbara, Rup, Bonita, Shankar, Gopi, Smith, Holly, Thomas, Peter, Wierda, Dan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-07-2009
• Subjects: Animals; Antibody Formation - drug effects; Biopharmaceutics - methods; Biopharmaceutics - statistics & numerical data; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Evaluation, Preclinical - methods; Humans; Immunogenicity; Nonclinical safety; Recombinant protein; Recombinant Proteins - administration & dosage; Recombinant Proteins - chemistry; Recombinant Proteins - immunology; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - toxicity; Species Specificity; Toxicity Tests - methods; Toxicity Tests - statistics & numerical data; Immunogenicity; Nonclinical safety; Recombinant protein
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2009.03.012

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.