title: A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs.
abstract: Bioanalytical assessments of anti-drug antibodies (ADAs) provide an understanding of the immunogenicity of biological drug molecules. The potential to induce ADAs after treatment with biologics is a safety issue that has become an important consideration in the development of biologics and a critical aspect of regulatory filings. US and European regulatory agencies are recommending that sponsors study immunogenicity using a risk-based approach, encouraging sponsors to formulate and implement their own risk management plans and to conduct discussions with the agencies when necessary. It follows from this that the greater the safety risks of ADAs, the more diligently one should clarify the immunogenicity of the product. Here we propose a general strategy to broadly assign immunogenicity risk levels to biological drug products, and present risk level-based 'fit-for-purpose' bioanalytical schemes for the investigations of treatment-related ADAs in clinical and nonclinical studies.
authors.affiliation: Centocor Research & Development, Inc., 145 King of Prussia Rd., Radnor, Pennsylvania 19087, USA. gshanka3@cntus.jnj.com
authors.forename: Gopi
authors.initials: G
authors.lastname: Shankar
authors.forename: Charles
authors.initials: C
authors.lastname: Pendley
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Stein
mesh_terms: D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D018448:Models, Immunological; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors