Assessing the Immunogenicity of Biopharmaceuticals.
Biopharmaceuticals have the potential to raise an immunogenic response in treated individuals, which may impact the efficacy and safety profile of these drugs. As a result, it is essential to evaluate immunogenicity throughout the different phases of the clinical development of a biopharmaceutical, including post-marketing surveillance. Although rigorous evaluation of biopharmaceutical immunogenicity is required by regulatory authorities, there is a lack of uniform standards for the type, quantity, and quality of evidence, and for guidance on experimental design for immunogenicity assays or criteria to compare immunogenicity of biopharmaceuticals. Moreover, substantial technological advances in methods to assess immune responses have yielded higher immunogenicity rates with modern assays, and limit comparison of immunogenicity of biopharmaceuticals outside of head-to-head clinical trials. Accordingly, research programs, regulatory agencies, and clinicians need to keep pace with continuously evolving analyses of immunogenicity. Here, we review factors associated with immunogenicity of biopharmaceuticals, potential clinical ramifications, and current regulatory guidance for evaluating immunogenicity, and discuss methods to assess immunogenicity in non-clinical and clinical studies. We also describe special considerations for evaluating the immunogenicity of biosimilar candidates.
Instituto Nacional de Rehabilitacion, Mexico City, Mexico.
Carlos
C
Pineda
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.|Centro Latinoamericano de Pesquisa em Biologicos, Rio de Janeiro, Brazil.
Gilberto
G
Castañeda Hernández
Pfizer Global Established Pharma GCMA, 235 East 42nd Street, New York, NY, 10017-5755, USA. ira.jacobs@pfizer.com.
Ira A
IA
Jacobs
Pfizer Inc., Collegeville, PA, USA.
Daniel F
DF
Alvarez
Pfizer Inc., Cambridge, MA, USA.
Claudio
C
Carini
D000068879:Adalimumab / Q000276:immunology; D000906:Antibodies / Q000032:analysis; D001688:Biological Products / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D001702:Biopharmaceutics / Q000379:methods / Q000592:standards*; D059451:Biosimilar Pharmaceuticals / Q000494:pharmacology; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
D000906:Antibodies; D001688:Biological Products; D059451:Biosimilar Pharmaceuticals; D000068879:Adalimumab