Fc glycans of therapeutic antibodies as critical quality attributes.
Critical quality attributes (CQA) are physical, chemical, biological or microbiological properties or characteristics that must be within an appropriate limit, range or distribution to ensure the desired product quality, safety and efficacy. For monoclonal antibody therapeutics that rely on fraction crystalizable (Fc)-mediated effector function for their clinical activity, the terminal sugars of Fc glycans have been shown to be critical for safety or efficacy. Different glycosylation variants have also been shown to influence the pharmacodynamic and pharmacokinetic behavior while other Fc glycan structural elements may be involved in adverse immune reactions. This review focuses on the role of Fc glycans as CQAs. Fc glycan information from the published literature is summarized and evaluated for impact on patient safety, immunogenicity, bioactivity and pharmacodynamics/pharmacokinetics.
Pharma Biotech Development Penzberg, Roche Diagnostics GmbH, Penzberg 82377, Germany dietmar.reusch@roche.com.
Dietmar
D
Reusch
Biological Technologies, Genentech, CA 94080, USA.
Max L
ML
Tejada
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007114:Immunization / Q000009:adverse effects*; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D011134:Polysaccharides
Fc glycans; biologic activity; critical quality attribute; immunogenicity; therapeutic antibody