title: Therapeutic monoclonal antibodies and consistent ends: terminal heterogeneity, detection, and impact on quality.
abstract: Monoclonal antibodies (mAbs) are biological macromolecules with complex post-translational modifications that can be observed when assessing product variants. The N- and C-terminal heterogeneities of commercially produced antibodies have been observed and extensively studied over the past 30 years. This review summarizes the current literature on detectable antibody termini variants from cultured cells. The presence of these heterogeneities can be detected by many different analytical methods, mostly based on sequence, charge and size differences. Examples are presented that highlight terminal heterogeneities, methods of detection, and their impact on the quality of mAbs. Regulatory considerations are also discussed regarding the potential impact on product quality, safety, and efficacy.
authors.affiliation: Office of Biotechnology Products, CDER/FDA, Silver Spring, MD 20903, United States. Electronic address: Kurt.Brorson@fda.hhs.gov.
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
authors.affiliation: Office of Biotechnology Products, CDER/FDA, Silver Spring, MD 20903, United States.
authors.forename: Audrey Y
authors.initials: AY
authors.lastname: Jia
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D001709:Biotechnology; D004356:Drug Storage; D018698:Glutamic Acid / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D018698:Glutamic Acid; D011761:Pyrrolidonecarboxylic Acid