title: Theoretical considerations and practical approaches to address the effect of anti-drug antibody (ADA) on quantification of biotherapeutics in circulation.
abstract: Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics. One area that has been getting increasing attention recently is in the assessment of "free" and "total" analyte and the impact of the assay format on those assessments. To compliment these considerations, the authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti-drug antibody on PK assay measurement. This challenge is of particular interest and importance since biotherapeutic drugs often elicit an immune response, and thus may have a direct impact on quantification of the drug for its PK and safety evaluations.
authors.affiliation: MKelley Consulting LLC, 1533 Glenmont Lane, West Chester, PA 19380, USA. mmk48@comcast.net
authors.forename: Marian
authors.initials: M
authors.lastname: Kelley
authors.forename: Ago B
authors.initials: AB
authors.lastname: Ahene
authors.forename: Boris
authors.initials: B
authors.lastname: Gorovits
authors.forename: John
authors.initials: J
authors.lastname: Kamerud
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: King
authors.forename: Thomas
authors.initials: T
authors.lastname: McIntosh
authors.forename: Jihong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000627:therapeutic use; D001688:Biological Products / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D001691:Biological Therapy / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006801:Humans
chemical_list: D000906:Antibodies; D001688:Biological Products
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