The AAPS Journal

, Volume 16, Issue 3, pp 488–498 | Cite as

A White Paper—Consensus and Recommendations of a Global Harmonization Team on Assessing the Impact of Immunogenicity on Pharmacokinetic Measurements

  • J. M. Sailstad
  • L. Amaravadi
  • A. Clements-Egan
  • B. Gorovits
  • H. A. Myler
  • R. C. Pillutla
  • S. Pursuhothama
  • M. Putman
  • M. K. Rose
  • K. Sonehara
  • L. Tang
  • J. T. Wustner
White Paper Theme: Best Practices for Bioanalytical Methods: Recommendations from the Global Bioanalysis Consortium
Part of the following topical collections:
  1. Theme: Best Practices for Bioanalytical Methods: Recommendations from the Global Bioanalysis Consortium


The Global Bioanalysis Consortium (GBC) set up an international team to explore the impact of immunogenicity on pharmacokinetic (PK) assessments. The intent of this paper is to define the field and propose best practices when developing PK assays for biotherapeutics. We focus on the impact of anti-drug antibodies (ADA) on the performance of PK assay leading to the impact on the reported drug concentration and exposure. The manuscript describes strategies to assess whether the observed change in the drug concentration is due to the ADA impact on drug clearance rates or is a consequence of ADA interference in the bioanalytical method applied to measure drug concentration. This paper provides the bioanalytical scientist guidance for developing ADA-tolerant PK methods. It is essential that the data generated in the PK, ADA, pharmacodynamic and efficacy/toxicity evaluations are viewed together. Therefore, the extent for the investigation of the PK sensitivity to the presence of ADA should be driven by the project needs and risk based.


global bioanalysis consortium immunogenicity pharmacodynamic pharmacokinetic risk-based approach 


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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • J. M. Sailstad
    • 1
  • L. Amaravadi
    • 2
  • A. Clements-Egan
    • 3
  • B. Gorovits
    • 4
  • H. A. Myler
    • 5
  • R. C. Pillutla
    • 5
  • S. Pursuhothama
    • 2
  • M. Putman
    • 6
  • M. K. Rose
    • 7
  • K. Sonehara
    • 8
  • L. Tang
    • 9
  • J. T. Wustner
    • 10
  1. 1.Sailstad and Associates Inc.DurhamUSA
  2. 2.Biogen IdecCambridgeUSA
  3. 3.Janssen Research and Development (Johnson & Johnson)RadnorUSA
  4. 4.PfizerAndoverUSA
  5. 5.Bristol-Myers SquibbPrincetonUSA
  6. 6.QPSGroningenThe Netherlands
  7. 7.Dr. Reddy’s LaboratoryHyderabadIndia
  8. 8.Sumika Chemical Analysis Service LtdOsakaJapan
  9. 9.Sanofi USBridgewaterUSA
  10. 10.Morphotek, Inc.ExtonUSA

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