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

  • White Paper
  • Theme: Best Practices for Bioanalytical Methods: Recommendations from the Global Bioanalysis Consortium
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Abstract

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.

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Author information

Authors and Affiliations

  1. Sailstad and Associates Inc., Durham, North Carolina, USA

    J. M. Sailstad

  2. Biogen Idec, Cambridge, Massachusetts, USA

    L. Amaravadi & S. Pursuhothama

  3. Janssen Research and Development (Johnson & Johnson), Radnor, Pennsylvania, USA

    A. Clements-Egan

  4. Pfizer, Andover, Massachusetts, USA

    B. Gorovits

  5. Bristol-Myers Squibb, Princeton, New Jersey, USA

    H. A. Myler & R. C. Pillutla

  6. QPS, Groningen, The Netherlands

    M. Putman

  7. Dr. Reddy’s Laboratory, Hyderabad, India

    M. K. Rose

  8. Sumika Chemical Analysis Service Ltd, Osaka, Japan

    K. Sonehara

  9. Sanofi US, Bridgewater, New Jersey, USA

    L. Tang

  10. Morphotek, Inc., Exton, Pennsylvania, USA

    J. T. Wustner

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  1. J. M. Sailstad
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  2. L. Amaravadi
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Correspondence to J. M. Sailstad.

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Guest Editors: Binodh DeSilva and Philip Timmerman

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Sailstad, J.M., Amaravadi, L., Clements-Egan, A. et al. A White Paper—Consensus and Recommendations of a Global Harmonization Team on Assessing the Impact of Immunogenicity on Pharmacokinetic Measurements. AAPS J 16, 488–498 (2014). https://doi.org/10.1208/s12248-014-9582-y

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  • DOI: https://doi.org/10.1208/s12248-014-9582-y

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