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Therapeutic Protein Drug–Drug Interactions: Navigating the Knowledge Gaps–Highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA Workshop

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Abstract

The investigation of therapeutic protein drug–drug interactions has proven to be challenging. In May 2012, a roundtable was held at the American Association of Pharmaceutical Scientists National Biotechnology Conference to discuss the challenges of preclinical assessment and in vitro to in vivo extrapolation of these interactions. Several weeks later, a 2-day workshop co-sponsored by the U.S. Food and Drug Administration and the International Consortium for Innovation and Quality in Pharmaceutical Development was held to facilitate better understanding of the current science, investigative approaches and knowledge gaps in this field. Both meetings focused primarily on drug interactions involving therapeutic proteins that are pro-inflammatory cytokines or cytokine modulators. In this meeting synopsis, we provide highlights from both meetings and summarize observations and recommendations that were developed to reflect the current state of the art thinking, including a four-step risk assessment that could be used to determine the need (or not) for a dedicated clinical pharmacokinetic interaction study.

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Acknowledgments

We thank all members of the TP-DDI Steering Committee (Fig. 1) and the in vitro TP-DDI and POP-PK TP-DDI Working Groups for their scientific contributions and valuable discussions. We also thank Dan Lu and Amita Joshi for concept discussions around Fig. 4 and Shannon Dallas, Manish Gupta, Amita Joshi, Eugenia Kraynov, and Min Zhu for critical review of this manuscript. Additionally, we acknowledge the contribution of the presenters and moderators of both the AAPS NBC meeting (Raymond Evers, Amita Joshi, Jane Kenny, Greg Slatter, Lei Zhang, and Honghui Zhou) and the workshop (Andrew Chow, Leslie Dickmann, Justin Earp, Raymond Evers, Eva Gill Berglund, Manish Gupta, Chuanpu Hu, Graham Jang, Jane Kenny, Eugenia Kraynov, Bernd Meibohm, Edward T. Morgan, Christophe Schmitt, Greg Slatter, Diane Wang, Lei Zhang, and Honghui Zhou). The roundtable was sponsored by the AAPS. The workshop was co-sponsored by the U.S. FDA and the International Consortium for Innovation and Quality in Pharmaceutical Development (www.iqconsortium.org), a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science-based and scientifically driven standards and regulations for pharmaceutical and biotechnology products worldwide.

Disclaimer

The manuscript reflects the views of the authors and should not be construed to represent FDA, IQ Consortium, or individual company views or policies.

Conflict of interest

Andrew Chow and Greg Slatter are employees and own stock of Amgen Inc. Jane Kenny is an employee of Genentech, Inc., a member of the Roche Group, and may have an equity interest in Roche. Diane Wang is an employee and owns stock of Pfizer. Honghui Zhou is an employee and owns stock of Johnson & Johnson. Justin Earp, Raymond Evers, Maggie Liu, and Lei Zhang have no conflict of interest to report.

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Authors and Affiliations

  1. Department of Drug Metabolism & Pharmacokinetics, Genentech Inc., South San Francisco, California, USA

    Jane R. Kenny

  2. Pharmaceutical Consortia Management Practice Group, Drinker Biddle & Reath LLP, Washington, District of Columbia, USA

    Maggie M. Liu

  3. Quantitative Pharmacology, Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., Thousand Oaks, California, USA

    Andrew T. Chow

  4. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA

    Justin C. Earp & Lei Zhang

  5. Merck & Co, PK/PD and Drug Metabolism, Rahway, New Jersey, USA

    Raymond Evers

  6. Medical Sciences/Early Development, Amgen Inc., Seattle, Washington, USA

    J. Greg Slatter

  7. Clinical Pharmacology, Oncology Business Unit, Pfizer, La Jolla, California, USA

    Diane D. Wang

  8. Biologics Clinical Pharmacology, Janssen Research and Development LLC, Spring House, Pennsylvania, USA

    Honghui Zhou

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  1. Jane R. Kenny
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Correspondence to Jane R. Kenny.

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Kenny, J.R., Liu, M.M., Chow, A.T. et al. Therapeutic Protein Drug–Drug Interactions: Navigating the Knowledge Gaps–Highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA Workshop. AAPS J 15, 933–940 (2013). https://doi.org/10.1208/s12248-013-9495-1

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