Abstract
Background
Communicating the clinical impact of immunogenicity in labeling is important for safe and effective use of certain prescription products. Current U.S. Food and Drug Administration (FDA) guidance does not provide comprehensive recommendations on the communication of clinical impact of immunogenicity in labeling. To understand current labeling practice, we evaluated the immunogenicity data and clinical impact information in labeling of selected prescription products.
Methods
We created a database of 71 therapeutic biologics and drug products that had an immunogenicity assessment initially approved by FDA’s Center for Drug Evaluation and Research between 2014 and 2018. We analyzed the content and format of immunogenicity information (e.g., anti-drug antibody incidence and/or immunogenicity impact on pharmacokinetics (PK), safety, and/or effectiveness) in the most recent approved labeling.
Results
Immunogenicity information was in the ADVERSE REACTIONS section in 98% of the reviewed labeling. Immunogenicity impact on PK was reported in 52% of the labeling, typically within the ADVERSE REACTIONS section, but supportive PK data were often not included in the CLINICAL PHARMACOLOGY section. Additionally, the immunogenicity impact on safety and/or effectiveness was communicated in 70% of the labeling, with 23% clearly communicating the effect as clinically meaningful, and 10% providing actionable recommendations.
Conclusions
Most of the reviewed labeling includes immunogenicity information within the ADVERSE REACTIONS section. However, there is inconsistency in providing supportive PK data and high variability in reporting immunogenicity impact on safety and effectiveness in labeling. Development of a communication framework that allows for consistent inclusion of immunogenicity impact statements in labeling could improve how immunogenicity risk is conveyed in prescription drug labeling.
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Acknowledgements
The authors wish to thank Drs. Joseph Grillo and Elimika Pfuma Fletcher for providing thoughtful comments. They would also like to thank our collaborators, Drs. Steven Kozlowski, Jeffry Florian, Sarah Schrieber, Jie Wang, and Anand Balakrishnan, for their contribution to research development.
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The views expressed in this article are those of the authors and do not necessarily reflect the official views of the FDA.
Funding
This project was supported, in part, by an appointment to the ORISE Research Fellowship Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.
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DG collected the data, performed the analyses, and drafted the manuscript. KM proposed the research concept and assisted in drafting the manuscript. All authors contributed to the design of the research and interpretation of the data. All authors also contributed to the editing of the manuscript and provided final approval.
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Guinn, D., Madabushi, R., Wang, YM. et al. Communicating Immunogenicity-Associated Risk in Current U.S. FDA Prescription Drug Labeling: A Systematic Evaluation. Ther Innov Regul Sci 54, 1363–1371 (2020). https://doi.org/10.1007/s43441-020-00161-z
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DOI: https://doi.org/10.1007/s43441-020-00161-z