Abstract
This report summarizes relevant insights and discussions from a 2022 FDA public workshop titled Best Practices for Utilizing Modeling Approaches to Support Generic Product Development which illustrated how model-integrated evidence has been used and can be leveraged further to inform generic drug product development and regulatory decisions during the assessment of generic drug applications submitted to the FDA. The workshop attendees discussed that model-integrated evidence (MIE) approaches for generics are being applied in the space of long-acting injectable (LAI) products to develop shorter and more cost-effective alternative study designs for LAI products. Modeling and simulation approaches are utilized to support virtual BE assessments at the site of action for locally acting drug products and to assess the impact of food on BE assessments for oral dosage forms. The factors contributing to the success of the model-informed drug development program under PDUFA VI were discussed. The generic drug industry shared that decisions on formulation candidate/formulation variant selection, on pilot in vivo bioavailability studies, and on alternative study designs for BE assessment are informed by modeling and simulation approaches. There was agreement that interactions between the regulatory agencies and the industry are desirable because they improve the industry’s understanding of scientific and other regulatory considerations on implementing modeling and simulation approaches in drug development and regulatory submissions.
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Acknowledgements
The authors thank Drs. Sameersingh Raney (FDA), James Polli (CRCG), Anna Schwendeman (CRCG), Vishalakshi Krishnan (CRCG), Ms. Dana Hammell (CRCG), and Ms. Jennifer Dick (CRCG), for helping organize the workshop. We would also like to thank all speakers and panelists who participated in the workshop. We would also like to thank Pradeep Bhadauri (Cipla, Ltd) who participated in the workshop as panelist.
Funding
This workshop was supported by the Food and Drug Administration (FDA) of the US Department of Health and Human Services (HHS) as part of a financial assistance award U18FD007054 totaling $1,000,000 with 100 percent funded by FDA/HHS.
Others’ work reported in this article is not funded or sponsored.
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E.T., L.F., Y.B., M. V.D. H., T. A., Y. C. T., R. L., A. R-H., L. Z. wrote and reviewed the manuscript.
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The opinions expressed in the manuscript are those of the authors and should not be interpreted as the position of their organizations/employers. The contents of the manuscript are those of the authors and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the US Government.
Conflict of Interest
TA is employee of Dr. Reddy’s Laboratories Ltd. and reports no conflicts interest. TA alone is responsible for the content and writing of this article.
ARH was co-founder of a PBPK Modelling and Simulation tool that is commercially distributed by Certara Inc and is part-time employee and shareholder of that company.
All other authors declared no competing interests for this work.
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Communicated by Fang Wu and Liang Zhao.
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Tsakalozou, E., Fang, L., Bi, Y. et al. Experience Learned and Perspectives on Using Model-Integrated Evidence in the Regulatory Context for Generic Drug Products—a Meeting Report. AAPS J 26, 14 (2024). https://doi.org/10.1208/s12248-023-00884-5
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DOI: https://doi.org/10.1208/s12248-023-00884-5