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Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report

Abstract

This publication summarizes the proceedings of day 3 of a 3-day workshop on “Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development.” Specifically, this publication discusses the current approaches in building clinical relevance into drug product development for solid oral dosage forms, along with challenges that both industry and regulatory agencies are facing in setting clinically relevant drug product specifications (CRDPS) as presented at the workshop. The concept of clinical relevance is a multidisciplinary effort which implies an understanding of the relationship between the critical quality attributes (CQAs) and their impact on predetermined clinical outcomes. Developing this level of understanding, in many cases, requires introducing deliberate but meaningful variations into the critical material attributes (CMAs) and critical process parameters (CPPs) to establish a relationship between the resulting in vitro dissolution/release profiles and in vivo PK performance, a surrogate for clinical outcomes. Alternatively, with the intention of improving the efficiency of the drug product development process by limiting the burden of conducting in vivo studies, this understanding can be either built, or at least enhanced, through in silico efforts, such as IVIVC and physiologically based pharmacokinetic (PBPK) absorption modeling and simulation (M&S). These approaches enable dissolution testing to establish safe boundaries and reject drug product batches falling outside of the established safe range (e.g., due to inadequate in vivo performance) enabling the method to become clinically relevant. Ultimately, these efforts contribute towards patient-centric drug product development and allow regulatory flexibility throughout the lifecycle of the drug product.

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Notes

  1. The agenda and power point presentations can be found at the following link: http://pharmacy.umaryland.edu/centers/cersievents/dissolution-and-translational-modeling-strategies/

  2. The terms physiologically based absorption M&S (PBAM) and physiologically based biopharmaceutics (PBBP) M&S are used interchangeable for the purpose of this publication.

  3. Note that for the purpose of this summary and to distinguish from Dr. Abend’s summary, the approaches referred in the past by this author as 1, 2, and 3 have been renamed as A, B, and C1/C2.

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Acknowledgements

The meeting organizers are indefinitely grateful to Drs. James Polli (University of Maryland, School of Pharmacy, Baltimore, MD) and Tzuchi (Rob) Ju (AbbVie, Inc.) and Ms. Ann Anonsen (UM) for their tremendous efforts in helping in the organization of this workshop.

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Correspondence to Sandra Suarez-Sharp.

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The authors declare that they have no conflicts of interest.

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This publication reflects the views of the authors and should not be construed to represent their organizations’ views or policies.

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Guest Editors: Marilyn N. Martinez, Sandra Suarez, and Andreas Abend

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Suarez-Sharp, S., Cohen, M., Kesisoglou, F. et al. Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report. AAPS J 20, 93 (2018). https://doi.org/10.1208/s12248-018-0252-3

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KEY WORDS

  • clinically relevant specifications
  • dissolution
  • IVIVC/IVIVR
  • PBPK absorption modeling and simulation
  • safe space