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Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations

  • Meeting Report
  • Theme: Current and Novel Approaches towards Dissolution Profile Comparison Harmonization
  • Published:
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Abstract

This report summarizes podium presentations and breakout sessions from the second day of the 2019 M-CERSI workshop on In Vitro Dissolution Similarity Assessment in Support of Drug Product Quality: What, How, and When? Presenters from the U.S. Food and Drug Administration (FDA), Health Canada (HC), European Medicines Agency (EMA), Brazilian Health Surveillance Agency (ANVISA), and the pharmaceutical industry shared experiences/concerns with dissolution profile similarity assessment supporting minor/moderate Chemistry, Manufacturing and Control (CMC) changes. Members from regulatory agencies explained that dissolution profile similarity testing is only part of the overall assessment of the acceptability of the proposed changes; decisions are usually made based on aggregate weight of evidence. Scientific shortcomings of f2 were highlighted but no proposal on how to replace it was made. Controlling dissolution timepoint variability and application of pairwise batch-to-batch comparisons (PBC) of dissolution profiles caused considerable debate. Several industry participants suggested increased sample sizes to raise confidence in decision-making and to avoid PBC. They proposed identification of a single mathematical method with predefined acceptance criteria and suggested that dissolution timepoint selection should follow EMA and HC guidance. A majority of meeting attendees favored applying clinically relevant dissolution specifications (CRDS) and dissolution safe space to determine the impact of minor/moderate CMC changes as opposed to dissolution profile similarity assessment via statistical methods. Day 2 of the workshop highlighted the need and opportunities for global harmonization including variability, timepoint selection, role of CRDS, and statistical methods to address the ambiguity globally operating pharmaceutical companies are currently facing.

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Notes

  1. Unless it is absolutely necessary, the terms “requirements” (i.e., the “how”) and “criteria” (i.e., acceptance criteria) will be used interchangeably throughout the rest of this report recognizing that it is sometimes impossible to separate them.

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Acknowledgements

The authors of this report are infinitely grateful to Dr. James Polli and Ms. Ann Anonsen for their tremendous efforts in organizing this workshop. Furthermore, the authors express their gratitude to all presenters, BO facilitators, and scribes.

Funding

This work was supported in part by a Center of Excellence in Regulatory Science and Innovation (CERSI) grant to the University of Maryland from the US Food and Drug Administration (Grant: U01FD005946).

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences, Merck, 770 Sumneytown Pike, West Point, Pennsylvania, 19486, USA

    Andreas M. Abend

  2. Analytical Strategies and Operation, Bristol Myers Squibb Company, New Brunswick, New Jersey, 08903, USA

    Limin Zhang

  3. Biowaivers, Biocorrelation and Statistical Support, Global Research and Development, Apotex Inc, Toronto, Canada

    Emilija Fredro-Kumbaradzi

  4. Global Biostatistics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany

    Thomas Hoffelder

  5. Global Chemistry Manufacturing and Controls, Pfizer Worldwide Research & Development, Groton, Connecticut, USA

    Michael J. Cohen

  6. Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA

    Om Anand, Poonam Delvadia & Haritha Mandula

  7. Division of Bioequivalence I, Office of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA

    Zhen Zhang

  8. European Medicines Agency, Pharmaceutical Quality Office, 1083 HS, Amsterdam, Netherlands

    Evangelos Kotzagiorgis

  9. Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate, Health Products and Food Branch, Health Canada, Toronto, Canada

    Susan Lum

  10. Office of Medicine Quality, Anvisa, SIA, Special Area 57, Brasília, DF, Brazil

    Victor Gomes Pereira

  11. Global Quality Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

    Amy Barker

  12. Analytical Commercialization Technology, Merck, 770 Sumneytown Pike, West Point, Pennsylvania, 19486, USA

    David Lavrich

  13. DISSO GmbH, 66424, Homburg, Germany

    Johannes Kraemer

  14. Regulatory Affairs, Simulations Plus Inc., Lancaster, California, USA

    Sandra Sharp-Suarez

Authors
  1. Andreas M. Abend
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  2. Limin Zhang
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  11. Susan Lum
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  15. Johannes Kraemer
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  16. Sandra Sharp-Suarez
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Contributions

All authors contributed to the manuscript, commented on previous versions, read, and approved the final manuscript.

Corresponding author

Correspondence to Andreas M. Abend.

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The authors declare no competing interests.

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

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Guest Editors: Andreas Abend, Dorys Argelia Diaz, and Sandra Suarez Sharp

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Appendix

Appendix

Table I List of frequently used acronyms used throughout the report
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Abend, A.M., Zhang, L., Fredro-Kumbaradzi, E. et al. Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations. AAPS J 24, 50 (2022). https://doi.org/10.1208/s12248-022-00691-4

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