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The AAPS Journal

, 20:93 | Cite as

Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report

  • Sandra Suarez-SharpEmail author
  • Michael Cohen
  • Filippos Kesisoglou
  • Andreas Abend
  • Patrick Marroum
  • Poonam Delvadia
  • Evangelos Kotzagiorgis
  • Min Li
  • Anna Nordmark
  • Nagesh Bandi
  • Erik Sjögren
  • Andrew Babiskin
  • Tycho Heimbach
  • Shinichi Kijima
  • Haritha Mandula
  • Kimberly Raines
  • Paul Seo
  • Xinyuan Zhang
Meeting Report Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development
Part of the following topical collections:
  1. Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development

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.

KEY WORDS

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

Notes

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Disclaimer

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

Supplementary material

12248_2018_252_MOESM1_ESM.doc (120 kb)
ESM 1 (DOC 120 kb)

References

  1. 1.
    Abend A, Heimbach T, Cohen M, Kesisoglou F, Pepin X, Suarez-Sharp S. Dissolution ad translational modeling strategies enabling patient-centric drug product development: M-CERSI workshop summary report. AAPS J. 2018;20:60.CrossRefGoogle Scholar
  2. 2.
    Dissolution testing in drug product development: summary of day 1 from the 2017 dissolution and translational modeling workshop at the M-CERSI. In preparation.Google Scholar
  3. 3.
    Dissolution and translational modeling strategies enabling patient-centric drug product development, M-CERSI Workshop Summary—establishing in vitro in vivo link using PBPK absorption modeling. In preparation.Google Scholar
  4. 4.
    Kotzagiorgis E, Framework of setting clinically relevant specifications: approach, information needed, and criteria, in dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  5. 5.
    European Medicines Agency, Reflection paper on the dissolution specification for generic solid oral immediate release products with systemic action. (EMA/CHMP/CVMP/QWP/336031/2017). 2017.Google Scholar
  6. 6.
    European Medicines Agency, Guideline on the Qualification and Reporting of Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulation. (EMA/CHMP/458101/2016). 2016.Google Scholar
  7. 7.
    Nordmark A, EMA draft Guideline on the Qualification and Reporting of Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulation, in Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development. 2017: Baltimore.Google Scholar
  8. 8.
    Abend A, Framework for setting clinically relevant dissolution specifications, in Dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  9. 9.
    Hermans A, Abend AM, Kesisoglou F, Flanagan T, Cohen MJ, Diaz DA, et al. Approaches for establishing clinically relevant dissolution specifications for immediate release solid oral dosage forms. AAPS J. 2017;19(6):1537–49.CrossRefGoogle Scholar
  10. 10.
    Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–83.CrossRefGoogle Scholar
  11. 11.
    U.S. Department of Health and Human Services - Food and Drug Administration, CDER, Guidance for industry—waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification, 2017.Google Scholar
  12. 12.
    European Medicine Agency (EMA), Guideline on the investigation of bioequivalence, 2010.Google Scholar
  13. 13.
    Suarez-Sharp S. In Case studies: models for establishing clinically relevant drug specifications. Washington, DC: AAPS Annual Meeting and Exposition; 2011.Google Scholar
  14. 14.
    Suarez-Sharp S. In Establishing clinically relevant drug specifications: FDA perspective. Chicago: AAPS Annual Meeting and Exposition; 2012.Google Scholar
  15. 15.
    Dickinson PA, Lee WW, Stott PW, Townsend AI, Smart JP, Ghahramani P, et al. Clinical relevance of dissolution testing in quality by design. AAPS J. 2008;10(2):380–90.CrossRefGoogle Scholar
  16. 16.
    Suarez-Sharp S, Li M, Duan J, Shah H, Seo P. Regulatory experience with In vivo-in vitro correlations (IVIVC) in new drug applications. AAPS J. 2016;18(6):1379–90.CrossRefGoogle Scholar
  17. 17.
    U.S. Department of Health and Human Services - Food and Drug Administration; CDER, Guidance for industry—immediate release solid oral dosage forms: scale-up and post-approval changes: chemistry, manufacturing, and controls; in vitro dissolution testing and in vivo bioequivalence documentation. 1995.Google Scholar
  18. 18.
    Suarez-Sharp S. Paving the road towards setting clinically relevant specifications: biopharmaceutics perspectives on information needed, approach, and criteria, in Dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  19. 19.
    U.S. Department of Health and Human Services - Food and Drug Administration, CDER., Guidance for industry–dissolution testing of immediate release solid oral dosage forms. 1997.Google Scholar
  20. 20.
    Suarez-Sharp S. In FDA experience on the application of modeling and simulation in setting clinically relevant drug specifications. Rockville: 3rd PQRI/FDA Conference on Advancing Product Quality; 2017.Google Scholar
  21. 21.
    Cohen M. The Role of Bio-predictive dissolution methods in the selection of CMAs, CPPS, and verification of design space (s): case studies, in dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  22. 22.
    U.S. Department of Health and Human Services - Food and Drug Administration, CDER., Guidance for industry—extended release oral dosage forms: development, evaluation, and application of in vitro/in vivo correlations. 1997.Google Scholar
  23. 23.
    U.S. Department of Health and Human Services - Food and Drug Administration, CDER, Guidance for industry—dissolution testing and specification criteria for immediate-release solid oral dosage forms containing biopharmaceutics classification system class 1 and 3 drugs. 2015. Draft Guidance.Google Scholar
  24. 24.
    Luzon E, Blake K, Cole S, Nordmark A, Versantvoort C, Berglund EG. Physiologically based pharmacokinetic modeling in regulatory decision-making at the European medicines agency. Pharmacol Ther. 2017;102(1):98–105.CrossRefGoogle Scholar
  25. 25.
    Li M, Zhao P, Pan Y, Wagner C. Predictive performance of physiologically based pharmacokinetic models for the effect of food on oral drug absorption: current status. CPT: Pharmacometrics & Systems Pharmacology. 2017;7(2):82–9.CrossRefGoogle Scholar
  26. 26.
    Kesisoglou F. The Utility of on level C IVIVC for setting clinically relevant specifications: case studies and implications, in Dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  27. 27.
    Kesisoglou F, Rossenu S, Farrell C, van den Heuvel M, Prohn M, Fitzpatrick S, et al. Development of in vitroin vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers. J Pharm Sci. 2014;103(11):3713–23.CrossRefGoogle Scholar
  28. 28.
    Kesisoglou F, Hermans A, Neu C, Yee KL, Palcza J, Miller J. Development of in vitroin vivo correlation for amorphous solid dispersion immediate-release suvorexant tablets and application to clinically relevant dissolution specifications and in-process controls. J Pharm Sci. 2015;104(9):2913–22.CrossRefGoogle Scholar
  29. 29.
    Davit B. Case study: use of in vivo pharmacokinetic data to develop a CRS for in vitro dissolution testing, in dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore.Google Scholar
  30. 30.
    Marroum P. Establishing clinically relevant specifications during product life cycle: case studies in dissolution and translational modeling strategies enabling patient-centric product development. 2017: Baltimore, MD.Google Scholar
  31. 31.
    Marroum P. Clinically relevant dissolution methods and specifications. American Pharmaceutical Reviews. 2012;15(1):36–41.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Sandra Suarez-Sharp
    • 1
    Email author
  • Michael Cohen
    • 2
  • Filippos Kesisoglou
    • 3
  • Andreas Abend
    • 3
  • Patrick Marroum
    • 4
  • Poonam Delvadia
    • 1
  • Evangelos Kotzagiorgis
    • 5
  • Min Li
    • 1
  • Anna Nordmark
    • 6
  • Nagesh Bandi
    • 3
  • Erik Sjögren
    • 7
    • 8
  • Andrew Babiskin
    • 9
  • Tycho Heimbach
    • 10
  • Shinichi Kijima
    • 11
  • Haritha Mandula
    • 1
  • Kimberly Raines
    • 1
  • Paul Seo
    • 1
  • Xinyuan Zhang
    • 12
  1. 1.Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical QualityCenter for Drug Evaluation and Research, Food and Drug AdministrationSilver SpringUSA
  2. 2.Pfizer IncGrotonUSA
  3. 3.Pharmaceutical SciencesMerck & Co., Inc.West PointUSA
  4. 4.Abbvie, Inc.ChicagoUSA
  5. 5.Human Medicines Research and Development Support Division, Specialized Disciplines DepartmentEuropean Medicines Agency - EMALondonUK
  6. 6.Department of Efficacy and Safety 2Medical Products Agency-MPAUppsalaSweden
  7. 7.Department of PharmacyUppsala UniversityUppsalaSweden
  8. 8.PharmetheusUppsalaSweden
  9. 9.Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic DrugsFood and Drug AdministrationSilver SpringUSA
  10. 10.Novartis Pharmaceuticals CorporationOne Health PlazaEast HanoverUSA
  11. 11.Advanced Review with Electronic Data Promotion GroupPharmaceuticals and Medical Devices Agency (PMDA)TokyoJapan
  12. 12.Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA

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