Advertisement

The AAPS Journal

, 21:21 | Cite as

Dissolution Testing in Drug Product Development: Workshop Summary Report

  • Andreas AbendEmail author
  • David Curran
  • Jesse Kuiper
  • Xujin Lu
  • Hanlin Li
  • Andre Hermans
  • Pramod Kotwal
  • Dorys A. Diaz
  • Michael J. Cohen
  • Limin Zhang
  • Erika Stippler
  • German Drazer
  • Yiqing Lin
  • Kimberly Raines
  • Lawrence Yu
  • Carrie A. Coutant
  • Haiyan Grady
  • Johannes Krämer
  • Sarah Pope-Miksinski
  • Sandra Suarez-Sharp
Meeting Report Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development
  • 235 Downloads
Part of the following topical collections:
  1. Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development

Abstract

This publication summarizes the proceedings and key outcomes of the first day (“Day 1”) of the 3-day workshop on “Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development.” The overall aims of the workshop were to foster a productive dialog between industry and regulatory agencies and to discuss current strategies toward the development and implementation of clinically relevant dissolution specifications as an integral part of enhanced drug product understanding and effective drug product life-cycle management. The Day 1 podium presentations covered existing challenges and concerns for implementing highly valuable, yet often unique and novel experimental dissolution setups as quality control tools. In addition, several podium presentations highlighted opportunities to replace conventional dissolution testing with surrogate test methods to enable robust drug product and process understanding within the context of quality by design (QbD), new manufacturing technologies, and real-time release testing (RTRT). The topics covered on Day 1 laid the foundation for subsequent discussions which focused on the challenges related to establishing an in vitro–in vivo link and approaches for establishing clinically relevant drug product specifications which are becoming an expectation in regulatory submissions. Clarification of dissolution-related terminology used inconsistently among the scientific community, and the purpose of various testing approaches were key discussion topics of the Day 1 breakout sessions. The outcome of these discussions along with creative ways to overcome challenges related to bridging “exploratory dissolution approaches” with methods suitable for end-product control testing are captured within this report.

KEY WORDS

biorelevant biopredictive clinically relevant dissolution discriminating power surrogate for dissolution 

Abbreviations

API

Active pharmaceutical ingredient

AUC

Area under curve

BA

Bioavailability

BCS

Biopharmaceutical Classification System

BE

Bioequivalence

Cmax

Maximum concentration

cGMP

Current good manufacturing practices

CMA

Critical materials attribute

CPP

Critical process parameter

CQA

Critical quality attribute

CRDPS

Clinically relevant drug products specification(s)

CSOP

Engineering Research Center for Structured Organic Particulate Systems at the New Jersey State University at Rutgers, NJ

EMA

European Medicines Agency

ER

Extended release

FDA

Food and Drug Administration

ICH

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use

IQ

International Consortium for Innovation & Quality in Pharmaceutical Development

IR

Immediate release

IVIVC

In vitroin vivo correlation

IVIVR

In vitroin vivo relationship

M-CERSI

Maryland-Center for Excellence in Regulatory Sciences and Innovation

M&S

Modeling and simulation

NIR

Near infrared

SUPAC

Scale-up and postapproval changes

PAT

Process analytical techniques

PBPK model

Physiologically based pharmacokinetic model

PBAM

Physiologically based absorption model

PCA

Principal component analysis

PK

Pharmacokinetic

PLS

Partial least square

PSD

Particle size distribution

QC

Quality control

QbD

Quality by design

QRA

Quality risk assessment

RTRT

Real-time release testing

RTQA

Real-time quality analysis

TPP

Target product profile

USP

United States Pharmacopeia

Notes

Acknowledgments

The meeting organizers are indefinitely grateful to Drs. James Polli (University of Maryland, School of Pharmacy, Baltimore, MD) and Ms. Ann Anonson (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.

Supplementary material

12248_2018_288_MOESM1_ESM.docx (38 kb)
ESM 1 (DOCX 37 kb)

References

  1. 1.
    Abend A, Heimbach T, Cohen M, Kesisoglou F, Pepin X, Suarez-Sharp S. Dissolution and translational modeling strategies enabling patient-centric drug product development: the M-CERSI workshop summary report. 2018. p 60.Google Scholar
  2. 2.
    Heimbach T, Kesisoglou F, Suarez S, Kakhi M, Nico Holmstock N, Olivares-Morales A, et al. 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. AAPS J. submitted.Google Scholar
  3. 3.
    Suarez-Sharp S, Cohen M, Kesisoglou F, Abend A, Marroum P, Delvadia P, et al. Applications of clinically relevant dissolution testing: workshop summary report. AAPS J. 2018;20(6):93.CrossRefGoogle Scholar
  4. 4.
    Dokoumetzidis A, Macheras P. A century of dissolution research: from Noyes and Whitney to the Biopharmaceutics Classification System. Int J Pharm. 2006;321(1):1–11.CrossRefGoogle Scholar
  5. 5.
    United States Pharmacopeia and the National Formulary (USP-NF). Chapter <711> Dissolution. Rockville: US Pharmacopeial Convention; 2015.Google Scholar
  6. 6.
    Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25:781–91.CrossRefGoogle Scholar
  7. 7.
    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
  8. 8.
    Koenigsknecht MJ, Baker JR, Wen B, Frances A, Zhang H, Yu A, et al. In vivo dissolution and systemic absorption of immediate release ibuprofen in human gastrointestinal tract under fed and fasted conditions. Mol Pharm. 2017;14(12):4295–304.CrossRefGoogle Scholar
  9. 9.
    U.S. Department of Health and Human Services - Food and Drug Administration; Center for Drug Evaluation and Research (CDER). Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System—guidance for industry. Silver Spring: FDA; 2017.Google Scholar
  10. 10.
    Miksinski SP. Clinical relevance—seeing the big picture. In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  11. 11.
    Miksinski SP. New drug applications: the evolution of quality review. In 2nd FDA/PQRI conference on advancing product quality, Bethesda, MD. 2015.Google Scholar
  12. 12.
    Ju R, Grady H. Industry perspective on the current status and future of dissolution testing for product development and quality control. In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  13. 13.
    Mann J, Dressman J, Rosenblatt K, Ashworth L, Muenster U, Frank K, et al. Validation of dissolution testing with biorelevant media: an OrBiTo study. Mol Pharm. 2017;14(12):4192–201.CrossRefGoogle Scholar
  14. 14.
    Kuiper J, Coutant C. Use of bio-predictive methods during early formulation screening with case studies. In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  15. 15.
    Sugano K, Okazaki A, Sugimoto S, Tavornvipas S, Omura A, Mano T. Solubility and dissolution profile assessment in drug delivery. Drug Metab Pharmacokinet. 2007;22(4):225–54.CrossRefGoogle Scholar
  16. 16.
    Kuiper J, Harmon P. Dissolution rate limiting AUC: simple methodology for measuring dissolution rate of the entire dose in biorelevant media. In AAPS annual meeting, San Diego, CA, USA. 2014.Google Scholar
  17. 17.
    Psachoulias D, Vertzoni M, Goumas K, Kalioras V, Beato S, Butler J, et al. Precipitation in and supersaturation of contents of the upper small intestine after administration of two weak bases to fasted adults. Pharm Res. 2011;28:3145–58.CrossRefGoogle Scholar
  18. 18.
    Bhattachar SN, Perkins EJ, Tan JS, Burns LJ. Effect of gastric pH on the pharmacokinetics of a bcs class II compound in dogs: utilization of an artificial stomach and duodenum dissolution model and gastroplus simulations to predict absorption. J Pharm Sci. 2011;100(11):4756–65.CrossRefGoogle Scholar
  19. 19.
    Lu X, Han J-H, Mattocks D. Dissolution methodologies from biorelevant to quality control: challenges and gaps. In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  20. 20.
    Wang Q, Fotaki N, Mao Y. Biorelevant dissolution: methodology and application in drug development. Diss Technol. 2009;16(3).Google Scholar
  21. 21.
    Blanquet SP, Zeijdner E, Beyssac E, Meunier J-P, Denis S, Havenaar R, et al. A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions. Pharm Res. 2004;21:585–91.CrossRefGoogle Scholar
  22. 22.
    Zhang L, Hermans A. The use of surrogates for dissolution testing for IR formulations: when is it feasible?. In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  23. 23.
    International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH). ICH Harmonized Tripartite Guideline: Specifications: Test Procedures and Acceptance Criteria for new Drug Substances and new Drug Products: Chemical Substances, Q6A,. In 1999.Google Scholar
  24. 24.
    Drazer G, Pawar P, Wang Y, Keyvan G, Callegari G, Cuitino A, Muzzio F. Enabling real time release testing (RTRt) with NIR-based prediction of dissolution for tablets made by continuous direct compression (CDC). In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD. 2017.Google Scholar
  25. 25.
    Pawar P, Wang Y, Keyvan G, Callegari G, Cuitino A, Muzzio F. Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC). Int J Pharm. 2016;512(1):96–107.CrossRefGoogle Scholar
  26. 26.
    Li H, Prichard J, Swinney KA. Dissolution modeling for real time release testing (RTRT). In Dissolution and translational modeling strategies enabling patient-centric product development, Baltimore, MD 2017.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Andreas Abend
    • 1
    Email author
  • David Curran
    • 2
  • Jesse Kuiper
    • 1
  • Xujin Lu
    • 3
  • Hanlin Li
    • 4
  • Andre Hermans
    • 1
  • Pramod Kotwal
    • 1
  • Dorys A. Diaz
    • 5
  • Michael J. Cohen
    • 5
  • Limin Zhang
    • 3
  • Erika Stippler
    • 6
  • German Drazer
    • 7
  • Yiqing Lin
    • 8
  • Kimberly Raines
    • 9
  • Lawrence Yu
    • 9
  • Carrie A. Coutant
    • 10
  • Haiyan Grady
    • 11
  • Johannes Krämer
    • 12
  • Sarah Pope-Miksinski
    • 13
  • Sandra Suarez-Sharp
    • 9
  1. 1.Pharmaceutical SciencesMerck & Co., Inc.West PointUSA
  2. 2.Analytical Sciences and DevelopmentGlaxoSmithKlineKing of PrussiaUSA
  3. 3.Drug Product Science and TechnologyBristol Myers Squibb CompanyNew BrunswickUSA
  4. 4.Vertex Pharmaceuticals Inc.BostonUSA
  5. 5.Worldwide Research and Development, Global Chemistry and Manufacturing ControlsPfizer Inc.GrotonUSA
  6. 6.United States PharmacopeiaRockvilleUSA
  7. 7.Department of Mechanical and Aerospace EngineeringRutgers, The State University of New JerseyNew BrunswickUSA
  8. 8.Analytical DevelopmentBiogen Inc.CambridgeUSA
  9. 9.Office of Pharmaceutical Quality, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  10. 10.Small Molecule Design & DevelopmentEli Lilly & Co., Lilly Corporate CenterIndianapolisUSA
  11. 11.Takeda Pharmaceutical InternationalCambridgeUSA
  12. 12.Eurofins-PHAST GmbHHomburgGermany
  13. 13.AstraZeneca PharmaceuticalsGaithersburgUSA

Personalised recommendations