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Dissolution Testing in Drug Product Development: Workshop Summary Report

  • Meeting Report
  • Theme: Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development
  • Published:
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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.

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Notes

  1. The term PBAM applied to drug product quality is evolving. The terms PBAM and physiologically based biopharmaceutics modeling (PBBM) were used interchangeably in the subsequent manuscripts following the workshop and are part of the theme.

  2. At the time of the workshop, a director at the US FDA

Abbreviations

API:

Active pharmaceutical ingredient

AUC:

Area under curve

BA:

Bioavailability

BCS:

Biopharmaceutical Classification System

BE:

Bioequivalence

C max :

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 vitro–in vivo correlation

IVIVR:

In vitro–in 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

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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.

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences, Merck & Co., Inc., West Point, Pennsylvania, 19486, USA

    Andreas Abend, Jesse Kuiper, Andre Hermans & Pramod Kotwal

  2. Analytical Sciences and Development, GlaxoSmithKline, King of Prussia, Pennsylvania, 19406, USA

    David Curran

  3. Drug Product Science and Technology, Bristol Myers Squibb Company, New Brunswick, New Jersey, 08903, USA

    Xujin Lu & Limin Zhang

  4. Vertex Pharmaceuticals Inc., 50 Northern Ave., Boston, Massachusetts, 02210, USA

    Hanlin Li

  5. Worldwide Research and Development, Global Chemistry and Manufacturing Controls, Pfizer Inc., Eastern Point Road, Groton, Connecticut, 06340, USA

    Dorys A. Diaz & Michael J. Cohen

  6. United States Pharmacopeia, 12601 Twinbrook Parkway, Rockville, Maryland, 20852, USA

    Erika Stippler

  7. Department of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA

    German Drazer

  8. Analytical Development, Biogen Inc., Cambridge, Massachusetts, 02142, USA

    Yiqing Lin

  9. Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Kimberly Raines, Lawrence Yu & Sandra Suarez-Sharp

  10. Small Molecule Design & Development, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

    Carrie A. Coutant

  11. Takeda Pharmaceutical International, 35 Lansdowne Street, Cambridge, Massachusetts, 02139, USA

    Haiyan Grady

  12. Eurofins-PHAST GmbH, Kardinal-Wendel-Str. 16, 66424, Homburg, Saarland, Germany

    Johannes Krämer

  13. AstraZeneca Pharmaceuticals, One MedImmune Way, Gaithersburg, Maryland, 20878, USA

    Sarah Pope-Miksinski

Authors
  1. Andreas Abend
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  2. David Curran
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  3. Jesse Kuiper
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  4. Xujin Lu
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  5. Hanlin Li
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  6. Andre Hermans
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  7. Pramod Kotwal
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  8. Dorys A. Diaz
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  9. Michael J. Cohen
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  10. Limin Zhang
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  11. Erika Stippler
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  12. German Drazer
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  13. Yiqing Lin
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  14. Kimberly Raines
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  15. Lawrence Yu
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  16. Carrie A. Coutant
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  17. Haiyan Grady
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  18. Johannes Krämer
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  19. Sarah Pope-Miksinski
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  20. Sandra Suarez-Sharp
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Corresponding author

Correspondence to Andreas Abend.

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Conflict of Interest

The authors declare that they have no conflicts of interest.

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

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Abend, A., Curran, D., Kuiper, J. et al. Dissolution Testing in Drug Product Development: Workshop Summary Report. AAPS J 21, 21 (2019). https://doi.org/10.1208/s12248-018-0288-4

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  • DOI: https://doi.org/10.1208/s12248-018-0288-4

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