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AAPS J. 2018 Aug 27;20(6):93. doi: 10.1208/s12248-018-0252-3.

Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report.

Author information

1
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. Sandra.Suarez@fda.hhs.gov.
2
Pfizer Inc, Eastern Point Road, Groton, Connecticut, 06340, USA.
3
Pharmaceutical Sciences, Merck & Co., Inc., 770 Sumneytown Pike, West Point, Pennsylvania, 19486, USA.
4
Abbvie, Inc., 1 North Waukegan Road North, Chicago, Illinois, 60064, USA.
5
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.
6
Human Medicines Research and Development Support Division, Specialized Disciplines Department, European Medicines Agency - EMA, 30 Churchill Place, London, E14 5EU, UK.
7
Department of Efficacy and Safety 2, Medical Products Agency-MPA, Uppsala, Sweden.
8
Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
9
Pharmetheus, 752 37, Uppsala, Sweden.
10
Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Food and Drug Administration, Silver Spring, Maryland, USA.
11
Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey, 07936, USA.
12
Advanced Review with Electronic Data Promotion Group, Pharmaceuticals and Medical Devices Agency (PMDA), Tokyo, Japan.
13
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.

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.

KEYWORDS:

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

PMID:
30151612
DOI:
10.1208/s12248-018-0252-3

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