Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms—Workshop Report

Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R.; Buhse, Lucinda F.; Cecil, Todd L.; Keitel, Susanne; Kraemer, Johannes; Morris, John; Shah, Vinod P.; Stickelmeyer, Mary P.; Yomota, Chikako; Brown, Cynthia K.

doi:10.1007/s11095-014-1348-9

Cited by 21 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A biorelevant dissolution method, which by a definition suggested by the FIP is performed in aqueous media resembling the intraluminal environment the drug product passes through during administration, can also be clinically relevant. In contrast, a clinically relevant dissolution method can be performed in Bnon-biorelevant^dissolution media as long as the method and acceptance criteria are capable of confirming or predicting in vivo performance of the drug (20)(21)(22). Every drug product manufacturing process is subject to variability, and it is expected that a clinically relevant dissolution method is capable of discriminating if these variations have, or do not have, an impact on product in vivo performance.…”

Section: Clinically Relevant Specification Roadmapmentioning

confidence: 99%

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms

Hermans

Abend

Kesisoglou

et al. 2017

AAPS J

View full text Add to dashboard Cite

Abstract.This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.KEY WORDS: BCS; biowaivers; clinically relevant dissolution specifications; PBPK modeling; SUPAC.This article was developed with the support of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ, www.iqconsortium.org). IQ is a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader research and development community. PURPOSEThe purpose of this paper is to describe a roadmap for the development and leverage of clinically relevant dissolution specifications (CRS) for immediate release oral solid dosage forms of non-narrow therapeutic window drugs. There are three objectives for presenting this roadmap: (1) to describe multiple approaches for establishing clinical relevance for dissolution methodology, (2) to outline how to leverage clinically relevant dissolution methodology and specifications for the confirmation of the final drug product quality, and (3) to suggest recommendations on supporting scale-up and post-approval changes using the established CRS.Historically, dissolution specifications have been set by controlling the formulation and process within prec...

show abstract

Section: Clinically Relevant Specification Roadmapmentioning

confidence: 99%

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms

Hermans

Abend

Kesisoglou

et al. 2017

AAPS J

View full text Add to dashboard Cite

show abstract

“…The solid form from either undissolved or precipitated material should also be assessed as a change in polymorphic form can affect solubility and dissolution [37]. A number of excellent reports discuss the comparative features and applications of the wide variety of biorelevant dissolution technologies available [38,39]. Figure 3 illustrates an absorption modeling flow scheme, incorporating the in vitro absorption parameters, the available non-clinical pharmacokinetic data, and an in silico absorption model to derive clinical absorption parameters in the context of the planned clinical dose range.…”

Section: Absorption Modeling To Facilitate Delivery and Formulation Amentioning

confidence: 99%

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

2017

View full text Add to dashboard Cite

Abstract. This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

show abstract

“…Biorelevant dissolution testing is a topic of other scientific organizations as well. A report about the progress is available for a recent AAPS/FIP workshop in Bethesda, MD (26).…”

Section: Contract Research Oranizations Specialized In Ipdmentioning

confidence: 99%

Meeting Report: In Vivo Predictive Dissolution Conference

Krämer¹,

Stippler²

2015

Dissolution Technol.

View full text Add to dashboard Cite

Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms—Workshop Report

Cited by 21 publications

References 27 publications

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

Meeting Report: In Vivo Predictive Dissolution Conference

Contact Info

Product

Resources

About