Meeting Report: In Vivo Predictive Dissolution Conference

Abstract

This report details discussions held over three days, August 4–6, 2014, in Ann Arbor, MI, on current research on in vivo predictive dissolution (IPD) testing. Participants hailed from academia, industry, and governmental bodies, and focused their attention on the role of IPD in various drug products. Academia was well represented at this conference with speakers mainly from the University of Michigan, but also from Europe and Japan. Their approach for development of IPD is mainly based on solubility characteristics of the drug substance. A great deal of attention was drawn to the composition and mechanical properties of dissolution media. Examples presented by speakers from the pharmaceutical industry showed how the findings from academia are implemented in their method development processes. FDA strongly supports the implementation of new approaches to improve the predictive power of dissolution testing. For decades, the pharmaceutical scientific community has been debating whether to separate or consolidate the dissolution testing methodologies used in different stages, from development to market supply, of a drug product lifecycle. Moreover, regulatory authorities are consistently challenged to accelerate their decisions on ascertaining bioequivalence (BE) of pharmaceutical drug products (within one product or from product to product). The proof of bioavailability (BA) requires human studies. In vivo predictive dissolution (IPD) testing may reduce the number of BA studies required and could help to speed up marketing authorization and the total time-to-market process for industry. More than 100 scientists from the United States, Europe, and Japan gathered for three days in Ann Arbor, Michigan, in early August 2014 to develop a white paper that was to serve as an important contribution to the field of in vivo predictive dissolution. U.S. regulatory authorities stimulated the discussions and were ready to consider novel methodologies in their decision-making process. This report summarizes the scientific presentations given at the conference by experts from pharmacopeias, regulatory authorities, academia, and industry around the globe. This report does not discuss a summary of the white paper, since this document will be published separately (1). USP—WHERE DISSOLUTION METHODOLOGY IS STANDARDIZED Erika Stippler (United States Pharmacopeial Convention, USPC) provided a frequency distribution of the dissolution apparatus stipulated in drug product monographs of the current United States Pharmacopeia (USP). The majority of the dissolution methods approved by regulatory authorities in the United States were developed using the compendial paddle or basket apparatus. USP dissolution methods and specifications are the same as those approved by the FDA, and USP General Chapter Dissolution describes the commonly used apparatus for dissolution testing of oral drug products. In the current USP, there are several chapters that are relevant for dissolution/ drug release testing for various dosage forms. The use of a particular dissolution apparatus depends on the specifics of the drug substance and the dosage form under investigation. A survey of all drug product monographs shows that the most commonly used dissolution apparatus is Apparatus 2, followed by Apparatus 1. Additionally, there are drug product monographs that call for the use of modified compendial apparatus (i.e., alternative basket mesh size, peak vessel, or noncompendial apparatus such as the device termed the reciprocating shaker or tube rotator). For the submission of an abbreviated new drug application (ANDA), the appropriate USP method should be used. If no such method is available, the recently revised USP General Chapter The Dissolution Procedure: Development and Validation may provide guidance for the development and validation of a suitable method (2). GREAT INCREASE OF SCIENTIFIC KNOWHOW AND DEMAND AT FDA FDA Office of Pharmaceutical Science Lawrence Yu defined his understanding of the roles of dissolution testing for new and generic drug products to be twofold: • Quality control tool for the evaluation of batch-to-batch consistency. • Surrogate for in vivo performance. The quality standard is a specification established through the clinical performance of the drug product, thus connecting the standard to safety and efficacy; therefore, the quality standard should not be established based on dx.doi.org/10.14227/DT220215P66 e-mail: ceo-phast@phast.com *Corresponding author.