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James Polli

James Polli, Ph.D., is a professor at the University of Maryland School of Pharmacy.

In vitro in vivo correlation analysis (IVIVC) concerns predicting a drug’s pharmacokinetic performance from in vitro dissolution results. During product development, a drug’s rate and extent of absorption is very important, since these factors directly impact drug safety and efficacy. A complicating factor is that a tablet or capsule’s composition and manufacturing often changes during the course of drug development, which can impact clinical trial results. Unfortunately, relying on human bioequivalence (BE) testing to check each and every formulation change is time-consuming and costly. Hence, an in vitro dissolution test that predicts a drug’s pharmacokinetic performance is valuable.

Interestingly, most pharmaceutical companies don’t produce an IVIVC early enough to be of use in development, instead doing so later in the process, for identification of dissolution specifications of the to-be-marketed product. Such late development IVIVC studies are often conducted with a focus on performing IVIVC analysis. Such studies are critical, and point toward the value of product understanding.

Some experts, myself included, believe that there are many lost opportunities to generate data during routine clinical drug development (e.g., first-in-man drug-drug interaction and early bioavailability studies) before late development. Other companies leverage these studies that must be done in earlier development and, thus, benefit in late development. Even so, many companies do not feel comfortable using such data for IVIVC, as it was mainly generated for a different purpose, or at least they are not used to applying such data towards IVIVC analysis. Of perhaps more importance, some companies find it most expedient to perform the familiar bridging BE test to move a drug project forward rather than to consider IVIVC analysis during development.

Collectively, many such bridging BE studies are conducted, with lost opportunity to learn more about formulation in early development, including opportunity to develop an optimal in vitro dissolution method. Such a reliance on BE studies inhibits a more direct focus on product understanding through IVIVC analysis.

The 2011 AAPS workshop Facilitating Oral Product Development and Reducing Regulatory Burden through Novel Approaches to Assess Bioavailability/Bioequivalence and, emanating from it, a subsequent theme issue in The AAPS Journal have focused on best practices in oral drug product development, as well as evolving BE approaches.

A video description of workshop outcomes is also available.

Do you feel that there is a need for the scientific and regulatory community to harmonize on newer (BE) methodologies?