Equivalence-by-Design: Targeting In Vivo Drug Delivery Profile

Abstract

In the United States (U.S.), drug products are considered therapeutically equivalent if they meet regulatory criteria of pharmaceutical equivalence and bioequivalence. These requirements can be traced back to 1977 when the U.S. Food and Drug Administration (FDA) published the regulations on bioavailability and bioequivalence. Over the years, to keep up with the advancement in science and technology, the FDA has been constantly updating the regulatory approaches to assessing and ensuring equivalence. In view of the recent growth in novel pharmaceutical dosage forms and delivery systems, this paper examines the current framework for documentation of therapeutic equivalence and explores the opportunities of further advancing equivalence methods for complex drug products. It is proposed that equivalence may be established by matching the in vivo drug delivery profile (iDDP) between drug products in comparison. This can be achieved by characterizing the iDDP of the reference formulation with application of an equivalence-by-design approach for pharmaceutical development. Critical variables can be identified to serve as in vitro markers or biomarkers for mapping the desired drug delivery profile in vivo. A multidisciplinary approach may be necessary to develop these markers for characterization of iDDPs.

Pharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products

“…In this context, based upon an understanding of the RLD and its in-vivo delivery profile (iDDP) (20), the QTPP serves as an element to Pharmaceutical Equivalence by Design for Generic Drugs facilitate the understanding of critical targeted formulation attributes that may be needed to successfully design a drug product bioequivalent to the RLD. First, by taking into consideration that the PPI is acid labile through pH 3-4 and given the in-vitro release profile for the RLD is indicative of an enteric coating designed to protect the active ingredient from degradation up through pH 4.5, a plausible QTPP target would guide the design of generic product prototypes with an enteric coat having similar integrity and providing a similar degree of protection against acid degradation as the RLD.…”