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

Abstract

The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design."

Understanding Pharmaceutical Quality by Design

“…Consequently, the lack of a well-defined QTPP has resulted in wasted time and valuable resources. A recent paper by Raw et al (12) illustrates the significance of defining the correct QTPP before conducting any development. Also, QbD examples exemplify the identification and use of QTPPs (20)(21)(22).…”

“…There is confusion among industry scientists, academicians, and regulators despite recent publications (10)(11)(12)(13). This paper is intended to describe the objectives of pharmaceutical QbD, detail its concept and elements, and explain implementation tools and studies.…”

An algorithm for the rational choice of a drug for the treatment of infections in rhinology. What should be preferred: a brand-name or generic antibiotic?

“…2) при изучении биоэквивалентности рассмат ривается действие разовых доз препаратов, при ре гулярном применении параметры фармакокинети ки, по крайней мере некоторых препаратов, могут существенно меняться [8];…”

A Report from the Pediatric Formulations Task Force: Perspectives on the State of Child-Friendly Oral Dosage Forms

“…Bioequivalence requires a statistical equivalence in the rate and extent of drug release available at the site of action. Drugs are considered to be therapeutically equivalent which are both pharmaceutically equivalent and bioequivalent (43).…”