For Generic and Branded Oral Solid Dosage Immediate Release (IR) formulations (BCS Class I and Class III drugs) by USFDA / EMEA approved In vitro methods – BCS based In vitro Biowaiver.
BCS based In vitro Biowaiver studies replace clinical BA-BE studies to classify the equivalence of two pharmaceutical products for approval. These studies were initially applied for scale up and post approval changes (SUPAC) of generic product, and later extended to approval of orally administered BCS class I (high solubility and high permeability) and class III (high solubility and low permeability) IR formulations.
BCS based In vitro Biowaiver studies involve characterizing comparative dissolution of Test and Innovator formulation, and solubility, gastrointestinal (GI) stability, and Caco-2 permeability of active pharmaceutical ingredient (API).
A drug product (BCS class I) is considered rapidly dissolving when more than 85% of the labelled amount of drug substance dissolves within 30 minutes in three different media (pH 1.2, 4.5 and 6.8) in a paddle (50 rpm) or basket (100 rpm) apparatus at 37 °C in a volume of 900 mL.
A drug product (BCS class III) is considered ultra-rapidly dissolving when more than 85% of the labelled amount of drug substance dissolves within 15 minutes in three different media (pH 1.2, 4.5 and 6.8) in a paddle (50 rpm) or basket (100 rpm) apparatus at 37 °C in a volume of 900 mL.
The aqueous solubility of the drug is considered to be high when the highest single unit dose is completely soluble in 250 mL or less of aqueous solution at pH 1.2, 4.5 and 6.8 or 7.5 and 37 °C.
A drug substance is considered highly permeable when extent of absorption in humans is determined to be more than 85% of an administered dose, based on a mass balance determination or in comparison to an intravenous reference dose, in the absence of evidence suggesting instability in the gastrointestinal tract. Intestinal permeability is assessed by validated in vitro permeability models such as Caco-2.