BEBAC   Ing. Helmut Schütz

US – FDA

Dissolution Testing and Specification Criteria for IR Solid Oral Dosage Forms Containing BCS Class 1 and 3 Drugs

On 1 August 2015 the FDA’s Center for Drug Evaluation and Research (CDER) published the draft Guidance for Industry

Drug absorption from a solid dosage form after oral administration depends on the release of the drug substance from the drug product, the dissolution or solubilization of the drug under physiological conditions, and the permeation across the gastrointestinal membrane. NDAs and ANDAs submitted to FDA contain bioavailability (BA) or bioequivalence (BE) data and in vitro dissolution data that, together with chemistry, manufacturing, and controls (CMC) data, characterize the quality and performance of the drug product. In vitro dissolution data are generally obtained from batches that have been used in pivotal clinical and/or bioavailability/bioequivalence studies, and from other human studies conducted during product development. Knowledge about the solubility, permeability, dissolution, and pharmacokinetics of a drug product is considered when defining dissolution test specifications for the drug approval process.

The BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. The definitions of high and low solubility and high and low permeability are used as described in the Biopharmaceutics Classification System (BCS) Guidance. The different classifications are:

  1. High Solubility – High Permeability Drugs
  2. Low Solubility – High Permeability Drug
  3. High Solubility – Low Permeability Drugs
  4. Low Solubility – Low Permeability Drugs

This classification can be used as a basis for determining when in vivo BA and BE studies are needed and can be used to determine when a successful in vitro-in vivo correlation (IVIVC) is likely. The BCS suggests that, for certain high solubility drugs, dissolution testing can be standardized. Owing to their high solubility, BCS class 1 and 3 drugs are considered to be relatively low risk regarding the impact of dissolution on performance, provided the in vitro performance meets or exceeds the recommendations discussed herein.

This guidance establishes standard dissolution methodology and specifications that are appropriate for BCS class 1 and class 3 drugs in IR dosage form. The availability of these standards will facilitate the rapid development of dissolution methodology and related specifications for these classes during drug development and application review.

BEBAC