Contains Nonbinding Recommendations
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
II. BACKGROUND
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 substance
under physiological conditions, and the permeation across the gastrointestinal membrane.
5,6
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: (1) batches used in pivotal clinical and/or BA/BE studies, (2) batches
used as stability registration batches, and (3) batches used in other human studies conducted
during product development. In general, knowledge about the solubility, permeability,
dissolution, and pharmacokinetics of a drug substance and drug product are considered when
defining dissolution acceptance criteria as part of the drug approval process.
Immediate-release solid oral dosage form drug products containing high solubility drug
substances are considered to be relatively low risk regarding the impact of dissolution on in vivo
performance, provided the in vitro performance meets or exceeds the recommendations
discussed herein.
This guidance establishes standard dissolution methodology and acceptance criteria that are
appropriate for highly soluble drug substances that are formulated in IR dosage forms. The
availability of these standards will facilitate the rapid development of dissolution methodology
and related acceptance criteria with no requirement to show discriminatory ability of the
dissolution method for these products during drug product development. In addition, these
standards will facilitate FDA’s evaluation of the data submitted in the application.
III. ELIGIBLE DRUG PRODUCTS
In addition to being an IR dosage form, the drug product should meet all of the following
conditions in order for the dissolution standards in this guidance to apply. The FDA’s
Biopharmaceutics Classification System (BCS) guidance should be followed to establish that the
drug product contains highly soluble drug substance.
7
Sponsors/applicants may contact FDA for
5
Amidon GL, Lennernas H, Shah VP, and Crison JR, 1995, A Theoretical Basis for a Biopharmaceutic Drug
Classification: The Correlation of In Vitro Drug Product Dissolution and In Vivo Bioavailability, Pharm Res,
12(3):413-420.
6
Amidon GL, Lennernas H, Shah VP, and Crison JR, 2014, A Theoretical Basis for a Biopharmaceutic Drug
Classification: The Correlation of In Vitro Drug Product Dissolution and In Vivo Bioavailability, Pharm Res 12,
413-420, 1995-Backstory of BCS, The AAPS Journal, 16(5):894-898.
7
See guidance for industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release
Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.