Regulations on biowaivers already existed at that time, according to which an in vitro instead of an in vivo assessment could be used to assess bioequivalence for a new tablet or capsule, or a new formulation of an existing immediate release dosage form. On the basis of the in vitro assessment, a new drug product could be considered bioequivalent to its reference product, without having to perform a pharmacokinetic study in human volunteers. To generally describe the use of an in vitro assessment to waive the need for in vivo (bio) studies, the term “biowaiver” was coined. As this term was originally applied to waiving in vivo studies for registration of lower dosage strengths of drug products, the more precise term “BCS based biowaiver” is sometimes used to distinguish biowaivers based on BCS considerations from biowaivers used for the approval of lower dose strengths of a product.
Scope : The dissolution toolkit provides a description of best practices associated with the mechanical calibration and performance verification test for the USP basket and paddle dissolution apparatuses and test assemblies. The best practices have been developed based on experience gained by the USP laboratory (9, 13, 14, 15) and with suggestions from the USP Expert Committee on Biopharmaceutics. While not a standard requiring rigid compliance, the dissolution toolkit is intended to provide information aiding the dissolution laboratory in the effort to obtain valid dissolution testing results.
This general information chapter Apparent Intrinsic Dissolution—Dissolution Testing Procedures for Rotating Disk and Stationary Disk 1087 discusses the determination of dissolution rates from nondisintegrating compacts exposing a fixed surface area to a given solvent medium. Compact, as used here, is a nondisintegrating mass resulting from compression of the material under test using appropriate pressure conditions. A single surface having specified physical dimensions is presented for dissolution. Determination of the rate of dissolution can be important during the course of the development of new chemical entities because it sometimes permits prediction of potential bioavailability problems and may also be useful to characterize compendial articles such as excipients or drug substances. Intrinsic dissolution studies are characterization studies and are not referenced in individual monographs. Information provided in this general information chapter is intended to be adapted via a specific protocol appropriate to a specified material.
Used in the private or public USP Performance test, dissolution testing plays an important role in both product development and quality assurance for nonsolution oral dosage forms. The dissolution procedure itself, as described in USP General Chapter Dissolution , is sensitive and specific but requires special care in execution. Results of a recent USP collaborative study of new Lot P Prednisone Reference Standard Tablets indicate much higher reproducibility (interlaboratory variance) than repeatability (intralaboratory variance) (1, 2). To improve reproducibility, the USP Biopharmaceutics Expert Committee recommends careful IQ, OQ, and PQ (mechanical calibration), aswellasaPerformanceVerificationTest (PVT); the latter two typically are performed at six-month intervals. Several variables such as shaft rotation speed, shaft and vessel alignment, basket/paddle height, and bath levelness have been cited as factors that contribute to high variability of the dissolution procedure. Missing from this list are factors relating to vessel dimension and irregularities, which are the subject of this report.