News from Europe's pharmaceutical manufacturing industry coupled with upcoming events, and exclusive articles and interviews from industry experts. WEEKLY
Table III: Intra-experiment %CV (Apparatus 2, Study 3, using six analysts)*.
The intent of the USP PVT for nonsolution orally administered drug products is to ensure continuing equivalence between the
clinical trial material on which safety and efficacy conclusions were made and the manufactured article following approval.
US regulatory approaches do not require postapproval reconsideration of bioequivalence for drug products, barring postapproval
change. Thus, reliance on the USP performance test becomes a key, if not the sole, means of ensuring consistency in drug product
performance both within and among manufacturers over many years of drug product manufacture.
Table IV: Intra-experiment %CVs, assembly epsilon (Apparatus 2, Study 4, using two analysts)
The dissolution procedure described in Dissolution ‹711› requires an assembly that allows a kinetic measure of drug release
over time. Combining effects from the analyst and analytic procedure, the experimental study of drug product dissolution is
performed at batch release and also as part of stability studies. The assembly is a complicated mechanical device with many
factors that can influence results. In part, the complexity results from the need to provide some sense of surrogacy for the
in vivo condition. For this reason, USP emphasizes the importance of a periodic PVT together with careful mechanical calibration to
ensure that the combined experimental study yields consistent results. General Chapter ‹711› has been revised, and the term
Apparatus Suitability Test has been replaced with the term Performance Verification Test (1). Although USP reference standard tablets have been referred to as calibrators, this is a misnomer. The tablets are not,
and cannot, be used for calibration.
Table V: Intra-experiment %CVs from collaborative studies for USP prednisone tablets (Study 5).
The recent FDA draft guidance for industry attributes the current wide acceptance criteria for USP's PVT to the quality of
the USP Prednisone RS Tablet (6). The studies summarized here addressed this issue by determining the contribution to variability
that may be attributed to the tablets. Across the studies, one notes that the intra-experiment %CV for USP Lot P Prednisone
RS Tablets is consistently below 6–9%, sometimes much below (see Tables I and II). Because the tablets remain relatively constant
across the studies and laboratories of Study 5, variability in the %CVs probably is due to factors other than the tablets.
If the USP laboratory can achieve 4–5% CV with these prednisone tablets, these numbers reflect the variability contribution
from the tablets together with the assay because that cannot be separated out.
The original Lot M of the 10-mg USP prednisone tablet was designed to reproduce FDA's National Center for Drug Analysis #2
10-mg prednisone tablets used for dissolution testing in FDA laboratories. It is of some interest then, that FDA reports for
its prednisone tablets a residual variability of a magnitude similar to that seen in the USP laboratory for USP prednisone
Lot P, namely 4–5% (17).
Walter W. Hauck, PhD, is senior scientific fellow at United States Pharmacopeia (USP), 12601 Twinbrook Parkway, Rockville, MD 20852-1790, tel. 301.816.8390, wh@usp.org
Articles by Walter W. Hauck, PhD
Gang Deng
Gang Deng, PhD, is group leader at United States Pharmacopeia (USP).
Articles by Gang Deng
