William F. Koch

USP Responses to Comments on Stimuli Article, "Proposed Change to Acceptance Criteria for Dissolution Performance Verification Testing"

Pharmacopeial Forum 33(3) [May–June 2007] included a Stimuli article titled “Proposed Change to Acceptance Criteria for Dissolution Performance Verification Testing.” This Stimuli article proposed changing the form of the acceptance criteria for the Performance Verification Test (PVT) associated with USP Dissolution to make the PVT consistent with the International Organization for Standardization’s recommendations for proficiency testing. The article elicited five comments, which are abstracted here with USP responses.

Establishing New Acceptance Limits for Dissolution Performance Verification of USPC Apparatus 1 and 2 Using USPC Prednisone Tablets Reference Standard

ABSTRACTPurposeOn 1 March 2010, the US Pharmacopeial Convention released into commerce Lot P1I300 of its Prednisone Tablets Reference Standard for use in periodic performance verification testing (PVT) of dissolution Apparatus 1 and 2. This report presents the collaborative study data, development of the acceptance limits, and results from supporting work for this Lot.MethodsThe collaborative study involved 25 collaborators who provided data for Apparatus 1 and 31 who provided data for Apparatus 2. These limits are for the geometric mean and percent coefficient of variation (%CV) instead of per-individual results as for prior lots. Stability of results and sensitivity to test performance parameters were also studied.ResultsTo determine new PVT acceptance limits, the authors calculated geometric mean and variance components as percent coefficient of variation. The move to the geometric mean and %CV criteria brings the acceptance criteria in line with current accepted statistics and provides a more realistic assessment of the system’s performance. Results for Apparatus 1 are stable over time, but for Apparatus 2, the mean decreases over time. Acceptance criteria are adjusted for this trend. Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing).ConclusionsApparatus 1 results are stable over time. Those in Apparatus 2 show a decrease over time in the geometric mean but show no trend in variability. The current tablets are shown to remain sensitive to two operational parameters, degassing and vessel dimensions, not covered by mechanical calibration. The new acceptance limits for Lot P1 are based on geometric mean and %CV for Prednisone Tablets Reference Standard Lot P1I300. The limits better control variability than the prior per-individual-result limits.

Change in criteria for USP dissolution performance verification tests.

The US Pharmacopeial Convention has been evaluating its performance verification tests (PVT) for several years. These tests help ensure the integrity of the US Pharmacopeia performance test when a dissolution procedure, as described in General Chapter Dissolution <711>, is relied upon to test a nonsolution orally administered dosage form. One result of the evaluation is a change in the PVT criterion from one based on individual tablet results to one based on the mean and variability of a set of tablets. This paper describes the new PVT and its criterion and how its acceptance limits are derived from results of a collaborative study, explains a two-stage option for the test, and presents operating characteristics.

Measurement Science for Food and Drug Monographs: Toward a Global System

ABSTRACTThis article continues USP’s public dialogs about applications of modern measurement science (metrology) to public or private specifications (monographs) of food and drug articles. An objective of the discussion is to promote understanding of traceability and uncertainty of measurement results. Adoption of modern metrologic principles helps ensure that a measurement of one or more property values (attributes) of a food or drug article are acceptable without regard to when (time), where (space), or how (technology) the measurement was conducted. The approach is applicable to both in-process and end-product measurements and facilitates and supports understanding of manufacturing and measurement variability relative to acceptance criteria. Application of modern metrologic principles to measurement of food and drug articles expands opportunities to ensure availability of good quality food and drugs in national and international markets.

Erratum to: “Establishing New Acceptance Limits for Dissolution Performance Verification of USPC Apparatus 1 and 2 Using USPC Prednisone Tablets Reference Standard”

Fig. 5 GM and %CV by Laboratory, Apparatus 2. Error bars are 95% confidence intervals based on each laboratory ’s between-position variability. Horizontal lines are the combined value from the collaborative study and the single-stage Lot P1 PVT limits for an instrument with six positions. Limits for sevenand eight-position instruments are tighter. The limits for the geometric mean are those at the time of the collaborative study The online version of the original article can be found at http://dx.doi.org/ 10.1007/s11095-010-0295-3.