Calculation Tool for the Performance Verification Test of Dissolution Assemblies

 

 

 

 

 

 

The Performance Verification Test (PVT) allows the evaluation of the performance of a dissolution assembly by comparing the results obtained from the PVT to limits given in the Acceptance Criteria for PVT Tablets. These limits are established from a statistical evaluation of data from a multi-lab collaborative study. The current evaluation criteria and the form of the accept/reject decision are based on the evaluation of the geometric mean (GM) and coefficient of variation (%CV) obtained with the dissolution assembly and the PVT-reference material. The scope of the evaluation criteria has moved from the individual apparatus position to the entire assembly. In order to facilitate the new approach, USP provides this PVT calculation tool. The use of this calculation tool is not a requirement of General Chapter <711>, and any validated reporting system can be used for the data entry and results reporting of the PVT.

More information on the background, statistics, and acceptance ranges, or proper way to set up a dissolution apparatus can be found in the list provided at the bottom of this page.

Data and Validation

The PVT calculation tool is designed to accept dissolution input data of any number of significant figures. It is recommended that input dissolution data should be raw (not rounded) % dissolved results with not less than three decimal places (e.g. 90.544, see General Notices, Section 7.20). Alphabetic input, numeric input outside of the range 0.001 to 115.000, or other symbols within the test result fields will result in a 'Please input decimal number between 0.0001 and 115.000' message. When valid data are entered in all required dissolution data fields, the correct geometric mean and %CV are calculated, the values compared with the range of acceptable values for the lot of PVT tablets used in testing, and a pass / fail message is displayed. Please note that the PVT calculation tool applies USP rounding rules as described in the General Notices.

Data Collection and Outputs

In addition to the dissolution data for the PVT, this calculation tool allows the option to enter the data collection date, operator identification, notebook reference, and test assembly identification. USP will not acquire or store any of the information from the data entry or additional information sections of the PVT calculation tool. The completed data sheet can be printed by the user for convenience and record keeping purposes.

Single- Or Two-Stage Testing

The design of the PVT allows the use of either a Single-Stage or a Two-Stage testing approach. The choice of Single- or Two-Stage testing is significant. Valid use of this approach to the PVT requires that the laboratory make the choice of Single-Stage testing or Two-Stage testing as a standard procedure. Documentation of that choice will support the validity of the PVT by the individual laboratory.

In the Single-Stage test two consecutive runs are to be performed on the dissolution assembly and all data generated are collected. Then the overall geometric mean and the %CV of the variances of both runs are evaluated and compared with the applicable acceptance limits. Both values have to meet the applicable acceptance criteria to pass the PVT. If either the geometric mean or %CV is not within the respective acceptance range, the PVT failed and the assembly is not suitable for routine usage.

In the Two-Stage test, a singlet of data (one run) is collected from the test assembly and the geometric mean and %CV are compared with the applicable acceptance limits. If the geometric mean and the %CV are within the ranges given, the criteria are met and the test is concluded. If either the geometric mean or %CV is not within the respective acceptance range, a second set of data should be collected. Then the geometric mean and %CV for the combined data are calculated and compared with respective acceptance ranges for the second stage. Both values have to meet the applicable acceptance criteria to pass the PVT. If either the geometric mean or %CV is not within the respective acceptance range, the PVT failed and the assembly is not suitable for routine usage. The acceptance criteria are more stringent for the first stage than for the second stage of the Two-Stage Test. This reflects the risk of falsely accepting the performance of an assembly based on the smaller first-stage data set.

Table showing data set size for Single- and Two-Stage testing

Number of positions in test assemblyNumber of data in Single-Stage testNumber of data for first stage of Two-Stage testTotal number of data at second stage of Two-Stage test
612612
714714
816816
1212--
14*14*--

[Note that for twelve and fourteen position test assembly only the one stage test is performed.]

*In addition to the criteria for 6-, 7-, 8-, and 12-position assemblies given with Lot P1I300, Lot Q0H398 criteria increases to include 14-position test assemblies.

References

Hauck WW, Abernethy DR, Williams RL. Metrologic approaches to setting acceptance criteria: Unacceptable and unusual characteristics. J. Pharm Biomedical Analysis 2008;48:1042–1045

Hauck WW, DeStefano AJ, Stippler ES, Brown WE, Abernethy DR, Koch WF, Williams RL. Description of the Upcoming Change in Data Analysis for USP Dissolution Performance Verification Tests. Pharm Forum. 2008;34(6):1630–1635.

Hauck WW, Manning RG, Cecil TL, Brown WE, Williams RL. Proposed change to acceptance criteria for dissolution performance verification testing. Pharm Forum. 2007;33(3):574–579.

Hauck WW, Cecil TL, Brown WE, Abernethy DR, Koch WF, Williams RL. USP responses to comments on Stimuli article,"Proposed change to acceptance criteria for dissolution performance verification testing." Pharm Forum. 2008;34(2):474–476. Dissolution Toolkit