Software-based workbook for statistical evaluation of residue depletion data for veterinary drugs
JECFA has used on several occasions a statistical approach for the evaluation of marker residue depletion data when estimating MRLs. The approach is primarily based on linear regression analysis and statistical estimation of one-sided upper tolerance limits for the marker residue depletion in the individual target tissues. An iterative procedure is then used to calculate for different time points on the depletion curve the intake of residues of concern in the food basket. The calculated intake of residues is compared with the ADI and the time point of depletion below the ADI is selected to determine the MRLs.
At the 62nd meeting of JECFA the FAO Joint Secretariat proposed to the Committee an Excel-based workbook facilitating the complex calculations required to use this approach. The Committee investigated the workbook and recommended that the Secretariat should continue with its development. In order to take the necessary steps, the Secretariat requested comments from interested parties on both the features and the documentation of the tool. Comments were received from Argentina, Canada, the European Medicines Agency (EMEA) and the International Federation for Animal Health. The Committee reviewed all comments at its 66 th meeting and noted that all respondents agreed that the mathematical/statistical approach was scientifically sound. Some comments analysed the advantages and the limitations of the use of the workbook.
The Committee concluded at the 66 th meeting that the workbook would primarily be of value in assisting the experts to statistically evaluate available depletion data during the development of MRL recommendations. The Committee also concluded that it would use the statistical approach in future whenever it was appropriate and the experts drafting the working documents should explain to the Committee the reasons when not using it.
Features of the work-book
Linear regression analysis of data describing the terminal depletion of a suitable marker residue in edible tissues following the (last) administration of the drug under approved conditions of use;
Subsequent use of the results of the regression analysis for the estimation of upper limits of the 95% (alternatively, 99%) confidence interval (CI) for the upper one-sided tolerance limit on the 95th (alternatively, 99th) percentile of the population sampled;
Iterative calculation of statistical limits, such as a function of time over the whole phase of terminal elimination of the marker residue;
The statistical method includes a mechanism for the derivation of MRLs for veterinary drugs from a set of data.