2019 Vet Drug Residues ERP - Review Book

III. Review of Supporting Information 1. Are the definitions specified in the SMPR used and applied appropriately in the supporting documentation (manuscripts, method studies, etc...)? If not, please explain the differences and if the method is impacted by the difference. 2. Is there information demonstrating that the method meets the SMPR Method Performance Requirements using the Reference Materials stated in the SMPR? If not, then specify what is missing and how this impacts demonstration of performance of the method.

The definitions specified in the SMPR are used applied appropriately in the supporting documentation. The validation data supplied in Annex 1 specifically addresses the MRL and POD for each compound. Other definitions used in this package, particularly “Screening Target Concentration (STC)” and “Cut-off level” are defined several times throughout the supporting information. The relationship (fold change) between the STC and the MRL is shown in Annex-1 with the STC levels typically between 0.1X and 0.5X of the MRL which is appropriate for a screening method. False positive/false negative values are also calculated in addition to POD. The manuscripts cited at the beginning of the submission (in the Notes to ERP) primarily cite false positive/false negative values to characterize the screening method results. To validate the method the developers primarily used fortified samples. There were several representative types of each matrix class. For example, milk products included milk fractions, formulas, cereals and baby foods and meat products included fresh, powdered, processed from several species of animals. Adequate information was provided with each method stream for sample preparation. The validation plan in terms of levels (blanks, spikes at 1 STC (~ 0.1-0.5 MRL) and spikes at 2 STC) and numbers of samples (60-80) was specified in Section 7.1 of each method stream and meets the requirements of the SMPR. The results are shown in Annex 1 (it was noted that the exact numbers differ slightly between the Validation Plans and the results in Annex 1 – maybe results from different laboratories?). Also, I did not understand how the Table on page 54 of the submission package relates to the number of samples specified in the Validation Plans and/or documented in Annex 1. Certified reference materials are not available for these drug/matrix combinations. There were examples of analysis of proficiency testing samples included with the validation. For example, a proficiency sample for containing spectinomycin was tested with the screening method and the correct results of “Suspect” was obtained. Other examples of proficiency sample testing are included in attached manuscripts (e.g. tetracyclines).