2019 Vet Drug Residues ERP - Review Book

2. Does the method contain system suitability tests or controls as specified by the SMPR? If not, please indicate if there is a need for such tests or controls and which ones.

The method specifies system suitability and QC controls that should be performed with the method. The positive and negative controls that should be run with each batch are described for each method stream. In general, these include a solvent based QC standard corresponding to 1X STC (~0.5X MRL) or 2X STC levels of analytes. Matrix based QC samples include a blank matrix, and a positive control that is fortified at 1X STC and also at 2X STC to simulate actual samples analyzed unfortified and fortified, respectively.

In addition, the strategy of analyzing each sample “as is” as well as fortified is described and helps mitigate matrix effects for any given sample.

Information was provided to demonstrate how cutoff values were determined.

The “identification criteria” initially described initially on page 29 may not be adequate. The criteria in the submission states “Each analyte surveyed is identified when the following criteria are fulfilled: A signal is visible at two diagnostic transition reactions and the retention time of the analyte in the extract should correspond to that of the QC solutions within a ± 0.2 min tolerance “, but does not require any calculation of ion ratios. See additional comments below in part IV.6. There is adequate information to demonstrate that the system suitability tests, controls samples worked appropriate as expected. The criteria needed for system suitability (RSD of solvent QC standards < 30%) as well as matrix negative and positive QC samples analyzed with each batch (analytes in negative QC need to be < STC and positive controls need to have all analytes characterized as “suspect”). Based on all of the validation data provided, these QC guidelines seem appropriate and criteria were met as expected.

3. Is there information demonstrating that the method system suitability tests and controls as specified in the SMPR worked appropriately and as expected? If no, please specify. 4. Based on the supporting information, is the method written clearly and concisely? If no, please specify the needed revisions. 5. Based on the supporting information, what are the pros/strengths of the method?

The method was written clearly and concisely. The method submitters did an excellent job of presenting a large amount of data in a very organized, easy to follow format. In my experience it is difficult to document these large multi- residue methods in a thorough, yet assessable way, and I was very impressed by this submission.

The methods include most of the analytes listed in the SMPR.

The method developers’ approach and strategy both in terms of how the classes of analytes were divided between the different method streams and how the screening was performed (fortifying each samples) was logical and thorough. Implementing these methods will allow for a complete investigation of samples to determine compliance or non-compliance for the presence of these 154 veterinary drug residues at the levels of interest. The data package submission was well -organized and easy to follow. The validation information was included and supported the methods’ applicability to the requirements of the SMPR.