2019 Vet Drug Residues ERP - Review Book

II. Review of the Method Only 1. Does the applicability of the method support the applicability of the SMPR? If not, please explain what is missing.

The suite of methods submitted is applicable and meets the general requirements of the SMPR 2018.010. The SMPR states that “A single method is not required to cover all drug/matrix combinations, but method developers should strive to include as many relevant drug residues as possible for each matrix claimed. Method developers may choose to claim one or more matrices”. Many of the residues listed in Table 1 of the SMPR are included in the scope of the methods submitted. However, the list of analytes covered by the submitted methods and those listed in the SMPR do not match completely. Most of the analytes listed in the SMPR, but not covered by the suite of methods submitted, can be classified as pesticides (organophosphate and pyrethroid compounds), hormones, or metabolites of primary analytes. In addition, many drugs listed on the SMPR list but not included in the suite of methods submitted have MRLs only for chicken. It does appear that chicken was included in the “meat-based products” category of matrices validated (see description on page 208 of submission), so not including some of these drugs may be a gap in addressing the SMPR that should be discussed. There are also several (~30) analytes included in the 154 compound list of the methods submitted that were not part of the SMPR Table 1 including several quinolones, β -lactams and macrolide compounds. Some prohibited substances, such as chloramphenicol and phenylbutazone, are also included in the submitted methods. The analytical methods meet the requirements of the SMPR. The SMPR stated that the methods should be liquid chromatography mass spectrometry and the methods submitted are based on this technique. Although there is a suite of methods submitted (using 4-5 different sample preparation/ instrument conditions) all are LC-MS/MS triple quadrupole methods utilizing electrospray ionization and selected reaction monitoring (SRMs) with two transitions per analyte. The definitions specified in SMPR are used and applied appropriately in the method. The two definitions included in the SMPR are Maximum Residue Limit (MRL) and Probability of Detection (POD). The MRLs from Table 1 of the SMPR were used by the method developers to optimize and validate the appropriate residues levels for analytes in their methods. Probability of Detection values were determined for each analyte and are listed in Annex-1 Validation. In the introduction to Annex -1, it might be helpful to include the citation to the AOAC document describing POD (Appendix H cited in the SMPR) as well as an example calculation, even if it very simple (POD = x/N where x is number found positive and N is total number tested). The methods as written contain all appropriate precautions and warning related to safety and potentially hazardous reagents or procedures. Each of the four method streams contains a section (“Section 4 Safety Precautions” on pages 12, 72, 111, 152) that addresses any possible safety concerns that might be encountered when preforming the methods.

2. Does the analytical technique(s) used in the method meet the SMPR? If not, please specify how it differs from what is stated in the SMPR. 3. Are the definitions specified in the SMPR used and applied appropriately in the method? If no, please indicate how the terms are used.

4. Does the method, as written, contain all appropriate precautions and warnings related to the method's reagents, components, instrumentation, or method steps that may be hazardous? If no, please suggest wording or option(s).