2018 Sugar ERP - Method Review Book

IV. General Submission Package 1. Based on the supporting information, were there any additional steps in the evaluation of the method that indicated the need for any additional precautionary statements in the method?

Yes, as with any analytical chemistry method, this method should have a safety section at the beginning calling attention to potential hazards and the precautions that can be taken to minimize risk. As the method provides no precautionary statement, there should be an addition added. From a quality aspect, the method should add a precautionary statement presenting clear criteria for determining the mobile phase concentration. The method states that the mobile phase concentration varies to achieve good separation of analytes, with the concentration ranging from 75% Acetonitrile at the beginning of column lifetime to 82% Acetonitrile at the end of the column's lifetime. However, the actual concentration used is left to the complete discretion of the user with no criteria provided as to what constitutes "achieving [sic] good separation of analytes." Without providing clear criteria for this determination, there is significant risk of the method not meeting performance criteria for reproducibility as the mobile phase concentration is determined at the sole discretion of individual operators. The SMPR states that the method should include blanks and appropriate check standards as system suitability tests and/or analytical quality control. The method does not contain either blanks or check standards as specified by the SMPR. While one of the sugar standards can act as a internal standard blank, as it contains only the internal standard ribose and 0% of each of the sugar analytes, no data is shown for such a blank. No data is shown for running blanks between samples to demonstrate that there is no carryover between sample injections. The method does not provide any information regarding how often the set of five sugar standards should be run to act as a quality check. Ideally, the method should specify that the set of five sugar standards be run at the beginning and end of the batch of samples, so that the linear regression can be performed with bracketed standards. Additionally, an appropriate check standard should be injected every X number of samples as a quality check, with X dependent on method repeatability/drift. There is clearly a need for these tests and controls since the method did not clearly demonstrate that it met the method performance requirements for repeatability. Not applicable. As the method does not include any data with regards to system suitability tests and controls there is no demonstration whether or not they work appropriately or as expected. While the method is written concisely, there are possible opportunities for improving method clarity. As discussed above in IV.1. the authors should provide more clarity regarding the mobile phase concentration and the criteria used to determine it. Under step 5 of the procedure, additional detail should be provided regarding the microwave instructions. In step 18 of the procedure, additional detail should be provided for set-up of the chromatographic run, ie. how often to inject the standards, how many samples can be analyzed in a batch, how often a check sample should be injected, parameters for the strong and weak needle and seal wash, etc. The method utilizes equipment that common in most analytical laboratories that analyze food, and no additional instrumentation, such as Ion Chromatography, is required. Likewise, the method uses sample separation and analyses work-flows familiar to trained operators in the field.

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.

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?