Low Lactose ERP - 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? 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? 6. Based on the supporting information, what are the cons/weaknesses of the method?

YES

(1) Chromatographical part The method is applying isocratic conditions. Preventative column rinsing/ regeneration steps might be considered as recommendation. (2) Sampling and applied sample type: The method description is very short on the sample preparation side. An extraction time of 20 seconds might not suite all sample types. Also, the amount of sample to start with (here mentioned 0,1-0,5g) might not be enough for representative sampling, especially for inhomogenous samples. YES The SMPR is requesting to include blanks and appropriated check standards. Both are included in the method.

YES Blanks (water injection) do not show any signals in the analytical window of the target compound. Check std are included in 2 conc. levels. However, it might be mentioned that the check std are dependent on the stock solution used for the calibration curve.

YES

They are not explicitly mentioned in the supporting information. For evaluation of the reviewer, see 7. General comments

They are not explicitly mentioned in the supporting information. For evaluation of the reviewer, see 7. General comments

7. Any general comments about the method?

An expected PRO of the method could be, that the built-in inline dialysis could help to remove potential inferences. So far, no examples are given to fortify that.

A CON might be that the method requires a very special and expensive apparatus.