Low Lactose 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.

Yes, especially this method sufficiently demonstrates the key information regarding how to handle/address potential adulterants, listed in Table 1 of SMPR 2018.009, at the very least. The reviewer considers that the method’s capability to demonstrate adequate separation of potential interferents as essential. Two groups of compounds (sugar alcohols and lactose analogs) amongst those listed in the Table 1 of SMPR 2018.009 are important. The report provided the detailed explanation under the section of Selectivity and interferences (pp. 28 ~ 31). A. This method stated that the most sugar alcohols eluted earlier than the analyte. Table with the retention times is provided, but no chromatogram is provided in the report. B. Utilization of more specific β -galactosidase could be considered. How do you discern the contribution from lactose analogs vs. that of lactose? The reviewer is not 100% certain whether β -galactosidase used in the method would not cleave lactulose and/or 1,6- β -D-allolactose (few examples of lactose analogs among others) to results in D-glucose and/or D-galactose? β -galactosidase from E. coli (Section B. 8 of page 8 on the report) is reported as non-specific or less specific in the literature. D-galactosyl-D-glucose disaccharides (or oligosaccharides) might form during the production of low-lactose or lactose-free milk products (transglycosylation). C. Table 10 of page 15 lists chromatographic resolution between lactulose vs. lactose.

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).

Yes

Yes

Mostly, yet somewhat rudimentary (and redundant) information regarding how to handle the eluents and wastes during the IC analysis could be added.