SPDS EXPERT REVIEW PANEL

II. Review of the Method Only:

A. Does the applicability of the method support the applicability of the SMPR? If not, please explain what is missing. B. 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. C. Are the definitions specified in the SMPR used and applied appropriately in the method? If no, please indicate how the terms are used. D. 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).

The SMPR indicates that the applicability of the method presented with the application of tablets and capsules. In the proposal, the results related with the tablet formulation were performed. However, I could not see the results of a capsule formulation.

They used HPLC and it can be accepted in the SMPR.

Definitions used properly.

No. Safety caveats were not mentioned in any part of the proposal. As an example, they shall be stated “acid, base and organic solvents were prepared in the ventilation hood” under “Reagent Preparation” in the section of “Method”. Or, the preparation of the solutions should be prepared based on the laboratory safety cautions.

III. Review of Information in Support of the Method

A. Are the definitions specified in the SMPR used and applied appropriately in the supporting documentation (manuscripts, method studies, etc...)? If not, please explain the differences and if the method is impacted by the difference.

Supporting documentations are not easily understandable. It is somehow mixed up with each other. There are not any chromatograms illustrated in proposed method by using new conditions (flow rate, columns, etc.) Selectivity studies are not enough in the draft and the proposal. So that part is not met with the SMPR.