SPDS EXPERT REVIEW PANEL

A. Does the applicability of the method support the applicability of the SMPR? If not, please explain what is missing.

YES. SMPR2017.015 requires that the method is able to quantitatively determine five phenolic compounds, caftaric acid, chlorogenic acid, cichoric acid, cynarin, and echinacoside in the aerial and root parts of three Echinacea species: E. angustifolia, E. pallida, and E. purpurea, as well as to be used to analyze these phenolic compounds in different ingredient matrixes and different dosage forms. The method has been proven to be suitable for the analysis of the products in the forms of powders, tablets, capsules, softgel capsules, alcohol tincture, gelcaps, etc. No tests were reported in the submitted method on the analysis of samples made of chewable and gummy products, which I guess there are no such dose forms can be found in marketplace, although they are required by SMPR. Poor precision in the analysis of glycerite tincture products was reported due to inhomogeneous samples caused by high viscous glycerin, suggesting that the method is not suitable for the analysis of glycerite tincture products. Other than this, the applicability of the method meets the SMPR criteria. YES, HPLC-UV is used in this method. A number of HPLC methods on the studies of Echinacea chemical compositions including phenolic compounds can be found in literature.

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).

YES, The SMPR specifies the method to be used for the analysis of the dietary ingredients and dietary supplement products. By definition, Echinacea raw materials and derived products are used as dietary supplements. The manuscript does demonstrate the applicability to analyze various Echinacea samples.

YES. A general precautionary statement is presented in the method.

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.

YES. Three publications are provided by the method authors as supporting documentation including two SLVs and one 15 laboratories participated collaborative study. The manuscript is the summary of these studies, where the HPLC-UV method for the determination of the 5 phenolic compounds in three different Echinacea species with different plant parts and dosage forms were validated.