SPDS EXPERT REVIEW PANEL

SPDS EXPERT REVIEW PANEL ALOE VERA – ECHINACEA – GINGER – GINSENG – KAVA SAME – SKULLCAP – VITAMIN B12

ERP CHAIR: HOLLY JOHNSON

AMERICAN HERBAL PRODUCTS ASSOCIATION

SEPTEMBER 24-25, 2018 | 1:00PM – 5:00PM ET SHERATON CENTRE TORONTO MEETING ROOM: PINE

Sheraton Centre Toronto 123 Queen Street W Toronto, ON, M5H 2M9

AOAC Expert Review Panels for Dietary Supplement Methods

Sheraton Centre Toronto Hotel 123 Queen Street W, Toronto, ON, Canada Friday, August 24, 2018 | 1:00 pm – 5:00pm ET and Saturday, August 25, 2018 | 8:30am – 12:00pm ET A G E N D A

1. Welcome and Introductions (1:00pm – 1:15pm) Holly Johnson, American Herbal Products Association (ERP Chair) and Dawn Frazier, AOAC INTERNATIONAL 2. Review of AOAC Volunteer Policies & ERP Process Overview and Guidelines (1:15pm – 1:30pm) Deborah McKenzie, AOAC INTERNATIONAL 3. Review of Methods (1:30pm – 6:00pm) For each method of each ERP, the assigned ERP members will present a review of the methods and manuscripts, after which the ERP will discuss the method and reach consensus on the status for each method. a. Echinacea Methods I. ECH-001 1. He Review 2. Es-Safi Review 3. Discussion and Vote b. Ginseng I. GSG-001 1. Zhang Review

2. Bzhelyansky Review 3. Discussion and Vote

II. GSG-002

1. Park Review 2. Chan Review

c. Kavalactones

I. KAV-001

1. Metcalfe Review 2. Bzhelyansky Review 3. Discussion and Vote 1. Zhou Review 2. Chan Review 3. Discussion and Vote 1. Szpylka Review 2. Solyom Review 3. Discussion and Vote 1. Rimmer Review 2. Tuzimski Review 3. Discussion and Vote

II. KAV-002

III. KAV 003

IV. KAV-004

d. Skullcap Methods I. SKU-001

1. Rimmer Review 2. Zhang Review 3. Discussion and Vote

Draft meeting agenda. Subject to change.

SPDS

SATURDAY, AUGUST 25, 2018 4. Review of Methods, Continued (8:30am – 12:00pm) For each method of each ERP, the assigned ERP members will present a review of the methods and manuscripts, after which the ERP will discuss the method and reach consensus on the status for each method. a. Aloe Vera I. ALO-001 1. Edwards Review 2. He Review 3. Discussion and Vote b. SAMe I. SAM-001 1. Yang Review

2. Gumustas Review 3. Discussion and Vote

c. Vitamin B 12

I. B12-001

1. Zielinski Review 2. Rithruthai Review 3. Discussion and Vote

d. Ginger

I. GIN-001 (Resubmission) 1. Solyom Review 2. Brown Review

3. Discussion and Vote

5. Review and Next Steps AOAC staff will recap the deliberations of the ERPs and the next steps for each method, and for the ERP.

6. Adjourn

Aloe Vera Expert Review Panel

First Name

Last Name

Organization

1 2 3 4 5 6 7 8 9

Michael Steven

Chan

British Colombia Institute of Technology

Dentali Edwards

Dentali Botanical Sciences Process NMR Associates

John

Nour Eddine ES-SAFI

Mohammad V University in Rabat

Kan

He

Herbalife

Holly Dana Jasen

Johnson Krueger

American Herbal Products Association

Dana Krueger

Lavoie

Lily of the Desert Custom Analytics

Charles

Metcalfe Rimmer

10 Catherine

NIST

Echinacea Expert Review Panel

First

Last

Organization

1 Paula 2 Anton 3 Michael

Brown

British Colombia Institute of Technology

Bzhelyansky USP

Chan

British Colombia Institute of Technology Mohammad V University in Rabat (Morocco)

4 Nour Eddine

Es-Safi

5 Kan 6 Holly

He

Herbalife

Johnson Rimmer Tuzimski

American Herbal Products Association

7 Catherine 8 Tomasz

US NIST

Medical University of Lublin (Poland)

9 Joseph

Zhou

Sunshineville Health Products

Ginger Expert Review Panel

Name

Organization

1

Paula. Brown

British Columbia Institute of Technology

2

Anton Bzhelyansky

US Pharmacopeia (USP)

3

Congmei Cao

Herbalife International Of America, Inc.

4

Nour Eddine Es-Safi

Mohammed V University in Rabat

5

Holly E. Johnson

American Herbal Products Association

6

Philip J. Koerner

Phenomenex

7

Dana A. Krueger

Krueger Food Laboratories, Inc.

8

Catherine A. Rimmer

NIST

9

Brian T. Schaneberg

Starbucks Coffee Company

10 Aniko Solyom

GAAS Analytical

11 Jinchuan Yang

Waters Corporation

12 Kurt Young

GNC/Nutra Manufacturing

13 Yanjun Zhang

Herbalife International Of America, Inc

Ginseng Expert Review Panel

First

Last

Organization

1 2 3 4 5 6 7 8 9

Anton

Bzhelyansky USP

Michael

Chan

British Colombia Institute of Technology Mohammad V University in Rabat (Morocco)

Nour Eddine

Es-Safi

Kan

He

Herbalife

Holly Mimi

Johnson

American Herbal Products Association

Park

The Nature’s Bounty Co.

Catherine

Rimmer Solyom

US NIST

Aniko

GAAS Analytical

Yanjun

Zhang

Herbalife

10 Joseph

Zhou

Sunshineville Health Products

Kava Expert Review Panel

First

Last

Organization

1 2 3 4 5 6 7 8 9

Anton

Bzhelyansky USP

Michael Steven

Chan

British Colombia Institute of Technology

Dentali Es-Safi

Dentali Botanical Sciences

Nour Eddine

Mohammad V University in Rabat (Morocco)

Kan

He

Herbalife

Holly

Johnson Metcalfe Rimmer Solyom Szpylka Tuzimski

American Herbal Products Association

Charles

Custom Analytics

Catherine

US NIST

Aniko

GAAS Analytical

10 John

Merieux NutriSciences

11 Tomasz 12 Joseph

Medical University of Lublin (Poland)

Zhou

Sunshineville Health Products

SAMe Expert Review Panel

First

Last

Organization

1 Michael

Chan

British Colombia Institute of Technology Mohammad V University in Rabat (Morocco)

2 Nour Eddine

Es-Safi

3 Mehmet

Gumustas

Ankara University (Turkey)

4 Holly

Johnson Koroma Rimmer Solyom

AHPA

5 Mohamed 6 Catherine

Pharmavite

US NIST

7 Aniko

GAAS Analytical

8 Jinchuan

Yang

Waters Eurofins

9 Hong

You

Skullcap Expert Review Panel

First

Last

Organization

1 Paula

Brown

British Colombia Institute of Technology British Colombia Institute of Technology Mohammad V University in Rabat American Herbal Products Association

2 Michael

Chan

3 Nour Eddine

Es-Safi

4 Holly 5 Maria

Johnson Monagas Rimmer

USP

6 Catherine

US NIST Herbalife

7 Yanjun

Zhang

8 Hui

Zhao

Agilent

Vitamin B 12

Expert Review Panel

First Sneh

Last

Organization

1 2 3 4 5 6 7 8 9

Bhandari

Mérieux NutriSciences

Nour Eddine

Es-Safi

Mohammad V University in Rabat

Quanyin

Gao

Herbalife

Holly

Johnson Joseph Koerner Koroma Rimmer Ritruthai Solyom Szpylka Tuzimski Park

AHPA

George

AsureQuality New Zealand

Philip

Phenomenex Pharmavite

Mohamed

Mimi

The Nature’s Bounty Company

Catherine

US NIST Herbalife

10 11 12 13 14 15 16

Vicha Aniko

GAAS Analytical

John

Mérieux NutriSciences

Tomasz Jinchuan

Medical University of Lublin (Poland)

Yang

Waters Eurofins

Hong

You

Garrett

Zielinski

Covance Laboratories

AOAC Expert Review Panel  Meetings An Orientation

Deborah McKenzie רב Sr. Dir., Standards Development AOAC INTERNATIONAL Sr. Dir., AOAC Research Institute Staff Liaison ‐ Official Methods Board

AOAC Policies & Procedures

Policy on Use of  Association Name,  Identifying Insignia,  Letterhead, Business  Cards

Policy on Volunteer  Conflict of Interest

Policy on Antitrust

Expert Review Panel  Policies and Procedures

OMA Appendix G

1

Policies and Procedures for Adoption of  Official Methods of Analysis 

• OMA, Appendix G: Procedures and Guidelines for the Use of AOAC Voluntary Consensus Standards to Evaluate Characteristics of a Method of Analysis – Expert Review Panels, Official Methods Board, First and Final Action Official Methods – First Action to Final Action Methods: Guidance for AOAC Expert Review Panels • Expert Review Panels – Policies and Procedures • Appendix F: Guidelines for Standard Method Performance Requirements • OMA, About the AOAC Official Methods SM Program

Road to First Action OMA Status

Three modes of entry  and (program  administration)

Expert Review Panels will  review all methods for all  three modes of entry.

2

ERP Meetings

Quorum

Presence of 7  vetted ERP  members 

Presence of  2/3 vetted  ERP members

OR

WHICHEVER IS GREATER IF NO QUORUM, NO OFFICIAL MEETING

Candidate Method Reviews

 In your judgment, does the method sufficiently meet the Standard Method Performance Requirements (SMPR) or community‐based guidance?

 In your judgment, is the method scientifically sound and can be followed?  In your judgment, what are the strengths and weaknesses of the method?  In your judgment, how do the weaknesses weigh in your recommendation for the method?  In your judgment, will the method serve well the stakeholder community that will use the method?  In your judgment, what additional information may be needed to further support the method meeting the SMPR or community‐based guidance?  Members of both Committee on Safety and Committee on Statistics serve as  advisory resources for all ERPs

3

ERP Meetings – Review for First Action  ERP CHAIR & MEMBERS:    Present reviews and discuss the method,  supporting data, and any resulting issues or questions on the method,  review and agree upon final draft of method proposed for decision, and  chair calls for ERP decision in accordance to procedures.

CONSENSUS:   Method must be adopted by unanimous decision of ERP  on first ballot. If not  unanimous, negative votes must delineate   scientific reasons. Negative voter(s) can be overridden by 2/3 of non‐ negative voting ERP members after due consideration.    Abstentions do not count towards vote; in case of multiple abstentions the results will  need to be evaluated.  Staff will monitor  and record consensus voting.

STAFF:   Will organize and coordinate meeting,  record  ERP  actions and decisions, draft ERP report and distribute after  chair approval,  work with chair and OMB liaison to complete  checklist and assemble recommendation package  for OMB.

Consensus – First Action to Final Action

 The ERP may then reach consensus on any additional information that it needs to review to be able to make a recommendation for Final Action Official Methods status.

 This is a separate motion.

4

Road to Final Action OMA  Status

Method reproducibility must be  demonstrated before Final Action  consideration. 

ERP determines if sufficient  evidence merits a  recommendation for Final Action  status or repeal. • Only the OMB promotes a  method to “Final Action” status or repeal the method. • Methods that did not meet the  bar would be repealed. • Same for all method submissions

ERP Methods Review & Approval

Methods should be scientifically sound with demonstrating  that it will meet the needs of those using the method  (evidenced by meeting the standard, or other acceptance  criteria) 

ERPs have approved methods with evidence of high potential  to First Action and request additional work or support be  submitted for review prior to ERP convening to recommend an  action to OMB

OMB requires a justification or rationale for methods that are  deemed acceptable and adopted but may not fully meet the  standard set or acceptance criteria.

5

OMB Expectations for First Action

• Safety review needed prior to First Action status

• SLV type of supporting information available per the SMPR – Applicability, Method Performance Requirements Table, System Suitability, Reference Materials, and Validation Guidance • Comparison to SMPR – Documented method performance versus a SMPR – Document reasons for acceptability if method does not meet the SMPR

Publication of First Action Methods

 Any approved method(s) along with supporting manuscript(s) and  documentation sent to AOAC Publications after themeeting.

1. Method incorporating ERP revisions (preferably in AOAC Format) 2. Method Manuscript incorporating specified ERP revisions (in AOAC  Format) 3. Signed AOAC Copyright Authorization form

NO OMA NUMBER ASSIGNED  UNTIL ALL DOCUMENTATION SUBMITTED

 Method and method manuscript prepared for publication  in the Official Methods of Analysis of AOAC  INTERNATIONAL and in Journal of AOAC INTERNATIONAL

 Updates on methods approved or status changes are  published in the Inside  Laboratory Management magazine  and on the AOAC website

6

ERP Meetings – Method Tracking METHOD AUTHOR:    present any method feedback obtained  and any resulting changes to the method, any reproducibility  information, any implemented ERP recommendations, final  draft of method proposed for decision ERP MEMBERS:    present any method feedback obtained and 

discuss any resulting changes to the method, any  reproducibility information, any implemented ERP  recommendations, review and agree upon final draft of  method proposed for decision, and make a recommendation  to OMB. CONSENSUS:    2/3 vote in favor of a motion.    Abstentions do not count towards vote; in case of  multiple abstentions.  Staff will monitor  and record  consensus voting.

STAFF:   Will organize and coordinate meeting,  record   ERP actions and decisions, draft ERP report and  distribute after chair approval,  work with chair and  OMB liaison to complete checklist and assemble  recommendation package  for OMB.

Documentation Needed

Method Safety Evaluation

Reference Materials

Evidence of Single Laboratory Validation or equivalent 

Evidence of Reproducibility Assessment 

Published First Action OMA

Method Performance versus SMPR or acceptance criteria

Final draft of First Action OMA to be considered for status update

Rationale or Justification for Repeal or Continuance of First Action OMA

7

Documentation and Communication • AOAC carefully documents the actions of Stakeholder Panel and the Working Groups • AOAC will prepare summaries of the meetings – Communicate summaries to the stakeholders – Publish summaries in the Referee section of AOAC’s  Inside Laboratory Management • AOAC publishes its voluntary consensus standards and Official Methods – Official Methods of Analysis of AOAC INTERNATIONAL – Journal of AOAC INTERNATIONAL • AOAC publishes the status of standards and methods in the Referee section of AOAC’s  Inside Laboratory Management General Expectations for ERPs • You can expect to have a minimum of three weeks to review methods prior to ERP meeting. – You are requested to submit written reviews by specified deadline.  Please alert staff if you are not able to complete on time. – You may have individually assigned methods to review or all of the methods to review.  Please be prepared to discuss these methods during meeting. – You may use the OMA appendices as guidance for types of validation work that can be expected.  If additional information is needed, please ask staff. • ERP Meeting Quorum – If there is no quorum, there is no official meeting.  Please alert staff as early as possible if you are not able to attend a meeting. • ERP Consensus – ERP consensus may not reflect your own personal view – There may be times when a method may not meet all of the criteria exactly; however, the ERP can adopt the method.

8

Ethical Expectations of AOAC Expert  Review Panel Members • Respect for your peer ERP members and chair – Each member has been vetted for expertise relevant to the review of the method(s) in the ERP • Be considerate of each others perspectives and points of view • Be considerate of the ERP’s consensus even if you disagree – Inform staff as early as possible if you cannot attend the scheduled ERP meeting • Be considerate in that your absence can impact the quorum of the ERP and its ability to have an official meeting to make decisions – Notify staff and/or disclose in the ERP meeting if you have a direct or perceived conflict of interest for a specific method • Please review AOAC’s policy on Volunteer Conflict of Interest Ethical Expectations of Expert Review Panel  Members  (con’t) • Respect for Method Authors and Intellectual Property – Each Method Author is encouraged to attend the ERP meeting – Each candidate methods (not yet adopted or published as Official Methods of Analysis of AOAC INTERNATIONAL ) are still the intellectual property of the method author.  Therefore, the information is shared only with the vetted ERP members and is available during the meetings.  Please do not distribute the information without expressed written permission from an appropriate AOAC staff liaison. – Be clear about and justify how additional recommended work is a requirement for First Action, a requirement for Final Action consideration, or something recommended, but not necessary. – Keep your focus on the science

9

ERP Chair Responsibilities

Before Meeting

During Meeting

Moderate discussions based  on agenda

Work with staff on meeting  coordination

Engage staff to encourage  members to reach decision  points

Review submitted and/or  assigned methods

Engage staff on procedural  questions

Review method reviews if  applicable

Engage discussion on feedback  mechanism

Review SMPR(s) and/or  relevant guidance and criteria

ERP Chair Responsibilities

Other Efforts and  Recognitions Can nominate methods for  OMB Award

After Meeting Review Meeting Report  and Approve Final Version

Can nominate ERP members  for OMB Award

Assist with any follow up on  methods

Can assist in identifying  methods for review

Assist in Publication  Reviews

Can serve as a guest editor for  the Journal

10

Roles and Responsibilities

AOAC Official Methods Board Vet and approve stakeholder panel chair & voting members Vet and approve ERP membership and AOAC Experts Render decisions on status of First Action methods (Final Action,  repeal, etc…) Assign a liaison to each stakeholder panel and ERP Coordinate OMB Awards AOAC Expert Review Panels Review methods and meet in person to render decisions on  methods for First Action Official Methods SM status. Track First Action Official Methods SM and modify, if necessary Recommend First Action methods after 2 years or less to OMB  for Final Action, continuance, or Repeal Participate in Consulting Service and PTM reviews for OMA and  harmonized PTM and harmonized OMA method studies AOAC Experts Review and approve PTM validationtesting protocol documentation Peer review of PTM validation manuscript and supporting  documentation AOAC Research Institute ‐ PTM Expert Reviewers Peer Review of PTM validationmanuscripts and supporting  documentation

AOAC Research Institute Independent Laboratories Conduct independent evaluation of candidate method using AOAC  approved testing protocols AOAC Stakeholder Panels Develop  voluntary consensus standards  Assign working groups to  draft standards method performance  requirements Voting members demonstrate  consensus on behalf of  stakeholders AOAC Staff Coordinate method reviews and method approval activities Coordinate OMB meetings Provide trainings and orientations Maintain website and communication Document and publish actions and decisions Coordinate standards development activities Publish standards and methods AOAC Research Institute Technical Consultants Draft validation protocols in Consulting Service for assigned methods

Facilitate PTM evaluation of assigned candidate methods Facilitate comments/responses for assigned OMA reviews

Questions?

Thank you 

11

Candidate Method  #

Reviewers

Method Title

Method Authors

Primary Reviewer Secondary Reviewer

ALO‐001

Raw Materials and Finished Products

Charles Metcalfe

Edwards 

He

Determination of Phenolic Compounds in Dietary Supplements and  Dietary Ingredients Containing Echinacea

Michael Chan, Elizabeth Mudge, Paula Brown

He

Es Safi

ECH‐001

GIN‐001  (Resubmission)

Determination of Select Nonvolatile Ginger Constituents by HPLC  with UV‐Vis Detection

Hong You, Bailey Ireland, Michael Moeszinger, Haoshu Zhang, Laura  Snow, Scott Krepich, Vivian Takagawa

Solyom

Brown

Determination of Ginsenoside Content in Panax ginseng and  Panax  quinquefolius Root Materials and Finished Products

Paula N. Brown, Jamie Finley, Ronan Yu and Michael Chan (BCIT)

Zhang

Anton

GSG‐001

Hee‐Won Park, Gyo In, Sung‐Tai Han, Myoung‐Woo Lee, So‐Young  Kim, Kyung‐Tack Kim, Byung‐Goo Cho, Gyeong‐Ho Han, and Il‐Moo  Chang (Waters) Park

Simultaneous Determination of 30 Ginsenosides in Panax ginseng  preparations using ultra performance liquid chromatography

Chan

GSG‐002

Determination of Kavalactones and Flavokavains in Kava Dietary  Supplements and Dietary Ingredients

Paula N. Brown, Ying Liu, Jensen A. Lund, Susan J. Murch (BCIT)

KAV‐001

Bzhelyansky

Metcalfe

HPLC Analysis Method Development for Kavalactones and  Flavokavains in Kava Extract

Yijn Tang and Chris Fiends (Applied Food Sciences, Inc.)

KAV‐002

Zhou

Chan

KAV‐003

Detection of Flavokavines (A, B, C) in Cultivars of Kava Using HPLC

V. Lebot, T.K.T. Do, L. Legendre

Szpylka

Solyom

Meissner and Haberlein, validation report provided by Mathias  Schmidt and conducted by Steffen Radtke, Gabriele Adis, Eva  Maute, Katherina Kardos, and Janina Schnabel

HPLC Analysis of Flavokavins and kavapryones from Piper  methysticum

Rimmer

Tuzimski

KAV‐004

SAM‐001

Unknown SAMe Method – Submission Pending

Joseph Zhou, Sunshineville Health Products  

Yang

Gumustas

SKU‐001

Unknown Skullcap Method – Submission Pending

Sidney Sudberg, Alkemist Labs

Rimmer

Zhang

Xiao Qiu – Eurofins Supplement Analysis Center, Eurofins Scientific,  Inc.  Haoshu Zhang – Eurofins Supplement Analysis Center, Eurofins  Scientific, Inc. 

Determination of active Vitamin B12 (Cobalamin) in Dietary  Supplements and Ingredients by Reversed‐phase Liquid  Chromatography: Single‐laboratory validation

B12‐001

Zielinski

Rithruthai

AOAC STAKEHOLDER PANEL ON DIETARY SUPPLEMENTS EXPERT REVIEW PANELS

• Method Access [ERP Only – Password Required]

• SPDS Standard Method Performance Requirements

AOAC Candidate Method #ECH-001 Determination of Phenolic Compounds in Dietary Supplements and Dietary Ingredients Containing Echinacea

Author(s): Michael Chan, Elizabeth Mudge, Paula Brown Submitted by: Elizabeth Mudge, BCIT

Method applicability: Attached is the SLV and collaborative study for analysis of phenolic compounds in echinacea raw materials and finished products. This method is suitable for the determination of major phenolic compounds in raw materials and select finished products containing E. purpurea, E. angustifolia, and E. pallida parts, including hard-shell capsules and tinctures. The phenolic compounds determined using this method are caftaric acid, chlorogenic acid, cynarin, echinacoside, and cichoric acid.

Attachments: 0

Submitter notes: See above.

Primary reviewer: Kan He, Herbalife Secondary Reviewer: Nour Eddine ES-SAFI, MohammadV University

2018 SMPR ERPs - METHOD REVIEW FORM

Submission ID

4103431460326220968

Submission Date

2018-08-17 14:25:46

AOAC Expert Review Panel: Method Review

Reviewer Information

Name

Kan He

E-mail

kanh@herbalife.com

Organization

Herbalife Nutrition

Remember, the main purpose of your review is to ensure the method conforms to the applicable SMPR. View and download SMPRs here:

SPDS SMPRs SPSFAM SMPRs

Method Review

Determination of Phenolic Compounds in Dietary Supplements and

Title of Method

Dietary Ingredients Containing Echinacea

AOAC Candidate Method Number (e.g. ALN-01)

ECH-001

Applicable SMPR

I. Summary of the Method SMPR2017.015

A. Summary of the Method

The method describes the determination of five major phenolic compounds (caftaric acid, chlorogenic acid, cichoric acid, cynarin, and echinacoside) in herbal raw materials and herbal extracts of three most used Echinacea species including E. angustifolia, E. pallida, and E. purpurea through a chromatographic analysis using RP-18 column (150 x 4.6 mm i.d., 5µm) and quantitated by UV detector at 330nm wavelength.

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.

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.

B. Is there information demonstrating that the method meets the SMPR Method Performance Requirements using the Reference Materials stated in the SMPR? If not, then specify what is missing and how this impacts demonstration of performance of the method. method performs within the SMPR Method Performance REquirements table specifications for all analytes in the SMPR applicability statement? If not, please specify what is missing and whether or not the method's applicability should be modified. C. Is there information demonstrating that the

YES. The reference materials used in the method are five phenolic standards, caftaric acid, chlorogenic acid, cichoric acid, cynarin, and echinacoside from legitimate botanical standard suppliers.

YES. The required method performance parameters by SMPR include analytical range, LOQ, recovery, repeatability (RSDr) and reproducibility (RSDR). The method authors reported 6 calibration points for the 5 phenolic standards for linearity determination. The tested concentration range for each analyte is around 0.2 to 1000, 1 to 1000, or 2 to 1000 µg/mL, which is equivalent to the analytical range of 0.004% to 20%, 0.02% to 20% or 0.04% to 20% by w/w when weighing 125mg sample and dissolving in 25 mL of solvent. The method authors also give an effective analytical range as 0.004% to 6% for total phenolic contents (five of the phenolic compounds) after testing many different samples. These ranges meet the SMPR criteria for analytical range of 0.01% to 5% requirement. In the two SLVs from the supporting documents, the obtained limits of quantification were from 0.007% to 0.036% (w/w) and 0.003% to 0.012% for the five individual phenolic compounds, respectively, while the SMPR requires a general LOQ is not more than 0.01%. Therefore the LOQs meet or closely meet the SMPR criteria. In the same supporting documents, the recoveries were obtained in the range of 94.1% to 108% for the five individual phenolic compound and 97.6% to 99.8% for all the 5 phenolic compounds, respectively, meet the SMPR 90% to 107% criteria. In an interlaboratory collaborative study, the method authors reported the repeatability RSDr values 0.6% to 5.0% and the reproducibility RSDR 3.6% to 7.9% for precision evaluation after many tests on the different samples of three different Echinacea species, different plant parts (aerial or roots), and different dose forms (raw powder, powdered extracts, alcohol tincture). The results satisfy the SMPR RSDr and RSDR, which are not more than 6% and 8%, respectively, excepting for the high RSDr (6.9%) and RSDR (21.7%) for Echinacea glycerite tincture, which is suggested by the authors that the method is not suitable for the analysis of the analytes in tincture preparations.

IV. General Submission Package

A. 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?

NO. Since the chemicals and reagents related to the method are commonly used in analytical labs, such as acetonitrile, methanol, and phosphoric acid, plus the 5 individual botanical standards, no further precautionary statement is needed.

B. 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. C. 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. D. Based on the supporting information, is the method written clearly and concisely? If no, please specify the needed revisions.

YES, partially. In the manuscript, the system suitability test was performed by making 5 replicate injections of the check standard at the lowest point of the analytical range. However, SMPR also requires a check standard with the middle point of the analytical range, a blank sample, and a control sample for system suitability tests, while the manuscript does not provide such tests.

YES, partially. Same procedure was performed as described in manuscript.

YES. Overall, the method is written clearly and concisely. However, some descriptions may be oversimplified. For example, it cannot follow how are the different concentrations of mixed calibration standard solutions were made from the individual standard stock solutions without reading the original publications. In the determination of analytical range, the manuscript claimed that the analytical range tested for each analyte was up to 1000 µg/mL. No testing data were presented in the manuscript or supporting documents. No sonication is involved in sample preparation, while ultrasonic bath is listed in the section of Apparatus. Good resolution of the five analytes of interest is achieved under the HPLC chromatographic condition in all the three Echinacea spp. The sample preparation is straight forward and was optimized for the sample weight, particle size, extraction solvent, ratio, and extraction efficiency. The method demonstrated good precision and also the recoveries from both blank and plant matrixes for the five phenolic compounds. Analytes were stable in the use of extraction condition and course of analysis. The method is not suitable for the analysis of the proposed analytes in glycerite tincture. The LOQs for some compounds were higher than SMPR, e.g. 0.036% for echinacoside, while SMPR is not more than 0.01%. Sample size for raw materials (125mg) might be too small and may affect precision analysis. Use of guard column was not included in method validation. The manuscript presents a typical HPLC method and is a summary of the method validation date from two SLVs and one interlaboratory collaborative study. The method allows for the determination of five major phenolic compounds in three Echinacea species and is applicable to raw materials, extracts and dietary supplements and most commonly used dosage forms found in marketplace. The data collected from SLVs and collaborative study meets most SMPR criteria.

E. Based on the supporting information, what are the pros/strengths of the method?

F. Based on the supporting information, what are the cons/weaknesses of the method?

G. Any general comments about the method?

Recommendation for the Method

Do you recommend this method be adopted as a First Action and published in the Official Methods of Analysis of AOAC INTERNATIONAL? Please specify rationale.

YES, the method has proven its performance as mentioned above.

Do you recommend this method be adopted as a First Action and published in the Official Methods of Analysis of AOAC INTERNATIONAL? Please specify rationale.

YES, the method has proven its performance as mentioned above.

2018 SMPR ERPs - METHOD REVIEW FORM

Submission ID

4102753691227342077

Submission Date

2018-08-16 19:36:09

AOAC Expert Review Panel: Method Review

Reviewer Information

Name

Nour Eddine ES-SAFI

E-mail

nouressafi@yahoo.fr

Organization

Mohammed V University in Rabat

Remember, the main purpose of your review is to ensure the method conforms to the applicable SMPR. View and download SMPRs here:

SPDS SMPRs SPSFAM SMPRs

Method Review

Title of Method

Determination of Phenolic Compounds in Dietary Supplements and Dietary Ingredients Containing Echinacea

AOAC Candidate Method Number (e.g. ALN-01)

AOAC Candidate Method # ECH-001

Applicable SMPR

AOAC SMPR 2017.015

I. Summary of the Method

A. Summary of the Method

The ECH-001 method presents results dealing with the use of an HPLC-UV method for the quantitative analysis of phenolic compounds (caftaric acid, chlorogenic acid, cynarin, echinacoside, and cichoric acid) in raw materials, dietary ingredients and dietary supplement producst containing echinacea (Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida).

The proposed method is proposed with three publications giving more details of the obtained results.

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).

Yes. The proposed method has been applied for the quantitative analysis of caftaric acid, chlorogenic acid, cynarin, echinacoside, and cichoric acid which are the phenolic compounds indicated in the SMPRs. The used Echinacea matrixes include raw materials (whole and powdered), dietary ingredients (aerial and root extracts) and dietary supplements (tinclure, powders, hard capsules and sof gels) as indicated in the SMPRs.

Yes. The analytical technique used in the method meet the SMPR.

Yes

Yes

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. The definitions specified in the SMPR are used and appropriately applied in the proposed method.

B. Is there information demonstrating that the method meets the SMPR Method Performance Requirements using the Reference Materials stated in the SMPR? If not, then specify what is missing and how this impacts demonstration of performance of the method. method performs within the SMPR Method Performance REquirements table specifications for all analytes in the SMPR applicability statement? If not, please specify what is missing and whether or not the method's applicability should be modified. C. Is there information demonstrating that the

No. In the proposed method, there is no indication of the use of reference material indicated in tables 2 & 6 of the SMPR.

In of the given publication (Brown et al., 2010) the 5 phenolic compounds used as standards were those indicated as reference testing material in the SMPR.

Yes, the method presents several data showing that it performs within the SMPR. Some of the given results are however out of those indicated in the SMPRs.

1- Analytical range of caftaric acid and cichoric acid : 0.02 to 20 % (0.01 to 5 % in the SMPR).

2- LOQ: caftaric acid (0.013 %), echinacoside (0.036 %), cichoric acid (0.015 %). The indicated values are out of what is requested in the SMPR (less or equal to 0.01 %). 3- Recovery: The authors indicated that the recovery for total phenolics was determined to be 97.6 % and 99.8 % which are within the values indicated in the SMPR. An examination of one of one of the given publication (Brown et al., 2010) showed that echinacosde recovery was 108.4 % which is out of the SMPR (90-107 %). This was also the case of caftaric acid and chlorogenic acids where recovery values of 108 and 114 % are indicated (Brown et al., 2011). 4- Repeatability: Some of the given RSDr values are out of those of the SMPRs. This is the case of echinacoside for which values of 3.39 and 3.37 % (Brown et al., 2010) were indicated (less or equal to 3 in the SMPR).

5- Reproducibility: Many RSDR values (Brown et al., 2016) are not within the range indicated in the SMPRs.

IV. General Submission Package

A. 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? B. 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.

No

Yes

C. 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. D. Based on the supporting information, is the method written clearly and concisely? If no, please specify the needed revisions. E. Based on the supporting information, what are the pros/strengths of the method? F. Based on the supporting information, what are the cons/weaknesses of the method?

Yes

The proposed method refers to previously reported publications (Brow et al., 2010, 2011 & 2016). I think that the obtained results need to be gathered and the proposed method be reformatted from existing publications into a single document. This will enhance the quality of the method and make easier its reading and understanding.

Procedure is well described. Peaks of the obtained chromatographic profiles are well separated.

The proposed method needs to be formatted in a new complete one.

G. Any general comments about the method?

None

Recommendation for the Method

Do you recommend this method be adopted as a First Action and published in the Official Methods of Analysis of AOAC INTERNATIONAL? Please specify rationale.

I think that the method ECH-001 is a promising method for the quantitative analysis of the indicated phenolic compounds (caftaric acid, chlorogenic acid, cynarin, echinacoside and cichoric acid) in raw materials, dietary ingrédients and dietary suppléments containing Echinacea. I would then support this method for First Action but would recommend the method to be rewritten and proposed in a more complete form making it easy to read and to understand and where the SMPR requirements will be clearly indicated for each individual phenolic compounds.

AOAC Candidate Method #GSG-001 Determination of Ginsenoside Content in Panax ginseng and Panax quinquefolius Root Materials and Finished Products

Author(s): Paula Brown, Jamie Finley, RonanYu and Michael Chan Submitted by: Paula Brown, BCIT

Method applicability: Determination of Ginsenoside Content in Panax Ginseng and Panax quinquefolius root materials and finished products

Attachments: 2

Submitter notes: See above.

Primary reviewer: Yanjun Zhang, Herbalife Secondary Reviewer: Anton Bzhelyansky, US Pharmacopeia

2018 SMPR ERPs - METHOD REVIEW FORM

Submission ID

4108131349472263746

Submission Date

2018-08-23 00:58:55

AOAC Expert Review Panel: Method Review

Reviewer Information

Name

ANTON BZHELYANSKY

E-mail

ANB@USP.ORG

Organization

USP

Remember, the main purpose of your review is to ensure the method conforms to the applicable SMPR. View and download SMPRs here:

SPDS SMPRs SPSFAM SMPRs

Method Review

Title of Method

Determination of Select Ginsenosides in Dietary Supplements and Dietary Ingredients

AOAC Candidate Method Number (e.g. ALN-01)

GSG-001

Applicable SMPR

AOAC SMPR® 2017.014

I. Summary of the Method

A. Summary of the Method

A gradient method utilizing conventional chromatography with low-wavelength UV detection. Malonyl ginsenosides are subjected to base hydrolysis prior to analysis. Methodology, its single-lab validation and interlaboratory study were published in JAOAC in 2011 and 2013.

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). 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. B. Is there information demonstrating that the method meets the SMPR Method Performance Requirements using the Reference Materials stated in the SMPR? If not, then specify what is missing and how this impacts demonstration of performance of the method.

Six ginsenosides specified in the Applicability statement are adequately addressed, as is their determination in Panax ginseng and P. quinquefolius. Pseudoginsenoside (F11) and notoginsenoside R1, indicated as optional, have not been covered; P. notoginseng, indicated as an optional analyte, was not evaluated.

Yes

Yes

Sure does

III. Review of Information in Support of the Method

Analytical terminology beyond reproach

Yes

C. Is there information demonstrating that the

The supplied published data supports the LOQ roughly an order of magnitude lower than SMPR requires. Analytical range, recovery, repeatability and reproducibility all meet SMPR requirements; Data from additional studies such as solution stability at different storage conditions and extraction efficiency significantly enhance the value of the method and should make it into the final version of the method.

method performs within the SMPR Method Performance REquirements table specifications for all analytes in the SMPR applicability statement? If not, please specify what is missing and whether or not the method's applicability should be modified. A. 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? B. 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. C. 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. D. Based on the supporting information, is the method written clearly and concisely? If no, please specify the needed revisions.

IV. General Submission Package

No

Considering incomplete resolution of the protopanaxatriols, Rg1 and Re, method could benefit from specifying a minimum resolution requirement

The participants of the interlaboratory study were required to successfully complete system precision (%RSD NMT 5% for replicate standard injections), resolution NLT 1.5 and peak tailing NMT 2. Should the latter be specified, it is suggested to consider adding a decimal to the peak tailing requirement, if not reduce it to NMT 1.5%.

Minor editorializing of the procedure is desirable: e.g., removal of references to notoginseng, clarity with the recommended analytical column, references to kava in the title of Table 5, the mention of a 100-µL volumetric pipet

E. Based on the supporting information, what are the pros/strengths of the method?

• Chromatography looks good, but it would be desirable to see actual sample chromatograms. It would be ultimately beneficial to transfer the method to a core-shell column and to achieve more reliable separation between Rg1 and Re. • The extraction procedure for the root powder omits the final 1-mL rinse of the sample that is used in reference [1]. This is a minor point, but worth addressing. • Hesitations arise from deriving the total post-hydrolysis volume from a combination of 70% methanol, and two aqueous solutions. The magnitude of error may be small, but this is a source of uncertainty that could be eliminated. E.g., procedure could be conducted in a 10-mL volumetric by combining 8 mL sample solution with 800 µL each of base hydrolysis solution and neutralizing solution, and subsequent adjustment to volume. • Another instance of small-volume jitters: filtration of the 1 mL of post- derivatization solution through a syringe filter. It would be ideal to confirm non- retention of analytes on the filter; the common practice is to filter a larger volume and discard the first couple of mLs of the filtrate, but it would be beneficial to check. • Are samples thermo-labile? Can sitting on the bench during the hydrolysis step and repeated sonication affect recovery? A short study can answer this. • Analytical column conundrum: 1. The reference [1] lists the column as C18(2) – presumably, Phenomenex Luna (?); 2. In reference [2] it is listed as Phenomenex Luna C18; 3. In the method draft the column is alternatively referred to as Poroshell 120 Bonus-RP (p. 47) or C18(2) (p. 48). It is likely that the former is a typo, although it could be a chromatographer's slip, and it would be desirable to try implementing the method on a superficially porous column. • Not certain why the method would instruct to make single injections of each test solution; most labs have internal SOPs and most analysts are comfortable with at least duplicate injections.

F. Based on the supporting information, what are the cons/weaknesses of the method?

None substantial, but minor tweaks are proposed above

G. Any general comments about the method?

Despite the fact that the publication in JAOAC presumes rigorous peer review, it would be desirable to have access to raw analytical data, with weights, peak areas and concentrations, not just the summary tables

Recommendation for the Method

Do you recommend this method be adopted as a First Action and published in the Official Methods of Analysis of AOAC INTERNATIONAL? Please specify rationale.

Yes

Made with FlippingBook Learn more on our blog