Cannabis ERP

SPSFAM EXPERT REVIEW PANEL FOR CANNABIS METHODS

ERP Chair: Melissa Phillips, NIST

AUGUST 13, 2018 - Teleconference

contact: spsfam@aoac.org

AOAC Stakeholder Panel on Strategic Food Analytical Methods Cannabis Expert Review Panel

Monday, August 13, 11:00am – 1:00pm ET ERP Teleconference

A G E N D A

1. Welcome and Introductions

Melissa Phillips, NIST (ERP Chair)

2. Review of AOAC Volunteer Policies & ERP Process Overview and Guidelines Deborah McKenzie, AOAC INTERNATIONAL

3. Review of Methods For each method, the assigned ERP members will present a review of the revised method manuscripts, after which the ERP will discuss the method and render a decision on the status for each method.

A. CAN-001

a. Indick Review b. Hudalla c. Schaffer Review d. Discussion and Vote

B. CAN-002

a. Johnson Review b. Sweeney Review c. Discussion and Vote

4. Final Action Requirements for Approved Method(s) 5. Adjourn

SPSFAM Sugar and Fructan ERP 08/01/2018 – v1.0

AOAC SPSFAM CANNABIS EXPERT REVIEW PANEL

METHODS AND SMPR ACCESS

• AOAC SMPR 2017.001 (Concentrates) • AOAC SMPR 2017.002 (Plant Material) • METHOD ACCESS (ERP ONLY – PASSWORD REQUIRED)

AOAC INTERN AT TO N AL

STAKEHOLDER PANEL ON STRATEGIC FOOD ANALYTICAL METHODS (SPSFAM):

EXPERT REVIEW PANEL (ERP) FOR Cannabinoid Quantitation

in Extracts and/or Plant Material

OFFICIAL CHAIR’S EXPERT REVIEW PANEL REPORT

ACKNOWLEDGMENT

The undersigned Chair hereby confirms that the following document has been reviewed and constitutes the final revised version of the Official Chair’s Report for the SPSFAM Cannabis Expert Review Panel held on December 15, 2017. n MELISSA PHILLIPS, SPSFAM CANNABIS ERP CHAIR

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STAKEHOLDER PANEL ON STRATEGIC FOOD ANALYTICAL METHODS EXPERT REVIEW PANEL ON QUANTITATION OF CANNIBINOIDS IN EXTRACTS AND PLANT MATERIALS

METHODS FOR CONSIDERATION: Conclusion: The Expert Review Panel (ERP) reviewed two (2) methods for cannabinoid quantitation, which were submitted in response to an AOAC Call for Methods issued on June 9, 2017. Methods Reviewed: Each method collected by AOAC for consideration by this ERP was assigned a set of reviewers. Methods reviewed included: • CAN-01: Quantitation of Cannabinoids in Cannabis Dried Plant Materials and concentrates Using Liquid Chromatography – Diode Array Detection Technique with Optional Mass Spectrometric Detection o Author(s): Lukas Vaclavik, Frantisek Benes, Ales Krmela, Veronika Svobodova, Jana Hajslova and Katerina Mastovska o Submitted by: Katerina Mastovska, Covance • CAN-02 : Leaner and Greener Analysis of Cannabinoids o Author(s): E Mudge, SJ Murch, PN Brown The methods were reviewed against AOAC SMPR 2017.001, Quantitation of Cannabinoids in Cannabis Concentrates and/or AOAC SMPR 2017.002, Quantitation of Cannabinoids in Dried Plant Materials. The decisions of the December 15, 2017 ERP session are shown below.

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CANNABIS ERP MEETING – DECEMBER 15, 2017 Cannabis ERP Members Present: Melissa Phillips, US NIST (Chair) Susan Audino, S.A. Audino & Associates Yohei Arao, Shimadzu Ramkumar Dhandapani, Phenomenex Nour-Eddine ES-SAFI, Mohammad V University, Rabat Peter Indick, Microbac Laboratories Holly Johnson, Alkemist Labs Katerina Mastovska, Covance Elizabeth Mudge, BCIT Curtis Phinney, Curtis S. Phinney CNS Paul Reibach, Smithers Viscient Kate Rimmer, US NIST Christian Sweeney, Cannabistry Tomasz Tuzimski, Medical University of Lublin Rodger Voelker, OG Analytical Sudhakar Yadlapalli, First Source Laboratory Solutions

Cannabis ERP Members Absent:

Heather Harris, Hills Beaver Creek Schools Christopher Hudalla, Waters Corporation Janah Marcu, Green Standard Diagnostics Markus Roggen, OutCo Michael Schaffer, Psychemedics

AOAC Staff: Scott Coates, Christopher Dent, Dawn Frazier, Deborah McKenzie, Tien Milor

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Cannabis ERP Method Reviews and Decisions

AOAC Method #

Manuscript Title, Submitter and Reviewers

ERP Decisions / Consensus

Title: Quantitation of Cannabinoids in Cannabis Dried Plant Materials and Concentrates Using Liquid Chromatography- Diode Array Detection Technique with Optional Mass Spectrometric Detection Author(s): Lukas Vaclavik, Frantisek Benes, Ales Krmela, Veronika Svobodova, Jana Hajslova and Katerina Mastovska

MOTION to move this method to First Action Official Methods of Analysis Status (Rimmer/Audino) 10 in favor, 2 opposed, 1 abstentions. The motion failed.

Reasoning of Dissenters:

Indick: The SMPRs clearly call for Limit of Quantitation (LOQ) and recovery data and neither are clearly provided. Further, he had concerns about the extraction and processing. Yadlapalli: Agreed, LOQ and recovery data is needed.

Submitted by: Katerina Mastovska, Covance

After further discussion, the ERP agreed that more data is required. ____________________________________________________________ First Action Requirements:

Primary Reviewer: Pete Indick, Microbac Secondary Reviewers: Mike Schaffer, Psychemedics and Christopher Hudalla, Waters

• Processing information o Ideal bulk sample size recommendations o Grinding size • Spiked recovery o Spike addition (low level plant acceptable)

CAN-001

o Well characterized standard mixture used for spiked recovery. o Required compounds: CBDA, THC o Levels: LOQ (Low and Mid Range, as per SMPR, on the compounds listed above) • Present LOQ data in matrix data as a consolidated table for all compounds. MOTION to accept the First Action Official Methods recommendations as presented (Sweeney / Johnson). 13 in favor, 0 opposed, 1 abstention. The motion passed.

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AOAC Method #

Manuscript Title, Submitter and Reviewers

ERP Decisions / Consensus

Title: Leaner and Greener Analysis of Cannabinoids

MOTION to move this method to First Action Official Methods of Analysis Status (Johnson/Sweeney) 8 in favor, 3 opposed, 3 abstentions. The motion failed. Reasoning of Dissenters: Audino: Does not meet SMPR requirements. LOQ not met for CBD. Fortification issues. Indick: SMPR requirements not completely satisfied. Reibach: Fortification is an issue. ____________________________________________________________ First Action Requirements: Spiked recovery o Spike addition (low level plant acceptable) o Well characterized standard mixture used for spiked recovery. o Required compounds: CBDA, THC o Levels: LOQ (Low and Mid Range, as per SMPR, on the compounds listed above) • SMPR: o Redo LOQ study (CBD) o Recovery • Add column temperature MOTION to accept the First Action Official Methods recommendations as presented (Audino / Voelker). 13 in favor, 0 opposed, 1 abstention. The motion passed. • Processing information o Grinding size •

Author(s): E Mudge, SJ Murch, PN Brown

Submitted by: Elizabeth Mudge, BCIT Primary Reviewer: Holly Johnson, Alkemist Labs Secondary Reviewers: Christian Sweeney, Cannibistry

CAN-002

Action Items: AOAC Staff to prepare ERP report and distribute to method authors and ERP members.

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CAN-001 Re-submission Review Form

Submission Date

2018-08-10 09:00:43

Name

Pete Indick

Email

peter.indick@microbac.com

Organization

Microbac Laboratories

Has the resubmitted method CAN-001 met the requirements outlined on December 15, 2017?

Yes

Please provide justification for your answer.

Section F - "Preparation of Test Samples" now includes bulk sample size and the maximum grinding size.

Spiking is discussed on pages 12 & 13 and demonstrates acceptable recoveries (Table 8) on both the low and mid range concentrations for both CBDA and THC.

Table 7 presents LOQ (and MDL) data in a matrix for all compounds

CAN-001 Re-submission Review Form

Submission Date

2018-08-12 16:55:59

Name

Christopher Hudalla

Email

Chris.Hudalla@ProVerdeLabs.com

Organization

ProVerde Laboratories

Has the resubmitted method CAN-001 met the requirements outlined on December 15, 2017?

Yes

Please provide justification for your answer.

- The bulk sample sizes and grinding have been specified.

- The spike recovery was evaluated for THC and CBDA in dried plant material at low and mid range spiking, with acceptable levels of recovery.

- The LOQs were presented for dried plant material, concentrate and for oils.

CAN-001 Comments – Chris Hudalla - Use of laboratory blender to powderize cannabis flower: Blender type homogenization damages product and ruptures trichomes, unless cryogrinding is employed. A more gentle grinding or sieve grinding method should be considered if cryogrinding is not available. - The term “Oils” as used multiple times in this documents is vague. Is it meant to signify the oil extracted from the plant (which would be a concentrate)? Is it flower that is extracted with, or concentrate that is subsequently dissolved in an oil, like hemp seed oil or coconut oil? If it is this latter definition, there is no mention of the potential for matrix interferences, which often co- elute with cannabinoid signals, interfering with quantitation by UV methods. For UV quantitation, the UV spectrum for a collected peak should be matched against a library reference spectrum to ensure peak purity. The same issues may arise in the analysis of food or other complex matrices. - For cannabis oils, many regulatory requirements include reporting concentration in terms of mg/unit, which for liquids (oils), is typically in mg/mL. Would recommend adding in a density calculation. Maybe instead of weighing out 0.5g, use a glass syringe to or positive displacement pipette to weigh out 0.5mL of oil. Use the recorded weight in the measurement for weight percent, but based on density, can also report mg/mL. All other prep for these samples would remain the same. - Has extraction efficiency of ethanol been evaluated against other options? Isopropanol? More non-polar solvents tend to have higher efficiency in extracting cannabinoids. - Validation activities appear to be fairly comprehensive, hitting all the key elements of a robust validation.

CAN-002 Re-submission Review Form

Submission Date

2018-08-13 06:45:17

Name

Holly Johnson

Email

hjohnson@ahpa.org

Organization

American Herbal Products Association

Has the resubmitted method CAN-002 met the requirements outlined on December 15, 2017?

Yes

Please provide justification for your answer.

Revisions were made as per the ERP recommendations for First Action:

1. Grinding size: • Particle size was determined t be less than 0.5mm. 2. Spike Recovery:

• Additional spike recovery studies were performed with CBDA and THC at 2 levels each, a low and mid-range spike. Recovery was calculated within acceptable ranges as per the SMPR, except for the lowest level spike of CBDA which was spiked at 0.006% (w/w); no recovery parameters were given in the SMPR for spike levels under 0.1%. 3. Redo LOQ study for CBD: • LOQ study was redone specifically for CBD using a low CBD strain. LOQ was determined at 0.04% (w/w) which is below the SMPR requirement of 0.1%. 4. Column temperature was clarified at 25C, as requested.

CAN-002 Re-submission Review Form

Submission Date

2018-08-08 09:47:28

Name

Christian Sweeney

Email

csweeney@cannabistry.com

Organization

Cannabistry Labs

Has the resubmitted method CAN-002 met the requirements outlined on December 15, 2017?

No

Please provide justification for your answer.

First Action Requirements were all addressed, but clarifications need to be made as the work does not appear to match the FAR/SMPR in all cases.

The processing information regarding grinding size in the summary of revisions is acceptable based on the ERP report.

The spiked recovery experiments were carried out on low level plant as requested by the ERP and well characterized standard mixtures were used for spiked recovery on CBDA and THC as requested. Some clarification around the 19.17mg/mL THC solution would be helpful, but not critical. According to the FAR document the spiked recovery levels were meant to be tested at the Low and Mid Range per the SMPR which represents 0.1-1% (Low) and >1-25% (Mid). This submission failed to test spike recovery in the Mid Range for either compound and both CBDA spike levels fell below the Low Range. Because the CBDA samples fell below the low range parameter per the SMPR the recovery values cannot be determined to be within specification. The Recovery values for THC are both within specification for the Low Range. The LOQ study determined the CBD LOQ to be well below the LOQ SMPR of 0.1%. It would be helpful to clarify the spike amount as it is initially referred to as a 0.25ug spike and then later referred to as 0.25ppm. This would suggest a 1mL dilution, but that is not referenced in the method.

The column temperature for the LC method was added as requested.

Based on the First Action Requirements as listed, this addendum does not satisfy the ERP/SMPR requirements.

Cannabis Expert Review Panel, August 13, 2018 1. Melissa Phillips, NIST (Chair) 2. Yohei Arao, Shimadzu 3. Ramkumar Dhandapani, Phenomenex 4. Nour Eddine ES-SAFI, Mohammed V University, Rabat

5. Heather Harris, Hills Beaver Creek Schools 6. Christopher Hudalla, Waters Corporation 7. Peter Indick, Microbac Laboratories 8. Holly Johnson, Alkemist

9. Janan Marcu, Greed Standard Diagnostics 10. Katerina Mastovska, Covance Laborator 11. Elizabeth Mudge, BCIT 12. Curtis Phinney, Curtis S. Phinney, CNS 13. Paul Reibach, Smithers Vincent 14. Kate Rimmer, NIST 15. Markus Roggen, OutCo 16. Michael Schaffer, Psychemedics 17. Christian Sweeney, Cannibistry Labs 18. Tomasz Tuzimski, Medical University of Lublin 19. Rodger Voelker, OG Analytical 20. Sudhakar Yadlapalli, First Source Laboratory Solutions

TWO THIRDS OF THIS EXPERT REVIEW PANEL MUST BE PRESENT (14)

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

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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.

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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

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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.

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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.

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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

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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

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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.

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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

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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

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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 

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AOAC INTERNATIONAL

First Action Official Methods of Analysis SM Guidance Documents

I.

Process Flowchart

II. Process Guidelines III. Expert Review Panel – Policies & Procedures

Alternate Pathway to Official First Action Method Status

Funded Stakeholder Panel

x x x

Managed by AOAC HQ Properly vetted by OMB

Carefully documented and transparent

Working Groups

Standard Method

x Managed by AOAC HQ x Properly vetted by OMB x Carefully documented and transparent

Performance Requirements

Expert Review Panels

Call for Methods & Literature Search

x Managed by AOAC HQ x Properly vetted by OMB x Carefully documented and transparent

Official First Action Method

JAOAC OMA Web ILM

x ERPs continue to monitor for two years, until method is either advanced or removed from system (period is extendable for active data collection) x ERP recommends Final Action to OMB x OMB grants Final Action status

Updated 2011Ͳ5Ͳ11

AOAC INTERNATIONAL (updated 2011-0ϱ-ϭϭ by APOFAMS Task Force) ALTERNATIVE PATHWAY to OFFICIAL FIRST ACTION METHOD STATUS REQUIREMENTS Expert Review Panels -Must be supported by relevant stakeholders. -Constituted solely for the ERP purpose, not for Standard Method Performance Requirements (SMPR) purposes or as an extension of an SMPR. -Consist of a minimum of seven members representing balance of key stakeholders. -ERP constituency must be approved by the Official Methods Board (OMB). -Holds transparent public meetings only. -Remains in force as long as method in First Action Status. Official First Action Method Status decision -Must be made by an ERP constituted or reinstated post 2011-03-28 for Official First Action Status Method Approval (OFASMA). -Must be made by an ERP vetted for OFASMA purposes by OMB post 2011-03-28. -Method adopted by ERP must ƉĞƌĨŽƌŵ ĂĚĞƋƵĂƚĞůLJ ĂŐĂŝŶƐƚ the SMPR set forth by the stakeholders. -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 - Method becomes Official First Action on date when ERP decision is made. -Methods to be drafted into AOAC format by a knowledgeable AOAC staff member or designee in collaboration with the ERP and method author. -Report of OFAMS decision complete with ERP report regarding decision including scientific background (references etc) to be published concurrently with method in traditional AOAC publication venues. Method in First Action Status and Transitioning to Final Action Status -Further data indicative of adequate method reproducibility (between laboratory) performance to be collected. Data may be collected via a collaborative study or by proficiency or other testing data of similar magnitude. -Two years maximum transition time (additional year(s) if ERP determines a relevant collaborative study or proficiency or other data collection is in progress). -Method removed from Official First Action and OMA if no evidence of method use available at the end of the transition time. -Method removed from Official First Action and OMA if no data indicative of adequate method reproducibility is forthcoming as outlined above at the end of the transition time. -ERP to recommend Method to Official Final Action Status to the OMB. -OMB decision on First to Final Action Status

EXPERT REVIEW PANELS --Policies and Procedures—

Introduction Expert Review Panels (ERP) are created to provide stakeholders with an expert resource to evaluate analytical solutions to identified needs and concerns. The ERP will be tasked to search for appropriate methods, issue a “Call for Methods” in the ILM and other avenues, and critically evaluate all collected methods. The ERP will then recommend appropriate methods (as submitted or modified) for adoption as Official First Action methods or for further validation. The ERP, if requested by the Committee/Topic Advisor, would be expected to assist in identifying appropriate materials to be used in the validation studies and in reviewing the protocols for such studies. Outline of ERP establishment process An Expert Review Panel is established as follows: A stakeholder or stakeholder body submits a request for the creation of an ERP to the AOAC staff. The request includes a description of the subject area, the desired outcome, and should include a list of recommended subject experts with supporting documentation (see "Qualifications of Expert Reviewers"). Included with this list of recommended subject experts could be a recommendation for an ERP Chair. The request is forwarded to the appropriate AOAC Chief Science Officer (CSO) who identifies potential members for the ERP from a recognized Pool of Experts, a Call for Experts on the AOAC website, and from the stakeholder recommendations. The candidate list and supporting documentation are forwarded to the Chair of the OMB who will assign the review to at least two OMB members. The OMB reviewers will review the candidates for expertise and perceived conflicts of interest and the OMB may then approve the members of the ERP. A Chair for the ERP is also selected. The Chair of the ERP will organize meetings of the ERP to discuss and make recommendations relative to method recommendations, the method(s) to be further validated, and the materials to be used in the validation studies. The conclusions and recommendations of the ERP will be transmitted by the ERP Chair to the OMB and stakeholder body. The stakeholder body will proceed with implementation of the ERP's recommendations by organizing the appropriate SLV study and other items needed for application. Pool of Potential Expert Reviewers : Candidates for ERPs are pulled from the following sources. Upon acceptance of the request for the formation of an ERP, a Call for Experts is posted on the AOAC website for a minimum of two weeks. Candidates can then contact AOAC with their interest and credentials. Also, AOAC maintains a Pool of Experts database containing a list of

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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AOAC members willing to serve as experts and cataloging their education, experience, and other applicable credentials. Candidates can also be recommended by the stakeholder(s). Note: Candidates (except for the chair) do not need to be members of AOAC. The appointment of experts to an ERP will be for a minimum of 3 years. Qualification of Expert Reviewers: To qualify as an Expert Reviewer, the candidate must meet one of the following requirements: (1) Demonstrated knowledge in the appropriate scientific disciplines. (2) Demonstrated knowledge regarding data relevant to adequate method performance. (3) Demonstrated knowledge of practical application of analytical methods to bona fide diagnostic requirements. These qualifications must be clearly described in a CV submitted to the CSO and kept on file at AOAC headquarters. Duties: Members of the Pool of Experts will be called upon to serve on ERPs as needed, and to review documents prepared in the course of the project. These documents may include: (1) procedural documents on how methods will be selected and how single laboratory validation studies will be done; (2) methods submitted for consideration as Official First Action Methods; (3) methods submitted for selection for further validation studies; (4) protocols to be used for single laboratory validation studies; (5) the selection of methods to be considered for full collaborative studies; and (6) validation study reports. Expert Review Panel: The CSO selects candidates for an ERP from the Pool of Experts database, the Call for Experts on the AOAC website, and from candidates recommended by the stakeholders. Selection of ERP candidates is based upon their knowledge and experience to adequately evaluate the scope of the study and the anticipated number of submitted methods. The size of the ERP will be sufficient to assure the necessary expertise is present. The CSO may recommend one of the Panel members to serve as Chair. The CSO submits the following to the OMB Chair: The original submission package, a list of all candidates considered for inclusion on the ERP, the slate of recommended candidates, and a list of possible alternates. Explanations for the ERP choices may be included by either the CSO or a stakeholder if desired. The OMB Chair will delegate two members of the OMB to perform a review. The reviewers submit their recommendations in writing to the OMB. The OMB then votes on the reviewers’ recommendations. This vote can be either by email or during an OMB meeting. The OMB may choose not to select one or more individuals on the Panel as submitted and may or may not accept the recommendation of the CSO for the panel Chair. A majority of those voting will be required for approval. The vote of the Chair will break any tie. The CSO, ERP members, and stakeholder body are notified of the vote within one week. Conflict of Interest: It is incumbent upon each ERP member to avoid any known or potential conflicts of interest and make these known to the CSO and OMB Chair. Each pool member chosen for an ERP will be asked to agree to the AOAC Policies and Procedures on Conflicts of Interest evidenced by completing a Conflict of Interest Form.

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If a Pool member being considered to serve on any particular panel is an author, or his/her laboratory is the source of a method under consideration by the Panel, they must so indicate to the CSO or OMB Chair. At the discretion of the CSO or OMB, the names of such Pool members may be removed from consideration, or they may be considered to serve on the ERP with the understanding that a deliberate effort will be required to avoid any known or potential conflicts of interest. In these latter cases, assignments of individual methods for peer review will be made in such a way by the Chair that ERP members will not review any method for which they are an author or co-author, or for which their laboratory is the source; and, most importantly, the Chair will require that they abstain from voting on such a method during the final method selection process. The CSO or OMB may also allow Pool members that qualify under the requirements of expert reviewers, but for whom there is a known or potential conflict of interest to be present as an observer on any particular Panel. In these cases, and only at the discretion of the Chair, observers may provide comments, but only if and when called upon by the Chair to do so. Non-disclosure Statement: All members of an ERP must have signed the AOAC Volunteer Acceptance Form. For certain contracts, each Pool member or observer chosen may be asked to sign a non-disclosure statement agreeing not to discuss or disclose confidential information presented and discussed during meetings of the ERP. Meetings of the ERP: The ERP Chair will organize meetings of the ERP, to review the methods and accompanying validation data, score them numerically, and prepare a summary report. Meetings of the ERP can include voting members of the Panel, and non-voting members (AOAC staff, stakeholder members, and observers). The CSO may assist the Panel Chair in facilitating meetings. The members of the Panel are to review distributed documents before the meeting. To facilitate the process, the Chair may assign primary and secondary reviewers for each method. The primary and secondary reviewers prepare a short critique of the method that is distributed or presented to the ERP. If both the primary and secondary reviewers conclude that the method should not be considered further, the ERP Chair may call for a vote by the Panel; if a unanimous vote to drop a method without further discussion results, the Chair removes the method from further consideration. The Panel then discusses each of the remaining methods in turn. Method Selection Process: The ERP will evaluate all of the methods in a scientifically unbiased manner. Occasionally, a large number of analytical methods of variable quality are encountered. When this occurs, the following “pre-screening” procedure is suggested to eliminate methods that are not satisfactory. The Chair of the ERP with the assistance of at least one other member of the ERP may review all of the methods and remove unsatisfactory methods from consideration. The remainder of the methods would be sent to the ERP members for review.

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The basic requirements for selection of methods for further validation studies will be: fitness for purpose, applicability to the scope needed, clarity of method description, satisfactory performance characteristics, and single laboratory validation data. To assist the Panel, the AOAC will provide a “Methods Selection Worksheet,” which may be modified at the discretion of the ERP. ERP members will identify the best method(s) for further validation, and identify any modifications to be made to the method. An example of the Method Selection Worksheet is attached. Samples: The ERP will be asked to recommend the specific materials (matrices) to be included in the subsequent validation studies, along with detailed justifications. Summary Report: The Chair of the ERP prepares a Summary Report clearly enunciating the recommendations of the Panel, the manner in which these conclusions were reached, any modifications of the method(s) chosen, and the materials (matrices) to be included in the validation studies. The report is to be submitted to the ERP in a timely fashion after the concluding ERP meeting. Comments are also due back to the ERP Chair in a timely fashion. The report is then sent to the stakeholders and a copy is forwarded to the Chair of the OMB. Post-ERP Activities: AOAC retains the right to call on the panelists, as well as members of the Industry Groups, for continued assistance in the subsequent validation studies. This may include (1) help in obtaining the required samples for use in the subsequent validation studies, as well as participating laboratories; (2) help in developing and reviewing the validation study protocols; and (3) help in reviewing the data resulting from the validation studies and reviewing the manuscript describing the results. These activities will be coordinated by the CSO.

Method Selection Worksheet

Method Title: Method Number: Overall evaluation score (1being lowest, 10 being highest): Additional Factors to Consider:

Recommendation: Signature (date):

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Expert Review Panel Selection Criteria: 1. AOAC paid consultants and AOAC staff should not act as Chairs of ERPs. 2. Members of the BoD may act as voting members but it is recommended that they sit as non-voting members of the panel, unless the CSO can demonstrate that there are so few experts in the field available to the community that they are needed to move the project forward.

3. Paid consultants of AOAC and AOAC staff may not serve as voting members on ERPs.

4. If a single business location is represented by more than one person on an ERP, that location shall have only one vote.

5. The Chair of the ERP must be a member of AOAC INTERNATIONAL.

Appeals Process: ERP - Openness of Process and Appeals:

The entire ERP review process is fully open. Any interested party (person, agency, organization, association, company, Chief Scientific Officer (CSO), or group) shall have the right to comment. Appeals or comments are sent to the AOAC Staff. Technical decisions by the ERP are final and are not subject to review or appeal. Other questions or issues regarding procedures, conflict of interest, or impropriety may be

appealed to the President of the AOAC INTERNATIONAL. All written concerns will be considered and given a response.

If there is disagreement between the CSO and the Official Methods Board reviewers, the CSO may appeal to the Chair of the Official Methods Board for consideration. The Official Methods Board can select an impartial panel to review the issue, which must report to the Official Methods Board with a resolution within 21 days of its assignment.

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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