SPSFAM Meeting eBook March 2017

AOAC INTERNATIONAL Presents… the Stakeholder Panel on Strategic Food Analytical Methods (SPSFAM)

MONDAY, MARCH 13, 2016, 1:00 p.m . Room: Salon C-D-E

MARRIOTT WASHINGTONIAN CENTER 9751 WASHINGTONIAN BLVD. GAITHERSBURG, MARYLAND UNITED STATES

contact: spsfam@aoac.org

AOAC INTERNATIONAL Presents… the Stakeholder Panel on Strategic Food Analytical Methods (SPSFAM)

MONDAY, MARCH 13, 2016, 1:00 p.m . Room: Salon C-D-E

MARRIOTT WASHINGTONIAN CENTER 9751 WASHINGTONIAN BLVD. GAITHERSBURG, MARYLAND UNITED STATES

contact: spsfam@aoac.org

Stakeholder Panel on Strategic Food Analytical Methods - Chair Biography

Co‐Chair, SPSFAM Erik Konings Nestle Research Center Erik Konings studied higher professional laboratory education with majors in analytical and clinical chemistry. After graduating in 1984, he started his professional career at the then called Food Inspection Service in Maastricht, the Netherlands. In 2001 he completed his PhD study “Dietary folates in human nutrition” at Maastricht University. During this study, he obtained an MSc-degree in epidemiology. He is (co)author of more than 30 scientific publications. In September 2008 he started at the European Food Safety Authority (EFSA) in Parma, Italy, for a secondment as Scientific Officer at the Data Collection and Exposure Unit, and from there accepted, in June 2009, a position at the Nestlé Research Centre in Lausanne, Switzerland, currently in a role as Food Safety & Quality expert. He is active in several Standard Developing Organisations as AOAC INTERNATIONAL (Past-President), ISO, CEN, and IDF, and participates in the Codex Committee on Methods of Analysis and Sampling (CCMAS).

PRESENTER BIOS

SUSAN AUDINO, Audino & Associates, LLC Susan Audino obtained her PhD in Chemistry with an analytical chemistry major, physical and biochemistry minor areas. Susan was the recipient of NSF Chemometric Graduate Fellowship and was a visiting scientist at NIST where she completed her graduate research. She currently owns and operates a consulting firm to service chemical and biological laboratories, is an A2LA Lead Assessor and Instructor, and serves as a Board Member for the Center for Research on Environmental Medicine in Maryland. She is also serving as Quality Director for several laboratories and has worked with a variety of laboratories to establish and/or improve their quality management systems. Susan has been studying the chemistry and applications of cannabinoids and provides scientific and technical guidance to medical marijuana dispensaries, testing laboratories, medical personnel, and regulatory agencies. Dr. Audino’s interest most directly involves marijuana/cannabis consumer safety and protection, and promotes active research towards the development of Official Test methods specifically for this industry. In addition to serving on Expert Review Panels, she has been working closely with AOAC to develop interest and movement toward the development of scientifically sound methodologies for the cannabis sector. Prior to her study of chemistry, Dr. Audino received advanced degrees and practiced psychology for more than a decade. THIERRY DELATOUR, Nestlé Dr. Delatour is a Lead Scientist at Nestlé Research Centre in Lausanne, Switzerland where he specializes in response in analytical chemistry to emerging issues and crises. Prior to this, he was a Group Leader at Nestlé Research Centre where he managed a team of experts dedicated to the development of analytical methods in the Quality & Safety Department. These methods have been implemented in R&D Centre, PTC and NQAC. Dr. Delatour obtained his Ph.D. from Centre d’Etudes Nucléaires de Grenoble in France, a Master of Advanced Studies at Université Joseph Fourier, and an Engineer in Chemistry Degree at Institut de Chimie et Physique Industrielles. BRIAN SCHANEBERG, Starbucks Coffee Co. Brian Schaneberg, Ph.D., is the Global Scientific & Regulatory Affairs Director for Starbucks Coffee Company. Brian has over 15 years of natural products experience in the area of dietary supplements and herbals. Brian was also the Quality & Food Saftey and Scientific & Regulatory Affairs Director for Mars Botanical, a division of Mars, Inc. focusing on cocoa flavanol science and products. Before Mars Botanical, he was the Director of Technical Services at ChromaDex, Inc. in Irvine, California and was an Associate Research Scientist at the National Center for Natural Products Research at the University of Mississippi under the guidance of Dr. Ikhlas Khan, in a position funded by the US FDA for the development of methods to ensure the quality and safety of botanicals and dietary supplements. Over the years, Brian has worked closely with trade groups, industry, academia and government leaders. He has been a member of various

review committees including NIH grants, analytical validation ERPs at AOAC and the Registry of Carcinogens. Brian also had the pleasure of holding an adjunct faculty position at the University of Colorado, Denver, advising a student that received his MS in Analytical Chemistry isolating phytochemicals and developing analytical testing procedures for Horse Chestnut. Brian has a Ph.D. in Organic Chemistry from Virginia Commonwealth University and a B.A. in Chemistry with a minor in Biology from Central College in Iowa. He has authored or co-authored more than 50 publications and presentations. DARRYL SULLIVAN, Covance Laboratories Darryl Sullivan is a Fellow of AOAC and has been an active member since 1980. He has served terms as secretary, president-elect, president, past president, and director of the Board of Directors, and previously served a three-year term as chair of the Official Methods Board, and is currently serving as Chair of the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals. In 2012 Darryl lead a very successful AOAC engagement with government and industry thought leaders in India and China on behalf of SPIFAN. He is also active with the Stakeholder Panel for Strategic Food Analytical Methods and the Stakeholder Panel for Agent Detection Assays. Sullivan also served a three-year term as a director on the AOAC Research Institute Board of Directors. He was a founding member and chair of the Presidential Task Force on Dietary Supplements and a member of the Task Force on Bacillus anthracis, as well as the AOAC Task Force on Nutrition Labeling and the AOAC Task Force on Sulfites. Prior to chairing the OMB, he served as a member and chair of the Methods Committee on Commodity Foods and Commodity Products. Sullivan was a founding member of the AOAC Technical Division on Reference Materials and served three terms on the Division's Executive Board. A staunch supporter of the Association, Sullivan was active in the e-CAM and Scholar I projects at AOAC, has exhibited at the annual meetings for many years, has presented hundreds of papers and posters at AOAC meetings and regularly publishes his research in the journal of the AOAC. He has also presented a significant number of papers on behalf of AOAC at other scientific meetings in many different parts of the world.

Draft, Do Not Distribute

AOAC Stakeholder Panel on Strategic Food Analytical Methods (SPSFAM)

Meeting Minutes Sunday, September 18, 2016, 8:30 a.m. – 12:00 p.m.

Attendees

SPSFAM Members (Present during all or part of the meeting):

Erik Konings, Nestlé (SPSFAM Chair) Susan Audino, SA & Associates, LLC Lei Bao, Nestlé Justin Bickford, ELISA Technologies François Bourdichon, Danone Dan Braese, LGC Group Amy Brown, Florida Dept. of Agriculture Paula Brown, BCIT Carolyn Burdette, NIST Anton Bzhelyanski, USP Bob Clifford, Shimadzu Scientific Instruments David Cunningham, Ocean Spray Cranberry Thierry Delatour, Nestlé Jon DeVries, DeVries & Associates Quanyin Gao, Herbalife Russell Gerads, Brooks Applied Labs Esther Campos Gimenez, Nestlé Tetsu Goto, Shinshu University (Ret.) Cathy Halverson, US Tax and Trade Bureau Norma Hill, US Treasury (Ret.), AOAC President Greg Hostettler, Perrigo Holly Johnson, Alkemist Labs George Joseph, AsureQuality NZ Diana Kavolis, The Hershey Company

Travis Ruthenburg, SC Labs André Santos, Agilent Olga Shimelis, MilliporeSigma Darryl Sullivan, Covance Brian Schaneberg, Starbucks Jayant Shringarpure, Tyson Foods Inc. Christopher Smith, Coca-Cola Lanny Smith, Vicam Matt Snyder, SPEX Kathy Stenerson, MilliporeSigma Cheryl Stephenson, Eurofins Joan Stevens, Agilent Rebecca Stevens, Restor Corp. John Szpylka, Mérieux NutriSciences Eric Verdon, ANSES Jian Wang, CFIA Wayne Wargo, Abbott Paul Winkler, SCIEX Bryan Wirthwine, Q Laboratories Seth Wong, TEQ Analytical Jason Wubben, Archer Daniels Midland Sudhakar Yadlapalli, First Source Lab

Estela Kneeteman, INTI Barbro Kollander, National Food Agency of Sweden Terry Koerner, Health Canada

John Lawry, Covance Cindy Ludwig, AOCS Soo K. Lee, FDA Alex Liu, SCIEX Huafen Liu, SCIEX

Lifu Ma, Certified Labs Sandy Mangan, SPEX Farzaneh Maniei, Coca-Cola Vicki Manti, Danone Kate Mastovska, Covance

Mary McBride, Agilent Josh Messerly, Eurofins Ang Wei Min, HAS Singapore Bill Mindak, FDA Allen Misa, Phenomenex Deepali Mohindra, Thermo Fisher Lee Sun New, SCIEX Gary Niehaus, NEOMED/CDX Vincent Paez, SCIEX Josephine Pompei, WSDOH Eric Poitevin, Nestlé Rick Reba, Nestlé

Dorothy Yang, Agilent Jinchaun Yang, Waters Yang Zhou, Eurofins Jerry Zweigenbaum, Agilent Richard Zywicki, Covance

Klaus Reif, Phytolab Joe Romano, Waters Adam Ross, LGC Standards

AOAC Staff Members (Present during all or part of the meeting):

Jim Bradford Scott Coates Christopher Dent

Dawn Frazier Nora Marshall Tien Milor

Robert Rathbone

Draft, Do Not Distribute

Minutes

I.

Welcome and Introductions

Jim Bradford opened the meeting and led introductions throughout the room. He then gave the floor to Erik Konings, Chair of SPSFAM. Konings highlighted the AOAC policies and procedures found in the meeting eBook 1 and advised all SPSFAM members to familiarize themselves with it. Konings then asked for a motion to approve the meeting minutes from the March 24, 2016 SPSFAM meeting minutes.

MOTION by Winkler to approve the March 16, 2016 Meeting Minutes. Second by Boison. 22 in favor, 0 opposed, 0 abstentions. The motion passed.

Konings then provided a presentation 2 regarding the history of SPSFAM and the success of the 2015 Working Group Initiative, which allows standards development working groups to be formed by organizations coming together to support them. Konings also updated SPSFAM on the status of current Expert Review Panels (ERPs): Kombucha ERP will be held in the afternoon of September 18, 2016 and Food Allergens ERP will be held in the afternoon of September 19 th . Konings invited Rick Reba, Chair of the Heavy Metals ERP, to the floor to update the panel on their work. Reba explained that the protocol for the heavy metals in food method has been drafted and Reba is coordinating a collaborative study. Reba invited any interested labs to contact him. Samples are expected to be shipped in November. Konings advised that the Heavy Metals Working Group will not be reconvened without support from new or existing Organizational Affiliates (OAs). Konings then introduced Susan Audino, Chair of the SPSFAM Working Group on Cannabis Potency. Audino took the floor and gave a presentation 3 on the background and fitness for purpose of cannabis potency. Audino acknowledged and thanked the sponsors of this working group – GW Pharmacuticals, SC Laboratories, SCIEX, SPEX, Sigma Aldrich and CEM. She proceeded to review the background of medical cannabis, its use in foods, the significance of testing these foods, analytical needs, major challenges, existing methods, and lack of regulatory guidance before proposing the following fitness for purpose: Working Group Launch: Cannabis Potency

II.

Standard Method Performance Requirements (SMPRs) for quantitative methods for various measurements of cannabinoids in raw materials and extracts.

After a lengthy discussion regarding the legal and analytical challenges facing cannabis testing, the group returned to the proposed fitness for purpose and modified it to read:

1 https://griegler-aoac-org.cld.bz/September-2016-SPSFAM-Book 2 ATTACHMENT 1: SPSFAM UPDATE PRESENTATION 3 ATTACHMENT 2: LAUNCH PRESENTATION: CANNABIS POTENCY WORKING GROUP

Standard Methods Performance Requirements (SMPRs) for quantitative methods for various measurements of cannabinoids in raw materials, extracts, topical applications and foods. MOTION by Audino to accept the fitness for purpose statement as amended. Second by Konings. 20 in favor, 0 opposed, 2 abstained.

The motion passed and the SPSFAM Working Group on Cannabis Potency was formally launched.

III.

Working Group Launch: Proanthocyanidins in Cranberry (PAC) Products

Konings then introduced Brian Schaneberg, Chair of the SPSFAM Working Group on PAC. Schaneberg provided a presentation 4 on the issue of proanthocyanidins in cranberry products. He reviewed the background of the analyte, including the uniqueness of PACs in cranberries, the significance of the issue, the general analytical needs (quick and easy), the challenges, existing methods and regulatory guidance. He then proposed the following fitness for purpose for the PAC Working Group: The method should be applicable to the analysis of cranberry fruit, juice, beverage, dried cranberry, cranberry sauce, ingredients (concentrates, extracts and powders) and dietary supplement formulations, applicable to two potential purposes: (1)Quantitative QC method able to quantify total proanthocyanidin content, preferentially as the total sum of all individual oligomers and polymers present, or alternatively as the total sum with reference to a suitable surrogate standard, in samples typically ranging from 0.01% to 55% on a w/w basis; and (2) a Qualitative method to verify authenticity, able to provide information on the distribution of proanthocyanidin oligomers and polymers present and confirm presence of A-type versus B-type

After a brief discussion, Konings called for a motion on the proposed fitness-for-purpose statement.

MOTION by Schaneberg to accept the PAC fitness-for-purpose as presented. Second by Mastovska. 22 in favor, 0 opposed, 0 abstentions.

The motion carried and the SPSFAM Working Group on PAC was formally launched.

IV. Update on the International Stakeholder Panel on Alternative Methodologies (ISPAM)

Konings provided a brief update on ISPAM. 5 He indicated that ISPAM working groups are looking into rapid food allergen detection focusing on egg, milk, tree nuts and peanuts; which in some ways compliments the SPSFAM work on allergens. Konings said that he looks forward to continuing collaboration between ISPAM and SPSFAM.

V. Potential Future Topic: Emerging Contaminants and Multi-Residue Analysis of Veterinary Drugs

Konings invited Thierry Delatour to the floor. Delatour is Suggroup Chair of AOAC’s Chemical Contaminants & Residues in Food Community. Konings explained that this presentation, on behalf of the Community, does not constitute a working group launch; rather it is a potential topic for SPSFAM to work on if there is enough interest among the panel to generate funding for such an

4 ATTACHMENT 3: LAUNCH PRESENTATION - PROANTHOCYANIDINS IN CRANBERRY PRODUCTS WORKING GROUP 5 ATTACHMENT 4: ISPAM UPDATE PRESENTATION

effort. Delatour then provided a presentation 6 detailing AOAC’s current activities in the areas of contaminants and veterinary drugs, current regulations and health issues, quality testing, available literature and existing methods, and the current analytical needs. He stated that a method is needed that will demonstrate full compliance of veterinary drugs , and he encourages SPSFAM members to seek support for a working group on this topic. Following a brief discussion on the topic, Frazier took an action to work with the community to identify specific needs and get the support to potentially launch a working group in March, 2017.

VI.

Other Business and Next Steps

Konings continued the conversation on potential new topics for SPSFAM. By straw poll, he determined that about one-third of those present would be interested in a working group on sugars, and a smaller number of those present would be interested in a project on plastic microbeads; giving SPSFAM three potential future projects to work on. With no further business, Konings adjourned the meeting at 11:30 a.m.

Actions

1. All who are interested in joining the cannabis and/or PAC working groups should sign up for them at https://form.jotform.com/52325189177158

2. AOAC Staff to work with working group chairs to set up first teleconference meetings

3. Frazier to work with the communities to secure support for the potential new SPSFAM topics

Attachments

Attachment 1: SPSFAM Update Presentation Attachment 2: Launch Presentation: Cannabis Working Group Attachment 3: Launch Presentation: P roanthocyanidins in Cranberries Working Group Attachment 4: ISPAM Update Attachment 5: Presentation: Emerging Contaminants & Multi Residue Analysis of Veterinary Drugs

6 ATTACHMENT 5: DELATOUR PRESENTATION

MARCH 13, 2017 GAITHERSBURG MARRIOTT WASHINGTONIAN CENTER 9751 WASHINGTONIAN BLVD., GAITHERSBURG, MD, 20878 CONFERENCE ROOM: SALON C-D-E 1:00pm – 6:00pm Eastern Standard Time Registration Opens at 12:00pm STAKEHOLDER PANEL ON STRATEGIC FOOD ANALYTICAL METHODS SPSFAM Chair: Erik Konings, Nestlé A G E N D A

Welcome and Introductions (1:00pm – 1:15pm) Jonathan Goodwin, AOAC and Erik Konings, Nestlé, SPSFAM Chair a. Policies and Procedures b. Approval of September 18, 2016 Minutes SPSFAM Activities Updates (1:15pm – 1:45pm) Erik Konings, Nestlé, SPSFAM Chair a. Working Group Initiative Updates b. SPSFAM Expert Review Panel Updates

I.

II.

III. SMPR Approval Presentations and Consensus* (1:45pm – 3:15pm)

a. Proanthocyanidins in Cranberries (PAC) Working Group (1:45pm – 2:30pm) Brian Schaneberg, Starbucks; Chair of the SPSFAM PAC Working Group b. SMPR Presentation: Cannabis Working Group (2:30pm – 3:15pm) Susan Audino, Audino & Associates, LLC; Chair of SPSFAM Cannabis Working Group Launch of New SMPR Working Groups (3:30pm – 5:00pm) a. Working Group Launch: BPA in Beverages and Water (3:30pm – 4:15pm) Chair: Darryl Sullivan, Covance b. Working Group Launch: Cannabis in Food Products (4:15pm – 5:00pm) Chair: Susan Audino, Audino & Associates, LLC

IV.

V. Future Working Group: Veterinary Drug Residues (5:00pm – 6:00pm) a. Veterinary Drug Residues Joe Boison, Canadian Food Inspection Agency Thierry Delatour, Nestlé Dawn Frazier, AOAC

Adjourn (6:00pm)

VI.

*Item requires a vote

V6

Afternoon Break: 3:15pm-3:30pm

3/07/2017

Stakeholder Panel on Strategic Food Analytical Methods (SPSFAM)

SPSFAM Updates: Working Groups and ERPs

Erik J.M. Konings Nestlé Research Center, Nestec Ltd. Lausanne, Switzerland

Working Group (WG) Initiative

• December 2014, AOAC Board of Directors initiates  WG Initiative  – as an a mechanism for AOAC Organizational Affiliate  members to initiate  relevant standard development  projects using existing AOAC stakeholder panels • Expressed a need for a consensus standards and scientifically  valid fit for purpose consensus methodology • WG supported through AOAC Organizational Affiliates funded  and formed through AOAC staff  • AOAC works with Organizational Affiliates to find additional  Organizational Affiliates with the same need for scientifically  valid fit for purpose methodology – WG will develop SMPR to present to an existing  stakeholder panels for review

Why the new WG Initiative?

• Offers companies the opportunities to solve  challenges without waiting on priorities of existing  stakeholder panels – Advisory Panel participation and discussion • WG’s funded by current OA’s and new companies  interested in addressing immediate needs  – for analytical standards/standard method performance  requirements; and  – scientifically valid fit for purpose methodology

Success for the SPSFAM Working Group Initiative

• Selected Food Allergens – SCIEX Sponsored Working Group to develop SMPR for Selected Food Allergens.   SMPR 2016.002 was developed and approved in March, 2016 • Ethanol in Kombucha – Sponsored by a consortium of Kombucha manufacturers, this working group  developed SMPR 2016.001 which was approved in March, 2016. • Cannabis – Sponsored by a consortium of interested companies, this working group has  drafted two SMPRs for approval at this meeting • Proanthocyanadins in Cranberries – Sponsored by Ocean Spray, this working group has drafted two SMPRs for   approval at this meeting. • BPA in Beverages and Wager – This new initiative has been sponsored by a consortium of companies and the  working group will be launched at this meeting.

SPSFAM Expert Review Panel (ERP) Updates

– SPSFAM ERP for Selected Food Allergens • Two methods submitted to meet AOAC SMPR 2016.002,  Quantitation of Selected Food Allergens. • No methods approved at that time; ERP reconvenes on March  13, 2017 (this morning)  – SPSFAM ERP for Ethanol in Kombucha • Five methods submitted to meet AOAC SMPR 2016.001,  Determination of Ethanol in Kombucha • One method approved at that time.  ERP reconvenes in September,  2017

Getting Involved

• Individuals. – Get involved in a working group – Provide feedback on SMPRs – Submit methods for consideration • Companies. – Consider becoming an AOAC OA and spearhead  a WG  – Provide feedback on SMPRs and submit  methods  – Indentify experts to participate in WG

3/8/2017

AOAC INTERNATIONAL STAKEHOLDER PANEL ON STRATEGIC FOOD  ANALYTICAL METHODS Brian Schaneberg, PhD  Starbucks Coffee Company Proanthocyanidins in Cranberries (PAC) Working Group  SMPR Presentation March 13, 2017

Marriott Washingtonian Center, Gaithersburg, Maryland, USA

Fitness for Purpose As Agreed September 18, 2016

The method should be applicable to the analysis of cranberry fruit, juice, beverage, dried cranberry, cranberry sauce, ingredients (concentrates, extracts and powders) and dietary supplement formulations, applicable to two potential purposes: (1)Quantitative QC method able to quantify total proanthocyanidin content, preferentially as the total sum of all individual oligomers and polymers present, or alternatively as the total sum with reference to a suitable surrogate standard, in samples typically ranging from 0.01% to 55% on a w/w basis; and (2) a Qualitative method to verify authenticity, able to provide information on the distribution of proanthocyanidin oligomers and polymers present and confirm presence of A-type versus B-type.

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SPSFAM PAC Working Group Members

• Brian Schaneberg, Starbucks • Paula Brown, BCIT • Anton Bzhelyansky, USP • Tony Chang, International Chemistry  Testing • David Cunningham, Ocean Spray  Cranberries • Monica Giusti, Ohio State University • Gunter Haesaerts, Pharmatoka • Amy Howell, Rutgers University • Jin Ji, Brunswick Laboratories • Holly Johnson, Alkemist Labs • Erik Konings, Nestlé

• Scott Kuzdzal, Shimadzu • Haiyan Liu, Ocean Spray Cranberries • Kate Merkh, Lassonde Pappas • Masayuki Nishimura, Shimadzu • Melissa Phillips, NIST • Jess Reed, University of Wisconsin • Kate Rimmer, NIST • John Szpylka, Mérieux Nutrisciences • Xianli Wu, USDA

• Scott Krepich, Phenomenex • Christian Krueger, Complete  Phytochemical Solutions

PAC Working Group Work to Date

• 6 teleconferences  (October 2016 – December 2016) • 2 SMPRs Drafted  • Public comment period (January, 2017) • SMPRs made ready for SPSFAM review and  approval

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Background

• Product formulations to deliver effective and  consistent concentrations of proanthocyanidins

• Standardize products for clinical studies

• Impact of processing on and the shelf‐life of  proanthocyanidins in various forms

SMPR Key Points

• (1) Quantitative QC method to support product  manufacture

• (2) Qualitative method to verify authenticity

3

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SMPR Key Challenges

• Liquid and solid products will require different  ranges and system suitability requirements. • Alignment on definition of PACs. • Determined methods would only focus on solubles. • ID method would only focus on A‐type detection. • Reference materials and standard compounds may  be difficult. • ID specificity my be limited due to methods  available.

Comments Submitted

• (1) Quantitation – "Syrups" have not been separately identified as  a dietary supplement matrix in any of the other  dietary supplement SMPRs. No change to SMPR  proposed. • (2) Identification – "Syrups" have not been separately identified as  a dietary supplement matrix in any of the other  dietary supplement SMPRs.  No change to  SMPR proposed.

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Quantitation SMPR

• Applicability – The method will be able to quantify total  proanthocyanidin content as the sum of all  extractable oligomers (> DP2) and polymers  present in cranberry ( Vaccinium macrocarpon )   fruit, juice, beverage, dried cranberry fruit,  cranberry sauce, ingredients (concentrates,  extracts, powders, and presscake) or dietary  supplements (Table 3).

Quantitation SMPR

• Performance Requirements Parameter Requirement

Limit of Quantitation (LOQ)  (%)

≤ 0.01

Analytical Range (%)

≤ 0.03 – 55

Liquids

Solids

Ranges

0.03 – 15% 97 – 103

> 15% ‐ 55%

0.03 – 15 % > 15% ‐ 55%

Recovery (%)

97 – 103

90 ‐ 107

97 – 103

% RSD r % RSD R

< 10   

< 5 < 8

< 15 < 20

< 10 < 15

< 15

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Identification SMPR

• Applicability – The method will be able to identify the  presence of Type‐A proanthocyanidin in 

cranberry ( Vaccinium macrocarpon )  fruit, juice,  beverage, dried cranberry fruit, cranberry  sauce, ingredients (concentrates, extracts,  powders, and presscake); or dietary  supplements (listed in table 2).

Identification SMPR

• Performance Requirements

90% probability of identification with 95% confidence  (33 correct identifications out of 33 samples known  to contain Type‐A proanthocyanidin).*

Selectivity Study

*Some aberrations may be acceptable if the aberrations are investigated, and  acceptable explanations can be determined and communicated to method users.

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Motion

Move to accept the Standard Method  Performance Requirements for: • Quantitation of proanthocyanidin content in  cranberry fruit, juice, beverage, dried cranberry,  cranberry sauce, ingredients (concentrates, extracts  and powders) and dietary supplement formulations. • Identification of Type‐A Proanthocyanidins in  Cranberry Based Foods and Dietary Supplements as presented.

Discussion?

7

DRAFT AOAC SMPR 2016.XXX; Version 5; 19 December 2016 1 2 Method Name: 3

Identification of Type-A Proanthocyanidins in Cranberry -Based Foods

4 5

and Dietary Supplements

Intended Use : 6 7 1. Purpose: AOAC SMPRs describe the minimum recommended performance characteristics 8 to be used during the evaluation of a method. The evaluation may be an on-site 9 verification, a single-laboratory validation, or a multi-site collaborative study. SMPRs are 10 written and adopted by AOAC Stakeholder Panels composed of representatives from the 11 industry, regulatory organizations, contract laboratories, test kit manufacturers, and 12 academic institutions. AOAC SMPRs are used by AOAC Expert Review Panels in their 13 evaluation of validation study data for method being considered for Performance Tested 14 Methods or AOAC Official Methods of Analysis , and can be used as acceptance criteria for 15 verification at user laboratories. Consensus-based reference method.

16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

2. Applicability :

The method will be able to identify the presence of Type-A proanthocyanidin in cranberry ( Vaccinium macrocarpon ) fruit, juice, beverage, dried cranberry fruit, cranberry sauce, ingredients (concentrates, extracts, powders, and presscake); or dietary supplements (listed

in table 2).

3. Analytical Technique :

Any analytical technique that detects the analytes of interest and meets the method

performance requirements is acceptable.

4. Definitions :

Dietary supplements

A product intended for ingestion that contains a "dietary ingredient" intended to add further nutritional value to (supplement) the diet. Dietary supplements may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders.

Identification

Identification is the characterization of the substance being analyzed, including its chemical, mineral, or biological classification, as applicable. In many investigations the identity of the analyte is assumed and the correctness of the assumption is merely confirmed.

39 40 41

5. Method Performance Requirements :

Table 1: Method Performance Requirements

90% probability of identification with 95% confidence (33 correct identifications out of 33 samples known to contain Type-A proanthocyanidin).*

Selectivity Study

*Some aberrations may be acceptable if the aberrations are investigated, and acceptable explanations can be determined and communicated to method users.

42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80

6. System suitability tests and/or analytical quality control:

Suitable methods will include blank check samples, and check standards at the lowest point

and midrange point of the analytical range.

7. Reference Material(s):

SRM 3281 Cranberry (Fruit)*

SRM 3282 Low Calorie Cranberry Juice Cocktail*

SRM 3283 Cranberry Extract*

SRM 3284 Cranberry-Containing Solid Oral Dosage Form*

*Characterized for organic acids, not proanthocyanidins, but provides a standard,

homogeneous material.

Please contact Dr. Catherine Rimmer, Research Chemist, NIST, for materials.

catherine.rimmer@nist.gov , (301) 975-3651.

Refer to Annex F: Development and Use of In-House Reference Materials in Appendix F: Guidelines for Standard Method Performance Requirements , 19 th Edition of the AOAC

INTERNATIONAL Official Methods of Analysis (2012). Available at:

http://www.eoma.aoac.org/app_f.pdf

8. Validation Guidance :

Information on analytical performance for all claimed matrixes must be submitted. Method developers should evaluate at least 33 samples known to contain Type-A proathocyanidin and at least 33 samples that contain non Type-A proanthocyanidin. Validation data must include examples of non Type-A matrices listed in tier 1 of table 3. Additional non Type-A matrices are listed in tier 2 of table 3. Validation test samples should be blind coded, and randomly mixed with respect to presence or absence of Type-A proanthocyanadin. Appendix D : Guidelines for Collaborative Study Procedures To Validate Characteristics of a Method of Analysis; 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis

(2012). Available at: http://www.eoma.aoac.org/app_d.pdf

Appendix F : Guidelines for Standard Method Performance Requirements; 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis (2012). Available at:

http://www.eoma.aoac.org/app_f.pdf

81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99

Appendix K : Guidelines for Dietary Supplements and Botanicals; 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis (2012). Available on line at:

http://www.eoma.aoac.org/app_k.pdf

9. Maximum Time-To-Result: None

Table 2: Examples of Dietary Supplements

capsules (containing dried cranberry fruit powder, dry extract)

extracts gummies

liquids

powders

softgel capsules (oil &/or water-based)

tablets (containing dried cranberry fruit powder, dry extract)

100 101 102 103

tinctures

104 105 106 107 108 111 112 113 114 115 116 117 118 119 120 121

Table 3: Sources of Non Type-A Proanthocyanidins

Tier 1 (required)

Apple ( Malus domestica Borkh. )

Grape skins, grapeseed extract ( Vitis vinifera L.) 109 Black chokeberry ( Aronia melanocarpa (Michx.) Elliott) or Purple chokeberry ( Aronia arbutifolia 110 (L.) Pers.)

Tier 2 (additional)

Ginkgo biloba L.

Hawthorn ( Crataegus laevigata (Poir.) DC. , Crataegus monogyna Jacq.)

Dragon’s blood ( Croton lechleri Müll.Arg.) Japanese horse chestnut (Aesculus turbinata Blume) Pine bark ( Pinus sylvestris L., Pinus pinaster Aiton )

Plum ( Prunus domestica L.) 122 Other Vaccinium species: huckleberry ( V. ovatum Pursh), highbush blueberry ( V. corymbosum 123 L.), lowbush blueberry ( V. angustifolium Aiton), lingonberry ( V. vitis-idaea L.), European 124 cranberry ( V. (Turcz. ex Rupr.) Schmalh.) 125 Cocoa ( Theobroma cacao L.) 126 Barley ( Hordeum vulgare L.) 127 Sorghum ( Sorghum bicolor (L.) Moench) 128 Blackcurrant ( Ribes nigrum L.) 129 Gooseberry ( Ribes uva-crispa L.) 130 Common bean ( Phaseolus vulgaris L.) 131 Hazelnut ( Corylus avellana L.) 132 Pecan ( Carya illinoinensis (Wangenh.) K.Koch) 133 Pistachio ( Pistacia vera L.) 134

DRAFT AOAC SMPR 2016.XXX; Version 5; November 29, 2016 1 2 Method Name: Quantitation of proanthocyanidin content in cranberry fruit, 3 juice, beverage, dried cranberry, cranberry sauce, ingredients 4 (concentrates, extracts and powders) and dietary supplement 5 formulations. 8 9 1. Purpose: AOAC SMPRs describe the minimum recommended performance characteristics to be 10 used during the evaluation of a method. The evaluation may be an on-site verification, a single- 11 laboratory validation, or a multi-site collaborative study. SMPRs are written and adopted by AOAC 12 Stakeholder Panels composed of representatives from the industry, regulatory organizations, 13 contract laboratories, test kit manufacturers, and academic institutions. AOAC SMPRs are used by 14 AOAC Expert Review Panels in their evaluation of validation study data for method being considered 15 for Performance Tested Methods or AOAC Official Methods of Analysis , and can be used as 16 acceptance criteria for verification at user laboratories. 6 7 Intended Use : Reference method for cGMP compliance.

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

2. Applicability :

The method will be able to quantify total proanthocyanidin content as the sum of all extractable oligomers (> DP2) and polymers present in cranberry ( Vaccinium macrocarpon ) fruit, juice, beverage, dried cranberry fruit, cranberry sauce, ingredients (concentrates, extracts, powders, and

presscake) or dietary supplements (Table 3).

3. Analytical Technique :

Any analytical technique(s) that measures the analytes of interest and meets the following method

performance requirements is/are acceptable.

4. Definitions :

Cranberry Proanthocyanadins

A mixture of oligomeric and polymeric flavan-3-ols, primarily epicatechin and catechin, of the A and

B type.

Dietary Ingredients

A vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent,

extract, or combination of any of the above dietary ingredients. 1

Dietary supplements

A product intended for ingestion that contains a "dietary ingredient" intended to add further nutritional value to (supplement) the diet. Dietary supplements may be found in many forms such as

tablets, capsules, softgels, gelcaps, liquids, or powders.

Limit of Quantitation (LOQ)

1 Federal Food Drug and Cosmetic Act §201(ff) [U.S.C. 321 (ff)

46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96

The minimum concentration or mass of analyte in a given matrix that can be reported as a

quantitative result.

Quantitative method

Method of analysis which response is the amount of the analyte measured either directly (enumeration in a mass or a volume), or indirectly (color, absorbance, impedance, etc.) in a certain

amount of sample.

Repeatability

Variation arising when all efforts are made to keep conditions constant by using the same instrument and operator and repeating during a short time period. Expressed as the repeatability

standard deviation (SD r

); or % repeatability relative standard deviation (%RSD r ).

Reproducibility

The standard deviation or relative standard deviation calculated from among-laboratory data.

Expressed as the reproducibility standard deviation (SD R

); or % reproducibility relative standard

deviation (% RSD R ).

Recovery

The fraction or percentage of spiked analyte that is recovered when the test sample is analyzed

using the entire method.

5. Method Performance Requirements :

See table 1 and 2.

6. System suitability tests and/or analytical quality control:

Suitable methods will include blank check samples, and check standards at the lowest point and

midrange point of the analytical range.

7. Reference Material(s):

Refer to Annex F: Development and Use of In-House Reference Materials in Appendix F: Guidelines for Standard Method Performance Requirements , 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis (2012). Available at: http://www.eoma.aoac.org/app_f.pdf

8. Validation Guidance :

Appendix D : Guidelines for Collaborative Study Procedures To Validate Characteristics of a Method of Analysis ; 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis (2012). Available

at: http://www.eoma.aoac.org/app_d.pdf

Appendix F : Guidelines for Standard Method Performance Requirements; 19 th Edition of the AOAC

INTERNATIONAL Official Methods of Analysis (2012). Available at:

http://www.eoma.aoac.org/app_f.pdf

Appendix K : Guidelines for Dietary Supplements and Botanicals; 19 th Edition of the AOAC INTERNATIONAL Official Methods of Analysis (2012). Available on line at:

http://www.eoma.aoac.org/app_k.pdf

97 98 99

9. Maximum Time-To-Result: None

100 101

Table 1: Method performance requirements (part 1)

Parameter

Requirement

Limit of Quantitation (LOQ) (%)

≤ 0. 01

Analytical Range (%)

≤ 0. 03 – 55

102 103

Table 2: Method performance requirements (part 2)

Liquids

Solids

Ranges

0.03 – 15%

> 15% - 55%

0.03 – 15 %

> 15% - 55%

Recovery (%)

97 – 103

97 – 103

90 - 107

97 – 103

% RSD r % RSD R

< 10 < 15

< 5 < 8

< 15 < 20

< 10 < 15

Table 3: Examples of Dietary Supplements capsules extracts liquids powders softgel capsules tablets

tinctures gummies

3/9/2017

AOAC INTERNATIONAL STAKEHOLDER PANEL ON STRATEGIC FOOD 

ANALYTICAL METHODS Susan Audino, Audino & Associates Cannabis Working Group ‐ SMPR Presentation March 13, 2017

Marriott Washingtonian Center, Gaithersburg, Maryland, USA

Fitness for Purpose  As Agreed September 18, 2016

Standard Methods Performance  Requirements (SMPRs) for quantitative  methods for various measurements of  cannabinoids in raw materials, extracts,  topical applications and foods.

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SPSFAM Cannabis Working Group Members

• Susan Audino, Audino & Associates • Patricia Atkins, SPEX • Roger Brauinger, A2LA • Paula Brown, BCIT • Carolyn Burdette, NIST • Bob Clifford, Shimadzu • Jo Marie Cook, Florida Dept. of Ag • Peter Gibson, GW Pharmaceuticals • Thomas Hartlein, Teledyne Tekmar • Dorota Inerowicz, Indiana State Chemist • Holly Johnson, Alkemist • Erik Konings, Nestlé • Jennifer Donelson, VUV • Kevin George, Eurofins

• Kate Mastovska, Covance • Elizabeth Mudge, BCIT

• Gary Niehaus, Crystal Diagnostics • Masayuki Nishimuram Shimadzu • Melissa Phillips, NIST • Curtis Phinney, Consultant • Klaus Reif, PhytoLab GmbH • Mitzi Rettinger, Millipore Sigma • Kate Rimmer, NIST • Adam Ross, LGC Standards • Travis Ruthenburg, SC Labs • Alicia Stell, CEM • Alan Sutton, GW Pharma • Aniko Solyom, GAAS Analytical • Kathy Stenerson, MilliporeSigma • John Szpylka, Mérieux Nutrisciences

• Julie Kowalski, Phenomenex • Mary Kay Krogull, Eurofins • Julie Kowalski, Restek • Scott Kuzdal, Shimadzu • Robert Lockerman, CEM • Cynthia Ludwig, SAgE

• Jane Weitzel, Consultant • Seth Wong, TEQ Analytical • Josh Wurzer, SC Labs • Hong You, Eurofins

Background

Perspective:  Cannabis Industry Expected to be Worth $50  Billion by 2026 (Bloomberg Markets Report,  September 12, 2016)  Estimated size of the legal US industry (MMJ  and Recreational):  $7.1 Billion in 2016,  increased more than 25% from 2015  89% of Americans support legalization of  medicinal use.  Increased 15% since 2011.  56% Physicians support nationwide legalization  of medicinal cannabis.

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Background: States Assume Control

As of March 2, 2017

Background:  Matrices

• Edible Products – Incorporated into recipes/preparations – Topical • Transdermal • Sublingual/Oral • Inhalation

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Background:  Testing

Most states require testing, including: Chemical • Heavy Metals • Residual Solvents • Content (potencies of select cannabinoids) • Terpenes • Pesticide Residues Microbiological • Aflatoxin B 1 , B 2 , G 1 , G 2 • Ochratoxin A • STEC

Background : Challenges of Testing

To date… o There are no established action levels or  tolerance levels of cannabis contaminants, such  as pesticide residues. o There are no established product label  requirements.

o There is no harmonization of testing  requirements between/among states.

o Active Pharmaceutical Ingredients (APIs) are  not fully characterized in terms of “medicines”

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Background: Challenges of Testing

To date:

There are no consensus or standard  test methods for chemical or  biological testing.

Background : The Cannabis AP & WG

• Six Organizational Affiliates stepped up to  the plate, forming an Advisory Panel to  address the testing issue(s). • Many needs were identified and then  prioritized. • The Working Group focused on the need to  determine most interested cannabinoids in: – Dried Plant Material – Concentrates

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Cannabis Working Group Work to Date

• 1 In Person Meeting (September 2016) • 5 teleconferences  (October 2016 – December 2016) • 2 SMPRs Drafted  • Public comment period (January, 2017) • SMPRs made ready for SPSFAM review and  approval 

SMPR Key Points

• SMPR: Quantitation of cannabinoids in Dried  Plant Materials

• SMPR: Quantitation of cannabinoids in Cannabis  Concentrates

• Identify & Quantify: – Required Cannabinoids:  CBD, CBDA, CBN, THC,  THCA – Additional & Desirable:  CBC, CBCA, CBDVA,  CBG, CBGA, CBDV,  ᇞ 8 THC, THCV, THCVA

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SMPR Key Points

Concentrates

Dried Plant Material

Requirement  (Additional,  Desirable  Cannabinoids  (Table 1b),  including CBN)

Requirement (Pertains to Cannabinoids  in Table 1b)

Parameter

Requirement  THC, THCA, CBDA, CBD,  Individually Reported

Parameter

Limit of Quantitation (LOQ)  (%)

≤ 0.1

Limit of  Quantitation (LOQ)   (% w/w)

≤ 0.3

≤ 0.3

Analytical Range (%)

0.1 – ca. 50*

Analytical Range  (% w/w)

≤ 0.3 – ca. 100

≤ 0.3 – ca. 50

*Lower concentrations may be acceptable as applicable for  cannabinoids listed in Table 1B.

Ranges (%) (Pertains to Cannabinoids in Table 1b)

Ranges (% w/w)

Parameters

Parameters

≤ 0.3 – 1

> 1 ‐ 10 > 10 – ca.  100

0.1 – 1

> 1 ‐ 25 > 25 – ca. 50

95 – 105

97 ‐ 103 98 ‐ 102

Recovery (% w/w)

Recovery (%)

95 – 105

97 ‐ 103

98 ‐ 102

≤ 5

≤ 4

≤ 2

% RSD r

% RSD r

≤ 5

≤ 4

≤ 2

≤ 7

≤ 5

≤ 3

% RSD R

% RSD R

≤ 7

≤ 5

≤ 3

Comments Submitted

5 Comments were received for SMPR –dried  materials. 1. The proposed procedures should add (a)  Instrument Detection Limit (IDL), and (b)  Method Detection Limit (MDL)  Action: WG decided to use LOD which is the  equivalent of IDL, which uses blank matrix  samples;  LOD uses matrix samples.  MDL was  purposefully removed by the WG.

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Comments Submitted

2. LOQ:  The  method should be able to  quantify at lower levels for the minor  cannabinoids because most are below  0.1% in the flowers. ‐ LOQ should be lowered to 0.03‐0.05%  to account for the minor cannabinoids  Action:  Amended Dried Material Tables 2 and 3 to specify  performance requirements are relative to cannabinoids  listed in Table 1b.

Comments Submitted

3. If the LOQ isn’t low enough, additional  columns should be added for the low  contents with expected RSDs. ‐ Additional RSD information should be added.   These could be higher RSDs,  8‐10% because of  the minor levels and inherent variability of the  plants.

 Action: RSD information is consistent with the  current LOQ. No further action is necessary.

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Comments Submitted

4. There should be some kind of information to help an ERP understand the  homogeneity issues that are possible with these plants. 1. They are  resinous, cannabinoids are concentrated in the resin, which can clump  during grinding. 2. Between flower variation can be high, grinding multiple  flowers can impact the homogeneity. 3. Grinding can introduce heat,  which will cause degradation of cannabidiolic acids into neutral forms,  resulting in less accurate results. Grinding would be the best option for  homogeneous samples, but in some cases there are issues with clumped  resin, highly variable samples and additional grinding would impact the  results and lead to inaccurate data. ‐ There should be a comment stating that the method performance should be  demonstrated with homogeneous samples, and note that in some cases materials 

may not meet these criteria due to inherent variation.  Action: Amended Section 8:  Validation Guidance

5. Tables 2 and 3 should identify which  cannabinoids apply ‐ Propose the following changes to Tables 2  and 3 headers:  ”These performance  requirements apply only to the cannabinoids  in Table 1a”

 Action:  Amendments per recommendation.

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Motion

Move to accept the Standard Method  Performance Requirements for: • Quantitation of cannabinoids in Dried Plant  Materials • Quantitation of cannabinoids in Cannabis  Concentrates as presented.

Discussion?

10

DRAFT AOAC SMPR 2016.XXX; Version 2; 21 December 2016 1 2 Method Name:

3 4

Quantitation of cannabinoids in cannabis concentrates

Intended Use : 5 6 1. Purpose: AOAC SMPRs describe the minimum recommended performance characteristics to be 7 used during the evaluation of a method. The evaluation may be an on-site verification, a single- 8 laboratory validation, or a multi-site collaborative study. SMPRs are written and adopted by AOAC 9 Stakeholder Panels composed of representatives from the industry, regulatory organizations, 10 contract laboratories, test kit manufacturers, and academic institutions. AOAC SMPRs are used by 11 AOAC Expert Review Panels in their evaluation of validation study data for method being considered 12 for Performance Tested Methods or AOAC Official Methods of Analysis , and can be used as 13 acceptance criteria for verification at user laboratories. Consensus-based reference method.

14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44

2. Applicability :

The method will be able to identify, and quantify individual cannabinoids (as listed in Table 1a and

Table 1b) present in cannabis concentrates.

3. Analytical Technique :

Any analytical technique(s) that measures the analytes of interest and meets the following method

performance requirements is/are acceptable.

4. Definitions :

Cannabis Concentrates

A product resulting from chemical or physical processing of cannabis sativa or any of its hybrids, largely free of solvents with cannabinoid content higher than the starting material.

Limit of Quantitation (LOQ)

The minimum concentration or mass of analyte in a given matrix that can be reported as a

quantitative result.

Quantitative method

Method of analysis which response is the amount of the analyte measured either directly (enumeration in a mass or a volume), or indirectly (color, absorbance, impedance, etc.) in a certain

amount of sample.

Repeatability

Variation arising when all efforts are made to keep conditions constant by using the same instrument and operator and repeating during a short time period. Expressed as the repeatability

standard deviation (SD r

); or % repeatability relative standard deviation (%RSD r ).