2019 AOAC CASP Book

INAUGURAL MEETING TUESDAY, MARCH 12, 2019

MARRIOTT WASHINGTONIAN CENTER

9751 WashingtonianBlvd Gaithersburg, MD, 20878, USA CONFERENCE ROOM: SALONC/D/E

1:00PM – 5:00PMET Registration at 12:30

INAUGURAL MEETING TUESDAY, MARCH 12, 2019

MARRIOTT WASHINGTONIAN CENTER

9751 WashingtonianBlvd Gaithersburg, MD, 20878, USA CONFERENCE ROOM: SALONC/D/E

1:00PM – 5:00PMET Registration at 12:30

Cannabis Analytical Science Program PROSPECTUS

CASP Objectives • Facilitate a forum where the science of cannabis analysis can be discussed. • Provide a home for the development and maintenance of cannabis standards and methods.

Cannabis-Related AOAC Standard Method Performance Requirements: SMPR 2017.001 Cannabinoids in Cannabis Concentrates

SMPR 2017.002 Cannabinoids in Dried Plant Materials SMPR 2017.019 Cannabinoids in Chocolate

Leveraging its extensive heritage as a global leader in food and agriculture safety standards and analytical methods, AOAC INTERNATIONAL is answering the call of regulators and private sector laboratories to convene experts and approve consensus methods for the analysis of cannabis and hemp in food, feed, plant materials, or other substances of interest to determine the best available science to promote public health.

SMPR 2018.011 Pesticides in Cannabis AOAC Official Methods of Analysis:

AOAC 2018.10 Cannabinoidin Dried Flowers and Oil

AOAC INTERNATIONAL — At a Glance AOAC’s history is intertwined with the development of food safety science in the US:

AOAC 2018.11 Quantitation of Cannabinoids in Cannabis Dried Plant Materials and Concentrates, and Oils

• Consensus Builder • Official Methods of Analysis Publisher • Academic, Industry & Regulatory Collaboration • Laboratory Proficiency Testing Program

• Formed in 1884 at USDA, later part of FDA, AOAC became independent in 1970s • Leader in Standards Development • Global Trade Facilitator • International Member Base

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INITIAL FOCUS

PROPOSAL

Food and food products Consumption of cannabis products is legal and/or becoming legal in a growing number of US states and in Canada. Consumable products include beverages, brownies, butter, chews, cookies, gummies, honey, edible oils, and more. AOAC proposes to begin the CASP program with a focus on food and food products. Potential areas for the development of SMPRs and methods include: accuracy in label claim potency; and/or public safety issues such as detection of pathogens and/or residual solvents. SMPRs may address standards for screening methods that may eventually become Performance Tested Methods . Hemp With the passage of the Agriculture Improvement Act of 2018 (commonly known as the ‘Farm Bill’), the hemp-derived CBD market is projected to increase from about $591 million this year to $22 billion by 2022. AOAC proposes to also focus on development of SMPRs and methods for accurate measurement of CBD in hemp plants, intermediate CBD ingredients, and/or dietary supplements, as well as determination of CBD in pet foods.

Create an AOAC program, to be known as the Cannabis Analytical Science Program (CASP). Government, academic, and contract laboratories; technology providers; private sector organizations; and allied associations will form the analytical community of CASP.

POTENTIAL SERVICES

• Forum to reach consensus for science-based problems, i.e., product / commodity specific guidelines, speciation, best practices • Standard Method Performance Requirements (SMPRs) • Performance Tested Methods (PTM) and Official Methods of Analysis (OMA) • Laboratory operating recommendations (TDLM) • Proficiency testing • Reference materials (TDRM) • Training workshops

AOAC Programs

Examples of Matrix / Analyte Combinations

Accreditation Criteria / Guidelines

SMPRs Methods Education

Training

Testing Materials

Beverages

Cannabinoids Metals Microbial loads Mycotoxins Pathogens Trace materials Cannabinoids Metals Microbial loads Mycotoxins Pathogens Trace materials Cannabinoids THC CBD

Ingredients/ Intermediates

Pet foods

Hemp

THC CBD

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PHASE I GOALS

certification mark. These AOAC-adopted reference methods will result in reliable data to support effective compliance-driven quality control of products and enhance public health .

• Development of a series of SMPRs for cannabis and hemp. The number of SMPRs will depend on funding and direction from the Advisory Panel. • Call for Methods for each of the completed SMPRs. • Creation of one or more Expert Review Panels for candidate methods submitted in response to SMPRs and Call for Methods. TIMETABLE • January to March 2019: Organize an advisory panel consisting of contributors. • March 2019: Advisory panel or townhall meeting to determine priorities. • April – June 2019 : AOAC will identify • June 2019 to Sept 2019 : The working groups will meet by teleconferences to draft SMPRs, recommendations, and guidance documents. • September 2019: The working group chairs will present draft SMPRs for approval during the 2019 AOAC Annual Meeting. • October 2019: Issue a Call for Methods • March 2020: AOAC Expert Review Panel to review methods. You will participate in the development of standards for hemp and cannabis methods . These standards will then be used by method developers to develop methods, and by AOAC to evaluate methods so that resulting Performance Tested Methods and Official Methods of Analysis are fully validated to the high standards of AOAC INTERNATIONAL and meet the analytical needs of the community . AOAC may also offer use of a specially designed AOAC CASP renowned subject matter experts to participate in the working groups and a working groups chair. BENEFITS TO YOU

WHAT AOAC IS ASKING OF YOU *

CASP Pioneer - $10,000 CASP Partner - $5,000 CASP Affiliate - $2,500

All supporters will be listed as Pioneer, Partner, or Affiliate in AOAC communications and outreach, have access to a standing group of technical experts, and the opportunity to participate in the advisory panel at varying levels. As a CASP Pioneer, you would enjoy the benefits highlighted above, plus the use of the AOAC CASP Logo on your related communications, underscoring your leadership in the AOAC CASP program.

AOAC is still seeking additional co-funders for 2019.

CONTACT INFORMATION

If interested in this project and to partner with AOAC, please contact: Alicia Meiklejohn, ameiklejohn@aoac.org AOAC INTERNATIONAL, 2275 Research Blvd., Suite 300 Rockville, MD 20850, Tel: 301-924-7077; ext. 101 www.aoac.org

* NOTE: AOAC INTERNATIONAL cannot accept funding from any organization involved in the cultivation, manufacture, distribution or possession of cannabis as long as it is illegal in the US. (view complete policy: AOAC Policy on Funding CASP 8/26/2018 )

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INITIAL PROJECT SPONSORS - ĂƐ ŽĨ DĂƌĐŚ ϳ͕ ϮϬϭϵ

CASP PIONEER

PerkinElmer R-Biopharm AG Supra Research & Development TEQ Analytical Laboratories Titan Analytical Trilogy Analytical

ABC Testing, Inc. Association of Food and Drug Officials (AFDO) Bia Diagnostics Bio-Rad Industrial Laboratories Materia Medica Labs

CASP PARTNER

CV Sciences Eurofins Scientific

Trace Analytics

CASP AFFILIATE

Charm Sciences ^ >ĂďƐ

Lazarus Naturals DĞĚŝĐĂů 'ĞŶŽŵŝĐƐ

AOAC INTERNATIONAL Cannabis Analytical Science Program (CASP) DRAFT AGENDA Tuesday, March 12, 2019 1:00PM – 5:00PM EDT Room Location: Salons C/D/E Moderator: Palmer A. Orlandi, Jr., Ph.D. (Deputy Executive Director & Chief Science Officer, AOAC INTERNATIONAL) I. WELCOME & INTRODUCTION (Palmer Orlandi – 1:00PM – 1:15PM) Orlandi will open the meeting and welcome attendees, lead introductions of the attendees and outline the purpose of the meeting. ABOUT AOAC, PROCESSES, AND PREVIOUS WORK WITH CANNABIS (Scott Coates, Senior Director, AOAC Research Institute– 1:15PM – 1:35PM) Coates will present an overview of the AOAC processes and summarize AOAC’s previous efforts with cannabis, including an overview of the SMPRs and Official Methods approved. REGULATORY LANDSCAPE FOR CANNABIS AND HEMP (Holly Johnson, Chief Science Officer, American Herbal Products Association – 1:35PM – 1:55PM) Johnson will provide a regulatory overview of cannabis and hemp analysis and the challenges within states that have legalized use of cannabis. Additionally, Johnson will share the impact on regulatory agencies and their challenges for oversight of hemp considering the 2018 signing of the Farm Bill. ORGANIZATIONAL LANDSCAPE (Susan Audino, Audino and Associates – 1:55PM – 2:15PM) Audino will provide an overview of other organizations that have ongoing cannabis and hemp efforts with relevance to CASP. (Palmer Orlandi – 2:15PM – 4:30PM) Based on the priorities identified by the Advisory Panel members, Orlandi will lead a discussion that further defines priorities into specific working groups that will become part of the scope of work for 2019 and prospective work in subsequent years. a. CASP WG1 – Chemical Contaminants (Cannabis & Hemp) - Pesticides, Heavy Metals, Mycotoxins, etc… (Audino) b. CASP WG2 – Cannabinoids (Cannabis and Hemp) in Consumables (Edibles/Beverages, etc…) (Johnson) c. CASP WG3 – Microbial Organisms (Cannabis & Hemp) (Coates) d. Outreach and education opportunities NEXT STEPS (Orlandi/Alicia Meiklejohn, Director of Business Development & Governance, AOAC INTERNATIONAL – 4:30PM – 5:00PM) Orlandi will summarize the top priorities and desired overall scope for CASP with next steps. Meiklejohn will outline the proposed workplan for 2019 resulting from the CASP meeting discussions. III. IV. V. INITIAL PRIORITIES FOR CASP VI. II.

2-26-2019 v5 Version 1 – Subject to Change Without Notice Mid-Afternoon Break at 3:00pm.

AOAC INTERNATIONAL – Cannabis Analytical Science Program, March 12, 2019, Presenter Bios

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.

SCOTT G. COATES, AOAC INTERNATIONAL

Scott was appointed as the Senior Director of the AOAC Research Institute on July 1, 2018. He is responsible for daily management of and business development for the AOAC Research Institute. Scott served as the Chief Science Office from 2009 until June 2018. In this capacity, he served as the technical lead for many AOAC projects. Scott led the writing and development of Appendix F in the Official Methods of Analysis of AOAC INTERNATIONAL that describes validation requirements and the development

of Standard Method Performance Requirements . Before joining AOAC, he worked for 10 years as the Operations Manager for an in-vitro diagnostic manufacturer making medical test kits such as Strep tests and specialized bacterial culture media. Scott holds a B.S. in Microbiology (1978) and a M.S. in Biotechnology Management (1994) from the University of Maryland. Contact Scott at: scoates@aoac.org , (301) 924-7077 x137

AOAC INTERNATIONAL – Cannabis Analytical Science Program, March 12, 2019, Presenter Bios

HOLLY E. JOHNSON, AMERICAN HERBAL PRODUCTS ASSOCIATION

Holly E. Johnson Ph.D., is the Chief Science Officer for the American Herbal Products Association (AHPA). She previously served for three years as Laboratory Director for Alkemist Labs, an ISO 17025 accredited natural products testing lab specializing in botanical dietary supplements. Dr. Johnson took her Ph.D. in Pharmacognosy at the College of Pharmacy, University of Illinois – Chicago (UIC), under renowned Pharmacognosist and

researcher Dr. Norman Farnsworth. Holly was awarded a National Institutes for Health (NIH) Fellowship and trained at the UIC/NIH Center for Botanical Dietary Supplements. She was a Postdoctoral Research Fellow at the Institute for EthnoMedicine studying the etiology of neurodegenerative disease, and also worked for Waters Corporation conducting technical training and regulatory consulting for pharmaceutical and supplements companies. She is currently a Research Associate with the National Tropical Botanical Garden and serves on AOAC working groups, stakeholders’ panels, and expert review panels for Foods and Dietary Supplements. She is a member of the United States Pharmacoepia’s (USP) Medical Cannabis Expert Panel, the Editorial Board of the Journal of AOAC International, and she serves on the Advisory Boards of the American Botanical Council and the American Herbal Pharmacoepia. Holly has over 20 years’ experience working with natural products & botanicals and spent many happy years conducting research on medicinal plants and giving courses at the University of Hawaii. In addition to serving as Chair of the Skullcap Working Group, Holly is currently serving as Chair for the AOAC SPDS Expert Review Panels.

AOAC INTERNATIONAL – Cannabis Analytical Science Program, March 12, 2019, Presenter Bios

PALMER A. ORLANDI, AOAC INTERNATIONAL

Dr. Palmer A. Orlandi was named the Deputy Executive Director and Chief Science Officer at AOAC INTERNATIONAL in December, 2018. In his new role he is responsible for overseeing the AOAC Research Institute, Standards Development Activities and the Proficiency Testing Program. In addition, he handles business development responsibilities to include developing strategic partnerships with the goal of advancing voluntary consensus standards setting activities and strengthening international relations. He has an extensive background in government relations, food science and safety, regulatory affairs, and public health in the federal government. Prior to joining AOAC INTERNATIONAL, he served more than 22

years at the U.S. Food and Drug Administration, most recently as CSO and research director in the Office of Food and Veterinary Medicine where he provided strategic direction and leadership for all FDA FVM science and research programs. In the course of his career, he developed rapid molecular detection methods for emerging food- and waterborne microbial pathogens for regulatory and surveillance applications; and, coordinated collaborative analytical methods programs for the FDA field laboratories and the Food Emergency Response Network (FERN). Palmer holds a B.A. in Chemistry from Lafayette College and a Ph.D. in Biochemistry from the University of Kentucky. He was also an officer in the Commissioned Corps of the Public Health Service since 1991, earning the rank of Rear Admiral and Assistant Surgeon General in 2017.

ABOUT AOAC, PROCESSES,  AND PREVIOUS WORK WITH CANNABIS Scott Coates Senior Director,  AOAC Research Institute

AOAC INTERNATIONAL 2019 Midyear Meeting March 12, 2019

Previous Work in Cannabis

• AOAC organized a Cannabis Working Group  under the Stakeholder Panel on Strategic  Food Analytical Methods (SPSFAM) in 2016.

• Chair :  Susan Audino, Audino & Associates,  LLC.

Previous Work in Cannabis

 Developed 4  Standard Method Performance  Requirements (SMPRs):  Quantitation of Cannabinoids in Cannabis Concentrates   (2017.001).  Quantitation of Cannabinoids in Dried Plant Materials  (2017.002)  Quantitation of Cannabinoids in Edible Chocolate  (2017.019)  Identification and Quantitation of Selected Pesticide  Residues in Dried Cannabis Materials (2018.011)

Previous Work in Cannabis

Standard Method Performance Requirements (SMPRs)

• AOAC voluntary consensus standard. • Adopted by a stakeholder panel. • Published in the Official Methods of  Analysis of the AOAC INTERNATIONAL . • Used by AOAC Expert Review Panels to  evaluate candidate methods.

Previous Work in Cannabis

Standard Method Performance Requirements (SMPRs) • Detailed document describing the minimum  acceptable performance requirements for: – Probability of Detection – Limit of Detection – Limit of Quantitation – Accuracy or Bias or Recovery – Repeatability (RSD r ) – Reproducibility (RSD R )

Previous Work in Cannabis

Standard Method Performance Requirements Common Name  Abbrev‐ iation IUPAC Name CAS Number Molecular  Structure Reference  Material Cannabidiol CBD 13956‐29‐1

Restek Cerilliant

2‐[(1R,6R)‐6‐isopropenyl‐3‐ methylcyclohex‐2‐en‐1‐yl]‐5‐ pentylbenzene‐1,3‐diol

Sigma‐Aldrich API Standards Echo Pharm Lipomed AG

Cannabidiolic Acid 

CBDA

1244‐58‐2

Cerilliant USP Restek Lipomed AG Echo Pharmaceutical

2,4‐dihydroxy‐3‐[(1R,6R)‐3‐methyl‐6‐ prop‐1‐en‐2‐ylcyclohex‐2‐en‐1‐yl]‐6‐ pentylbenzoic acid

[SGC: name corrected]

Cannabinol

521‐35‐7

Cerilliant Restek

CBN

6,6,9‐Trimethyl‐3‐pentyl‐ benzo[c]chromen‐1‐ol

Tetrahydro‐ cannabinol

1972‐08‐3

Cerilliant  USP Echo Pharmaceuticals Cerilliant  USP Echo Pharmaceuticals

THC

(−)‐(6aR,10aR)‐6,6,9‐Trimethyl‐3‐pentyl‐ 6a,7,8,10a‐tetrahydro‐6H‐ benzo[c]chromen‐1‐ol

Tetrahydro‐ cannabinolic acid

23978‐85‐0

THCA

(6aR,10aR)‐1‐hydroxy‐6,6,9‐trimethyl‐3‐ pentyl‐6a,7,8,10a‐tetrahydro‐6h‐ benzo[c]chromene‐2‐carboxylic acid

Previous Work in Cannabis

• AOAC Official Method 2018.10 Cannabinoids in Dried Flowers and Oil

• AOAC Official Method 2018.11 Quantitation of Cannabinoids in Cannabis Dried  Plant Materials, Concentrates, and Oils Liquid  Chromatography–Diode Array Detection  Technique with Optional Mass Spectrometric  Detection

The Past meets the Future

ERPReviewofFirst  ActionOMAMethods&  any recommendations  forFinalAction  Status/Repeal/etc..

Call forMethods Call  forExperts (if  needed)

WorkingGroups (Stakeholderpanels  conveneasneeded)

ERPReviewofMethods  andFirstActionOMA  status 

OMB review& rendered  decisionsonFinalAction  status/Repeal

Established  Standards/SMPRs

Advisory  Panel

Advisory  Panel

Alternative  Methods ISPAM

Working Groups (Stakeholder panels  convene asneeded)

The  Analytical  Solutions  Forum

Test Kit Certifications

ERPReviewof First  ActionMethods&  any  recommendations  for FinalAction  Status/Repeal/etc..

Strategic Food  AnalyticalMethods SPSFAM aka “The FOOD  PANEL”

AOAC   Standards  Developing  Communities

OMB review&  rendered decisions  onFinalAction  status/Repeal

AgentDetection  Assays SPADA

Call forMethods Call  forExperts (if  needed)

ERPReviewof  Methodsand First  Action status 

Establish SMPRs

Advisory  Panel

Working Groups (Stakeholder panels  convene asneeded)

Working  Groups

Training and Education  Program Development

Dietary  Supplements SPDS

Infant Formula and  AdultNutritionals SPIFAN

Advisory  Panel

WorkingGroups (Stakeholder panels  conveneasneeded)

Proficiency Testingor  QualityManagement  ProgramDevelopment 

Advisory  Panel

Multiple forms of deliverables

Flexibility to address opportunities not defined or confined  by existing stakeholder panels.

• Standard Method Performance Requirements. • Method review. • Sampling plans, validation guidelines. • Harmonization, training/workshop development,  proficiency testing. • Consulting service. • Method certification, publication projects, special  meetings.

ABOUT AOAC, PROCESSES, AND PREVIOUS WORK WITH CANNABIS

Questions?

CASP WG3 – Microbial  Organisms  (Cannabis & Hemp) March 12, 2019 AOAC Mid Year Meeting Rockville, Maryland, USA

CASP WG3 – Microbial Organisms  (Cannabis & Hemp)

Goals • Identify organisms / matrices of  concern. • Prioritize organisms / matrices . • Discuss needed outcomes / deliverables. • Recruit working group members. • Identify missing subject matter experts

Identify organisms / matrices of  greatest concern.

Examples: Organism • Salmonella  muenchen • Klebsiella  pneumoniae • Enterobacter cloacae • E. agglomerans • Aspergillus

Matrices • Plant materials • Ingredients • Finished foods

Possible Deliverables

• Standard Method Performance  Requirements • Performance Tested Methods • Official Methods of Analysis • Reference / testing materials

• Proficiency Testing • Laboratory Training • Accreditation  Guidelines

Working Group Deliverables

Analyte (s)

Matrix

Deliverable (s)

Subject Matter Experts Needed

Name (s)

Affiliation

Extra

AOAC MID - YEAR MEETING MARRIOTT HOTEL GAITHERSBURG, MD MARCH 13, 2019

Susan Audino, PhD S.A.Audino & Associates, LLC Susan.Audino@gmail.com 410.459.9208

CANNABIS: AN ORGANIZATIONAL LANDSCAPE

A sampling of organizations currently involved in the cannabis space with specific interest in laboratory testing.

Applications: Marijuana and Hemp; Adult Use and Medicinal Intentions

D37 D37.01 Indoor and Outdoor Horticulture and Agriculture D37.02 Quality Management Systems D37.03 Laboratory D37.04 Processing and Handling D37.05 Security and Transportation D37.06 Personnel Training,Assessment, Credentialing D37.07 Industrial Hemp D37.90 Executive D37.91 Terminology

CONSENSUS METHOD DEVELOPMENT

LABORATORY TESTING

National Cannabis Industry Association (NCIA)  Cannabis Packaging And Labeling: Recommendations  For Sensible And Consistent Regulations Across States  And Nations (February 2019)

 Cannabis Testing Policy: Recommendations  For More Thoughtful And Consistent  Regulations (July 2018)

LABORATORY TESTING

Non-Profit Educational Organization under American Council of Independent Laboratories (ACIL)

CannabisWorking Group Current Topic: Sampling

LABORATORY TESTING

National Association of Cannabis Business Article 4. Lab Testing and Product Integrity Definitions Standard 4.01. Potency Variance. Standard 4.02. Laboratory Independence. Standard 4.03. Laboratory Accreditation. Standard 4.04. Contaminant Testing and Claims. Standard 4.05. Effective Date.

PATIENT ADVOCACY

Cannabis Laboratory Committee The FOCUS Laboratory Committee develops cannabis-specific standards for laboratories that process cannabis samples.

Industry Training;  Cultivation  Manufacturing

 Distribution  Laboratory

ACCREDITATION BODIES

Cannabis-Centric Curriculum  ISO/IEC 17025 – stand alone MOU with ASA for laboratories:  ISO/IEC 17025 & PFC Cannabis Requirements

PROFICIENCY

 Seeking ISO/IEC 17043 Accreditation (2019)

 National Research Council: Developing PT Program

 Health Assessment Measurements Quality Assurance Program (HAMQAP) – Toxic Elements in Hemp

BUILDING ONAOAC EXPERTISE

THANKYOU

QUESTIONS?

Susan Audino, PhD Susan.Audino@gmail.com 410.459.9208

Quality Assurance of  Cannabis & Hemp under  cUSA Regulations  Holly E. Johnson, Ph.D. Chief Science Officer American Herbal Products Association  hjohnson@ahpa.org

Challenges in Quality Testing of  Cannabis & Hemp under US Regulations  • Complex biological matrix • Lack of standard test methods 

& proficiency testing • Reference materials

• Myriad finished products  • Food, drug, supplement?? • Lengthy prohibition (stigma) • Industry evolving.. 

Technical & Regulatory uncertainty…

Challenges 

• The world changes quickly..

Parke Davis tincture

Cannabis was included in the  United States Pharmacoepia for 92 years, 1850‐1942.

ISO  17025  required  in CA

Differing Regulations & Challenges  with Cannabis Quality Testing: 

• Batch/lot criteria • Homogeneity/Sampling • Fit for purpose methods! • Regulatory chaos…

Cannabis Regulation in  the USA ‐Federal: 

Cannabis  • DEA – Completely illegal under Federal law;  defined in schedule 1 under the Controlled  Substances Act (21 U.S.C. Sec. 802 (16)) as  follows: “The term ‘marihuana’ means all parts  of the plant Cannabis sativa  L., whether  growing or not; the seeds thereof; the resin  extracted from any part of such plant; and  every compound, manufacture, salt, derivative,  mixture, or preparation of such plant, its seeds  or resin. Such term does not include the mature  stalks of such plant, fiber produced from such  stalks, oil or cake made from the seeds of such  plant, any other compound, manufacture, salt,  derivative, mixture, or preparation of such  mature stalks (except the resin extracted  therefrom), fiber, oil, or cake, or the sterilized  seed of such plant which is incapable of  germination.”

Cannabis Regulation in  the USA ‐ States:

Cannabis  • States – “Marijuana” is legal  in many states under state  laws for some degree of  medical or general adult use  (Aside about Nomenclature:  marijuana vs cannabis; recreational  vs adult use…. )

Hemp: the Farm Bill and the AMA

Amends the Agricultural Marketing Act… “The term ‘hemp’ means the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis .” Hemp as an agricultural commodity under the federal purview of USDA Defines hemp “plans” to be submitted to USDA by States and Tribal governments

The Farm Bill and the CSA Amends the Controlled Substances Act “The term ‘marihuana’ means all parts of the plant Cannabis sativa L., whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin. The term ‘marihuana’ does not include (i) hemp, as defined in section 297A of the Agricultural Marketing Act of 1946; or (ii) the mature stalks of such plant, fiber produced from such stalks, oil or cake made from the seeds of such plant, any other compound, manufacture, salt, derivative, mixture, or preparation of such mature stalks (except the resin extracted therefrom), fiber, oil, or cake, or the sterilized seed of such plant which is incapable of germination.”

The Farm Bill and the CSA

Amends the Controlled Substances Act “Tetrahydrocannabinols , except for tetrahydrocannabinols in hemp…” [re: CSA Schedule I]

Hemp under the FDCA As a food, beverage, or cosmetic/personal care ingredient: Hemp seed oil and other derivatives have been freely used Marketers need to comply with the FDA regulations applicable to these product categories

Hemp (NMT 0.3% THC)

February 21, 2019

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Hemp under the FDCA As a dietary supplement: 201(ff)(1)(C): The herb itself (any part) 201(ff)(1)(F): Any concentrate,

constituent, or extract [or metabolite or combination]

Marketers need to comply with the FDA regulations applicable to dietary supplements

Hemp = (NMT 0.3% THC)

February 21, 2019

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FDA DS regulations: Basics Facility registration. Register with FDA (every 2 years); applicable to manufacturing, labeling,  packing, and holding operations (except home‐based). Claim limits. Allowance for “structure‐function” claims, nutrient content claims, and FDA‐authorized  health/qualified claims. No claims related to “disease” permitted . Claim notification. Notify FDA within 30 days of first marketing of structure function claims; assert  substantiation on file for such claims. Disclaimer. “This statement has not been evaluated by the Food and Drug Administration. This  product is not intended to diagnose, treat, cure, or prevent any disease.” cGMP. Manufacture, pack, label and hold products in accordance with current good manufacturing  practice regulations (21 CFR 111). NDIs.  Submit premarket notifications to FDA, where required, regarding new dietary ingredient  (post‐1994) in any supplement. Safety. “ Under the FD&C Act, a manufacturer or distributor is responsible for ensuring that the  dietary supplements are safe….” SAERs. Submit all serious adverse event reports received to FDA; maintain records of all adverse  event reports received.  Labels‐Generally. Label products with Supplement Facts; identify all ingredients; provide name and  address of manufacturer or distributor; provide all information that is “material in light of … claims …  and the consequences that may result from … use.” Labels‐Allergens. Meet food label rule for major food allergens (milk, eggs, fish, Crustacean shellfish,  peanuts, tree nuts, wheat, soy).

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21 CFR part 111 Subpart E 111.70  requires establishment of specifications for  identity, purity, strength & composition: • Sec. 111.70 What specifications must you establish? • (b) For each  component that you use in the manufacture of a dietary  supplement, you must establish component specifications as follows: • (1) You must establish an  identity  specification; • (2) You must establish component specifications that are necessary to  ensure that specifications for the purity, strength and composition of  dietary supplements manufactured using the components are met; and • (3) You must establish  limits on those types of contamination that may  adulterate or may lead to adulteration of the finished batch of the  dietary supplement to ensure the quality of the dietary supplement. In hemp, THC considered is a contaminant that  may adulterate – limit is NMT 0.3% 

21 CFR part 111 • Subpart E 111.75 What must you do to determine whether specifications are  met? • (a) Before you use a component, you must: • (1)(i) Conduct at least one appropriate test or examination ….. • (h)(1) You must ensure that the tests and examinations that you use to  determine whether the specifications are met are appropriate,  scientifically valid methods. • (2) The tests and examinations that you use must include at least one of  the following: • (i) Gross organoleptic analysis; • (ii) Macroscopic analysis; • (iii) Microscopic analysis; • (iv) Chemical analysis; or • (v) Other scientifically valid methods. • (i) You must establish corrective action plans for use when an established  specification is not met.

Selecting Scientifically Valid Methods Standards setting organizations are working on standard  methods specific to cannabis and hemp:

2 AOAC Official Methods of Action for cannabinoids in cannabis flower & extracts

21 CFR part 111 • Subpart J 111.320 What requirements apply to laboratory  methods for testing and examination? • (a) You must verify that the laboratory examination and testing  methodologies are appropriate for their intended use . • (b) You must  identify and use an appropriate scientifically valid  method for each established specification for which testing or  examination is required to determine whether the specification is  met.   Standard methods are scientifically valid for common  materials, but must verify & document for complex  finished products – scope matters . 

Do not set a spec without asking – what tests will we use to support that spec?

) and  Intermediate Precision  (RSD i ) 

Repeatability (RSD r

for Cannabinoids in a Dried Plant Material

Analyst 1

Analyst 2

Analyst 1 & 2

Analyte

Mean conc.  (%, w/w)

RSD r (n=5)

Mean conc.  (%, w/w)

Mean conc.  (%, w/w)

RSD r (n=5)

RSD i (n=10)

CBDVA CBDV CBDA CBGA

0.0389 0.0496 0.257 0.0390 0.697 0.0437 0.0845 0.0347 3.94

2.2 4.7 1.6 2.1 3.5 4.2 3.2 1.7 2.0

0.0355 0.0508 0.258 0.0393 0.699 0.0452 0.0856 0.0343 3.78

1.8 1.5 0.9 0.6 1.2 0.3 1.3 0.4 1.6

0.0372 0.0502 0.258 0.0391 0.698 0.0444 0.0851 0.0345 3.86

5.1 3.5 2.4 1.4 2.5 2.8 2.9 1.3 1.8

CBG CBD

Δ 9 ‐THC THCA

CBC

Data: Courtesy of K. Mastovska, Eurofins  Food Integrity & Innovation (Method  AOAC First Action Official status)

Accurate, precise, specific methods for each matrix!

Challenges in Quality Testing of  Cannabis & Hemp under US Regulations  • Complex biological matrix • Lack of standard test methods 

& proficiency testing • Reference materials

• Myriad finished products  • Food, drug, supplement?? • Lengthy prohibition (stigma) • Industry evolving.. 

Technical & Regulatory uncertainty…

Challenges with Cannabis Quality: Legal stigma may influence staffing

Vanity Fair feature on store opening on 5 th Avenue in Manhattan

Things change..

Chloroform was  considered a “valuable 

ingredient” in this  preparation, but  would now be a  residual solvent  contaminant. 

Thank You!

Holly E. Johnson, Ph.D. Chief Science Officer American Herbal Products Association hjohnson@ahpa.org

40

Appendix W

POLICY AND PROCEDURES ON VOLUNTEER CONFLICT OF INTEREST

Statement of Policy

While it is not the intention of AOAC INTERNATIONAL (AOAC) to restrict the personal, professional, or proprietary activities of AOAC members nor to preclude or restrict participation in Association affairs solely by reason of such activities, it is the sense of AOAC that conflicts of interest or even the appearance of conflicts of interest on the part of AOAC volunteers should be avoided. Where this is not possible or practical under the circumstances, there shall be written disclosure by the volunteers of actual or potential conflicts of interest in order to ensure the credibility and integrity of AOAC. Such written disclosure shall be made to any individual or group within the Association which is reviewing a recommendation which the volunteer had a part in formulating and in which the volunteer has a material interest causing an actual or potential conflict of interest. AOAC requires disclosure of actual or potential conflicts of interest as a condition of active participation in the business of the Association. The burden of disclosure of conflicts of interest or the appearance of conflicts of interest falls upon the volunteer. A disclosed conflict of interest will not in itself bar an AOAC member from participation in Association activities, but a three-fourths majority of the AOAC group reviewing the issue presenting the conflict must concur by secret ballot that the volunteer's continued participation is necessary and will not unreasonably jeopardize the integrity of the decision-making process. Employees of AOAC are governed by the provision of the AOAC policy on conflict of interest by staff. If that policy is in disagreement with or mute on matters covered by this policy, the provisions of this policy shall prevail and apply to staff as well. 1. A volunteer who is serving as a committee member or referee engaged in the evaluation of a method or device; who is also an employee of or receiving a fee from the firm which is manufacturing or distributing the method or device or is an employee of or receiving a fee from a competing firm. 2. A volunteer who is requested to evaluate a proposed method or a related collaborative study in which data are presented that appear detrimental (or favorable) to a product distributed or a position supported by the volunteer's employer. 3. A referee who is conducting a study and evaluating the results of an instrument, a kit, or a piece of equipment which will be provided gratis by the manufacturer or distributor to one or more of the participating laboratories, including his or her own laboratory, at the conclusion of the study. 4. Sponsorship of a collaborative study by an interest (which may include the referee) which stands to profit from the results; such sponsorship usually involving the privilege granted by the investigator to permit the sponsor to review and comment upon the results prior to AOAC evaluation. Illustrations of Conflicts of Interest

5. A volunteer asked to review a manuscript submitted for publication when the manuscript contains information which is critical of a proprietary or other interest of the reviewer.

The foregoing are intended as illustrative and should not be interpreted to be all-inclusive examples of conflicts of interest AOAC volunteers may find themselves involved in.

Do's and Don't's

Do avoid the appearance as well as the fact of a conflict of interest.

Do make written disclosure of any material interest which may constitute a conflict of interest or the appearance of a conflict of interest.

Do not accept payment or gifts for services rendered as a volunteer of the Association without disclosing such payment or gifts.

Do not vote on any issue before an AOAC decision-making body where you have the appearance of or an actual conflict of interest regarding the recommendation or decision before that body.

Do not participate in an AOAC decision-making body without written disclosure of actual or potential conflicts of interest in the issues before that body.

Do not accept a position of responsibility as an AOAC volunteer, without disclosure, where the discharge of the accepted responsibility will be or may appear to be influenced by proprietary or other conflicting interests.

Procedures

Each volunteer elected or appointed to an AOAC position of responsibility shall be sent, at the time of election or appointment, a copy of this policy and shall be advised of the requirement to adhere to the provisions herein as a condition for active participation in the business of the Association. Each volunteer, at the time of his or her election or appointment, shall indicate, in writing, on a form provided for this purpose by AOAC, that he or she has read and accepts this policy. Each year, at the spring meeting of the AOAC Board of Directors, the Executive Director shall submit a report certifying the requirements of this policy have been met; including the names and positions of any elected or appointed volunteers who have not at that time indicated in writing that they have accepted the policy. Anyone with knowledge of specific instances in which the provisions of this policy have not been complied with shall report these instances to the Board of Directors, via the Office of the Executive Director, as soon as discovered.

* * * * * *

Adopted: March 2, 1989 Revised: March 28, 1990 Revised: October 1996 Reviewed by outside counsel March 2000 (Fran Dwornik) and found to be current and relevant

Appendix U

ANTITRUST POLICY STATEMENT AND GUIDELINES

Introduction

It is the policy of AOAC INTERNATIONAL (AOAC) and its members to comply strictly with all laws applicable to AOAC activities. Because AOAC activities frequently involve cooperative undertakings and meetings where competitors may be present, it is important to emphasize the on-going commitment of our members and the Association to full compliance with national and other antitrust laws. This statement is a reminder of that commitment and should be used as a general guide for AOAC and related individual activities and meetings.

Responsibility for Antitrust Compliance

The Association's structure is fashioned and its programs are carried out in conformance with antitrust standards. However, an equal responsibility for antitrust compliance -- which includes avoidance of even an appearance of improper activity -- belongs to the individual. Even the appearance of improper activity must be avoided because the courts have taken the position that actual proof of misconduct is not required under the law. All that is required is whether misconduct can be inferred from the individual's activities. Employers and AOAC depend on individual good judgment to avoid all discussions and activities which may involve improper subject matter and improper procedures. AOAC staff members work conscientiously to avoid subject matter or discussion which may have unintended implications, and counsel for the Association can provide guidance with regard to these matters. It is important for the individual to realize, however, that the competitive significance of a particular conduct or communication probably is evident only to the individual who is directly involved in such matters. In general, the U.S. antitrust laws seek to preserve a free, competitive economy and trade in the United States and in commerce with foreign countries. Laws in other countries have similar objectives. Competitors (including individuals) may not restrain competition among themselves with reference to the price, quality, or distribution of their products, and they may not act in concert to restrict the competitive capabilities or opportunities of competitors, suppliers, or customers. Although the Justice Department and Federal Trade Commission generally enforce the U.S. antitrust laws, private parties can bring their own lawsuits. Penalties for violating the U.S. and other antitrust laws are severe: corporations are subject to heavy fines and injunctive decrees, and may have to pay substantial damage judgments to injured competitors, suppliers, or customers. Individuals are subject to criminal prosecution, and will be punished by fines and imprisonment. Under current U.S. federal sentencing guidelines, individuals found guilty of bid rigging, price fixing, or market allocation must be sent to jail for at least 4 to 10 months and must pay substantial minimum fines. Antitrust Guidelines

Since the individual has an important responsibility in ensuring antitrust compliance in AOAC activities, everyone should read and heed the following guidelines.

1. Don't make any effort to bring about or prevent the standardization of any method or product for the purpose or intent of preventing the manufacture or sale of any method or product not conforming to a specified standard 2. Don't discuss with competitors your own or the competitors' prices, or anything that might

affect prices such as costs, discounts, terms of sale, distribution, volume of production, profit margins, territories, or customers.

3. Don't make announcements or statements at AOAC functions, outside leased exhibit space, about your own prices or those of competitors.

4. Don't disclose to others at meetings or otherwise any competitively sensitive information.

5. Don't attempt to use the Association to restrict the economic activities of any firm or any individual.

6. Don't stay at a meeting where any such price or anti-competitive talk occurs.

7. Do conduct all AOAC business meetings in accordance with AOAC rules. These rules require that an AOAC staff member be present or available, the meeting be conducted by a knowledgeable chair, the agenda be followed, and minutes be kept.

8. Do confer with counsel before raising any topic or making any statement with competitive ramifications.

9. Do send copies of meeting minutes and all AOAC-related correspondence to the staff member involved in the activity.

10. Do alert the AOAC staff to any inaccuracies in proposed or existing methods and statements issued, or to be issued, by AOAC and to any conduct not in conformance with these guidelines.

Conclusion

Compliance with these guidelines involves not only avoidance of antitrust violations, but avoidance of any behavior which might be so construed. Bear in mind, however, that the above antitrust laws are stated in general terms, and that this statement is not a summary of applicable laws. It is intended only to highlight and emphasize the principal antitrust standards which are relevant to AOAC programs. You must, therefore, seek the guidance of either AOAC counsel or your own counsel if antitrust questions arise.

Adopted by the AOAC Board of Directors: September 24, 1989 Revised: March 11, 1991 Revised October 1996

Appendix V

POLICY ON THE USE OF THE ASSOCIATION NAME, INITIALS, IDENTIFYING INSIGNIA, LETTERHEAD, AND BUSINESS CARDS

Introduction

The following policy and guidelines for the use of the name, initials, and other identifying insignia of AOAC INTERNATIONAL have been developed in order to protect the reputation, image, legal integrity and property of the Association. The name of the Association, as stated in its bylaws, is "AOAC INTERNATIONAL". The Association is also known by its initials, AOAC, and by its logo, illustrated below, which incorporates the Association name and a representation of a microscope, book, and flask. The AOAC logo is owned by the Association and is registered with the U.S. Patent and Trademark Office.

6JG HWNN #UUQEKCVKQP KPUKIPKC KNNWUVTCVGF DGNQY KU EQORTKUGF QH VJG NQIQ CPF VJG VCINKPG 6JG 5EKGPVKHKE #UUQEKCVKQP &GFKECVGF VQ #PCN[VKECN 'ZEGNNGPEG UJQYP DGNQY 6JG V[RGHCEG WUGF KU .CTIQ 6JG #1#% VCINKPG KU QYPGF D[ VJG #UUQEKCVKQP CPF KU TGIKUVGTGF YKVJ VJG 7 5 2CVGPV CPF 6TCFGOCTM QHHKEG

Policy

Policy on the use of the Association's name and logo is established by the AOAC Board of Directors as follows:

“The Board approves and encourages reference to the Association by name, either as AOAC INTERNATIONAL or as AOAC; or reference to our registered trademark, AOAC®, in appropriate settings to describe our programs, products, etc., in scientific literature and other instances so long as the reference is fair, accurate, complete and truthful and does not indicate or imply unauthorized endorsement of any kind. The insignia (logo) of AOAC INTERNATIONAL is a registered trade and service mark and shall not be reproduced or used by any person or organization other than the Association, its elected and appointed officers, sections, or committees, without the prior written permission of the Association. Those authorized to use the AOAC INTERNATIONAL insignia shall use it only for

the purposes for which permission has been specifically granted.

The name and insignia of the Association shall not be used by any person or organization in any way which indicates, tends to indicate, or implies AOAC official endorsement of any product, service, program, company, organization, event or person, endorsement of which, has not been authorized by the Association, or which suggests that membership in the Association is available to any organization.”

The Executive Director, in accordance with the above stated policy, is authorized to process, approve, fix rules, and make available materials containing the Association name and insignia.

It should be noted that neither the Association's name nor its insignia nor part of its insignia may be incorporated into any personal, company, organization, or any other stationery other than that of the Association; nor may any statement be included in the printed portion of such stationery which states or implies that an individual, company, or other organization is a member of the Association.

Instructions

1. Reproduction or use of the Association name or insignia requires prior approval by the Executive Director or his designate.

2. Association insignia should not be altered in any manner without approval of the Executive Director or his designate, except to be enlarged or reduced in their entirety.

3. Artwork for reproducing the Association name or insignia, including those incorporating approved alterations, will be provided on request to those authorized to use them (make such requests to the AOAC Marketing Department). Examples of the types of alterations that would be approved are inclusion of a section name in or the addition of an officer's name and address to the letterhead insignia.

4. When the Association name is used without other text as a heading, it should, when possible, be set in the Largo typeface.

5. Although other colors may be used, AOAC blue, PMS 287, is the preferred color when printing the AOAC insignia, especially in formal and official documents. It is, of course, often necessary and acceptable to reproduce the insignia in black.

6. Do not print one part of the logo or insignia in one color and other parts in another color.

7. The letterhead of AOAC INTERNATIONAL shall not be used by any person or organization other than the Association, elected and appointed officers, staff, sections, or committees; except by special permission.

Correspondence of AOAC official business should be conducted using AOAC letterhead. However, those authorized to use AOAC letterhead shall use it for official AOAC business only.

Copies of all correspondence using AOAC letterhead or conducting AOAC official business,