1. Moving Sustainable Medicines Forward™
Regulatory Compliance
And Analytical Testing
Jeffrey C. Raber, Ph.D.
© 2017 The Werc Shop, LLC

2. Cannabis Testing Overview
Changing and dynamic landscape
CO, MA, NV, CT, MD
Cannabinoids and full safety screening
Washington
Cannabinoids, microbiological, moisture, foreign matter
Recently updated pesticides
Oregon
Process Validation and robust pesticides
California
Evolving regulatory and legal frameworks

3. Importance of Testing Protecting consumer safety
Ensuring products are free from contaminants
Ensuring products are labelled properly
Product consistency, potency
Monitoring extraction, manufacturing processes
Optimization of cultivation practices
Patient confidence

4. Current Industry Guidance
American Herbal Pharmacopoeia
Created standards for identity, analysis, and quality control
American Herbal Products Association (AHPA)
Issued best practices for cultivation, manufacturing, testing, dispensing
Scientific Organizations
ACS, AOCS, AOAC, others
Third party certification/accreditation
A2LA, PFC, NIST, Clean Green

5. Common Testing Requirements
COMPOUNDS TESTED
ANALYTICAL TECHNIQUE
Cannabinoids
Plant Material
HPLC and UPLC
Pesticides
LC/GC-MS/MS
Extracts & Concentrates
Residual Solvent
GC-FID, GC-MS
Heavy Metals
ICP, AA, TXRF
Mycotoxins
LC, LC-MS, Affinity
Edible, Topical, Oil
Microbiological
Cultures, qPCR
Specific testing requirements vary by State and are updated often

6. California Legal Framework
Collectives
Prop 215 and SB420
MCRSA
AB 266 and other bills
AUMA
64 Page Voter Initiative
Lots of Hardcoded Framework
Limited and challenging assembly overrides
Defines details of advertising and testing

7. California License Structure
Dual Licensing Requirements
Local permit required before applying for State license
Cities are Slow to Act
Limited number of available jurisdictions
Different License Types
Cultivation
Manufacturing (Volatile vs Non-Volatile)
Dispensing (delivery permitted only from here)
Transportation
Distribution
Testing

8. MCRSA Has Testing Balance
Independent Laboratories Required
ISO Accreditation
What will State do about Proficiency Testing?
Distributor License – Wrong Name
Independent of other licenses, except Transportation
Responsible for sample collection and testing
What is the label accuracy limits?
Serious product implications

9. AUMA Complications Voter Initiative Overrides MCRSA
Initiative > Legislation > Regulation
Strong Desire For Harmonization
Other states have harmonized
Is it required to support medical
Same infrastructure is more economical
How can product diversity be maximized
Trailer Bill Makes Huge Changes
Laboratories pick the samples
Distribution can be done by manufacturer
Path to larger sized operations and verticalization

10. Advertising and Forms Many bills currently in legislature
Strong positions on integrity and harm reduction
Filling out the framework
Advertising is a concern
Billboards, TV, Radio
Greater than 71% adult viewers
Product forms are a concern
Not enticing to children
Animals, shapes, candy like
How is this defined, as what is a lozenge?

11. Some Testing Required Today
Locally Permitted Distribution
Secure a City or County Permit
Before Distribution Must Be Tested
Cannabinoids required
THCA, THC, CBD, CBDA, CBN
This must be done today
Required before delivery to a dispensary
Other tests will be defined by regulator
Contaminant and Purity Requirements

12. Contamination Concerns
Pesticides, Herbicides, Fungicides, & PGRs
Complex problem
Over thousands of known chemicals!
No application standards for cannabis
Try to understand what is often being used
Establish new working standards that can be adopted by medical cannabis producers
What levels make sense for these products?
Start with current ppm levels for foods
Method development is complicated and hardware costs extremely large

13. Pesticides are Inhalation Concern
Study compared different inhalation devices

14. Pesticides are Inhalation Concern
Study demonstrated volatility of pesticides

15. Pesticides are Inhalation Concern
Peer-Reviewed - J. Toxicology May 2013
Confirms pesticides can be inhaled & is device dependent

16. Microbiological Testing
Tests For:
Total Aerobic,
Yeasts & Mold, Enterobacteria
Broad Based – are all of them harmful?
Organism Specific – sensitivity?
Speed and Accuracy – sample homogeneity

17. Testing Helps Standardization
Reproducible dosing can be achieved from standardized rolled cigarettes
Elzinga, et. al. Nat Prod Chem Res 2015, 3:1

18. Dose Can Be Reasonably Calculated
Experiment
Replicate
THCmax
THC in absolute mg
in Starting Material
Mainstream
Sidestream
Ash
High Octane 1
219.8
101.0
30.9
14.4 2
221.1
87.4
18.3
17.1 3
218.6
81.6
6.7
14.7
XJ-13
238.8
64.6
21.2
13.7
240.2
105.7
29.6
16.1
237.7
87.9
9.0
19.6
King Louie
300.0
100.4
32.0
18.4
300.5
97.0
34.1
17.8
299.6
82.4
11.0
20.9
* Two (2) cannabis cigarettes containing an exactly known amount of approximately 800mg cannabis consecutively smoked

19. What’s In A Name Detailed Chemical Fingerprinting Needed
Chemical composition, what is consumed
Genetics set foundation, environment sets expression to yield final composition
Processing of plant material
Incredible variable in terms of composition
Which actual name went in to product?
High Purity = Less Like Cannabis
>95% is more like dronabinol than Cannabis
Lacking the Ensemble Effect

20. CA Labeling & Marketing Laws
Legislation Sets New Standards
Misrepresentation of a brand
Misrepresentation of label accuracy
Immense implications on product types
How will the regulator interpret
Limits on label accuracy %
Batch size
Accuracy of statistics needed
What is the definition of homogeneous

21. Calculating THC Max THCA = 17.81 wt % THC = 0.99 wt %
THCmax = wt % (NOT ADDITIVE)
Weight of the molecules:
THCA = g/mol & THC = g/mol
Calculating MAX from measured values:
THCA*( / )+THC = MAX Value
CBDA to CBD is the exact same math!!

22. Reported as mg / g 4.55 mg / g THC in Cookie Edible Values
Can calculate desired product g
Accounts for product variability
4.55 mg / g THC in Cookie
How many grams of cookie do I need?
My desired dose is 20 mg
20 mg / (4.55 mg/g) = g of cookie needed

23. Rational Regulations Significant Pesticide Exposure Via Inhalation
Limits need to be tightly controlled
Which pesticides should be used key issue
Where and went to test for these agents?
Dried Plant Material is Viable Medicine
How it is prepared and delivered is key
CA Law is Changing and Complex
What will the regulations state
How many changes lie ahead
Scientific Understanding Should Shape Regs!