Guidance for State Medical Cannabis Testing Programs (May 2016)

Guidance for State

Medical Cannabis

Testing Programs

MAY 2016

Table of Contents

Acknowledgments ........................................................................................................................................ 4

Introduction ................................................................................................................................................. 5

Risk Assessment ......................................................................................................................................... 5

Types of Product ........................................................................................................................................... 6

Characteristics of Various Forms ................................................................................................................ 9

Dealing with Schedule I Materials ............................................................................................................. 9

Analytes and Action Levels ........................................................................................................................ 14

Pesticides ............................................................................................................................................. 14

Solvents ................................................................................................................................................ 17

Microbiologicals ................................................................................................................................... 22

Metals ...................................................................................................................................................26

Cannabinoids ....................................................................................................................................... 26

Sampling and Analysis ..............................................................................................................................26

Sample Collection ................................................................................................................................ 27

Sample Analysis ...................................................................................................................................28

Pesticides ......................................................................................................................................28

Solvents .........................................................................................................................................28

Metals ............................................................................................................................................ 30

Cannabinoid Prole .......................................................................................................................30

Laboratory Certication/Registration/Accreditation ..............................................................................32

Colorado ............................................................................................................................................... 32

New York............................................................................................................................................... 32

Oregon .................................................................................................................................................. 34

Washington ..........................................................................................................................................34

Outreach ..................................................................................................................................................... 34

Efcacy & Side Effects of the Products ................................................................................................... 34

Appendix: Links to State Programs, Laws, Regulations .......................................................................... 35

Maine ................................................................................................................................................... 35

Maryland ..............................................................................................................................................35

Massachusetts ....................................................................................................................................35

Nevada ................................................................................................................................................. 35

New York............................................................................................................................................... 35

Table of Figures

Table 1: Pesticide analytes and their action levels in OR ........................................................................ 16

Table 2: USP Chapter 467 Solvents and their concentration limit ......................................................... 18

Table 3: List of solvents and their action levels ....................................................................................... 20

Table 4: Solvent maximum concentration limits by state........................................................................ 21

Table 5: US Pharmacopeia Microbial Limits .............................................................................................23

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Acknowledgments

Kenneth Aldous, PhD

Director, Division of Environmental Health Sciences

Wadsworth Center, NYS Department of Health

and Associate Professor, School of Public Health

State University at Albany

Jeremy Applen

Co-founder

Canopy Systems

Zhihua (Tina) Fan, PhD

Research Scientist/Program Manager

Chemical Terrorism, Biomonitoring and Food Testing

New Jersey Department of Health

Public Health Infrastructure, Laboratories & Emergency Preparedness.

Public Health & Environmental Laboratories

Mary A. Fox, PhD MPH

Assistant Professor, Health Policy and Management

Acting Director, Risk Sciences and Public Policy Institute

Johns Hopkins Bloomberg School of Public Health

Shawn Kassner

Senior Scientist

Neptune and Company, Inc.

Megan Weil Latshaw, PhD MHS

Director, Environmental Health Programs

Association of Public Health Laboratories

Marc A. Nascarella, PhD

Chief Toxicologist

Director, Environmental Toxicology

Massachusetts Department of Public Health

Gary Starr, MD

FOCUS Standards

Shannon Swantek

ORELAP Compliance Specialist

Oregon Public Health Lab

David Verbrugge

Manager, Analytical Toxicology

State of Alaska Public Health Lab

Guidance for State Medical Cannabis Testing Programs

Introduction

As part of the nation’s public health infrastructure, state and federal agencies establish programs

to protect population health. There are a wide variety of programs in place in different agencies

that test, monitor and evaluate whether human exposures from the use of air, water or consumer

products (including food and drugs) present potential risks to health.

On the basis of these testing and evaluation programs, agencies have authority to protect our

health by taking action to ensure that air, water, and consumer products are of good quality.

Protecting resources and consumer products may take many forms, e.g., preventing contamination

(pollution prevention, regulating production processes), reducing or preventing exposure (recalling

contaminated products) or restricting uses such that health protective conditions are met and

maintained. In the case of drugs, including cannabis, public health agencies have concerns for the

quality, therapeutic benet, and the balance between therapeutic benet and possible side-effects.

Medical cannabis has been approved for use in a number of states but remains outside federal

control. As has been reported, the absence of federal guidance when it comes to cannabis testing

has led states to develop their own approaches. Since 2014, the Association of Public Health

Laboratories (APHL) has convened a monthly community of practice call so that member laboratories

could share questions, advice, lessons learned and resources. During these calls, a theme emerged

where every new participant asked the same questions as others who came before. In order to

collect the knowledge being shared, APHL created this guidance document.

The main audience for this document is laboratorians who are being asked to develop new

cannabis testing programs. It can also be used to assess existing programs. Other audiences may

include state legislators and their staff, state health ofcials, and those working in the cannabis

industry.

Since the guidance was developed by a workgroup, it is heavily weighted toward those states that

participated in its writing. If you would like to add your perspective or suggest edits, please email

[email protected]. Given the rapid changes in this eld, APHL views this as a living document.

Risk Assessment

There are various approaches to the assessment

and management of hazards that can be applied

to cannabis programs. Drawing upon the variety of

tools and methods applied in product evaluation and

protection programs for other types of products such

as food or drugs,

the product protection pyramid

identies activities implemented by public health

agencies and by producers/product handlers to

evaluate and ensure product quality. At the base of

the pyramid, growers and processors implement good

practices (maintaining growing facilities, appropriate

use of insecticides, etc).

A Hazard Analysis and Critical Control Point (HACCP)

program is a management system designed to ensure

product quality from production to consumption. HACCP programs are developed to be specic to

each type of process, along the production, distribution and consumption continuum. Public health

Gorris 2005. Food safety objective: An integral part of food chain management. Food Control 16: 801–809.

Product protection pyramid

Adapted from Gorris 2005

Good Production Practices

HACCP Programs

Risk Analysis

Product Testing and

Health Surveillance

Health

Risks and

Benefits

Agency-level

Programs

Production-

level

Programs

Product Protection Pyramid

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

agencies conduct product testing and health surveillance programs; the resulting data can be used

for risk analysis to understand the potential health risks and benets of cannabis products. Results

of risk analysis inform HACCP and good production practices.

There are three types of data collected, evaluated and combined in a risk assessment:

• Sources/Hazards (contaminants, pesticides, microbes or active ingredients)

• Health effects/consequences/adverse events associated with each hazard

• Exposure which involves sampling of products to determine concentrations of ingredients/

contaminants and human exposure through use of the target product. Exposure scenarios

reect known uses of the product and include a range of scenarios from low to high exposure

depending on difference uses. They can also include human biomonitoring data—looking for

the analyte or its metabolite in human specimens, such as blood lead testing.

Using the estimation of risks, based on the exposure-hazard-health effect sets, public health can

better characterize risk and develop health protective approaches to managing it. Practitioners may

use screening approaches—risk ranking to identify the highest risk products, risk-driving hazards or

risk-driving processes—to inform product warnings and further sampling.

In order to develop a standard, practitioners must develop criteria for “acceptable risk” and identify

exposure-use scenarios that fall within or outside the acceptable risk criteria. Based on that

standard, it is possible to establish mechanisms for removal of products or to limit usage so that

human exposures remain below the acceptable risk criterion.

Types of Product

As with most programs in the United States, every state takes a different approach. For example as

of January 2016, New Jersey’s Public Health & Environmental Laboratories only test cannabis plant

material. Just across the Hudson, however, New York’s Public Health Laboratory will not be testing

any plant material, only cannabis extracts. In addition, the New York Department of Health will

provide an oversight role for commercial cannabis laboratories that are licensed by the federal Drug

Enforcement Administration (DEA) and approved for testing cannabis products. On the other hand,

New Jersey state government does all testing in-house for the medical cannabis program.

This section provides an overview the various types of products available across the country, as well

as some testing considerations.

Pill/Capsule

Commonly, these are heat-activated oils in medium-chain triglyceride (MCT) coconut oil diluent

that are placed in pharmaceutical grade gel-cap material. Testing would be similar to other

extracts, in addition to testing for any potentially harmful materials frequently tested for in the

pharmaceutical industry.

The dissolvable pill is meant for oral intake, but not to be swallowed. This is not to say it would

not be swallowed, only that it is designed to be absorbed by the oral mucosa, metabolizing like

an orally-absorbed tincture. Testing would be similar to extract testing but would also account for

relevant ingredients that might be introduced in the unique manufacturing process required for

the dissolvable matric tablet.

A method for test cannabinoids in urine can be found at Wei B, Wang L, Blount BC. Analysis of Cannabinoids and Their

Metabolites in Human Urine. Anal Chem. 2015 Oct 20;87(20):10183-7.

Guidance for State Medical Cannabis Testing Programs

Tincture

This form is for oral mucosal absorption (not swallowed) and is typically an extract dissolved in

alcohol at a dened percentage. Testing would be similar to extract testing and possibly verifying

alcohol content.

Spray

This is similar to tinctures above or extract oils below. When plastic components are used in

spray packaging, testing for contaminant related to packaging may be warranted. IF a solvent is

used, such as glycol or glycerin, these may also need analysis.

Oils for food or cooking

These are extracts of raw plant, homogenized with an edible lipid. These should be tested as an

extract and also tested for biologicals specic to the food manufacturing process.

Oils for combining and swallowing (i.e. for children with seizures) are extracts of raw plant, heat

activated and homogenized with an edible lipid, like MCT coconut oil and possibly avoring.

These should be tested as an extract and also tested for biologicals specic to the food-

manufacturing process.

Oils/ extracts for vaporizing

These are extracts of raw plant sold in various viscosities for the purpose of placing in a

“vaporizer” or “vape pan” and inhaled as vapor (not smoke). The vaporizing device heats the

material to a temperature below the combustion point (ideally) and causes the volatile active

ingredients (cannabinoids and terpenes) to enter a vapor form available for inhalation. To the

extent that the material is not heated to combustion (which can happen with low quality devices),

the risks of smoke inhalation are theoretically avoided (i.e., no particulate matter or other

products of combustion are inhaled). This is better from a medical standpoint. Additionally, since

a homogenized extract can be measured for content per vaporized inhalation, more accurate

dosing should theoretically be possible when compared to smoking raw plant material.

Extracts should commonly be tested for active ingredients; residual extraction solvents

(hydrocarbons or other); mycotoxins; any pesticides not typically removed in the extraction

process; any biological that might be introduced after extraction but before nal packaging; and

heavy metals (depending on the grow medium).

Some extracts are combined with solvent to make them less viscous. This has generated

controversy in the industry since the safety of these solvents for inhalation is debated. Propylene

glycol is most commonly used as the solvent and, though it has been considered generally safe

for oral consumption, it carries risk when heated and inhaled. Other potentially harmful solvents

are sometimes used. Processes that create a homogenized thinner oil for placing in a vape pen

or vape pen cartridge (prepackaged) without the use of solvent do exist but are not yet common

or cheap—making the debate a fast-evolving one.

Finally, other potentially harmful substances may be found in this form including any avorings

added by the manufacturer and any possible contamination by the device itself (glues, plastics,

sealants). These need to be identied and analyzed based on current health data for such

compounds. Heating these products to high temperature for combustion should be avoided for

reasons similar to smoking other plant material.

Plant mixes for vaporizing or smoking

Some states mandate a homogenization process for plant product which might be then smoked

or vaporized with a solvent. These products should be tested in the same way as a raw plant

product, ideally before and after homogenization.

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Plant for smoking

Testing plant material designed for smoking will mirror what has been studied the most,

as this

is the most commonly consumed form (recreationally and medically). However, it is the least

appropriate form from a medical standpoint due to the particulate and toxic substances created

when organic material is burned (heated above combustion temperature) and inhaled.

Creams/ointments for skin

Various topical products exist which combine extracts (heat activated and not) with a cream or

ointment base for topical application (to be absorbed through the skin to varying degrees). See

discussion on extracts above. Testing should also mirror the pharmaceutical topical cream/

ointment standard.

Patches

These are essentially similar to creams or ointments but are more convenient for application

and are generally longer-acting. These products contain synthetic elements (adhesive, plastics,

synthetic material, etc.) and testing should mirror the pharmaceutical industry standard for

medications applied via absorbable patch.

Eye drops

Much like the spray and oil preparations, these extract-based products also contain a solvent

or diluent that allow the active oil to be placed safely in the eye for absorption locally. Various

techniques using glycol, oils or white petroleum products and cyclodextrans have been

described. Testing should mirror that for extracts, sprays and oils as well as for any other possible

ingredients introduced in the packaging process (solvents, biological). Standards should mirror

that of medications intended for ocular application in the pharmaceutical industry.

Suppositories

Extract is combined with a glycerin or similar matrix in order for it to maintain form and be

inserted rectally and absorbed by mucosa. Testing should mirror that of extracts, pills and oils.

Air purier oil inserts

The intent is for passive inhalation in the local air but not for direct inhalation. Testing should

mirror that for vaporized extract.

IV/IM Injections

These are not industry standard forms but are hypothesized and testing standards should be

anticipated. Extracts or fractional distillates of raw plant can be combined with solvents that

enhance water solubility. Cyclodextrans (such as Captisol) have been used for this purpose

in the pharmaceutical industry (Geodon, Abilify, Amiodarone, etc.). Testing would mirror the

pharmaceutical IV/IM medication standard as well as the testing standard described in the

extracts portion here.

Raw plant consumed orally

Some patients include the leaves in salad or juice them, but often don’t wash it to avoid rinsing

off the active ingredient. This brings up concerns about residues, especially pesticides that might

remain on the product. See above for raw plant, smoked.

Daley, P, et al. Testing Cannabis for Contaminants. BOTEC Analysis Corp. September 12, 2013.

U.S. Pharmacopeial Convention. Topical and Transdermal Drug Products: Product Quality Tests. November 1, 2013.

Available at http://www.usp.org/sites/default/les/usp_pdf/EN/USPNF/revisions/topical_and_transdermal.pdf

U.S. Food and Drug Administration/ Center for Drug Evaluation and Research. Guidance for Industry

Orally Disintegrating Tablets. December 2008. Available at http://www.fda.gov/downloads/Drugs/

GuidanceComplianceRegulatoryInformation/Guidances/ucm070578.pdf.

Guidance for State Medical Cannabis Testing Programs

Characteristics of Various Forms

The forms described above are usually indicated for one of three reasons. First, ease of use and

historical application are considered. This mostly applies to raw plant forms for smoking or oral

consumption. Certain forms of extract are also encountered because they are easier or cheaper to

manufacture compared to other products (for example butane hash oil or BHO, water hash extracts

or using propylene glycol in vape pens). Secondly, the intended use often requires a specic form.

Eye drops used for glaucoma or topical products used for skin conditions are good examples. Data

for these use indications is variable.

Thirdly, the biochemical process in the human body must also be considered. THC (and other

cannabinoids) are metabolized to other compounds—some also active. How the native plant

or extract is consumed alters the biochemistry and the biological result. THCA needs to be

decarboxylated into Δ

-THC before consumption to achieve certain biological effects. The effects

of other forms are less well-studied. Consuming products orally so that they are absorbed in the

intestine results in a “rst pass metabolism,” where the liver has a chance to signicantly alter the

active compounds before they have a biological effect.

Absorption rates are highly variable and prolonged when products are orally ingested. But products

that are inhaled or absorbed through the mucous membranes of the mouth, eyes, nasal mucosa or

rectum enter the blood stream before being metabolized by the liver are absorbed much quicker and

have a different set of effects. Inhaled products are the most quickly absorbed. Parenteral (IV or IM)

products exist conceptually and would be similar to inhaled products, because you bypass rst-pass

metabolism in the liver. Topical applications result in a direct absorption (like oral mucosa) but are

usually slower and more variable. Some topical products may only have a local reaction and are not

systemically absorbed.

Risks for various products are different as well. The biological risks for various product contaminants

depend to a degree on whether the product is ingested orally (E. coli for example). Certain

contaminants might be more harmful if ingested orally or parentally (if they are not absorbed in the

GI tract). Topical, oral, rectal or ocular applications might cause local irritation depending on the

solvent and product. Smoked products contain a uniquely large amount of harmful byproducts of

combustion. Heated vape pen components may contain adhesive or other parts that are toxic when

heated beyond a certain degree. IV and IM preparations potentially carry an additional set of risks

(biological, allergic and chemical) given the bypass of the blood/endothelium barrier.

Products that are rapidly absorbed (inhaled, absorbed, parenteral) may cause immediate effects and

signicant side effects which may or may not be tolerated well, but which usually last a shorter period

of time. This quick feedback is helpful for dosing in the patient. Orally-ingested products are highly

variable in the rate and amount of absorption and are much slower in onset of action, which makes

dosing more difcult. This could easily result in an ingestion far beyond what is advised or intended

(because you can eat a lot before you feel anything).

All of these considerations indicate the importance of consulting toxicologists and physicians

when deciding which products will be available for use, and what type of testing should be done on

the products.

Dealing with Schedule I Materials

Marijuana is classied as a schedule I substance under the Controlled Substance Act (CSA) [21

U.S.C. {} 801 et seq].

This Act requires persons who handle controlled substances to register with

http://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

the Drug Enforcement Agency (DEA) in the Department of Justice, which administers and enforces

the Act.

In New York, medical marijuana and related products produced by a registered organization must be

examined in a laboratory located in New York State. The laboratory must be licensed by the federal

Drug Enforcement Administration (DEA) and approved for the analysis of medical marijuana by the

department in accordance with New York law. Relevant language is copied below.

The ordering and use of controlled substances must adhere to the requirements of the

Controlled Substance Act of 1970 and any local state enforcement agency, as well as the terms

and conditions of any Institutional Research or Analytical Licenses or Registrations issued in

accordance with proposed laboratory activities. Each approved facility must be preapproved

by both DEA and Local State Codes and have the license/registrations posted on or near the

primary inventory storage. A comprehensive standard operating procedures (SOP) covering all

aspects of oversight of controlled substances within the laboratory documenting substance

receipt to the nal depletion or destruction must be addressed.

Licenses/Registrations

will be required for the type of activity being conducted at each facility, including the need to

maintain controlled substances and record keeping within the activity.

Denitions

Refer to SPPM IV—Controlled Substance Program for a list of program specic denitions.

Responsibilities

The normal responsibility for security of controlled substances within a facility rests with the

individuals granted unescorted access and use of these substances. The following are specic

responsibilities for personnel assigned to the facility.

3.1 Licensees will be responsible for the submittal of all internal applications/forms/

requests needed to support this policy. Additionally, they will approve all usage requests

submitted, to support legitimate, authorized studies or programs.

3.2 All usage of Controlled Substances will require any usage requests be submitted by

the Investigator for approval before controlled substance activity takes place.

3.3 Licensees responsible for storing quantities of controlled substances will act as

or appoint an Inventory Custodian responsible to coordinate protective requirements

including monitoring orders, receipt verication, storage, accountability, and nal

distribution.

3.4 The Mail and Receiving Section is responsible to notify licensees or custodians of

the receipt of deliveries containing controlled substances, as identied under state and

federal law. All efforts will be made to ensure the rapid transition from the mailroom to

the custodian and into secure storage.

3.5 Controlled Substances Users, under the guidance of the Principal Investigators and

Licensees, are responsible to ensure compliance with Laboratory policy and all other

rules, regulations, and orders issued by the state and/or the US Drug Enforcement

Administration.

Guidance for State Medical Cannabis Testing Programs

Approved Storage Areas

The following is a list of approved storage situations for controlled substances designated as

Level II and III Assets.

4.1 Each licensed facility will maintain a Primary Storage location to support

registered activities.

4.2 Satellite Storage locations may be approved to support small quantity users and

should be coordinated with the Laboratory Director prior to approval.

Procedures

All controlled substances used in research or diagnostic procedures or as part of research will

be requested through the licensee and will refer to the corresponding license or registration on

requests.

1. A copy of your current DEA registration (DEA Form 223) along with your request for controlled

substances must be submitted. It is the research investigator’s responsibility to keep his/

her registration current and verify the drug code for drug/compound being requested. For

those investigators who request Schedule I drugs must provide DEA documentation that the

requested drug is covered under their current DEA registration.

2. Enclose an accurately completed DEA Form 222 (for controlled substances) with the

request. Note that a DEA Form-222 is not necessary for drugs in Schedules III V, but a valid

registration for the appropriate schedule is.

NOTE: No Controlled Substances should be transferred into the facility without the approval of

the Licensee responsible for the specic activity. Unregistered Controlled Substances will be

reported to DEA and/or state authorities for immediate seizure.

5.1 All purchases of Controlled Substances will be made by the Licensees; purchase

requests will list only the licensees or custodians to ensure they are placed into the

facility’s inventory.

5.1.1 Usage requests will be made using the appropriate facility protocol for

laboratory standards and controlled substances.

5.1.2 All requests will be accompanied by a usage protocol and include the

following information;

5.1.2.1 Type of activity conducted;

5.1.2.2 Type and form of controlled substances required;

5.1.2.3 Quantity of controlled substances expected to be used.

5.1.3 Controlled substances should be received by the Controlled

Substance Custodian, secured and logged into inventory as soon as

possible.

5.1.4 The Controlled Substance Inventory Record to maintain an

accurate Inventory of controlled substances that are maintained by

each licensed/registered activity at each facility.

5.1.5 Inventory records will be maintained within the security

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

container at each location and at an alternate location to ensure they

are not compromised during a theft.

5.1.6 Until being used, all controlled substances will be stored in a

security container under the control of the licensee or custodian.

5.1.7 All other scheduled substances can be stored in the same

area for safekeeping until dispersal to the Principal Investigator or

authorized User.

5.2 Transfer of Controlled Substances will be based upon a proper usage request,

consistent with approved protocols.

5.2.1 The custodian will be responsible to physically open the safe, retrieve

the substance and inventory records, and issue them to the authorized User

listed upon the Usage Request.

5.2.2 The Usage Record will be provided by the custodian along with the

controlled substances.

5.2.3 The Controlled Substance Inventory Record will be used to track the

program use of each controlled substance.

5.2.4 The completed Usage Records will be checked for accuracy and

completeness; any impropriety questioned and upon return used to reconcile

the custodial inventory record.

5.2.5 Users will not be issued quantities greater than what would be needed

for operational purposes, at the discretion of the licensee.

5.2.6 Controlled substance transfers will be “Hand Delivered” by either the

Licensee or Custodian or the requesting Principal Investigator (PI) or Users.

Movement within the facility will be coordinated with [sic].

5.2.7 Security escorts will be used whenever transfers are made between

the primary and satellite storage locations within a licensed facility/facilities.

Contact the Security Control Center at ext. 3-6153, as soon as possible, to

request escorts.

5.3 Upon depletion or expiration of the substance, the PI and/or user will return the

bottle to the controlled substance custodian, whether empty or not, with the usage

record to assure accurate record keeping and/or proper disposal.

5.4 Unused controlled substances being returned to inventory will be “Hand

Delivered” as specied above.

5.5 The requesting PI will be required to keep all controlled substances in secure

storage and record each use on the corresponding usage sheets as specied below.

5.6 Controlled substances will be returned, to the controlled substance safe from

which they were issued, inventoried, and stored, until such time that they are properly

used or disposed of.

5.7 Generally, during inventories or before transfer controlled substances should be

Guidance for State Medical Cannabis Testing Programs

checked for expiration dates and items nearing expiration should be replaced and/or

recalled.

5.8 The required New York State Bureau of Controlled Substances Forms DOH-2340

and DOH-166 will be completed by the controlled substance custodian, endorsed by

the licensee, and submitted for drug disposal approval.

5.8.1 Upon approval, at least two authorized personnel will be present to

carry out the approved disposal method.

5.8.2 The controlled substance will be disposed of in the timeframe and by

the method agreed to on the request forms.

Contamination, Spills or Breakage

Any time a controlled substance becomes unusable due to one of these unplanned events it will

be reported to the responsible PI and/or the issuing Licensee Custodian.

6.1 The cleanup will not begin until the responsible PI and/or Licensee Custodian

arrives to witness the cleanup and take a verication sample.

6.2 The absorbent material and/or liquid residue will be placed in an appropriate

container which will be secured by the Licensee Custodian until proper disposal can

be scheduled.

6.3 The verication sample will be tested, using one of the analytical laboratories, to

verify the presence of the regulated substance prior to nal destruction.

6.4 The appropriate usage record will be documented under Purpose to reect the

loss due to the contamination, spill, or breakage.

Suspected Loss

If for any reason, there is or appears to have been a Loss of a Control Substance the PI,

Custodian, and Licensee will be immediately notied and supplied with all pertinent information.

7.1 The custodian will contact Security Services, ext 473-6173, who will immediately

initiate an internal investigation.

7.2 Upon verication of the loss the Director of Security will submit a DOH 2094, Loss

of Controlled Substance Report specifying all known facts surrounding the loss.

Record Keeping

8.1 Inventory Custodian(s) will maintain accurate records documenting the following:

8.1.1 Records of Receipt (e.g., signed invoice, bill of laden, or packing slip)

8.1.2 Inventory Record, see Attachment I.

8.1.3 Usage Record, see Attachment II.

8.1.4 Copies of approved Animal and Non-Animal Usage Request Forms.

8.1.5 Records of Destruction

8.2 The Licensees and/or Principal Investigators shall initiate and monitor record

keeping activities to ensure accurate maintenance and inventory control.

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

8.3 Document all storage container combination changes using the Security

Combination Change Record, see Attachment V.

8.4 All records shall be maintained at the permitted premises for a period of not less

than three years unless otherwise extended by DOH Records Retention Policies.

Analytes and Action Levels

While medical cannabis products are often assumed to be inherently safe, factors such as

moisture content, bioburden, potency and the presence of contaminants play a signicant role

in determining the risk to patient health and safety. The three major categories of contaminants

targeted for testing include pesticides, solvents and microbiological contaminants.

Not all types of cannabis products need testing for all types of contaminants. Below is information

on some of the major categories of testing. In evaluating what analysis should be performed, it is

important to maintain perspective on the laboratory’s role in the product quality ecosystem.

Pesticides

Pesticides can lead to illness and therefore many states have included them on the list of analytes

that need to be tested. There are no pesticides specically approved for use on cannabis in the US.

However, any pesticides meeting the criteria described in the USEPA 40 CFR 180.950(a), (b), or

(c)

may be used as an inert ingredient in any minimum risk pesticide product applied to cannabis

cultivation.

Selections of target pesticides for testing vary by state. For example, Massachusetts’ Medical

Marijuana Program requires testing prohibited pesticides identied by the American Herbal

Pharmacopoeia,

which are commonly used in cannabis cultivation. But New Jersey’s program

selected pesticides for testing based on the EPA pesticide testing method 507,

9,10

with the addition

of some representative pesticides of different classes from the USDA’s “Pesticide Residue Testing of

Organic Produce.”

The remainder of this section presents the approach taken by Oregon,

which established a list of

target analytes related to pesticides. Oregon was not chosen as a model, they simply were chosen

because they participated in the drafting of this section. As mentioned above, other states have

taken different approaches, and as this document is updated APHL hopes to include more examples

here.

Oregon started by compiling lists from three laboratories already involved in testing cannabis

products for pesticides. Participating labs were members of a Rules Advisory Committee assembled

to guide the state in developing rules for testing cannabis. The rst list, was created as described in

https://www.law.cornell.edu/cfr/text/40/180.950

AHP. 2013. Cannabis Inorescence, Cannabis spp., Standards of Identity, Analysis, and Quality Control. American Herbal

Pharmacopoeia. 2013. Available at: http://www.stcm.ch/files/us-herbal-pharmacopoeia_cannabis-monography.pdf

EPA. Method 507: Determination of Nitrogen- and Phosphorus-containing pesticides in water by gas chromotagraphy with

a nitrogen-phosphorus detector. Revision 2.1. Edited by J.W. Munch (1995). Available at https://www.epa.gov/sites/pro-

duction/files/2015-07/documents/epa-507.pdf.

EPA. Inert Ingredients Eligible for FIFRA 25(b) Pesticide Products (Updated December 2015). Available at https://www.

epa.gov/sites/production/files/2015-01/documents/section25b_inerts.pdf.

USDA. 2010 – 2011 Pilot Study: Pesticide Residue Testing of Organic Produce. Available at https://www.ams.usda.gov/

sites/default/files/media/Pesticide%20Residue%20Testing_Org%20Produce_2010-11PilotStudy.pdf

Oregon Health Authority. Technical Report: Oregon Health Authority’s Process to Determine which Types of Contaminants

to Test for in Cannabis Products, and Levels for Action. Available at https://public.health.oregon.gov/PreventionWellness/

marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf.

Guidance for State Medical Cannabis Testing Programs

Appendix 1 of “Pesticide Use on Cannabis” from the Cannabis Safety Institute,

and contained 123

active ingredients. The Committee generated the second list by selecting compounds that overlapped

between various lists including the rst list, as well as regulation lists for medical or recreational

marijuana from Oregon, Nevada and Colorado. The third list was based on Integrated Pest

Management guidance for several crops grown in the Pacic Northwest and a search of Washington

State University’s Pesticide Information Center Online (PICOL) database.

The third list also included

active ingredients available in pesticide products sold at a local hardware store. Removal of

duplicates resulted in 188 pesticide analytes.

Action Levels

Ideally, action levels would be based on human health and toxicity thresholds. However, there

is insufcient exposure information available to establish toxicity-based tolerances for pesticide

residues in cannabis products. The variety of uses and exposure routes is too great, and there is not

enough information about the pyrolysis products of target pesticides relevant to cannabis products

when smoked.

Therefore, action levels for pesticides in cannabis in Oregon were developed based on laboratory

limits of quantication (LOQ) that were deemed reasonably achievable by analytical chemists

represented on the testing subcommittee of the rules advisory committee. The criterion for pass/fail

was set on whether or not an analyte is detected above the action level.

To set action levels, the Oregon Health Authority (OHA) asked commercial analytical laboratories

to submit their LOQs for each analyte on the target list. Two labs submitted LOQs, while a third lab

submitted limits of detection on the instrument types from published literature. For each instrument

type, OHA multiplied the higher of the LOQs from the two laboratories by a factor of two to get to

the action level. For analytes not tested by the laboratories, OHA selected the highest action level

from among analytes with the same published detection limits for the relevant analytical laboratory

equipment.

Regarding piperononyl butoxide and pyrethrins, OHA adopted Nevada’s action levels. For piperonyl

butoxide, the level is based on the Nevada state laboratory’s LOQ. The action level of 1 ppm for

pyrethrins is based on the lowest federal food tolerance for pyrethrins in edible plant material.

Washington’s Department of Health is also adopting Nevada’s action levels for these two

compounds.

For analytes not tested in cannabis by any analytical laboratory in Oregon, OHA used surrogate

analytes with similar published detection limits. While not ideal, this represented the best available

estimate at the time. Oregon rules requiring that labs submit their limits of detection along with their

LOQs will allow OHA to update action levels as appropriate in the future.

The Oregon limits in Table 1 are not thresholds; they are a best guess at the analytical LOQ for that

analyte. This is because allowing a detection at all for an off-label compound would violate federal

FIFRA laws. These limits are analytical in nature only and will probably be revised when Oregon has

enough data to be sure the labs can achieve lower limits.

http://cannabissafetyinstitute.org/wp-content/uploads/2015/06/CSI-Pesticides-White-Paper.pdf

http://cru66.cahe.wsu.edu/LabelTolerance.html

This pulls almost verbatim from reference 12 above.

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Table 1: Pesticide analytes and their action levels in OR

Analyte

Chemical Abstract Services

(CAS) Registry Number

Action Level ppm

Abamectin 71751-41-2 0.5

Acephate 30560-19-1 0.4

Acequinocyl 57960-19-7 2

Acetamiprid 135410-20-7 0.2

Aldicarb 116-06-3 0.4

Azoxystrobin 131860-33-8 0.2

Bifenazate 149877-41-8 0.2

Bifenthrin 82657-04-3 0.2

Boscalid 188425-85-6 0.4

Carbaryl 63-25-2 0.2

Carbofuran 1563-66-2 0.2

Chlorantraniliprole 500008-45-7 0.2

Chlorfenapyr 122453-73-0 1

Chlorpyrifos 2921-88-2 0.2

Clofentezine 74115-24-5 0.2

Cyuthrin 68359-37-5 1

Cypermethrin 52315-07-8 1

Daminozide 1596-84-5 1

DDVP (Dichlorvos) 62-73-7 0.1

Diazinon 333-41-5 0.2

Dimethoate 60-51-5 0.2

Ethoprophos 13194-48-4 0.2

Etofenprox 80844-07-1 0.4

Etoxazole 153233-91-1 0.2

Fenoxycarb 72490-01-8 0.2

Fenpyroximate 134098-61-6 0.4

Fipronil 120068-37-3 0.4

Flonicamid 158062-67-0 1

Fludioxonil 131341-86-1 0.4

Hexythiazox 78587-05-0 1

Imazalil 35554-44-0 0.2

Imidacloprid 138261-41-3 0.4

Kresoxim-methyl 143390-89-0 0.4

Malathion 121-75-5 0.2

Metalaxyl 57837-19-1 0.2

Methiocarb 2032-65-7 0.2

Methomyl 16752-77-5 0.4

Methyl parathion 298-00-0 0.2

Guidance for State Medical Cannabis Testing Programs

Analyte

Chemical Abstract Services

(CAS) Registry Number

Action Level ppm

MGK-264 113-48-4 0.2

Myclobutanil 88671-89-0 0.2

Naled 300-76-5 0.5

Oxamyl 23135-22-0 1

Paclobutrazol 76738-62-0 0.4

Permethrins

52645-53-1 0.2

Phosmet 732-11-6 0.2

Piperonyl_butoxide 51-03-6 2

Prallethrin 23031-36-9 0.2

Propiconazole 60207-90-1 0.4

Propoxur 114-26-1 0.2

Pyrethrins

8003-34-7 1

Pyridaben 96489-71-3 0.2

Spinosad 168316-95-8 0.2

Spiromesifen 283594-90-1 0.2

Spirotetramat 203313-25-1 0.2

Spiroxamine 118134-30-8 0.4

Tebuconazole 80443-41-0 0.4

Thiacloprid 111988-49-9 0.2

Thiamethoxam 153719-23-4 0.2

Trioxystrobin 141517-21-7 0.2

1617

Solvents

Various solvents (Table 2) are used during the manufacturing of cannabis extracts and concentrates

to remove cannabinoids from the plant material. The extraction process is a super critical uid

process in which the marijuana plant material is placed in a vessel with the solvent at high

pressures. Each solvent used has its own extraction efciency, toxicity and latency within the

extracted product. The compounds used for the extraction of cannabinoids may also pose a health

risk.

While no health-based solvent residual limits have been established specically for cannabis

extract or concentrate products, practices around pharmaceutical production and limits provide a

reasonable model, particularly for the oral route of exposure.

The US Pharmacopeia’s National Formulary

Chapter 467 provides guidance for the use of solvents

in the manufacturing of pharmaceutical products. This chapter has been adopted by many regulatory

agencies in selecting solvents that may be utilized for extraction, as well as in setting the limits for

residual solvents allowed in extracted products.

Permethrins should be measured as cumulative residue of cis- and trans-permethrin isomers (CAS numbers 54774-45-7

and 51877-74-8 respectively).

Pyrethrins should be measured as the cumulative residues of pyrethrin 1, cinerin 1, and jasmolin 1 (CAS numbers 121-

21-1, 25402-06-6, and 4466-14-2 respectively).

http://www.usp.org/usp-nf

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

The solvents are broken down into three different categories. Category 1 contains solvents that are

known or suspected carcinogens, or environmental hazards. Category 2 contains non-genotoxic

animal carcinogens or causative agents with irreversible toxicity. Category 3 contains compounds

that have low toxicity potential to humans with no health-based exposure limits. The analytes as

determined by the US Pharmacopeia are listed in Table 2 with their concentration limits and category.

Solvents found in categories 1 and 2 are either toxic or pose a signicant enough health risk not to

be utilized in the manufacturing of cannabis concentrates and extracts.

Table 2: USP Chapter 467 Solvents and their concentration limit

Solvent Concentration Limit (ppm) Category

Benzene 2 1

Carbon tetrachloride 4 1

1,2-Dichloroethane 5 1

1,1-Dichloroethene 8 1

1,1,1-Trichloroethane 1500 1

Acetonitrile 410 2

Chlorobenzene 360 2

Chloroform 60 2

Cyclohexane 3880 2

1,2-Dichloroethene 1870 2

1,2-Dimethoxyethane 100 2

N,N-Dimethylacetamide 1090 2

N,N-Dimethylformamide 880 2

1,4-Dioxane 380 2

2-Ethoxyethanol 160 2

Ethylene glycol 620 2

Formamide 220 2

Hexane 290 2

Methanol 3000 2

2-Methoxyethanol 50 2

Methylbutylketone 50 2

Methylcyclohexane 1180 2

Methylene chloride 600 2

N-Methylpyrrolidone 530 2

Nitromethane 50 2

Pyridine 200 2

Sulfolane 160 2

Tetrahydrofuran 720 2

Tetralin 100 2

Toluene 890 2

Trichloroethylene 80 2

Guidance for State Medical Cannabis Testing Programs

Solvent Concentration Limit (ppm) Category

Xylene 2170 2

Acetic acid 3

Acetone 3

Anisole 3

1-Butanol 3

2-Butanol 3

Butyl acetate 3

tert-Butylmethyl ether 3

Cumene 3

Dimethyl sulfoxide 3

Ethanol 3

Ethyl acetate 3

Ethyl ether 3

Ethyl formate 3

Formic acid 3

Heptane 3

Isobutyl acetate 3

Isopropyl acetate 3

Methyl acetate 3

3-Methyl-1-butanol 3

Methylethylketone 3

Methylisobutylketone 3

2-Methyl-l-propanol 3

Pentane 3

1-Pentanol 3

1-Propanol 3

2-Propanol 3

Propyl acetate 3

Action limits for solvents in cannabis products in Oregon (Table 3) are based on the International

Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals

for Human Use, ICH Harmonized Tripartite Guideline, Impurities: Guideline for Residual Solvents

Q3C(R5) (ICH Q3C).

The health-based action levels in this guideline are based on the toxicity of

individual solvents and the magnitude of exposure expected to occur from consuming 10 grams of a

pharmaceutical (which is an unlikely amount of cannabis to consume).

http://www.pmda.go.jp/files/000156308.pdf

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

2021

Table 3: List of solvents and their action levels

Solvent

Chemical Abstract Services

(CAS) Registry Number

Action Level (µg/g)

1,2-Dimethoxyethane 110-71-4 100

1,4-Dioxane 123-91-1 380

1-Butanol 71-36-3 5000

1-Pentanol 71-41-0 5000

1-Propanol 71-23-8 5000

2-Butanol 78-92-2 5000

2-Butanone 78-93-3 5000

2-Ethoxyethanol 110-80-5 160

2-methylbutane 78-78-4 5000

2-Propanol (IPA) 67-63-0 5000

Acetone 67-64-1 5000

Acetonitrile 75-05-8 410

Benzene 71-43-2 2

Butane 106-97-8 5000

Cumene 98-82-8 70

Cyclohexane 110-82-7 3880

Dichloromethane 75-09-2 600

2,2-dimethylbutane 75-83-2 290

2,3-dimethylbutane 79-29-8 290

1,2-dimethylbenzene 95-47-6 See Xylenes

1,3-dimethylbenzene 108-38-3 See Xylenes

1,4-dimethylbenzene 106-42-3 See Xylenes

Dimethyl sulfoxide 67-68-5 5000

Ethanol 64-17-5 5000

Ethyl acetate 141-78-6 5000

Ethylbenzene 100-41-4 See Xylenes

Ethyl ether 60-29-7 5000

Ethylene glycol 107-21-1 620

Ethylene Oxide 75-21-8 50

Heptane 142-82-5 5000

n-Hexane 110-54-3 290

Isopropyl acetate 108-21-4 5000

Methanol 67-56-1 3000

Methylpropane 75-28-5 5000

2-Methylpentane 107-83-5 290

Limit based on similarity to pentane

Limit based on similarity with n-hexane

Guidance for State Medical Cannabis Testing Programs

Solvent

Chemical Abstract Services

(CAS) Registry Number

Action Level (µg/g)

3-Methylpentane 96-14-0 290

N,N-dimethylacetamide 127-19-5 1090

N,N-dimethylfromamide 68-12-2 880

Pentane 109-66-0 5000

Propane 74-98-6 5000

Pyridine 110-86-1 200

Sulfolane 126-33-0 160

Tetrahydrofuran 109-99-9 720

Toluene 108-88-3 890

Xylenes

1330-20-7 2170

Oregon’s list was generated by members of their Rules Advisory Committee with analytical chemistry

experience as well as knowledge of common cannabis extraction and concentration techniques. They

note that selected action levels for solvents in cannabis products may not be sufciently protective

if the product is inhaled. However, there are no studies upon which to base separate action level

for products intended for smoking or vaping. ICH Q3C does assume 100% absorption by any route,

which would include inhalation.

Several states have developed a list of solvents considered safer for use as extraction solvents. Table

4 lists a few of these solvents, the agency and the maximum concentration levels. Massachusetts

Department of Public Health adopted their criteria from the residual solvent recommendations by the

Commission of the European Communities, Scientic Committee on Food (SCF, 1999).

Table 4: Solvent maximum concentration limits by state

State Agency

Solvent Units MA NV CO

Propane ppm 1000

n-Butane ppm 1000

Iso butane ppm 1000

Butanes ppm 500 800

Heptanes ppm 500 500

Propane ppm 500

Benzene** ppm <1

Toluene** ppm <1

Hexane** ppm <10

**Note: These solvents are not approved for use.

Combination of: 1,2-dimethylbenzene, 1,3- dimethylbenzene, 1,4-dimethylbenzene, and ethyl benzene

http://ec.europa.eu/food/fs/sc/scf/out26_en.pdf

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Other solvents such as alcohols and carbon dioxide, which are much less toxic, are becoming more

prevalent in the industry, even though these solvents do not have the same extraction efciency as

petroleum hydrocarbon based solvents.

Microbiologicals

24,25,26

A review of existing literature shows that the presence of mold on cannabis can result in severe

health complications and death.

27,28,29,30

Pathogenic bacteria may also be a cause of under-reported

or under-recognized adverse events. For example, in December 2011 a kidney transplant recipient

and New Mexico Medical Cannabis Program participant was hospitalized due to a gastrointestinal

infection linked to smoking cannabis which had previously failed testing for the presence of

enterobacteria and mold. The patient was encouraged to notify the Department of Health but

declined due perceived hostility towards patients and industry stakeholders by administration and

his relationship with the producer.

Available literature supports the idea of a causal relationship between smoking cannabis and

bacterial infections. Numerous human pathogens have been identied on cannabis and research

on tobacco products suggests that these organisms are likely not completely destroyed during

smoking.

25,32,33

In general, bacteria cannot survive either the drying or heating processes to which cannabis is

subjected. Salmonella, however, can survive at very low moisture levels and is highly infectious in

humans. E. coli itself does not usually pose a signicant health risk, but it is an indicator of poor

sanitary conditions and the possible presence of other fecal bacteria.

Aspergillus, the spores of which can withstand desiccation and high temperatures, can cause

respiratory infections in individuals who inhale it if they are severely immune-compromised and

there is a known clinical correlation with cannabis smoking. However, some consider it unlikely that

Aspergillus testing would be informative because it is so common in the environment. The Oregon

Testing Subcommittee recommended that cannabis products intended for smoking and other

inhalation uses include a warning about this risk for people with suppressed immune systems.

Some states have required testing of cannabis for aatoxins produced by certain Aspergillus species.

Aatoxins are highly carcinogenic mycotoxins which pose signicant threat to exposed individuals,

though concern of their presence on cannabis or in cannabis-derived products is debatable. United

States Pharmacopoeial guidelines indicate that mycotoxin quantication is not necessary for all

Dussy FE, Hamberg C, Luginbuhl M, Schwerzmann T. et al. Isolation of ∆

-THCA-A from hemp and analytical aspects

concerning the determination of ∆

-THC in cannabis products. For. Sci. Int. 2005;149:3-10.

Gargani Y, Bishop P, Denning DW. Too many mouldy joints—marijuana and chronic pulmonary aspergillosis. Mediterr. J.

Hematol. Infect. Dis. 2011;3:e201105

Szyper-Kravitz M, Lang R, Manor Y, Lahav M. Early invasive pulmonary aspergillosis in a leukemia patient linked to

aspergillus contaminated marijuana smoking. Leukemia and Lymphoma. 2004;42:1433-1437.

American Society of Addiction Medicine. Medical Marijuana Task Force White Paper Executive Summary. http://www.

ibhinc.org/pdfs/MedicalMarijuanaAGWhitePaper.pdf

Hamadeh R, Ardehali A, Locksley RM, York MK. Fatal aspergillosis associated with smoking contaminated marijuana, in a

marrow transplant recipient. Chest. 1988;94:432-433.

Hazekamp A. An evaluation of the quality of medicinal grade cannabis in the Netherlands. Cannabinoids. 2006;1:1.

Verweij PE, Kerremans JJ, Voss A, et al. Fungal Contamination of Tobacco and Marijuana. JAMA. 2000;22:2875.

Applen, J. Personal communication with patient. December 7, 2011.

Pauly JL, Paszkiewicz G. Cigarette smoke, bacteria, mold, microbial toxins, and chronic lung inammation. J. of Onc.

2011;doi:10.1155/2011/819129.

Sapkota AR, Berger S, Vogel TM. Human pathogens abundant in the bacterial metagenome of cigarettes. Env. Health.

Pers. 2010;3:351-356.

Guidance for State Medical Cannabis Testing Programs

botanical products. The majority of products which are required to be analyzed for mycotoxins

originate from root or rhizome material which THC-containing cannabis products presumably do not

possess.

There is no readily available evidence to support the contention that cannabis harbors signicant

levels of mycotoxins. A simple literature search for mycotoxins and cannabis returned only one

result: “Examination of fungal growth and aatoxin production on marihuana” by G.C. Llewellyn and

C.E. O’Rear published in Mycopathologia in 1977.

That paper examined illicitly grown cannabis

seized by law enforcement and found that “[a]ll natural ora cultures tested negative for aatoxins”

and the authors concluded “[m]arihuana appears not to yield large quantities of these mycotoxins.”

Given there is no readily available evidence to support the contention that cannabis harbors

signicant levels of mycotoxins and ongoing advancements in the cannabis industry such as the

introduction of requirements to test for microbiological contaminants and improvements in Good

Manufacturing Practices (GMP) oversight, it is unlikely that mycotoxins would be identied on ower

material.

There is one circumstance under which mandatory mycotoxin testing should be considered.

When UV-C light exposure is insufcient to remediate a ower product contaminated with mold,

that product is diverted to an extraction process. If the mold/fungi happens to be of a type which

produces mycotoxins, those carcinogenic compounds may be concentrated during the extraction

process and passed on to patients. It is strongly advised that concentrate derived from plant

material which entered into the extraction process due to mold contamination be tested for the

presence of mycotoxins.

Moisture present in herbal products is a primary determinant of the ability of microorganisms to

thrive and rise to harmful levels post distribution. The Dutch Ofce of Medical Cannabis species

that the water content of cannabis at the time of quality control (directly after packaging) must be

between 5-10%. Testing for water activity, and requiring water activity levels to fall below A

0.65, will

ensure the absence of microbial growth on cannabis products during storage and prior to sale.

Table 5: US Pharmacopeia Microbial Limits

Preparation Denition USP Microbial Limits

Chopped or Powdered

Botanicals

Hand-picked portions of the

botanical (e.g. leaves, owers,

roots, tubers etc.) that are air

dried and chopped, aked,

sectioned, ground or pulverized

to the consistency of a powder.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Bile Tolerant Gram-negative

Bacteria <10

Absence of Salmonella spp & E.

coli in 10 g

http://link.springer.com/article/10.1007%2FBF01259400

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Preparation Denition USP Microbial Limits

Powdered Botanical Extracts Extracts are solids or semisolid

preparations of a botanical that

are prepared by percolation,

ltration and concentration by

evaporation of the percolate.

The extracting material may be

alcoholic, alkaline, acid hydro-

alcoholic or aqueous in nature.

Typically an extract is 4-10

times as strong as the original

botanical. The extracts may

be semisolids or dry powders

termed powdered extracts.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of Salmonella spp & E.

coli in 10 g

Tinctures Tinctures are solutions of

botanical substances in alcohol

obtained by extraction of the

powdered, aked or sectioned

botanical.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Infusions Infusions are solutions of

botanical principles obtained by

soaking the powdered botanical

in hot or cold water for a

specied time and straining.

Typically infusions are 5% in

strength.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Decoctions Decoctions are solutions of

botanicals prepared by boiling

the material in water for at

least 15 minutes and straining.

Typically decoctions are 5% in

strength.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Fluidextracts A uidextract is an alcoholic

liquid extract made by

percolation so that 1 mL of the

uidextract represents 1 g of

the botanical.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Botanicals to be treated with

boiling water before use

Dried botanicals to which

boiling water is added

immediately prior to

consumption.

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of E. coli in 10 g

Guidance for State Medical Cannabis Testing Programs

Preparation Denition USP Microbial Limits

Other raw materials and

ingredients

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of E. coli in 10 g

Nutritional products with other

highly rened ingredients

Edibles Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of E. coli in 10 g

Rectal Use Products Rectal Suppositories

For nonsterile products for

pharmaceutical preparations

and substances for

pharmaceutical use

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Vaginal Use Ointments, Creams, Inserts,

etc.

For nonsterile products for

pharmaceutical preparations

and substances for

pharmaceutical use

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of Pseudomonas

aeruginosa, Staphylococcus

aureus and Candida albicans in

1g or 1mL

Transdermal Patches For nonsterile products for

pharmaceutical preparations

and substances for

pharmaceutical use

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of Pseudomonas

aeruginosa, Staphylococcus

aureus

Oral Mucosal, Gingival,

Cutaneous, Nasal or Auricular

use

For nonsterile products for

pharmaceutical preparations

and substances for

pharmaceutical use

Total Aerobic Microbial Count

<10

Total Combined Yeast and Mold

Count <10

Absence of Pseudomonas

aeruginosa, Staphylococcus

aureus

Opthalmic use Must meet the requirements

of USP 771 for Opthalmic

Preparations

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Metals

Metals are present in our soil and water, both naturally and as a result of anthropogenic activities.

Some of the activities include mining and smelting of metals, disposal of industrial wastes, burning

of fossil fuels, paints, the use of fertilizers and pesticides in agriculture, production of batteries and

other metal products, sewage sludge and municipal waste disposal. Metals in soil and water can be

absorbed by plants during cultivation, resulting in elevated metals in plants and thus a concern for

public health.

Cultivation of cannabis requires soil and water of a certain quality, i.e. it should be free of

contaminants. Since this might not always be the case, screening of heavy metals is recommended

to safeguard the cannabis user’s health. Heavy metals such as lead, cadmium, mercury, and

arsenic are toxic to both plants and humans, and therefore often the focus of testing.

Cannabinoids

It is well known that the potency of cannabis products may vary largely by strain. The goal in

determining what cannabinoids should be quantied is to support label accuracy. Although cannabis

contains more than 150 cannabinoids, delta-9-tetrahydrocannabinol (Δ

-THC) has received the most

attention since it is the principal psychoactive component of the plant. Other analytes often required

for analysis include cannabidiolic acid (CBD-A), cannabigerolic acid (CBGA), cannabidiol (CBD),

cannibigerol (CBG), tetrahydrocannabinol acid (THCA), cannabinol (CBN) and delta-8-THC (Δ

-THC).

Information of other cannabinoids can help understand the pharmacological properties of cannabis.

In Oregon, the rule requires testing for THC, THC-A, CBD, and CBD-A. Due to the potential of THC-A

decarboxylizing into Δ

-THC during sample processing and analysis, a total THC amount must be

calculated,

where M is the mass or mass fraction of Δ

-THC or Δ

-THCA:

M total Δ

-THC = M Δ

-THC + 0.877 x M Δ

-THCA

Total CBD must also be calculated, where M is the mass or mass fraction of CBD and CBDA:

M total CBD = M CBD + 0.877 x M CBDA

Oregon acknowledged that as seen analytically, the mass ratio scenario is not perfect. They expect

the equation for calculating Total THC to change after data is produced.

Sampling and Analysis

The potency of cannabis products varies by strain. Also, contaminants may be introduced to the plant

materials or cannabis products during growing, manufacturing and storage processes. To ensure the

quality of the product and compliance with the standards set forth by each state, testing of cannabis

products is recommended.

A comprehensive sampling and testing plan should be developed so that the testing results are

representative for the products tested. Although no standardized sampling or testing protocols exist

Tangahu BV, Abdullah SRS, Basri H, Idris M, Anuar N, and Mukhlisin M. International Journal of Chemical Engineering

Volume 2011 (2011). http://dx.doi.org/10.1155/2011/939161

Chibuike GU and Obiora SC. Applied and Environmental Soil Science, Volume 2014 (2014)

http://dx.doi.org/10.1155/2014/752708

Stern AH, Gochfeld M, Weisel C, Burger J. Mercury and methylmercury exposure in the New Jersey pregnant population.

Arch Environ Health. 2001 Jan-Feb;56(1):4-10.

http://www.nrcs.usda.gov/Internet/FSE_DOCUMENTS/nrcs142p2_053279.pdf

In Oregon, the total amount of THC must not exceed the maximum allowances for serving and package size even

when heated.

Guidance for State Medical Cannabis Testing Programs

for cannabis products, some examples can be found in programs from the United States, Canada

and Europe, as well as in peer-reviewed articles.

3,8,12,37,38,39

Specic sampling and testing approaches are outlined below. An overall reference for testing for

contaminants can be found in: Daley, P, et al. Testing Cannabis for Contaminants. BOTEC Analysis

Corp. September 12, 2013.

A quality management system, including validation of methods, is

important for assuring the quality of testing and the quality of the product overall.

Sample Collection

Representative sampling for any form of cannabis product must be conducted. Specic sampling

instructions have been developed by different states based on sampling guidance for food products

and herbal medicines developed by the Codex Alimentarius Commission

and the United States

Pharmacopeia

Generally, a random sample should be conducted. For example, to collect samples from cannabis

plant material, New Jersey collects ve ~5 g samples from the dry plant materials for each new

strain. The results are considered representative since the weight of the total samples collected is

approximately 5% of the total products from each harvest. Each sample is tested for potency and the

composite of the ve samples are also tested for potency, heavy metals, pesticides and mycotoxin.

The QA samples (5-10% of the testing samples or a minimum of two samples) are also collected,

stored under the same conditions as other products at the center and tested six months later to

examine whether there are changes in potency or contamination due to storage.

Massachusetts provides specic guidance for sampling from different matrices, such as cannabis

oil, resin or other solid products. The specic sample collection procedures (i.e., documentation) and

sampling tools required for sample collection can be found in their guidance

The homogeneity of liquid products is usually better than solid products. For liquid products, the

product should be well-mixed by stirring before sample collection.

Given the concern of homogeneity of solid cannabis products, a quartering method is

recommended

. Briey, the procedure includes the following steps:

1. Place the well-mixed ground products into a square shape.

2. Divide the material into four equal parts.

3. Take two parts from the opposite corners, mix them and collect samples needed.

4. Repeat steps until the designated number of samples are collected.

Every manufacturing run should have samples collected during manufacturing, representing 5% of

the total dosage units of the sampled lot. To ensure that samples are representative of the entire

lot, samples should be collected at random throughout the process. The samples will help determine

whether a lot can be released from manufacturing hold and distributed to patients.

http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/finished-mmj/final-revised-mdph-mmj-

mips-protocol.pdf

Health Canada (2008). Industrial Hemp Technical Manual. B. o. D. Surveillance. Canada, Therapeutic Products

Directorate.

https://www.health.ny.gov/regulations/medical_marijuana/docs/regulations.pdf

http://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.

org%252Fsites%252Fcodex%252FStandards%252FCAC%2BGL%2B50-2004%252FCXG_050e.pdf

Sexton M and Ziskind J. 2013. Sampling Cannabis for Analytical Purposes. BOTEC Analysis Corp. I-502 Project #430-1e.

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Another resource for sampling is the “Guidance on Obtaining Defensible Samples,” or

“GOODSamples,”

which includes a systematic approach to developing sampling protocols

for defensible decisions. Good sampling is key to improving analytical data equivalency among

organizations, a step in facilitating inter-agency data sharing. An archived APHL webinar

addresses

basic concepts, basic terminology and the need for program-wide understanding of sampling

principles for the improvement of data quality, data acceptability and more efcient use of resources.

Sample Analysis

Pesticides

Given the wide range of physical properties of pesticides, both liquid chromatography (LC) and gas

chromatography (GC) methods are required for testing.

Sample Preparation

Pesticides in a cannabis plant material can be extracted by QuEChERS extraction procedure and

analyzed by GC–MS. QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) is a general

purpose extraction procedure for the determination of organic compounds in fruits, vegetables and

vegetation.

It is applicable to a wide range of organic compounds that are partitioned from a fruit,

vegetable or vegetation sample to acetonitrile or other suitable solvents. Substituting acetonitrile

with ethyl acetate as an extracting solvent provides adequate recovery of a target pesticide while

minimizing extraction of other compounds in cannabis material, therefore minimizing interference.

The sample extract can also be used for LC-based analysis after a solvent exchange into an LC

mobile-phase-compatible solvent such as acetonitrile or methanol.

Sample Analysis

Quantication of pesticides can be performed by EPA Residue Analytical Methods (RAM)

or FDA

Pesticide Analytical Manual (PAM).

GC-MS or GC-MS/MS, LC-MS or LC-MS/MS methods are most

common methods for pesticides detection.

Solvents

The analysis of residual solvents is primarily performed using headspace gas chromatographic

ame ionization detection (HS GC-FID). The sample is placed in a septa-sealed volatile vial with a

non-interfering less volatile solvent and heated. This causes any solvents that may be present in

the sample to dissolve into the septa-sealed volatile vial. The instrument then punctures the septa,

removes a portion of the headspace and injects this into the GC-FID instrument for analysis. This

method has the potential to be used for the analysis of other cannabis matrices and products after

validating the method for a particular matrix or product.

The analysis is dependent on a partition coefcient being developed in the vial to allow the residual

solvents to dissolve into the headspace above the sample. The coefcient can be developed either by

adding a non-interfering less volatile solvent to the sample. This type of analysis is static headspace

analysis and has the potential to have matrix effects. The more complex the matrix becomes, the

more difcult it is to develop a partition to allow the residual solvents to migrate into the headspace

in the vial. A complex matrix allows the residual solvents to be absorbed into the matrix and affects

the quantitative ability of the analysis.

http://www.aafco.org/Portals/0/SiteContent/Publications/GOODSamples.pdf

http://bit.ly/1SJUx8N

Steven J. Lehotay , Kyung Ae Son, Hyeyoung Kwon, Urairat Koesukwiwat, Wusheng Fu, Katerina Mastovska, Eunha Hoh,

Natchanun Leepipatpiboon. Journal of Chromatography A Volume 1217, Issue 16, 16 April 2010, Pages 2548–2560

doi:10.1016/j.chroma.2010.01.044

https://archive.epa.gov/pesticides/methods/rammethods/web/html/ram12b.html

http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm2006955.htm

Guidance for State Medical Cannabis Testing Programs

The alternative to static headspace analysis is Full Evaporation Technique (FET). This type of

headspace analysis is where the sample is added to a vial with no solvent. The sample is heated

directly and the headspace in the vial is used for analysis. The FET version of the analysis does not

rely on the development of a partition, however, the homogeneity of the sample is very important.

The extracted cannabinoid material can be in many forms: liquid, wax or a harder, brittle solid

material known as “shatter.” For waxes and solids, the dispersion of solvents may be heterogeneous.

As the solid material becomes thinner, the solvent will out gas more readily from the material, this

causes diffusion of the solvent, which migrates to the thinner portions of the material, increasing

the concentration. When these materials are sampled for analysis, care must be used to take a

representative sampling from each thickness region of the sample. This sampling technique will

ensure a more representative analysis of the material and avoid high or low biases to the analytical

result.

Massachusetts has detailed instructions for testing residual solvents.

some of which is copied

below:

As discussed in Section 4.2.1, residual solvents testing is required only for cannabis resins

and concentrates where solvents have been used in the production process. In particular, a

production batch of cannabis oil may be dispensed as a nished medical marijuana product

or used to make another medical marijuana product only if:

• Laboratory analysis veries that all solvents used at any stage of cannabis oil

production, except in cleaning equipment, are below the limits provided in Exhibit 6;

and

• The production batch passes all other applicable testing requirements.

Only solvents listed in Exhibit 7 may be used in the production of cannabis oil. A RMD is

required to test only for those solvents used, and it is not required to test for any residual

solvents if it can document that no solvents were used in the cannabis oil production

process.

The upper limits for residual solvents in Exhibit 7 are given as milligrams of residual

solvent per kilogram of cannabis oil. DPH developed the upper limits based on residual

solvent standards provided by the United States Pharmacopeia (USP Chapter <467>), the

International Conference on Harmonization (ICH, 2011), and AHP (2013). Consistent with

the standards provided by these sources, “Class 1” solvents including benzene, carbon

tetrachloride, 1,2-dichloroethane, 1,1-dichloroethene, and 1,1,1-trichloroethane may not be

used in the production of any medical marijuana product.

Analyses to determine residual solvent concentrations in medical marijuana products must

be performed in accordance with the methods identied in USP Chapter <467>.

Quality Control and Quality Assurance (QC/QA)

QC/QA plan must be developed and implemented based on the requirement of the testing

purposes. For example, full validation of the method must be conducted to achieve accuracy,

precision and sensitivity. In addition, secondary sources of the standards for the target

analytes should be obtained and included in the testing plan. More, given the complex matrix

http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/finished-mmj/final-exhibit-7-residual-

solvent-limits.pdf

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

of the cannabis raw material, preparation of the calibration standards in the same matrix as

the sample extract is recommended when testing the plant material.

Currently, there is program established for prociency testing, which should be established in

the near future.

Metals

Atomic absorption and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly-used

methods for metal testing, while the US FDA ICP-MS method

is widely used for quantication of

metals in cannabis products. Analytes required for testing vary by state:

• New Jersey: arsenic, cadmium, iron, lead, manganese, mercury, nickel, selenium and zinc.

• Massachusetts: arsenic, cadmium, lead and mercury.

• New York:

arsenic, cadmium, chromium, copper, nickel, zinc, selenium, mercury and lead.

Cannabinoid Prole

The choice of instrumentation used to perform quantication of cannabinoids is important in

accurately determining potency and is based on the type of sample. Inaccuracies can cause patients

discomfort due to an inappropriate dose.

Several analytical methods have been established to characterize the cannabinoid prole of

cannabis products,

8,50,51,52

including thin layer chromatography (TLC), gas chromatography (GC) and

high pressure liquid chromatography (HPLC).

Among all of the analytical methods, the most common methods employed for cannabinoid analysis

are GC-MS, GC-FID and LC-DAD (diode array detector) methods. However, the analytical method

selected needs to match with the application.

In raw plant material, cannabinoids, particularly Δ

-THC, primarily exist in their non-psychotropic

acidic form (Δ

-THC-A-A). If characterization of cannabinoids in all forms is needed, the LC-DAD

method is recommended. All forms of the cannabinoids, whether in acid or neutral form, are stable

during analysis by liquid chromatography, whereas decarboxylation may occur when testing by gas

chromatography.

8,47,48

The GC method employs a high temperature inlet and oven heating program to volatilize, separate

and elute the material. Since cannabinoids in acid form are unstable and easily decarboxylated by

heating (> 60°C) this results in their changing from acid form to their neutral form, which in the case

of THC, is the psychotropic form.

In addition, if GC temperatures are sufciently high, the THC may be degraded, resulting in under-

reporting of potency. Dussy, F., et. al., determined their GC was reporting THC total values that

FDA. 2011. Analysis of Foods for As, Cd, Cr, Hg and Pb by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).

United States Food and Drug Administration, Center for Food Safety and Applied Nutrition, Current Method CFSAN/ORS/

DBC/CHCB April 25, 2011. Available at: http://www.fda.gov/downloads/Food/FoodborneIllnessContaminants/Metals/

UCM272693.pdf

New York State Department of Health-Wadsworth Center. Metals and Metalloids in Medical Marijuana Products by ICP-

MS. http://www.wadsworth.org/sites/default/files/WebDoc/760769119/LINC-250-01.pdf

De Backer B, Debrus B, Lebrun P, Theunis L, Dubois N, Decock L, Verstraete A, Hubert P, Charlier C. J Chromatogr B Ana-

lyt Technol Biomed Life Sci. 2009 Dec 15;877(32):4115-24. doi: 10.1016/j.jchromb.2009.11.004

Raharjo TJ and Robert Verpoorte, Phytochemical Analysis, Volume 15, Issue 2, pages 79–94, 2004 DOI: 10.1002/

pca.753

Giese MW, Lewis MA, Giese L and Smith KM. Journal of AOAC International, Volume 98, Number 6, November-December

2015, pp. 1503-1522(20) DOI: http://dx.doi.org/10.5740/jaoacint.15-116

Guidance for State Medical Cannabis Testing Programs

were as much as 30% lower than actual values, and therefore could not provide a full prole of

cannabinoids.

In order to report cannabinoid content accurately using a GC, samples must rst be

subjected to a derivatization step and the extent of decomposition must be qualied against a liquid

chromatographic method.

Below is an example to illustrate the importance of GC versus LC analysis and differentiating

between acidic and neutral for cannabinoids in a manufacturing process:

An infused product manufacturer was having its extract analyzed using GC and was told

that it contained approximately 87% w/w THC. When the nished product was distributed,

patient feedback suggested that the product was ineffective and did not elicit the desired

effect. After the extract was reanalyzed using a liquid chromatographic method, it was

discovered that the extract was 49% w/w THC. The difference was due to the GC having

decarboxylated the anti-inammatory THC-A to the psychotropic THC. Due to the error that

occurred during the initial analysis, the manufacturer added roughly half of the amount of

extract needed to achieve the dose listed on the package label resulting in a misbranded

product and dissatised patients.

Sample Preparation

A number of organic solvents are used to extract cannabinoids, including polar solvents such as

methanol, ethanol and chloroform, and less polar solvents such as benzene, petroleum ether and

n-hexane.48 Specic sample preparation procedures can be found in AHP (2013), DeBacker et al.

(2009), and Giese et al., (2015).

8,47,49

New Jersey reported that the mixture of methanol and chloroform (9:1) was an optimal solvent for

extracting cannabinoids.

The sample extract is ltered through a 0.2 mu Nylon, dried by nitrogen

without heating and re-dissolved in 200 uL of methanol:water (65:35). Proper dilution is needed

to minimize contamination of the instrument by the complex matrix while meeting the sensitivity of

the analytical method. Giese et al. (2015) reported an extraction method which includes one single

sample preparation, and the extract can be used for the analysis of both cannabinoids and terpenes

using HPLC-DAD and GC-FID, respectively.

Analysis by GC Method

The commonly-used analytical columns for separation of cannabinoids are fused silica non-polar

columns such as HP-1 (or DB-1) and HP-5 (or DB-5). Quantitation can be achieved by either ame

ionization detection (FID) or mass spectrometry (MS), the latter can provide identication of the

constituents as well. If the goal of the analysis is to quantify both acid and neutral compounds by

GC, prior derivatization is required.

Employment of internal standards, such as 5α-cholestane,

docosane and tetracosane are suitable for quantitation by GC-FID method, while deuterated

cannabinoids are good internal standards for MS detection.

Analysis by LC method

The commonly-used column for separation of cannabinoids includes the reversed-phase of the

octadecyl type, C

and C

, and the mobile phase is methanol:water (8:2 or other ratio) running at

isocratic condition or gradient.

8,47,49,50

Acetic acid is used to adjust the mobile phase pH to ~4.75.

This method can also be modied for the analysis of other cannabis products, such as foods and

cannabis oil. However, appropriate modication in sample preparation is needed and full validation

Patel B, Wene DJ, Hom SS, Parsa B. Quantitative Determination of Cannabinoids in Cannabis Plant Material Using High

Performance Liquid Chromatography – UV Diode Array-Mass Spectrometry (Trap) Detector. Abstract #445 available at

http://easinc.org/wordpress/wp-content/uploads/2015/11/EAS-2015-Abstract-Book.pdf

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

of the method needs to be conducted according to the US FDA guidance for bioanalytical method

validation (2013).

New York provides a method for analysis of the cannabis products in capsules, tinctures or

formulations for vaporization. Briey, approximately 10-200 mg of cannabis product is extracted

with methanol. A portion of the extract is then removed for analysis. Internal standard is added, and

the extract is diluted up to 100-fold for analysis based on the concentrations of cannabinoids in the

samples as declared by the submitting Registered Organization. The targeted analytes are separated

by HPLC and subsequently detected online by monitoring UV absorbance using a PDA detector. The

separation of ten cannabinoids is achieved on a C18 reverse-phase column 150 mm in length. The

limit of quantication for most of the cannabinoids is approximately 0.60 μg/mL. This method can be

used to quantify the cannabinoid components that are present as low as 0.04% (percent by weight)

in the medical cannabis products. The specic procedures for sample preparation and analysis can

be found in NYS DOH MML-301 and NYS DOH MML-300, respectively.

Laboratory Certiﬁcation/Registration/Accreditation

Laboratory accreditation is important to the industry as whole and extremely valuable in assuring

that data utilized in consumer and public health decisions is of high quality and defensible. It is key

to a successful medical cannabis testing program.

Although each state has taken a different approach, the overall process for accreditation remains

the same: a laboratory applies for accreditation and provides the appropriate quality and technical

standard operating procedures. The state agency performs an onsite assessment, and if deciencies

are observed, the laboratory performs root cause analysis and corrective action.

Below are some state web sites for cannabis testing laboratories:

Colorado

“We coordinate the inspection of retail marijuana testing facilities. We review all documentation

and practices to ensure the rules set forth by the Colorado Department of Revenue are being met

and to determine whether to recommend the testing facilities for certication to the Department of

Revenue. The Marijuana Enforcement Division is the certifying body of the Department of Revenue.”

New York

This link provides details of the Environmental Laboratory Approval Program’s (ELAP) corresponding

application forms and related accreditation information: http://www.wadsworth.org/labcert/

elapcert/appforms.htm.

For state certication it is necessary to return the completed application (Form 107—Application

Form

). An inspection by an ELAP Environmental Laboratory Consultant may also be required prior to

a laboratory’s certication.

• Develop a checklist for the licensing or certication process

• Decide whether the process will be done by in-house experts or third parties, like the

American Association for Laboratory Accreditation (A2LA)

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm368107.pdf

http://www.wadsworth.org/sites/default/files/WebDoc/576578963/MML-300-01.pdf

http://www.wadsworth.org/sites/default/files/WebDoc/1495494332/MML-301-01.pdf

http://www.wadsworth.org/sites/default/files/WebDoc/359205661/MML-303-01.pdf

https://www.colorado.gov/pacific/cdphe/inspection-retail-marijuana-testing-facilities

http://www.wadsworth.org/labcert/elapcert/appforms.htm

Guidance for State Medical Cannabis Testing Programs

• Find or develop a prociency testing program that includes enough information to assure a

certain level of accountability (i.e. includes QC data)

New York has a detailed process for certication,

the relevant pieces of which are copied below:

(l) For each lot of medical marihuana product produced, the registered organization shall

submit a predetermined number of nal medical marihuana products (e.g., sealed vials or

capsules; with the number of samples submitted, based on statistical analysis, determined to

be representative of the lot) to an independent laboratory/laboratories approved by the NYS

Department of Health (“department”). The laboratory verifying the cannabinoid content shall

be approved for the analysis of medical marihuana product by the department in accordance

with section ve hundred two of the public health law and subpart 55-2 of this title. Such

laboratory, or approved laboratories cumulatively, shall certify the medical marihuana

product lot as passing all contaminant testing and verify that the content is consistent with

the brand prior to the medical marihuana product being released from the manufacturer to

any dispensing facility.

§1004.14 Laboratory testing requirements for medical marihuana.

(a) Medical marihuana products produced by a registered organization shall be examined

in a laboratory located in New York State that is licensed by the federal Drug Enforcement

Administration (DEA) and approved for the analysis of medical marihuana by the department

in accordance with article 5 of the public health law and subpart 55-2 of this title.

(b) No board member, ofcer, manager, owner, partner, principal stakeholder or member of

a registered organization shall have an interest or voting rights in the laboratory performing

medical marihuana testing.

performed on, the nal medical marihuana product equivalent to the sealed medical

marihuana product dispensed to the patient (e.g., in a sealed vial or intact capsule).

(d) Testing of the nal medical marihuana product is mandatory. However, at the option of the

registered organization, testing may be performed on components used for the production of

the nal medical marihuana product including but not limited to water or growing materials.

Testing may also be performed on the nal marihuana extract prior to packaging e.g. for

cannabinoid prole verication or contaminant testing.

(e) Sampling and testing of each lot of nal medical marihuana product shall be conducted

with a statistically signicant number of samples and with acceptable methodologies such

that there is assurance that all lots of each medical marihuana product are adequately

assessed for contaminants and the cannabinoid prole is consistent throughout.

(f) Testing of the cannabinoid prole shall include, at a minimum, those analytes specied in

section 1004.11(c)(2) of this part.

(g) Testing for contaminants in the nal medical marihuana product shall include but shall

not be limited to those analytes listed below. The department shall make available a list of

required analytes and their acceptable limits as determined by the commissioner.

Analyte: E. coli, Klebsiella Pseudomonas (for products to be vaporized), Salmonella,

Streptococcus, Bile tolerant gram negative bacteria, Aspergillus Mucor species, Penicillium

species, Thermophilic Actinomycetes species, Aatoxin, Ochratoxin, Antimony, Arsenic,

ASSOCIATION OF PUBLIC HEALTH LABORATORIES

Cadmium, Chromium, Copper, Lead, Nickel, Zinc, Mercury, Any pesticide/herbicide/fungicide

used during production of the medical marihuana product, Any growth regulator used

during production of the medical marihuana product, Any other analyte as required by the

commissioner

(h) The laboratory shall track and destroy any quantity of medical marihuana product that is

not consumed in samples used for testing.

Oregon

58,59

“It is strongly recommended that laboratories interested in ORELAP accreditation for Cannabis apply

as soon as possible. The accreditation process takes several months.

“The nal analyte lists are complete. It is possible to apply for some technologies (such as LCMSMS)

and matrices (Cannabis plant is in the ‘Biological Tissue’ matrix, Cannabis products will likely be

in the ‘Solid’ matrix) and add other technologies later, OR add the technologies that you currently

perform with the analyte list.

“If your technology and method are accredited, adding additional analytes that are included in the

Rule will not require an additional site visit. However, it will require a document review of your new

Standard Operating Procedure (SOP) and method validation.

“Until a lab is fully accredited for all of desired methods, labs can subcontract non-accredited

analytes to an ORELAP accredited laboratory, per the TNI 2009 Standard. Laboratories are required

to be accredited before OLCC licensing per HB 3400.”

Washington

“Third party testing labs must meet certain accreditation criteria in order to be certied as a lab that

is allowed to test useable marijuana and marijuana products under the I-502 regulatory system. The

Board has contracted with the Center for Laboratory Sciences on the Campus of the Columbia Basin

College to conduct the certication process.”

Outreach

As with any program, a key to success is communication and partnership. Some groups that might

benet from understanding a laboratory’s capabilities and limitations include:

• Legislature

• Regulatory bodies

• State Poison Control Centers

• Epidemiologists

• Emergency Departments

Efﬁcacy & Side Effects of the Products

Data results will need to be stored and analyzed to see what poses a health risk and what doses

appear efcacious, so renements can be made over time. States should consider instituting

surveillance to capture both positive and negative effects of cannabis use. New York is planning a

https://public.health.oregon.gov/LaboratoryServices/EnvironmentalLaboratoryAccreditation/Pages/index.aspx

https://olis.leg.state.or.us/liz/2015R1/Measures/Overview/HB3400

http://www.liq.wa.gov/mj2015/testing-facility-criteria

Guidance for State Medical Cannabis Testing Programs

clinical trial involving feedback from the state system through self & physician reporting.

Minnesota

and Colorado will look at this data as well.

This type of data will also be critical to understanding

and addressing risk over time.

Appendix: Links to State Programs, Laws, Regulations

Maine

Information on Maine’s program can be found at http://legislature.maine.gov/legis/bills/

bills_127th/billtexts/HP072701.asp

Maryland

Information on Maryland’s program can be found at http://mmcc.maryland.gov/

Massachusetts

By way of background, on January 1, 2013, Chapter 369 of the Acts of 2012 became law allowing

qualifying patients with certain dened medical conditions the legal authority to obtain and use

marijuana for medicinal use in the Commonwealth of Massachusetts. This law required that MDPH

develop regulations that provide the regulatory framework to ensure that qualied patients have

timely access to safe marijuana for medical use. The purpose of their draft protocol below is to

provide Massachusetts Registered Marijuana Dispensaries with a health-protective framework

for the collection and analysis of medical marijuana products, and comply with Massachusetts

regulation 105 CMR 725.000, Implementation of an Act for the Humanitarian Medical Use of

Marijuana.

• For additional information about the Medical Use of Marijuana Program, including the

authorizing Medical Marijuana Statute, please visit the MMJ Program website at http://www.

mass.gov/eohhs/gov/departments/dph/programs/hcq/medical-marijuana/

• Laboratory Testing Protocol: http://www.mass.gov/eohhs/gov/departments/dph/programs/

hcq/medical-marijuana/laboratory-testing-protocols.html

• http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/nished-

mmj/nal-revised-mdph-mmj-mips-protocol.pdf

Nevada

Information on Nevada’s program can be found at http://dpbh.nv.gov/Reg/MME/dta/Policies/

Medical_Marijuana_Establishments_(MME)_-_Policies/

New York

https://www.health.ny.gov/regulations/medical_marijuana/docs/regulations.pdf

http://www.bizjournals.com/buffalo/news/2016/01/20/childrens-to-serve-as-medical-marijuana-clinical.html

http://www.modernhealthcare.com/article/20140911/NEWS/309119931

Association of Public Health Laboratories

The Association of Public Health Laboratories (APHL) works to strengthen laboratory systems serving

the public’s health in the US and globally. APHL’s member laboratories protect the public’s health by

monitoring and detecting infectious and foodborne diseases, environmental contaminants, terrorist

agents, genetic disorders in newborns and other diverse health threats.

8515 Georgia Avenue, Suite 700

Silver Spring, MD 20910

Phone: 240.485.2745

Fax: 240.485.2700

Web: www.aphl.org