Medical and Recreational Marijuana: Legal Issues, Operational Challenges and Regulatory Hurdles That Marijuana-Related Businesses Frequently Encounter
PART 3 of 6: An Overview of How the Lack of National Standards for Laboratory Tests of Marijuana Products Affects the Public Health and the Marijuana Industry
This article is the third part of a six-part series discussing the legal issues, operational challenges and regulatory hurdles that marijuana-related businesses (MRBs) frequently encounter. Part 1 discussed the various fire, health and safety risks that MRBs encounter while growing and cultivating marijuana plants inside large, indoor, commercial spaces. Part 2 discussed the three most common extraction methods that MRBs use when processing cannabis plant material to extract cannabinoids, terpenes and other components from the plant; the fire, health and safety risks associated with each cannabis extraction method; the National Fire Protection Association’s (N.F.P.A.) rules and regulations that govern cannabis extraction; and the Occupational Safety and Health Administration (OSHA) rules and regulations that MRBs must comply with in their extraction facilities.
Part 3 focuses on the lack of national standards for laboratories that test medical and recreational marijuana products. Specifically, it discusses how the lack of national standards for testing marijuana products impacts the public health of consumers and the marijuana industry. It also discusses the various methodologies, approaches and equipment that laboratories should be required to use to test marijuana products for: (1) Potency; (2) Heavy Metals; (3) Pesticides; (4) Residual Solvents; (5) Terpine Profiles; (6) Microbes, Fungi and Mycotoxins; and (7) Moisture Content and Water Activity. Finally, it presents specific, proposed national standards that the federal government should consider implementing to protect consumers who purchase marijuana products.
I. History of the Development of Food and Drug Regulations in the United States
Food and drug regulation in the United States didn’t begin until the mid 1800s. The Pure Food and Drug Act of 1906 established the Bureau of Chemistry under the auspices of the U.S. Department of Agriculture. The Bureau of Chemistry was tasked with enforcing the Pure Food and Drug Act. The Bureau of Chemistry became the U.S. Food and Drug Administration (FDA) in 1930. An additional Meat Inspection Act was assigned to the Food Safety and Inspection Service also as a part of the U.S. Department of Agriculture.
Early legislation focused on requiring truthful labels on food and drug products. Manufacturers are required to identify products that contain substances that the government deems dangerous. Likewise, a product can’t contain these labels if it doesn’t contain the substance. Manufacturers must clearly state active ingredients on a product’s label. Throughout the 20th century, lawmakers continued to pass regulations that impact the development and sale of food and drugs in the United States.
1. The FDA Has Broad Regulatory Authority Over Virtually All Consumers Goods and Services Sold in the U.S.
The FDA is responsible for protecting the public health by assuring that foods (except for meat from livestock, poultry and some egg products which are regulated by the U.S. Department of Agriculture) are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, and vaccines and other biological products and medical devices intended for human use are safe and effective. The FDA is also responsible for protecting the public from electronic product radiation; assuring cosmetics and dietary supplements are safe and properly labeled; regulating tobacco products; advancing the public health by helping to speed product innovations.
The FDA’s programs for safety regulation vary widely by the type of product, its potential risks and the regulatory powers granted to the agency. For example, the FDA regulates almost every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy and safety—yet the FDA’s regulation of cosmetics focuses primarily on labeling and safety. The FDA regulates most products with a set of published standards enforced by a modest number of facility inspections. Inspection observations are documented on Form 483.
In June 2018, the FDA released a statement regarding new guidelines to help food and drug manufacturers “implement protections against potential attacks on the U.S. food supply.” One of the FDA’s new guidelines includes the Intentional Adulteration (IA) rule, which requires strategies and procedures by the food industry to reduce the risk of compromise in facilities and processes that are significantly vulnerable.
The FDA also uses tactics of regulatory shaming, mainly through online publication of non-compliance, warning letters, and “shaming lists.” Regulation by shaming harnesses firms’ sensitivity to reputational damage.
2. The FDA Has Failed to Establish National Standards for Laboratories That Test Marijuana Products
Despite its massively broad regulatory authority and its on-going, concerted national effort to protect the health and safety of the general public, the FDA has failed to establish national standards that govern laboratories that test marijuana products because marijuana is still considered an illegal drug under federal law. Indeed, although 33 states, the District of Columbia, Guam and Puerto Rico have passed legislation legalizing medical marijuana (12 of those 33 states, and Washington D.C., have also legalized the drug for recreational use), the federal government still classifies marijuana as a Schedule 1 narcotic under the Controlled Substances Act (CSA). Consequently, while the FDA regulates virtually every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy and safety, it has not promulgated or implemented any national standards governing the testing of marijuana products.
Without regulatory guidance from the FDA, individual states that have legalized marijuana have been forced to promulgate and implement their own laboratory test standards to protect their citizens. However, this ad hoc, state-by-state approach has resulted in a confounding and varied assortment of rules and regulations that literally change from state-to-state, which creates a particularly onerous situation for MRBs that operate in multiple states. The practical effect of this mishmash of state-based standards is inconsistent and unreliable testing processes and procedures that result in low quality, potentially unsafe cannabis products, some of which have injured and even killed consumers.
Thus, as discussed below, the FDA must and should establish national standards that govern the testing of marijuana products by laboratories.
II. All Laboratories That Test Medical Marijuana Products Should Be Required to Utilize Specific Types of Equipment, Methodologies and Approaches
In states that have legalized marijuana, the FDA should require laboratories to utilize specific types of testing equipment, methodologies and approaches to test marijuana products. The following is a comprehensive summary of the various types of equipment, methodologies and approaches that laboratories currently use that are generally considered best practices:
1. High-Performance Liquid Chromatography (HPLC)
HPLC ideally uses a high-performance liquid chromatograph to pump a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase). The sample is carried by a moving carrier gas stream of helium or nitrogen. HPLC has the ability to separate, and identify compounds that are present in any sample that can be dissolved in a liquid in trace concentrations as low as parts per trillion. Because of this versatility, HPLC is used in a variety of industrial and scientific applications, such as pharmaceutical, environmental, forensics and chemicals.
2. Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
ICP-MS ideally uses an inductively coupled plasma mass spectrometer to detect heavy metals in cannabis by assessing the different masses of each element to determine which elements are present within a sample and at what concentrations. Make sure to include accompanying software that provides assistant functions to simplify analysis by developing analytical methods and automatically diagnosing spectral interference. This will provide easy operation and analytical results with exceptionally high reliability.
3. Liquid Chromatography Mass Spectrometry (LC-MS)
LC-MS ideally uses a liquid chromatography mass spectrometer or a high-performance liquid chromatograph with a triple quadrupole mass spectrometer that provides ultra-low detection limits, high sensitivity and efficient throughput. Advanced systems can analyze more than 200 pesticides in 12 minutes. It is a powerful tool for toxicology applications in the clinical laboratory. The primary use of an LC-MS in a toxicology laboratory is for drug confirmation testing following an immunoassay screen and for broad spectrum drug screening.
4. Gas Chromatography Mass Spectrometry (GC-MS)
GC-MS ideally uses a gas chromatography mass spectrometer with a headspace autosampler, which can also be used for pesticide and terpene analysis. GC-MS is the analysis method of choice for smaller and volatile molecules such as benzenes, alcohols and aromatics, and simple molecules such as steroids, fatty acids and hormones. It can also be applied towards the study of liquid, gaseous and solid samples. There are many advantages to using GC-MS for compound analysis, including its ability to separate complex mixtures, to quantify analytes and to determine trace levels of organic contamination.
GC-MS begins with the gas chromatograph, where the sample is volatized. This effectively vaporizes the sample (the gas phase) and separates its various components using a capillary column packed with a stationary (solid) phase. The compounds are propelled by an inert carrier gas such as argon, helium or nitrogen. As the components become separated, they elute from the column at different times, which is generally referred to as their retention times.
Once the components leave the GC column, they are ionized by the mass spectrometer using electron or chemical ionization sources. Ionized molecules are then accelerated through the instrument’s mass analyzer, which quite often is a quadrupole or ion trap. It is here that ions are separated based on their different mass-to-charge (m/z) ratios.
The final steps of the process involve ion detection and analysis, with compound peaks appearing as a function of their m/z ratios. Peak heights, meanwhile, are proportional to the quantity of the corresponding compound. A complex sample will produce several different peaks, and the final readout will be a mass spectrum. Using computer libraries of mass spectra for different compounds, researchers can identify and quantitate unknown compounds and analytes.
5. Gas Chromatography (GC)
GC ideally uses a gas chromatography mass spectrometer with a headspace autosampler, which can also be used for pesticide and terpene analysis. GC is an analytical technique for separating, identifying and measuring individual compounds within a mixture. In contrast to liquid chromatography, a stream of carrier gas serves as the mobile phase to carry volatilized samples through a solid or liquid stationary phase. Based on polarity, individual analytes adsorb to the stationary phase and flow through the column at different rates until they reach detectors, of which there are various types. The retention time, or the times at which compounds separately elute is the analytical basis of GC. GC and GC/MS are widely used in the life sciences in areas such as environmental monitoring, forensics, food and beverage analysis, drug detection and medical screening, and metabolomics.
III. All Laboratories Should Be Required to Test Marijuana Products for Potency, Efficacy, and Contaminants
In states that have legalized marijuana, the FDA should require laboratories to determine the potency and efficacy, and to detect the presence of any contaminants in all of the marijuana products that they test. The following is a description of these various aspects and components of marijuana and what types of tests that laboratories should perform on the drug to determine each such aspect and/or component of the drug:
The most important component of cannabis testing is the analysis of cannabinoid profiles, also known as potency testing. Cannabis plants naturally produce cannabinoids that determine the overall effect and strength of the cultivar, which is also referred to as the strain. There are many different cannabinoids that all have distinct medicinal effects. However, most states only require testing and reporting for the dry weight percentages of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD).
For potency testing, HPLC is recommended and has become the gold standard for analyzing cannabinoid profiles.
2. Heavy Metals
Different types of metals can be found in soils and fertilizers, and as cannabis plants grow, they tend to draw in these metals from the soil. Heavy metals are a group of metals considered to be toxic, and the most common include lead, cadmium, arsenic and mercury. Most labs are required to test and confirm that samples are under the allowable toxic concentration limits for these four hazardous metals.
Heavy metal testing is performed by (ICP-MS) testing.
The detection of pesticides in cannabis can be a challenge. There are many pesticides that are used in commercial cannabis grow operations to kill the pests that thrive on the plants and in greenhouses. These chemicals are toxic to humans, so confirming their absence from cannabis products is crucial. The number of pesticides that must be tested for varies from state-to-state, with Colorado requiring only 13 pesticides, whereas Oregon and California require 59 and 66 respectively. Canada has taken it a step further and must test for 96 pesticides, while the Association of Analytical Communities (AOAC) International is developing methods for testing for 104 pesticides. The list of pesticides will continue to evolve as the industry evolves.
Testing for pesticides is one of the more problematic analyses, possibly resulting in the need for two different instruments depending on the state’s requirements. Pesticides that do not ionize well in an LCMS source require the use of a GC/MS instrument. The principles of HPLC still apply – you inject a sample, separate it on a column and detect with a detector. However, in this case, a gas (typically helium) is used to carry the sample.
For a majority of pesticide testing, LC-MS is acceptable and operates much like HPLC but utilizes a different detector and sample preparation.
4. Residual Solvents
Residual solvents are chemicals left over from the process of extracting cannabinoids and terpenes from the cannabis plant. Common solvents for such extractions include ethanol, butane, propane and hexane. These solvents are evaporated to prepare high-concentration oils and waxes. However, it is sometimes necessary to use large quantities of solvent in order to increase extraction efficiency and to achieve higher levels of purity. Since these solvents are not safe for human consumption, most states require labs to verify that all traces of the substances have been removed.
Testing for residual solvents requires GC. For this process, a small amount of extract is put into a vial and heated to mimic the natural evaporation process. The amount of solvent that is evaporated from the sample and into the air is referred to as the “headspace.” The headspace is then extracted with a syringe and placed in the injection port of the GC. This technique is called full-evaporated technique (FET) and utilizes the headspace autosampler for the GC.
5. Terpene Profiles
Terpenes are produced in the trichomes of the cannabis leaves, where THC is created, and are common constituents of the plant’s distinctive flavor and aroma. Terpenes also act as essential medicinal hydrocarbon building blocks, influencing the overall homeopathic and therapeutic effect of the product. The characterization of terpenes and their synergistic effect with cannabinoids are key for identifying the correct cannabis treatment plan for patients with pain, anxiety, epilepsy, depression, cancer and other illnesses. This test is not required by most states, but it is recommended.
The instrumentation that is used for analyzing terpene profiles is a GC/MS with headspace autosampler with an appropriate spectral library.
6. Microbes, Fungi and Mycotoxins
Most states mandate that cannabis testing labs analyze samples for any fungal or microbial growth resulting from production or handling, as well as for mycotoxins, which are toxins produced by fungi. With the potential to become lethal, continuous exposure to mycotoxins can lead to a buildup of progressively worse allergic reactions.
LC-MS should be used to qualify and identify strains of mycotoxins. However, determining the amount of microorganisms present is another challenge. That testing can be done using enzyme linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR) or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), with each having their advantages and disadvantages.
7. Moisture Content and Water Activity
Moisture content testing is required in some states. Moisture can be extremely detrimental to the quality of stored cannabis products. Dried cannabis typically has a moisture content of 5% to 12%. A moisture content above 12% in dried cannabis is prone to fungal growth (mold). As medical users may be immune deficient and vulnerable to the effects of mold, constant monitoring of moisture is needed. Below a 5% moisture content, the cannabis will turn to a dust-like texture.
The best way to analyze the moisture content of any product is using the thermogravimetric method with a moisture balance instrument. This process involves placing the sample of cannabis into the sample chamber and taking an initial reading. Then the moisture balance instrument heats up until all the moisture has been evaporated out of the sample. A final reading is then taken to determine the percent weight of moisture that was contained in the original sample.
Another method for preventing mold is monitoring water activity (aW). Very simply, moisture content is the total amount of water available, while water activity is the “free water” that could produce mold. Water activity ranges from 0 to 1. Pure water would have an aW of 1.0. ASTM methods D8196-18 and D8297-18 are methods for monitoring water activity in dry cannabis flower. The aW range recommended for storage is 0.55 to 0.65. Some states recommend moisture content to be monitored, other states monitor water activity, and some states such as California recommend monitoring both.
IV. All Laboratory Workers Who Test Marijuana Products Should Be Trained and Certified to Perform the Testing
In states that have legalized marijuana, the FDA should require laboratory workers who test marijuana products to receive specialized training and obtain a corresponding certification establishing their expertise to perform the various tests necessary to determine the potency and efficacy of marijuana products as well as any contaminants in them, to confirm that they know how to operate the specialized equipment used to perform these various tests and to ensure that they know how to accurately interpret the test data.
Typically, there are primarily two lab workers involved in the process of testing marijuana products: an Analytical Chemist and an Extraction Technician. The following is a summary of each worker’s relative roles and responsibilities during the testing process:
1. Analytical Chemist
Analytical chemists know their way around the lab workbench and are required to have specific training on the lab equipment involved with testing such as gas chromatographs and mass spectrometers. Analytical chemists assist and direct lab technicians in the operation of this equipment.
The individuals who test marijuana product samples will need to possess knowledge of headspace, HPLC, ICP-MS, LC-MS and GC-MC testing methods. In addition, they need to be able to ensure proper operation of instrumentation via the review of raw analytical data. Sample preparation, handling and reporting knowledge is also required.
Analytical chemists also assist with other tasks related to lab operation, including participating in cleaning, sample staging and sample preparation. Because they also typically assist with the development of new testing methods, a thorough working knowledge of pesticides, solvents and all aspects of potency testing should be mandatory.
Analytical chemists should hold a PhD, Master’s or Bachelor’s degree in chemistry or a similar field, and they must have experience using testing equipment. They should also be comfortable working in a fast-paced lab environment and possess good interpersonal and communication skills.
2. Extraction Technician
An extraction technician is responsible for the preparation of equipment and plant materials for cannabinoid extraction. They should have significant experience as a lab or extraction technician, with a background in inorganic and organic chemistry. They should also be required to have oil extraction experience and be familiar with flammable storage cabinets and processes for CO2 extraction.
Extraction technicians also process extracts and concentrates and they clean and maintain equipment and the lab itself. Extraction technicians must be able to maintain a strict and current inventory of all equipment, chemicals and plants in the laboratory. They should also be able to repair and adjust the centrifuges, microscopes, pumps and chromatography equipment used in the lab. They may also be asked to store equipment and supplies, perform clerical tasks, conduct MS-DS maintenance and sterilize glassware used for testing.
They should have one or more years of experience working with extraction or concentrates in a lab setting. They must also have an understanding of the state-specific marijuana testing rules and regulations and industry applications for the state they will be working in.
It is preferable, but not mandatory, that extraction technicians have an Associate’s or Bachelor’s degree in chemistry, knowledge of medical marijuana benefits and law and experience with extraction analysis and purification.
As noted above, the FDA is responsible for protecting the public health by ensuring that foods are safe, wholesome, sanitary and properly labeled; and by ensuring that human and veterinary drugs, and vaccines and other biological products and medical devices intended for human use are safe and effective. Yet, because the federal government continues to classify marijuana as a Schedule 1 narcotic, the FDA refuses to set national standards for testing marijuana products, even in states that have legalized the drug.
The FDA’s refusal to regulate laboratory tests of marijuana products in this existing and burgeoning new industry has resulted in a bevy of state-specific rules and regulations for testing marijuana products that literally vary from state-by-state. This chaotic morass of varying rules and regulations not only adversely affects the public health, but it also wreaks havoc on the ability of MRBs that operate in multiple states to comply with each state’s unique set of laboratory testing requirements for marijuana products.
To provide predictability, consistency and continuity to the already expensive and technical task of testing marijuana products, the FDA should establish and enforce national standards. First, the FDA should coordinate with the various Departments of Health in each of the 33 states (and the District of Columbia) that have already legalized cannabis to promulgate national standards that will govern the testing of marijuana products across the country. Then, the FDA should consult with industry experts and academics about the types of tests that each laboratory should perform on all marijuana products, what aspects of the plant (e.g., potency, efficacy, contaminants, etc.) should those tests identify and why, and what types of equipment the laboratories should utilize to carry out these various tests.
In addition, the FDA should consider creating a National Registry of Marijuana Test Laboratories and require all laboratories that test marijuana products to join it. The member laboratories should then be required to report all of the empirical data that they collect about the marijuana products that they test and about the various tests that they perform on those products to a cloud-based database maintained by the FDA. The FDA should then compile and analyze all of this data comparing and contrasting results from different laboratories in various parts of the country to determine best practices for testing cannabis, eliminating inefficiencies, and quantifying potency, efficacy and safety standards that all laboratories should meet.
Ultimately, this national standard approach will allow the FDA to establish and enforce rules and regulations that will allow companies to grow, cultivate, process, manufacture, test and sell the marijuana products in the safest, most effective manner possible. And, it will create a regulatory vehicle that allows the FDA to fulfill its core mission—protecting the public health.
In Case You Missed It
 Id.; Other major pieces of legislation include: Food Additive Amendment of 1957; Delaney Clause of 1958; Food, Drug and Cosmetic Act of 1938; Kefaurer-Harris Drug Amendments of 1962; and Nutrition Labeling and Education Act of 1990.
 See https://www.fda.gov/about-fda/fda-basics/what-does-fda-do. The FDA oversees: (1) Medical Products and Tobacco; (2) Foods and Veterinary Medicine; (3) Global Regulatory Operations and Policy; and (4) Operations.
 Id.; FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.
 Id.; An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts. FDA investigators are trained to ensure that each observation noted on the FDA Form 483 is clear, specific and significant. Observations are made when in the investigator’s judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
 Id. citing Gottlieb, Scott (June 19, 2018). “Statement from FDA Commissioner Scott Gottlieb, M.D., on new guidance to help manufacturers implement protections against potential attacks on the U.S. food supply” (Press release). Food and Drug Administration. Retrieved June 20, 2018.
 Id. citing Yadin, Sharon (2019). “Regulatory Shaming”. Environmental Law (Lewis & Clark). 49: 41. SSRN 3290017.
 See https://www.dea.gov/drug-scheduling. Schedule 1 drugs also include much more dangerous and potent street drugs such as heroin and lysergic acid diethylamide (“LSD”). Under this classification, marijuana is viewed as an illegal drug with no currently accepted medical use, a high potential for abuse, and a lack of accepted safety for use even under medical supervision. Oddly, the federal government classifies other equally dangerous and highly addictive drugs such as cocaine, methamphetamine, methadone, fentanyl, and oxycodone as Schedule 2 drugs—a lower drug classification than marijuana.
 See https://mjbizdaily.com/contaminated-mmj-blamed-for-california-mans-death. The doctors that examined a cancer patient in California who died after using medical marijuana suspect that the patient’s death may have been caused by fungi present in the contaminated drug that he consumed.
 Id. Delta-9-tetrahydrocannabinolic acid (Δ9-THCA) can be converted to THC through oxidation with heat or light.
 See https://www.fda.gov/about-fda/fda-basics/what-does-fda-do. The FDA oversees: (1) Medical Products and Tobacco; (2) Foods and Veterinary Medicine; (3) Global Regulatory Operations and Policy; and (4) Operations.