Quality Standards in State Programs Permitting Cannabis for Medical Uses

Abstract

Currently in the United States, there exists a patchwork of state-level laws and regulations surrounding cannabis use. Although cannabis (excluding hemp under the Agricultural Improvement Act of 2018, Public Law 115-334) is illegal at the federal level and is not FDA (U.S. Food and Drug Administration) approved for any indication, many states allow patients with qualifying conditions to register for their medical cannabis program (MCP). To better understand the quality of cannabis found in these programs, we collected laws, regulations, and guidance documents available on public state-run websites and compared them with current good manufacturing practices (CGMPs) applicable to finished drug products. CGMPs for human drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packaging of a drug product to assure it is safe for use. Such a comparison will aid the development of consistent quality standards that could, in turn, improve the quality of a wide range of cannabis medical products in development that may be sold in the United States. States may likewise choose to have the cannabis and cannabis-derived products that fall within their MCP to follow quality-focused guidelines, such as those listed in CGMPs, to ensure the quality of these products and promote public health. This study further solidifies the need for standardized testing protocols and methodologies to keep consumers safe.

Keywords: cannabis; government; medical; quality; regulations; testing.

FIG. 1.

Laboratory testing of state-level CCDPs. The 10 tests listed in the figure have been identified from 37 state-level MCPs. These tests are important for determining the identity, strength, quality, and purity of CCDPs. Orange represents tests that are specific to CCDPs. The values listed on the right represent the number of state programs that had the test present in their regulations. No test was present in all 37 programs. One program did not include quality tests in their regulations. CCDPs, cannabis and cannabis-derived products; MCP, medical cannabis program. [Background image: Greola84/iStock/Getty Images Plus via Getty Images.]

FIG. 2.

Differences in pesticide and heavy metal testing between state MCPs. Pesticide (blue) and heavy metal (gray) testing from 37 state MCPs were further analyzed and 8 are represented in the figure. The values represent the number of pesticides or heavy metals that each program lists in their regulations. The programs vary greatly in the number of pesticides required for testing. The four metals commonly listed across the programs are As, Cd, Pb, and Hg, however, some list more (up to eight) or less (as low as zero) to be tested. As, arsenic; Cd, cadmium; Hg, mercury; Pb, lead.

FIG. 3.

Comparison of microbial testing across state MCPs reveals significant differences. The figure shows four different MCPs. Each program categorizes its products for microbial testing differently, with some being more detailed than others. In addition to categorizing products differently, MCPs also include a wide range of tests across product categories. In the four programs pictured, three to eight total tests were found across product categories listed for microbial testing. We also found inconsistencies in the action levels for each test for similar product categories. To demonstrate the complexity, the bold product categories in each box below are where a “cannabis brownie” would be categorized within each program. You can see how differently a brownie is characterized between programs. The table in the upper right shows the specific tests and action levels listed for a brownie undergoing microbial testing within each program. This highlights the vast differences in microbial testing for the same product across state-level MCPs. ^aDried usable cannabis not extracted; ^bextracted or processed cannabis product, that is, hash, bubble hash, rosin, kief; ^csolutions of cannabis in alcohol; ^dsolutions of cannabis in water; ^esolutions of cannabis derived by boiling in water for at least 15 min; ^fan alcoholic liquid extract made by percolation of cannabis so that 1 mL of the fluid extract represents 1 g of the cannabis; ^gdried cannabis to which boiling water is added immediately before consumption; ^hproducts infused with cannabis and other ingredients that are intended for use or consumption other than by smoking, including but not limited to edibles, ointments, and tinctures; ⁱproduced by extracting cannabinoids from cannabis. Includes concentrate consumed using a vaporizer delivery device or pressurized metered dose inhaler; ^jinhalable concentrate, which may comprise other ingredients inside a device that uses a heating element to create a vapor including, but not limited to, vaporizer cartridges and vaporizer pens; ^kremediation is the process of neutralization or removal of dangerous substances or other contaminants from regulated cannabis while changing the product type of the regulated cannabis; ^lincludes edible (chocolate, hard candy, brownie, beverages, etc.) and nonedible (lotions, balms, etc.) products; ^mextraction using ice water, rosin press, or dry ice (also includes kief); *these products are subject to additional testing because they may raise public health concerns, requiring additional safeguards and oversight.

FIG. 4.

Sample of MCP action levels for heavy metal testing compared to USP < 232 >. We compared a small sample of programs to USP < 232 > limits for a) inhalation and b) oral products. Green indicates state criteria matching at or below USP < 232 > limits. Red indicates state criteria exceeding USP < 232 > limits. When we analyzed MCPs with heavy metal testing listed (n = 33), only 12 programs specified acceptance criteria for both inhalation and oral products, even though nearly all 33 allow both ROAs. The remaining 21 programs only provided a single set of criteria for all ROAs or did not provide a list of specific heavy metals. If only one set of criteria was provided and the MCP allows inhaled products, we compared their action levels to USP < 232 > for inhalation.