Quality assurance is a challenge for all herbal companies. An increasingly globalized supply chain, economically-motivated adulteration, environmental contaminants, and limitations of analytical methods are just a few key issues that quality control managers must face.
For companies making hemp extracts, the challenges are compounded by a confusing regulatory landscape, the inherent complexity of the plant, the surging consumer demand for CBD, and the entrance of dozens of upstart brands with no prior herbal experience and little understanding of basic QA methods.
Responsible and ethical brands struggle to differentiate themselves amid a sea of competitors.
Product quality begins with total control of the company’s raw materials supply, says Vandana Kothari, a pharmacist who is Quality Control Supervisor for CV Sciences, one of a handful of hemp extract companies dedicating vast resources to quality assurance.
“We start with certified cultivars. When we receive oil at our door, we know exactly where it came from, and the genetics of the plants from seed to harvest. Every container is numbered, measured, sampled in house and also subjected to 3rd party testing.”
CV Sciences obtains its crude extract from well-characterized hemp strains grown in the Netherlands, where the crop has long been part of the country’s economy.
CEO Joseph Dowling said he is committed to eventually sourcing all raw materials from US growers as soon as the USDA finalizes its rules for hemp cultivation on US soil, and American farmers scale up for mass production.
Following are a number of other key issues to consider when evaluating hemp extracts containing CBD:
Compliance with GMPs & FSMA: The FDA does not consider isolated, purified CBD as a legal supplement ingredient, but hemp extracts that contain naturally occurring CBD are—for now—considered herbal supplements. Companies that make them should be in full compliance with the FDA’s good manufacturing practices (GMPs), and the Food Safety Modernization Act (FSMA).
FSMA requires companies to have a Preventive Control Qualified Individual (PCQI) on staff who is trained in food safety and certified as competent to manage safety programs as required by the law. Many hemp companies are not aware of these legal obligations. The conscientious ones are fully compliant.
GRAS Status: GRAS status—the acronym stands for “Generally Recognized as Safe”—is another basic quality and safety indicator.
According to FDA rules, general recognition of safety requires a company to present “the same quantity and quality of scientific evidence as is required to obtain approval of the substance as a food additive.” The determination involves extensive toxicological and safety testing, and review by a panel of scientists who decide whether the substance can be deemed safe, with “reasonable certainty,” when used as intended.
Hemp brands can proactively seek independent (aka self-affirmed) GRAS review from third-party labs, an expensive and laborious process. So far, only CV Sciences has done so. “It’s a key step toward credibility,” says Douglas MacKay, the company’s VP of Scientific and Regulatory Affairs.
FDA maintains a publicly accessible Inventory of GRAS Notifications.
Analytical Methods: Techniques for identifying and quantifying bioactive compounds in herbs are constantly in flux. This is particularly true for cannabis and hemp.
As it has done for many supplement ingredients, AOAC International—formerly the Association of Official Agricultural Chemists—has established a set of consensus standards for cannabis and hemp. MacKay says his company—and other ethical brands—adhere closely to AOAC guidelines.
The optimal method for quantifying cannabinoids in unprocessed hemp or hemp extracts is high performance liquid chromatography (HPLC) with UV detection, says Austin Stevenson, VP of Product Innovation at Nanogen Labs, a company providing herbal nanoemulsions—including hemp—to the food, beverage, and supplement industries.
Prior to joining Nanogen, Stevenson developed the hemp/CBD testing program at Eurofins—one of the world’s leading analytical testing labs.
HPLC can detect all major cannabinoids including THC, THCA, CBD, and CBDA, as well as many other compounds within the plant. Gas chromatography, another common analytic method for herbs, is not fit-for-purpose with hemp; the testing process decarboxylates THCA, leading to inaccurate THC readings.
“In general, analytical methodology for cannabis/hemp lags far behind product development,” says Stevenson.
Analytical testing can be confounded by the diverse forms of hemp products. One cannot assume a method that accurately quantifies cannabinoids in an alcohol tincture is appropriate for edible substances, beverages, or topical formulations, says Stevenson. This is a very important detail many companies overlook.
Methodological consistency—or lack thereof—is also an issue, says James R. Ott, CEO of CFH, Ltd.—a Colorado-based, vertically-integrated hemp grower/supplier.
“We’ve blind triplicate tested (hemp) with half a dozen different labs. We see a range of variability between 2% up to 20% from lab to lab. And when I blind triplicate test the same lab, it ends up showing variability of 1.5-2% on the same sample. That’s about as tight as they can get. So, we’ve got some issues there.”
Cannabinoid Spectrum: Terms like “Full Spectrum” and “Whole Plant” are popular with marketers who try to avoid the FDA’s regulatory wrath by sending a message that their hemp extracts are distinct from purified CBD isolates.
The problem is, there’s no consensus on what “full spectrum” really means.
“It’s a marketing term,” says CV’s MacKay. There is some industry agreement that a full-spectrum extract should contain a range of cannabinoids—there are 113 currently recognized—and only trace amounts of THC. But there’s no definitive standard.
IMAGINutrition, notes that cannabis produces over 1,000 unique chemicals, with more still to be characterized. While some brands have a clear biochemical fingerprint for a few cannabinoids in their products, the reality is that this plant has 10 “fingers.”Anthony Almada, a nutrition industry consultant who heads
At most, the “full-spectrum” products on the market are testing for 30-40 chemical constituents. “They’re ‘full-spectrum’ by virtue of the limitations on what’s being tested,” Almada said at Holistic Primary Care’s 7th annual Practitioner Channel Forum.
He likens hemp to wine grapes: one can predict the general chemical profile of a certain type of grape, but this profile changes depending on cultivation region, soil, weather conditions, harvesting and handling. The same is true for hemp, and really, for all herbs.
“Pharmaceutical companies have it down—they sell 98% to 99% pure CBD, either from hemp or synthetic. Non-pharmaceutical products have yet to reproduce consistent handprints for each batch,” he said.
Excessive THC: “No THC” on the label does not always mean no THC in the product, says Almada. FDA studies have shown that some hemp products labeled “No THC,” do indeed have THC well above the 0.3% threshold. Failure to quantify THC levels accurately is an indicator of slack quality control.
Chirality: CBD and THC have complex 3-D configurations. There are actually four mirror-image isomers of CBD, and four of THC. As is the case with many bioactive compounds—think L-carnitine or L-theanine—chiral conformation does affect physiological activity, says Almada.
“The four forms of CBD and THC are different. Chemically, with one exception, they’re identical. But biologically they are different. They are four different shapes, and those shapes are like hands that fit into gloves. A right hand does not fit in a left glove. It just doesn’t work.”
Standard analytical methods like HPCL and gas chromatography do not detect chirality. It requires specialized tests. According to Almada, none of the commercial hemp brands are assessing chirality. But they should be, because different hemp cultivars or strains
will have different ratios of CBD and THC enantiomers.
“The four forms of CBD and THC are different. Chemically, with one exception, they’re identical. But biologically they are different. They are four different shapes, and those shapes are like hands that fit into gloves. A right hand does not fit in a left glove. It just doesn’t work.” —Anthony Almada, IMAGINutrition
Hemp Extract vs Hemp Seed Oil: The oil pressed from hemp seeds is highly nutritious. It is rich in Omega-3, Omega-6, and other essential fatty acids. But it does not contain CBD. Only the flowering part of the hemp/cannabis plant produces cannabinoids. A true hemp extract containing CBD and other natural cannabinoids is an oil or tincture derived from hemp flowers, not seeds. Yet some unethical brands sell hemp seed oil spiked with synthetic cannabinoids and terpenes and market it as hemp extract.
Toxins & Contaminants: Hemp is an excellent accumulator of toxins. That’s one reason it is used as a bioremediator to clean up polluted land. But this means that analysis for toxins and contaminants is an essential aspect of hemp quality control.
According to Niagen’s Austin Stevenson, manufacturers should be testing for:
Residual solvents: “What type of solvent was used to make a product in question: cold water? CO2? Butane? Heptane? Hexane? You don’t want the solvents in the finished products.”
Heavy Metals: Hemp absorbs and concentrates a lot of soil metals. Companies should test raw materials and finished products for arsenic, cadmium, lead, mercury and other common environmental heavy metals. Stevenson says this should be done with Inductively Coupled Plasma Mass Spectrometry (ICPMS).
Heavy metal testing is required by law for all herbal supplements. But many start-up brands are unaware of the regs, or do not have the proper quality assurance procedures or testing equipment in place.
Pesticides and Herbicides: Pesticides are an unfortunate reality in the hemp market. The plants are expensive and farmers don’t want to lose them to cutworms or other hungry insects. As hemp cultivation scales up, pesticide and herbicide use will likely increase.
Extraction concentrates pesticides and herbicides in hemp. So hemp extract companies should be testing for a full range of common agricultural chemicals using liquid and gas chromatography in tandem with mass spectrophotometry according to methods outlined in the US Pharmacopeia.
Microbiology: As with any herb, microbial contamination can be an issue with hemp. Companies should be running petri films and quantitative PCR tests for E. coli, Salmonella, and other potential contaminants. The American Herbal Products Association’s (AHPA) monograph on cannabis provides thorough guidance on testing for microbes and environmental toxins.
Glyphosate: This controversial herbicide is not approved for use on hemp. According to AHPA’s president, Michael McGuffin, it should be deemed a contaminant under the FDA’s GMP rules. But it is not recognized as such, and few companies test for it.
Synthetic Cannabinoids and Terpenes: In addition to cannabinoids, hemp produces a spectrum of terpenes—they’re what give the plant its characteristic odor.
According to Almada, the least expensive way to make a “full spectrum extract” is to buy synthetic terpines—cheap and widely available—and put them in an oil base. “Companies boast about their “high terpene levels,” and the products will have the intense cannabis aroma. But it’s synthetic. This is a wonderful opportunity for class-action lawsuits.”
Terpene profiles can be analyzed using gas chromatography and flame ionization detection (GC-FID), but few brands are testing for them.
Synthetic CBD, THC, and other cannabinoids are also entering the market, says MacKay of CV Sciences. The FDA has yet to rule on whether these will be permitted in foods or supplements, but it is doubtful. Many biotech and pharma companies are working on synthetic cannabinoids for use as drugs. Given that, the agency and the pharma industry will not likely tolerate a lot of poorly characterized synthetics on the market.
Topical Delivery Systems: CBD-containing balms, creams, and other topical products are very popular. But many producers are unaware that any topical that can significantly raise blood levels of a bioactive like CBD must undergo full toxicology and cancer testing, per FDA regulations. Most brands are not doing that type of study. Almada expects a regulatory crackdown soon. “A product labeled as ‘transdermal CBD’ is basically waving a red flag.”
3rd Party Certification: Hemp quality assurance is evolving rapidly. Recently, the US Hemp Roundtable—a coalition of leading cultivators, raw materials suppliers, finished product brands, regulatory experts, and analytical scientists—launched a certification program aimed at harmonizing QA standards, assuring safety and quality, and raising consumer confidence.
The group developed stringent self-regulatory guidelines for growers, processors, and branded product makers. Certification, which is voluntary, involves thorough audits and extensive third-party lab testing of many of the parameters outlined in this article.
Companies that pass will be able to include a “US Hemp Authority Certified” seal on product labels.
Though not legally binding or federally recognized, Hemp Authority certification is a step in the right direction, especially given the absence of clear FDA guidance (see Regulatory Confusion Reigns as FDA Grapples with CBD).
Dalia Chandler, the QA/QC manager at CV Sciences says her company is a big fan of third-party audits. “We’ve been audited by Eurofins, which certified us as a cGMP manufacturing plant, and we’re now certified by the US Hemp Authority. We’re very proud of that because it was a very lengthy process.
“The message here is that what is on our label is what is in the bottle.”