Analytical testing laboratories are at the heart of all quality control endeavors in the dietary supplement industry.
Within these highly controlled, high-tech enclaves, analytical chemists employ a wide variety of tools to make determinations about the purity and consistency of the raw materials that go into supplement products, as well as the potency of the finished goods before they hit the shelves.
Many nutraceutical companies have their own in-house labs. Others rely on independent 3rd party labs. The most conscientious companies use both, performing some tests in-house but employing 3rd party labs for other more specialized tests, and for confirmation of their in-house results.
Under the Dietary Supplements Health Education Act of 1994 (DSHEA), supplement companies are required to manufacture in a way that “consistently meets the established specifications for identity, purity, strength, and composition, and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration.”
The regulations mandate that label claims about finished product potency be fully validated prior to the product leaving the manufacturing facility (provided there are scientifically valid methods for testing the ingredient(s) in question). In fact, ingredient identity and potency testing are the only parameters that are explicitly mandated under the FDA’s current Good Manufacturing Practices (cGMPs).
In practice, there can be considerable variability in product quality, even among companies that are cGMP compliant. That’s partly because for many parameters, DSHEA gives manufacturers wide latitude to define their own “established specifications.”
Further, analytical testing itself is a rapidly changing field. For some ingredients and for certain types of contaminants, analytical chemists have reached strong consensus on methodology. There are well-defined standards and widespread agreement on which techniques are most appropriate for a particular compound. But for others, the standards may not be so clear.
The market for natural products is extremely dynamic and trend-driven, especially in retail. Companies are on a constant quest to find new ingredients to introduce to a health-crazed public. But the desire to launch something new may be well ahead of analytical consensus on a particular ingredient. Scientists who do the analytics are often scrambling to catch up with the impulses of the market.
The ongoing debate over the role of DNA-based analysis for botanicals underscores the fact that while new and emerging techniques hold great promise, it often takes time for the scientific community to figure out how best to use new tests, and the purposes for which they are most fit.
And let’s not ignore the fact that ingredient suppliers that adulterate their products are also “evolving.” They, too, keep up with the literature and the latest standards in their effort to find new ways to elude the analytical tests.
Analytical testing for quality assurance is not easy. It is very technical, constantly changing, and not cheap. But it is the cornerstone of credibility and trustworthiness. To a large extent, a brand’s commitment to quality is reflected in the scope and depth of its analytical testing.
Few people know more about this fascinating field than chemist Elan Sudberg, CEO of Alkemist Labs, Garden Grove, CA, a contract testing laboratory he co-founded with his father, Sid, in 1997.
Alkemist is one of a small number of independent 3rd party facilities that renders comprehensive analytical testing solutions to the Food & Beverage, Nutraceutical, and Cosmeceutical industries, and helps companies achieve cGMP compliance and ensure product quality.
Alkemist specializes in identity and potency testing for botanical ingredients. The company has grown rapidly in recent years—a testament to the expansion of the natural products industry and the commitment many companies are now bringing to their QA programs.
Last Spring, Alkemist moved into a brand new, 21,000 square foot, state-of-the-art facility that expands the lab’s actual working space by a factor of six.
Together with his father, a research chemist who also studied and practiced Chiropractic and Traditional Chinese Medicine for many years, Elan has led Alkemist to the forefront of the analytical testing world.
Holistic Primary Care asked Elan to weigh in on the most pressing issues, challenges, and innovations in the realm of product testing and quality assurance.
QC: The American Botanical Council has stated that between 35% -45% of herbs sold in retail are potentially subject to adulteration. Does that jibe with what you see in testing actual products/raw materials? Based on what you see in the lab, how big a problem is botanical adulteration?
ES: My experience spanning over 20 years of testing the plants of this industry tells me that adulteration is a moving target. Cheaters cheat, they always will. We have to try and get ahead of them by being diligent and suspicious, always.
That said, the labs, the industry, and the consumers are far more sophisticated these days than they were. Compliance is on the rise as indicated by our growth, so that demonstrates more testing, and less adulteration.
There are a handful of herbs that are highly suspect (hot on the market, hard to source, or easy to adulterate) and perhaps that’s where the 35%-45% figure comes from. That is certainly not the rate at which we fail herbs in our lab. The fail rate is much lower, and mostly due to poor quality rather than straight up adulteration.
"My experience spanning over 20 years of testing the plants tells me that adulteration is a moving target. Cheaters cheat. They always will. We have to try and get ahead of them by being diligent and suspicious always. That said, the industry and the consumers are far more sophisticated these days, Compliance is on the rise, as indicated by our growth, so that demonstrates more testing and less adulteration."
Also, keep in mind there are different kinds of adulteration, the most common being attempts to boost potency of subpar material by adding substances designed to fool cursory testing or providing the wrong species, which means the label will not be accurate.
QC: In your experience, which herbs are most susceptible/vulnerable to adulteration?
ES: Certain supplement categories, specifically male enhancement (ED), body building and weight loss, seem to draw the unscrupulous into our industry. Such categories are fast moving, kinda sketchy, and generally sold through online sales channels. Any plant intended for those categories seems to be on our list of “likely adulterated.”
Hoodia is one example that burnt hot and burnt fast. It allegedly causes significant appetite cessation. But it is a plant that is slow to mature, and is endangered. There were several years in which more “hoodia” was sold commercially than was actually harvested.
Both the American Herbal Products Association and the American Botanical Council have their lists of likely adulterated herbs that are critical for every manufacturer and for every lab, in terms of day-to-day testing.
QC: An ingredient could be fraudulent, adulterated, or simply of poor quality without being harmful. How frequently are adulterations truly risky from a medical viewpoint?
ES: To paraphrase federal regulations, an adulterant is any component of a product for which the identity is not what is disclosed (on the label) or whose quality is such that the material value of the product is compromised in any way in terms of quality, purity, or safety. But that doesn’t mean it is harmful.
In the plant testing world, truly harmful adulterants or contaminants are so rare that I can't think of anything recent. The herbs we trade are mostly safe, and only a few have poisonous 'cousins.'
In their guidance policies, AHPA gives a number of examples of known potentially toxic adulterants or substitutions. These include:
- Eleuthero root (Eleutherococcus senticosus) with Periploca sepium root
- Plantain leaf (Plantago lanceolate) with Digitalis lanata leaf
- Skullcap herb (Scutellaria lateriflora) with Germander herb (Teucrium chamaedrys)
- Stephania root (Stephania tetrandra) with Aristolochia fangchi root (Guang fang ji)
- Black cohosh root/rhizome (Actaea racemosa) with Cimicifuga root/rhizomed (Actaea spp.)
- Ginkgo (Ginkgo biloba) leaf extract standardized to flavonol glycosides and terpenes with with added flavonol glycosides or aglycones (e.g., rutin, quercetin, etc.)
- Bilberry fruit extract with Red dye #2 (amaranth dye)
- Hoodia gordonii aerial parts powder with various other plant powders, possibly including Opuntia spp. and other Hoodia species
- Grapefruit Seed extract with Benzalkonium chloride, benzethonium chloride, triclosan, methyl paraben, or any other synthetic antimicrobial agent
QC: What are the key analytical methods that all reputable botanical medicine companies should be utilizing for basic quality assurance?
At Alkemist Labs our mantra is: Identify, Analyze, and then Verify.
The first step in cGMP compliance is identity testing. It makes no sense to go through all the other mandated tests (microbial, heavy metals, pesticides) if you don’t even have the correct material.
Second, we analyze. This means that we test to see if the material is within limits for microbes, metals and pesticides. More exciting, though, is constituent analysis, for example, How much caffeine is in that green tea? This is critical especially if the company is bold enough to make label claims.
Speaking of label claims, the last step is to verify. Most of the companies in our industry don’t have the luxury to grow their own plants, extract from them, and then combine one extract with others that come from plants they have grown and extracted. So finished product makers use ingredient suppliers and contract manufacturers, which means there are several hands along the chain of custody.
Each change in hands is an opportunity for failure. The most important thing, ultimately, is that pill, tablet, or drop of final product that makes it to the tongue of the customer. What's in that? Did all the ingredients make it in there? Can they be detected and match the label claims?
That’s what we look for in the Verification step, and only a small percentage of the industry seems to care or be concerned about developing test methods on their finished formulas. But we predict that will change as FDA increasingly asks about that step during inspections.
QC: There are a wide variety of technologies and methods used in analytical testing: Gas chromatography, thin layer chromatography, mass spectroscopy, microscopy, and now there’s DNA testing on the horizon. What are the basic pros and cons of the most common testing methods?
ES: In the cGMPs, the FDA’s guidance on methods is turbid at best. They basically say, “Use something that is scientifically valid.” Unfortunately, that can be interpreted five different ways by three different consultants!
To start with, ID testing can be achieved for plants in whole form by macroscopic and organoleptic examinations. Such must be performed by a trained (with documentation) person. Limitations here are that the material must be in whole form, which is generally not the case in our industry. Powders are the norm.
Next is Botanical Microscopy, which is simple inspection of a powdered material under a microscope, to identify its unique cellular characteristics. This must also be performed by a trained and credentialed person. Limitations are that you must have an extensive library of both reference texts and reference samples.
Botanical Microscopy has trouble speciating a handful of popular plants, and unfortunately it is a dying skill. But it is able to pick up on excipients better than most chemical tests.
High Performance Thin Layer Chromatography (HPTLC) is, in our professional opinion, the best way to ID plants in our industry as it’s possible to do so on whole, powder, extract, liquid and even in finished products. It is a state-of-the art technique that easily detects plant parts, adulterants, and closely related species.
HPTLC must be performed by a trained person with documentation, and there are not a lot of those. Plus, interpretation is part art, part skill, and it takes time to tune. Also, an extensive library of reference materials and methods is required.
DNA testing is the new kid on the block and there is still work to be done refining this method before it should be relied upon. In theory it has the capacity to narrow down to species and beyond. This is especially important when other techniques can’t.
Limitations are that it cannot determine plant parts (which is important in botanical medicine, because different plant parts contain different concentrations of desired constituents). And it is nearly impossible to get meaningful results with anything but whole, raw materials which are rarely used.
Further, plant DNA reference libraries are closed and proprietary, so the collaboration that would make DNA analysis a widely usable technology has not yet happened. For these reasons, the industry is still figuring out what to do with it.
So, we’ve covered the “Is it or is it not plant x” test methods, but not the methods to determine “how much.” HPLC and Gas Chromatography (GC) are the chosen techniques to quantify most market compounds. There are fancy attachments to both to take the analysis further, but those aren’t entirely necessary. As with all these techniques, GC must be performed by a trained, credentialed person. There’s a lot of skill and labor involved in all of this. The equipment is expensive to buy, run, and maintain, and they drink solvents and create gallons of chemical waste.
Undoubtedly you have noticed my recurring phrase: “Such must be performed by a trained (with documentation) person.” This is absolutely crucial. These methods don’t run themselves. Without well-trained and experienced humans running them, you might as well be dry labbing. One of the drawbacks with most in-house labs is too many of them have a small staff of people who are supposed to be proficient in all these techniques. That may look ok on paper, but in reality is a nightmare waiting to happen.
QC: Tell us more abut DNA testing. It certainly got a lot of press a few years ago. When do you think it will be ready for prime time, and what are its best uses?
ES: There is still a lot of confusion about this, unfortunately exacerbated by the fact that some companies were mandated to use it by former New York Attorney General Eric Schneiderman. Other companies have simply added it to their already thorough testing regimes, which is fine, since its limitations will be made up for by other fit-for-purpose methods.
The crucial point to remember is that it does not detect plant parts nor excipients, and it cannot be used alone for Identity testing. So it must be part of a group of tests. There is still so much work to do in developing DNA testing for plant identification, which is why we have yet to open our DNA platform up for commercial testing. At Alkemist, “official” statement is this:
“While various DNA testing techniques have been widely and successfully used in phylogeny to determine evolutionary relationships among plants, there is currently a lack of standard accepted consensus methods for the application of DNA testing to identification of commercial botanical materials. This presents a challenge in creating relevant and specific test service offerings with DNA sequencing. In practice, companies in the dietary supplements industry select methods of evaluation appropriate to determine identity of botanical materials based on the particular species and specification, and sometimes employ orthogonal methods to support the specification. DNA testing is one tool that can provide valid data in support of identity specifications, but it is yet to be seen how quickly authoritative validation guidance and consensus standard methods will be available and if indeed the platform will be widely adopted for routine use.”
QC: What do you consider to be the most significant and troubling quality issues in the dietary supplement space?
ES: Do It Yourself labs and substandard testing practices are the biggest threat to this industry. At worst, something bad goes unnoticed and someone gets sick or hurt. At best, they promote poor quality throughout the industry, which ultimately decreases product efficacy, which in turn undermines return customers.
Many companies think they can just buy the equipment, hire some fresh grads and use that extra space in the back of the warehouse to set up a lab. Trust me it's not that easy. The companies that sell these types of testing equipment are surely not going to tell you that though, as their job is to sell equipment.
We see a lot of material passed by internal labs that don’t meet the muster at ours.
Imagine this scenario: Jeff, who is recently promoted to Lab Director, also oversees Quality Assurance. He is best buddies with Sam in procurement. Both fear losing their jobs if they make decisions that cost a little more, because they are under pressure from their money-centric CFO. Both are also in control of the quality of the ingredients. See the problem?
Then there are the so-called dry labs. These are “labs” that simply approve test samples without doing any actual tests, without actually getting their equipment “wet.” Although this problem has decreased, there are still a few, and they thrive by undercutting the good labs for customers that are cheap and careless.
QC: With the rapid growth in demand for cannabis & CBD products, word is there are a lot of poor grade or fraudulent raw materials entering the supply chain, and poor quality finished products hitting the market. Is there truth to this? What are you seeing?
ES: It’s a tough market to understand. To start, California, for example, requires lab testing for all cannabis products. But lab testing of cannabis is illegal in the United States. California is in the United States. Alkemist Labs, arguably the most respected botanical testing lab in the country, is not legally able to test these products. I find it all very confusing!
That said, the pulse of the cannabis or CBD market is a strange one. Any time there is such hype over a product, poor quality material will find its way in. There are also a massive number of new faces, new companies that are not used to compliance, and the real costs of compliance. Many labs are offering “tests” that cost less than it does to actually turn on the lab equipment and make sure it is running properly.
Honestly, until the legal status gets straightened out, manufacturers don’t have access to the labs with the highest level of botanical expertise to test cannabis products.