Karina Basso Associate Editor
On November 19 last year, the FDA issued public notifications informing consumers that 10 “natural” weight-loss and sexual-enhancement products contained undeclared active pharmaceutical ingredients (APIs)1. That same week, the agency summarized the results of a yearlong sweep of dietary supplements, including “civil injunctions and criminal actions against 117 various manufacturers and/or distributors of dietary supplements and tainted products falsely marketed as dietary supplements”2.
In fact, the FDA discovers API-tainted dietary supplements nearly every week, creating a drumbeat of bad news that tarnishes the industry’s reputation. “Many of the challenges facing the nutraceutical industry today can be traced back to supply chain issues,” said Shaheen Majeed, marketing director at Sabinsa, East Windsor, NJ. His company manufactures, supplies, and markets dietary supplements, minerals, herbal extracts, and cosmeceuticals. The problem, he said, festered even after passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994. “DSHEA didn’t require GMPs for ingredient suppliers, so a lot of manufacturers began buying by price alone, often from brokers who aggregated ingredients from a variety of sources. Some companies were notorious for buying the cheapest ingredients they could find; some companies still practice this today.”
While focusing on low price or disregarding the possibility of adulteration makes sense to people who seek short-term profits and are willing to skirt the law, legitimate companies suffer. “For those manufacturers who play by the rules, adulteration of dietary supplements is a very negative issue because it casts a shadow of doubt on the whole nutraceutical industry,” said Katerina Mastovska, associate scientific director at Covance Laboratories, a contract research laboratory based in Madison, WI. “That’s why testing and monitoring of a supplement’s contents is so important to protecting the brand of those who manufacture and sell these nutraceutical products.”
Mastovska said there are two types of adulteration: replacing natural ingredients with cheaper botanical substitutes and adding APIs to natural ingredients. “When you are looking at the broad effects of both types of adulteration, you can clearly see that [using cheap materials] is cheating consumers and [using APIs] can cause these very same consumers serious and sometimes fatal health effects.”
Preventing adulterated ingredients from entering a manufacturer’s supply chain requires vigilance, said Eugene Ung, chief executive officer of Best Formulations, City of Industry, CA. His company provides contract formulation, production, and packaging of dietary supplements and pharmaceuticals. “Sometimes you get clients who will say, ‘Hey, I’ve got this herb that I’m sourcing myself and I’m going to supply it to you as our nutraceutical’s raw ingredient,’” he said. “We try to screen as best as we can to determine who these clients are. Are they new to the industry? What product are they making?” Product type makes a difference, because the majority of adulteration is found in weight-loss, sexual-enhancement, and muscle-building supplements.
“We tend to be conservative with the types of nutraceuticals we choose to manufacture,” Ung said. “We’re not known for making many weight-loss products or or sexualenhancement products.” Others don’t take that view, he said. “Sometimes the manufacturer may know and they close their eyes and do it anyway. However, sometimes the manufacturer may not know; they’re simply trusting that this client is sending them legitimate material. It’s a business decision. Do you want to take on these type of business opportunities?”
Outside Help
Regardless of a manufacturer’s product line and its business philosophy, by law it must test and authenticate the ingredients it uses3. Ingredient suppliers like Sabinsa also conduct tests. “Every batch of incoming raw material as well as finished product undergoes a series of tests to verify compliance to the specification of the material,” Majeed said. “Similarly, the processing stages are monitored for quality and to identify and correct any possible deviation.” The company also grows some of its own botanical ingredients and thus exercises greater control over quality.
Because testing is expensive and sometimes complicated, many companies rely on thirdparty laboratories, such as Covance. “We work with our clients to ensure that their raw materials and finished products are safe and free of adulterants,” Mastovska said. “It’s for their own protection and the protection of the supply chain.”
Best Formulations combines in-house and outside testing. “We have extensive in-house laboratory capabilities that cut down on testing costs and lead times tremendously,” Ung said. “But because we manufacture so many dosage forms from thousands of different materials, we simply are not able to test every single ingredient in-house.”
DNA Bar-Coding
One of the most discussed test methods uses DNA— more specifically, an organism’s unique genome—to identify ingredients. DNA bar-coding gained notoriety last year when Eric Schneiderman, New York attorney general, used it to support an enforcement action against four major retailers. But many people question the suitability of the test.
“Experts in the natural product industry are still debating the pros and cons of DNA technology, even while trying to find ways to make it work across a broad range of products for which there are no agreed-upon primers and sequences,” Majeed said. “We find that DNA technology, while being very useful in authenticating raw material, is not the solution to all the problems of ingredient authentication that the industry is currently facing.” Even when applied to the nutraceuticals it can reliably identify, DNA testing is quite complex and requires specialized knowledge in order to administer the test correctly.
In an April 2015 article, Danica Renaud, chief executive officer and chief science officer of AuthenTechnologies, Richmond, CA, said that performing DNA testing on botanical ingredients requires understanding botany and the nature of DNA in finished dietary supplement products. Finished dietary supplement products do not tend to have DNA left in them, she said, and if they do, it’s not very good quality. That can lead to false-negative results.
In the same article, Roy Upton, executive director for the American Herbal Pharmacopeia said that DNA barcoding cannot reliably identify the ingredients of botanical extracts. Extracts are made by a process that either does not preserve DNA or alters its characteristics, so DNA testing of an extract is inappropriate. Other drawbacks include the test’s inability to detect heavy metals and other non-biological contaminants and its lack of quantitative information about the contaminants it does detect.
“For someone to come out and say the end-all, be-all test is DNA bar-coding is a little presumptuous,” Ung said. “It lacks understanding of the science and what’s behind these products. We’re not trying to make excuses. The fact is that it does not make sense to apply DNA testing to every dietary supplement product, because it is simply not applicable to everything.”
Third-Party Certification
In addition to testing, many suppliers and manufacturers opt for third-party certifications. Although they are not officially recognized by the FDA, they promote a uniform approach to testing and other practices. “The Agency is working with these third-party auditors in getting comments and feedback from the industry,” Ung said. “We’re all trying to get on the same page and interpret the regulations the same way so that there are efficiencies and we are not doing the same thing four different ways.” NSF International, Ann Arbor, MI, is among the organizations offering a nutraceutical certification program. It includes reviewing label claims to certify that a product’s content matches what’s listed on the bottle; conducting a toxicology review; and testing to ensure the product is free of undeclared ingredients and/or unacceptable levels of contaminants.
While quality cannot be tested into products, enforcing the law should diminish the number of bad actors. “Testing on the enforcement side will help,” Mastovska said. “If you have more testing overall, people will know they can get caught.”
Ung also expressed optimism. “Over the last few years, the reputable material suppliers have come to understand transparency is required in a successful supply chain relationship,” he said. “This sort of communication and understanding amongst the raw material manufacturer, material distributor or supplier, contract manufacturer, and the brand owner have certainly improved tremendously. More transparency and trust helps breed efficiencies.”
References
1. What’s New Related to Drugs. Last modified Dec-ember 16, 2015, http://www.fda.gov/Drugs/NewsEvents/ucm130958.htm.
2. FDA takes action to protect consumers from potentially dangerous dietary supplements. Last modified November 17, 2015, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm 473099.htm.
3. FDA, 21 CFR Part 111. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements.
Further reading
Ingredient identity testing: The road to GMP compliance. Mara Whitten. Tablets & Capsules 9 (4) pp. 32C-32E.
What standard? Investigation raises questions about DNA testing. Evan Hansen. Tablets & Capsules 13 (3) pp. 32B-32E