By Mike Montemarano, Associate Editor09.15.22
Seventeen of 30 dietary supplement products purchased from Amazon.com that make claims related to immune health had inaccurate labels based on their Supplement Facts panels, 13 were misbranded, and nine had additional components detected but not claimed on the label, according to an analysis published in JAMA Network Open.
“Since December 2020, Amazon has been requiring sellers to provide outlined quality control documentation and a certificate of analysis (testing results) for supplements sold on their platform. These new requirements could help ensure products are less risky and not adulterated,” the authors of the study noted.
In order to capture a picture of how well supplements are meeting label specifications, the authors of the study searched the keyword “immune” in “all departments” and then sorted results by “featured.” They selected the first 30 dietary supplement products that appeared, and required the products to have four or more stars in order to be eligible and selected for analysis.
One sample of each selected product was purchased and sent to the University of Mississippi’s National Center for Natural Product’s Research for product analysis. Liquid chromatography–mass spectrometry was used to determine the quality of the 30 dietary supplement products.
“Thirteen of the 30 products had accurate labels based on the product analysis,” the authors wrote. “Of the 17 products with inaccurate labels, 13 had ingredients listed on the labels that were not detected through analysis, such that their labels were misbranded. Ingredients missing from products ranged from 1 to 6 ingredients from any single product.”
Most commonly, ingredients that were labeled but missing from products were plant extracts, including (in descending order) extracts of Aloe vera leaf, astragalus root, eleuthero root, garlic bulb, ginger root, horehound, Isatis tinctoria root, Japanese catnip, licorice, and slippery elm bark.
Vitamin B12 and folate were missing from two products, and one product that claimed to contain elderberry only included trace amounts. None of the products had third-party certification seals, though 16 products had other seals such as “#1 doctor recommended brand,” “third party tested,” “purity and potency,” “stimulant free,” “lab tested verified,” and “quality guaranteed.”
The total number of ingredients listed on Supplement Facts panels ranged from one to 32; the most frequent ingredients were echinacea, elderberry, vitamin C, vitamin D, and zinc.
General methods that aren’t specific enough to rule out adulterants are not sufficient, especially in a time of supply chain volatility, he noted.
“We have a global supply chain that has never been this disrupted,” Wyszumiala said. “I think that largely, there’s a higher chance of having poor-quality raw materials coming in and leading to adulteration issues, potentially leading to products that might not be 100% accurate to their label claims. Materials are scarce, or are experiencing shortages, and so when people are scrambling to get materials, you have big issues popping up.”
He said it’s “unfortunate” when analyses performed by outside groups, like the one published in JAMA, demonstrate problems in the market, “but these studies also help establish the breadth and scope of quality issues.”
“Maybe at one point it was high-priced botanicals that were most susceptible,” Wyszumiala said, “but we’re looking at materials we never had to worry about in the past. But if you have to go to a second- or third-tier supplier, you’re finding someone new on the fly; and how you qualify, test, and verify that raw material ahead of the finished dosage form is one of the biggest challenges for manufacturers out there today.”
Companies with longstanding supplier relationships often don’t budget much for their own raw material testing due to established, quality track records. But qualifying a new supplier can be costly. USP’s verification program ensures there are guard rails in place for when a company switches a supplier.
“If someone is switching a supplier, we ask for a change request to be submitted to USP, along with correlating documentation to show that the new material is meeting its specs,” Wyszumiala said. “If a supplier is meeting label specifications, we want to know how you confirmed that through testing and review, and what the plan is for continuous updates as part of USP requirements.”
Further, it’s crucial that testing of finished products is validated for the specific product matrix (e.g., gummy, beverage, or capsule). Otherwise, there will always be a certain percentage of variability, Wyszumiala noted.
Adding to the knowledge gap, there’s been significant turnover of quality experts, production, manufacturing, and lab operations due to COVID-19, Wyszumiala said. “Lots of experts have retired.”
As a result, there’s greater potential for new issues to come up, “because you have someone new to their position,” he noted. “You need to make sure that people are empowered and trained to ask the right questions.”
While retailer testing requirements are “better than nothing,” Wyszumiala said, “retailers lack the fundamental understanding of how to apply testing to every individual formulation.”
“Amazon is definitely on this journey within the supplements space,” he added. “They’ve been rolling out programs asking you to be part of a third-party certification like USP or to have independent test data, or GMP [Good Manufacturing Practice] audit reports to help qualify the supplements they’re selling on their platform. We’ve seen other retailers like CVS and Walgreens who will move a product to the front of the line if it checks all boxes through USP verification.”
With several programs that seek to harmonize testing standards and requirements across multiple retailer platforms, such as the Supplement Safety and Compliance Initiative and the Global Retailer and Manufacturer Alliance, standards are coming, and they’re coming fast, Wyszumiala said.
“Not to be political, but I think testing should be the easy part. Lots of organizations out there think they have something that’s unique and special because they meet GMPs but GMP regulations are 15 years old. That tells me you have quality systems in place but it doesn’t tell me anything about a specific product or knowledge of what you’re actually producing. So, as an industry, we should be beyond the baseline requirements in GMPs.”
With these studies grabbing attention, Wyszumiala hopes that USP can remain an authoritative voice that reaches consumers. Further, USP aims to be a bridge between healthcare practitioners and the medical community at large.
“I think that we have made a lot of headway in reaching consumers through media,” he said, “and our working relationship in quality testing with the drug industry helps us to translate the work we do in the supplements space with pharmacists and physicians who find dietary supplements very questionable. We have become a sort of bridge-builder through verification for these brands, especially those who make condition-specific claims.”
“Since December 2020, Amazon has been requiring sellers to provide outlined quality control documentation and a certificate of analysis (testing results) for supplements sold on their platform. These new requirements could help ensure products are less risky and not adulterated,” the authors of the study noted.
In order to capture a picture of how well supplements are meeting label specifications, the authors of the study searched the keyword “immune” in “all departments” and then sorted results by “featured.” They selected the first 30 dietary supplement products that appeared, and required the products to have four or more stars in order to be eligible and selected for analysis.
One sample of each selected product was purchased and sent to the University of Mississippi’s National Center for Natural Product’s Research for product analysis. Liquid chromatography–mass spectrometry was used to determine the quality of the 30 dietary supplement products.
“Thirteen of the 30 products had accurate labels based on the product analysis,” the authors wrote. “Of the 17 products with inaccurate labels, 13 had ingredients listed on the labels that were not detected through analysis, such that their labels were misbranded. Ingredients missing from products ranged from 1 to 6 ingredients from any single product.”
Most commonly, ingredients that were labeled but missing from products were plant extracts, including (in descending order) extracts of Aloe vera leaf, astragalus root, eleuthero root, garlic bulb, ginger root, horehound, Isatis tinctoria root, Japanese catnip, licorice, and slippery elm bark.
Vitamin B12 and folate were missing from two products, and one product that claimed to contain elderberry only included trace amounts. None of the products had third-party certification seals, though 16 products had other seals such as “#1 doctor recommended brand,” “third party tested,” “purity and potency,” “stimulant free,” “lab tested verified,” and “quality guaranteed.”
The total number of ingredients listed on Supplement Facts panels ranged from one to 32; the most frequent ingredients were echinacea, elderberry, vitamin C, vitamin D, and zinc.
Raw Materials Need Validated Testing
Studies like this should serve as a call-to-action for the industry to double-down on ensuring that raw materials, not just finished products, are tested frequently using validated methods, according to Ed Wyszumiala, director of verification at United States Pharmacopeia (USP).General methods that aren’t specific enough to rule out adulterants are not sufficient, especially in a time of supply chain volatility, he noted.
“We have a global supply chain that has never been this disrupted,” Wyszumiala said. “I think that largely, there’s a higher chance of having poor-quality raw materials coming in and leading to adulteration issues, potentially leading to products that might not be 100% accurate to their label claims. Materials are scarce, or are experiencing shortages, and so when people are scrambling to get materials, you have big issues popping up.”
He said it’s “unfortunate” when analyses performed by outside groups, like the one published in JAMA, demonstrate problems in the market, “but these studies also help establish the breadth and scope of quality issues.”
“Maybe at one point it was high-priced botanicals that were most susceptible,” Wyszumiala said, “but we’re looking at materials we never had to worry about in the past. But if you have to go to a second- or third-tier supplier, you’re finding someone new on the fly; and how you qualify, test, and verify that raw material ahead of the finished dosage form is one of the biggest challenges for manufacturers out there today.”
Companies with longstanding supplier relationships often don’t budget much for their own raw material testing due to established, quality track records. But qualifying a new supplier can be costly. USP’s verification program ensures there are guard rails in place for when a company switches a supplier.
“If someone is switching a supplier, we ask for a change request to be submitted to USP, along with correlating documentation to show that the new material is meeting its specs,” Wyszumiala said. “If a supplier is meeting label specifications, we want to know how you confirmed that through testing and review, and what the plan is for continuous updates as part of USP requirements.”
Further, it’s crucial that testing of finished products is validated for the specific product matrix (e.g., gummy, beverage, or capsule). Otherwise, there will always be a certain percentage of variability, Wyszumiala noted.
Adding to the knowledge gap, there’s been significant turnover of quality experts, production, manufacturing, and lab operations due to COVID-19, Wyszumiala said. “Lots of experts have retired.”
As a result, there’s greater potential for new issues to come up, “because you have someone new to their position,” he noted. “You need to make sure that people are empowered and trained to ask the right questions.”
How Does this Study Reflect on Retailer Requirements?
As noted in the study, Amazon recently tightened standards for selling supplements on its platform, requiring product manufacturers to submit certificates of analysis from an ISO 17025 accredited lab for each product. However, the JAMA study showed that meeting label specifications is still an issue.While retailer testing requirements are “better than nothing,” Wyszumiala said, “retailers lack the fundamental understanding of how to apply testing to every individual formulation.”
“Amazon is definitely on this journey within the supplements space,” he added. “They’ve been rolling out programs asking you to be part of a third-party certification like USP or to have independent test data, or GMP [Good Manufacturing Practice] audit reports to help qualify the supplements they’re selling on their platform. We’ve seen other retailers like CVS and Walgreens who will move a product to the front of the line if it checks all boxes through USP verification.”
With several programs that seek to harmonize testing standards and requirements across multiple retailer platforms, such as the Supplement Safety and Compliance Initiative and the Global Retailer and Manufacturer Alliance, standards are coming, and they’re coming fast, Wyszumiala said.
“Not to be political, but I think testing should be the easy part. Lots of organizations out there think they have something that’s unique and special because they meet GMPs but GMP regulations are 15 years old. That tells me you have quality systems in place but it doesn’t tell me anything about a specific product or knowledge of what you’re actually producing. So, as an industry, we should be beyond the baseline requirements in GMPs.”
Taking Part in Public Discourse
Consumers may not fully understand the complexity of a verification seal like USP’s, namely how specific a testing method needs to be for an individual product.With these studies grabbing attention, Wyszumiala hopes that USP can remain an authoritative voice that reaches consumers. Further, USP aims to be a bridge between healthcare practitioners and the medical community at large.
“I think that we have made a lot of headway in reaching consumers through media,” he said, “and our working relationship in quality testing with the drug industry helps us to translate the work we do in the supplements space with pharmacists and physicians who find dietary supplements very questionable. We have become a sort of bridge-builder through verification for these brands, especially those who make condition-specific claims.”
