On September 20, 2016, NBTY, Inc., the largest dietary supplement manufacturer in the United States, signed an agreement with the Office of the New York Attorney General (NY AG) to develop and incorporate enhanced herbal authentication methods, including DNA barcoding, into its quality control procedures.1,2
The agreement comes more than 18 months after an investigation initiated by the NY AG in February 2015 alleged that four out of five herbal dietary supplement products sold at retailers GNC, Walgreens, Walmart, and Target did not contain ingredients listed on the label. The allegations were based on the results of a controversial DNA barcoding approach, which suggested that only five of the 24 commercial products analyzed contained DNA of the labeled species. These results led the NY AG to demand that the four retailers remove the products from their shelves in the state of New York.3
The accuracy of the results, however, was immediately questioned by experts in the field of botanical ingredient authentication.4,5 Although details of the method used were not released, these experts indicated that because the majority of the products were made from herbal extracts, which contain plant DNA that is frequently fragmented or degraded, DNA barcoding was unlikely to provide useful or definitive results upon which to base regulatory action. The investigation reported finding DNA from species in the following genera: Oryza (found in 19 samples), which includes rice (O. sativa, Poaceae); Allium (in nine samples), which includes garlic (A. sativum, Amaryllidaceae) and onion (A. cepa); and Dracaena (Asparagaceae; found in seven samples), which includes popular non-medicinal houseplants. These findings strongly suggest that the DNA barcoding results were due to cross-contamination. In addition, one valerian (Valeriana officinalis, Caprifoliaceae) sample allegedly contained saw palmetto (Serenoa repens, Arecaceae) DNA, again raising the question of cross-contamination.6
The results of the investigation and subsequent cease-and-desist orders issues by the NY AG were publicized in national newspapers, including The New York Times and The Washington Post.7-9 Despite the apparent use of an inappropriate and inadequate test method, some news organizations did not question the results and were highly critical of the dietary supplement industry. A widely distributed Associated Press article published shortly after the NY AG’s initial announcement did attempt to cover the growing controversy surrounding the NY AG’s reliance on only the DNA barcoding analytical method.10 A detailed review on the investigation by the NY AG was published in HerbalGram issue 106.11
NBTY, which had contract-manufactured herbal supplements sold at Walgreens and Walmart under the retailers’ respective brands, responded to and fully cooperated with the NY AG’s investigation, providing documentation confirming that the supplements in question were produced and labeled in accordance with current good manufacturing practices (cGMPs), as required by federal law (i.e., none of the supplements were found to be deficient, adulterated, mislabeled, or a potential hazard to public health, as initially alleged by the NY AG).3,7,8
On March 27, 2015, in a highly publicized development, supplement retailer GNC signed an agreement with the NY AG to implement DNA-barcoding testing methods on all botanical ingredients in its dietary supplements before such ingredients were processed into extracts.12
While NBTY maintains that there are currently no scientifically valid testing methods for DNA barcoding-based identification of botanical ingredients, it has agreed to incorporate DNA barcoding into its quality control testing procedures no later than September 20, 2017, for at least 12 distinct botanical species (the 12 herbs are not named in the agreement). Also, as part of the agreement, NBTY will implement DNA barcoding authentication of all botanical ingredients for which scientifically valid methods exist* no later than September 20, 2018.
In addition, NBTY pledged to invest $250,000 to foster genetic authenticity research and education, to partner with academic institutions (e.g., Cornell University) to improve transparency and traceability of botanical dietary supplements, to work with industry organizations in the development of supplier cGMPs,** and to have their manufacturing facilities audited by a third-party accreditation body. Also included in the agreement is a commitment to allergen labeling and a campaign to improve consumer information, similar to the requirements outlined in the agreement between the NY AG and GNC from March 2015.12
The agreement terminates the investigation by the NY AG into NBTY’s supplement manufacturing processes, and it will cease to be in effect 36 months from the date of the agreement. A resolution between the NY AG and Target still appears to be pending.
Many members of the botanical dietary supplement industry have shown their willingness to embrace new analytical techniques for improved quality control processes as long as they are fit for the intended purpose, with the goal to provide the highest quality product for consumers. While DNA-based authentication is a promising technology, the uncritical use of DNA barcoding has led to an unfortunate situation in which regulatory action has been based on erroneous results. This investigation is an example of a lack of understanding by regulatory agencies of the manufacturing processes involved in the production of botanical dietary supplements and of scientifically valid testing methods.
* According to the agreement, existing scientifically valid DNA barcoding methods are those that meet one or more of the following criteria:
- DNA barcoding methods that are incorporated in a monograph associated with the relevant ingredient by the United States Pharmacopeia or the American Herbal Pharmacopoeia.
- The US Food and Drug Administration accepts or endorses the use of DNA barcoding, either as a standalone method or part of a multi-method protocol, as a scientifically valid method for confirming the identity of the relevant ingredient.
- Any US industry group in which NBTY is a corporate member identifies DNA barcoding as a valid or appropriate method for confirming the authenticity of the relevant ingredient, as either a standalone method or part of a multi-method protocol.
- Upon review of scientific literature and industry practice, NBTY or its Herbal Authenticity Program independently recognizes that reliable and scientifically valid DNA barcoding is available for that ingredient.
** cGMPs pertain to manufacturers and distributors of dietary supplements but not to the producers and suppliers of the ingredients used in the production of finished products. Several recent herb and dietary supplement industry initiatives have focused on creating guidelines for manufacturers to require of suppliers in the absence of federally mandated practices for ingredient suppliers.
- A.G. Schneiderman Announces Major Nationwide Agreement with NBTY, Herbal Supplement Maker for Walgreens and Walmart [press release]. Albany, NY: New York State Attorney General’s Office; September 28, 2016. Available at: http://ag.ny.gov/press-release/ag-schneiderman-announces-major-nationwide-agreement-nbty-herbal-supplement-maker. Accessed October 11, 2016.
- Albany, NY: New York State Attorney General’s Office; September 20, 2016. Available at: https://ag.ny.gov/sites/default/files/nbty_agreement.pdf. Accessed October 12, 2016.
- A.G. Schneiderman Asks Major Retailers to Halt Sales of Certain Herbal Supplements as DNA Tests Fail to Detect Plant Materials Listed on Majority of Products Tested [press release]. Albany, NY: New York State Attorney General’s Office; February 3, 2015. Available at: www.ag.ny.gov/press-release/ag-schneiderman-asks-major-retailers-halt-sales-certain-herbal-supplements-dna-tests. Accessed October 11, 2016.
- Harbaugh Reynaud DT, Mishler BD, Neal-Kababick J, Brown PN. The Capabilities and Limitations of DNA Barcoding of Botanical Dietary Supplements [white paper]. Richmond CA: AuthenTechnologies; March 2015. Available at: https://gallery.mailchimp.com/2d47ec72fa1542de734a46f71/files/Reynaud_DNA_Barcoding_White_Paper.pdf. Accessed October 11, 2016.
- Is DNA barcode testing appropriate for the conclusions reached by the New York Attorney General? Here’s what some of the experts say... . Council for Responsible Nutrition website. Available at: www.crnusa.org/NYAG/quotes.html. Accessed October 11, 2016.
- Parveen I, Gafner S, Techen N, Murch SJ, Khan IA. DNA barcoding for the identification of botanicals in herbal medicine and dietary supplements: strengths and limitations. Planta Med. 2016;82(14):1225-1235. DOI:10.1055/s-0042-111208. Available at: www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0042-111208.pdf. Accessed October 12, 2016.
- O’Connor A. New York Attorney General targets supplements at major retailers. New York Times. February 3, 2015. Available at: http://well.blogs.nytimes.com/2015/02/03/new-york-attorney-general-targets-supplements-at-major-retailers/. Accessed October 11, 2016.
- O’Connor A. What’s in those supplements? New York Times. February 3, 2015:A1. Available at: http://well.blogs.nytimes.com/2015/02/03/sidebar-whats-in-those-supplements/. Accessed October 11, 2016.
- Kaplan S. GNC, Target, Wal-Mart, Walgreens and accused of selling adulterated ‘herbals’. Washington Post. February 3, 2015. Available at: www.washingtonpost.com/news/morning-mix/wp/2015/02/03/gnc-target-wal-mart-walgreens-accused-of-selling-fake-herbals/. Accessed October 11, 2016.
- Esch M. Supplements industry derides NY attorney general’s DNA tests. February 10, 2015. Seattle Post-Intelligencer website. Available at: www.seattlepi.com/news/medical/article/Supplements-industry-derides-NY-attorney-6069689.php. Accessed March 9, 2015.
- Smith T. The Supplement Saga: A Review of the New York Attorney General’s Herbal Supplement Investigation. HerbalGram. 2015;106:44-55. Available at: http://herbalgram.org/resources/herbalgram/issues/106/table-of-contents/hg106-feat-nyag/. Accessed October 12, 2016.
- A.G. Schneiderman Announces Agreement with GNC to Implement Landmark Reforms for Herbal Supplements [press release]. Albany, NY: New York State Attorney General’s Office; March 30, 2015. Available at: www.ag.ny.gov/press-release/ag-schneiderman-announces-agreement-gnc-implement-landmark-reforms-herbal-supplements. Accessed October 11, 2016.