By Stefan Gafner, PhD
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 eae; 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, NBTY has agreed to incorporate DNA barcoding in 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 Pharmacopeia.
- 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.
References
- 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. Associated Press. 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://cms.herbalgram.org/herbalgram/issue106/hg106-FEAT-NYAG.html. 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.
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