[GNC Holdings Inc.]returns recalled herbal supplements to stores in New York in an agreement with the state’s attorney general that imposes requirements beyond FDA’s supplement GMPs, a move that could have a domino effect across the industry.

The New York AG’s investigation that led to the March 30 agreement, alleging GNC sold adulterated and misbranded herbal supplements at stores in the state, could lead other states also to look at requirements on supplement firms that exceed FDA’s good manufacturing practices 2007 final rule.

New York Attorney General Eric Schneiderman and other state attorneys general already are pushing federal lawmakers to investigate the herbal supplement industry and strengthen FDA’s stronger oversight.

Attorneys general of Connecticut, District of Columbia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Massachusetts, Mississippi, New Hampshire, Northern Mariana Islands, Pennsylvania and Rhode Island also stated their concerns about herbal and other dietary supplements in an April 2 joint letter to the chairmen and ranking members of the Senate Consumer Protection, Product Safety, Insurance, & Data Security subcommittee and the House Subcommittee on Health.

FDA’s supplement GMP final rule imposes comprehensive requirements so firms address intentional and unintentional adulteration of products through production and process control systems, but Schneiderman said his “investigation raised questions regarding the sufficiency of those requirements in relation to state consumer protection laws.”

The 36-month agreement with GNC hits the firm “in all of its more than 6,000 stores nationwide” and is “the first in the nation to require testing standards for herbal supplements that exceed current FDA requirements,” according to the New York agency.

Both GNC and Schneiderman’s office say the firm will employ DNA barcoding for ingredient-identity testing on plants that are sources for active ingredients in the firm’s products.

However, the firm and Schneiderman disagree on whether FDA’s regulation of supplement manufacturing, authorized by the Dietary Supplement Health and Education Act, is sufficient to ensure the safety of products available in the U.S.

“As our testing demonstrated, and this agreement affirms beyond any doubt, our products are not only safe and pure but are in full compliance with all regulatory requirements,” said GNC CEO Michael Archbold in the firm’s announcement.

Schneiderman’s office said it “found no evidence in the course of its investigation that GNC deviated from” FDA’s supplement GMPs or “standard industry practice in the production” of the tested supplements.

However, the state agency criticized federal regulatory oversight of the industry. “The FDA does not mandate the use of DNA-based technologies, like barcoding, to authenticate herbal supplements. Instead, the FDA allows companies to support their claims through other methodologies, including chemical analysis methods, like those employed by GNC. Given the existence of chemically-similar natural or synthetic substitutes, NY AG is concerned that standard chemical approaches provide inadequate assurance of the authenticity of herbal supplements,” Schneiderman states in the agreement.

Additionally, because FDA regulations “allow for low levels of inadvertent contamination, including from allergens,” Schneiderman “is concerned … there is no federal testing of products manufactured in [GMP-compliant] facilities to confirm that contamination falls below relevant safety thresholds.”

The agreement notes, though, that the New York AG and GNC agree “DNA barcoding holds great promise for further authentication” of supplement ingredients. “GNC has expressed its commitment to use DNA barcoding in its own supply chain, enhance other aspects of its operations, and lead the industry to adopt the same standards,” according to the agreement (see box below).

GNC said in its announcement that it will expand testing “deeper into its supply chain” through its leadership of “ongoing industry efforts to integrate source material traceability standards, including DNA barcoding where appropriate,” which will be “prior to extraction processes.”

Those changes, the Pittsburgh-based manufacturer and retailer said, “would not have impacted availability of the products subject to” the New York AG’s review.

Schneiderman’s investigation also required Target Corp., Walgreen Co. and [Wal-Mart Stores Inc.] to recall herbal-extract products from some stores in the state. However, the GNC agreement does not resolve New York’s litigation against those firms’ products, which are made by contract manufacturers.

DNA Barcoding Moved

DNA barcoding as an ingredient-identity testing methodology has been criticized widely by industry stakeholders and by experts from outside the industry and is described by FDA as unreliable.

Other stakeholders ask, why should a supplement firm compliant with FDA regulations agree to additional requirements suggested by a state attorney general? And, they tell “The Tan Sheet,” why would DNA barcoding be required when it is not currently recognized as valid for botanical ingredient-identity testing?

“I think it was a mistake and I think it sends the wrong message to consumers and the industry alike,” Council for Responsible Nutrition President and CEO Steve Mister.

“I don’t think it’s a win for the industry,” said United Natural Products Alliance President Loren Israelsen.

In DNA barcoding, GNC is taking on an onus that also affects its supply chain and that few if any companies are prepared to bear, Israelsen added.

“It will create a new requirement” for GNC and firms in its supply chain, “but a requirement without the infrastructure to support it,” he said.

‘Biological Connection’ Targeted

Schneiderman’s office says GNC is required within 18 months to begin testing the active plant ingredients in its products using DNA barcoding.

Under the agreement, GNC will begin using DNA barcoding to confirm the authenticity of all plants used as for ingredients in its herbal supplements prior to processing to “ensure the presence of a biological connection between the source plant and the extract that is eventually included in GNC’s supplements.”

Requiring a firm to use DNA barcoding on plants that are the sources for herbal ingredients appears to be Schneiderman’s response to the widespread criticism of his investigators’ use of the methodology for testing finished products.

Industry stakeholders, in their criticism of the investigation, and FDA officials, in their neutral comments, have explained that manufacturing processes often remove or damage DNA of botanical supplements, making DNA testing unreliable for analyzing the products.

Moving the DNA barcoding to the source-plant stage of the manufacturing process, however, likely will do little to improve the methodology’s reliability for botanicals without an adequate plant species library ([A#05150316003]).

“To mandate the use of this technology that lacks reference standards is problematic,” UNPA’s Israelsen said.

The GNC-New York agreement, though, anticipates that supplement firms need more comprehensive DNA barcoding data. It says when DNA barcoding references on certain plant materials that GNC would use in its Herbal Plus products are unavailable, either through a public domain source or a third-party vendor, within 24 months, the firm “agreed to contribute” those barcodes and its methods to identify them “to a publicly accessible database.”

FDA officials, being careful not to comment on the New York investigation, say relying on DNA barcoding alone is not an acceptable testing procedure. The agency is researching the development of validated DNA sequencing-based identification methods for botanical materials and is developing a plant species DNA library, according to an agency response to request by Sens. Orrin Hatch, R-Utah, and Martin Heinrich, D-N.M., to profile the federal supplement regulation framework ([A#05150323009]).

In an emailed statement, FDA’s Center for Food Safety and Applied Nutrition noted working with state agencies. CFSAN “will continue to work with our state partners and those in industry to ensure that dietary supplements are in compliance with federal law.”

Testing Flexibility An Expert Decision

Mandating use of a certain testing methodology is counter to the flexibility that is an integral component of the supplement GMPs.

And allowing industry flexibility in supplement ingredient testing was a decision the experts made, CRN’s Mister said.

“FDA is the expert in this area and it’s up to FDA and the companies to determine the appropriate testing methodology for type of ingredient,” Mister said.

Instead, GNC’s agreement “tells the state’s AG, ‘I can play FDA,’” he added.

“I don’t understand,” said Natural Products Association Executive Director and CEO Daniel Fabricant, “how the attorney general in New York has all of the sudden become an authority on manufacturing dietary supplements.”

American Herbal Products Association President Michael McGuffin also questioned the DNA barcoding requirement and said GNC‘s announcement is “clear evidence that current federal regulation of dietary supplement manufacturing is effective.”

“DNA testing will add no additional assurance of the correct identification of any herbal ingredient that has already been verified by one or more of the other long-established analytical tools now used by responsible herbal manufacturers,” McGuffin said.

‘Prominent Signage’ Coming In N.Y.

GNC also agreed to test materials for contamination with allergens before and after production, and “post prominent signage advising consumers of the processed, chemical nature of extracts,” Schneiderman’s office says. The firm will offer a template of this signage to other retailers that sell Herbal Plus products.

The New York AG also quotes Stony Brook University professor of pharmacological sciences, Arthur Grollman, as saying the GNC agreement is a model FDA should follow.

Agreement Touches Downstream Testing

Under its agreement with the New York AG, GNC will require its suppliers to implement a randomized allergen testing protocol on all active herbal/botanical raw material ingredients used in GNC Herbal Plus products line and to use a recognized, robust industrial sampling technique to identify samples for testing.

The allergen testing will employ the Polymerase Chain Reaction-Enzyme-Linked Immunosorbent Assay to detect the eight most common allergens, as defined by FDA. GNC also will test finished products in the line for those eight allergens annually using a scientifically validated technique and to confirm any affirmative representations on the bottle label about the absence of certain ingredients.

All GNC online product pages for Herbal Plus products listed as extracts will include in the product description section “prominent links” to an explanation of the differences between whole herbs and extracts and a description of GNC's extraction methods.

GNC will list all ingredients, including all excipients, on all Herbal Plus product labels, as required by “existing FDA rules.”

Semi-annually and at the conclusion of the agreement, GNC will report to NYAG on the number and species names of active herbal/botanical raw material ingredients in Herbal Plus products that were sourced after authentication using DNA barcoding; names and addresses of all facilities in which DNA barcode authentication was performed; a list of materials rejected as a consequence of DNA barcoding; and the results of the randomized testing for the eight most common allergens.

GNC also will, upon request by the New York AG, provide all additional documentation and information necessary for the agency to verify compliance with this agreement without the necessity for a subpoena.

"This agreement should serve as a model for other companies and, hopefully, for the federal government to enact similar regulations. Adoption of DNA barcoding to confirm the authenticity of all plants prior to processing is a major step forward in the regulation of herbs," said Grollman, who also is a physician.

The Connecticut and Indiana state attorneys general offices and Puerto Rico’s consumer protection agency previously formed a coalition with Schneiderman’s office to investigate supplements sold in their markets. The Connecticut and Indiana AGs also encourage other firms to follow GNC’s example.

While supplement firms want to return their products to the market after a recall, the GNC-N.Y. agreement could make it more likely other states – through enforcement by attorneys general or other officials or through enacting legislation – will put the industry under tighter regulations than FDA already does.

“We have New York doing precisely what you hope not to see,” Israelsen said.

“There’s a potential for setting a precedent there,” said Fabricant of NPA.

GNC also stated that it preserved specific lots of the five products targeted by the New York inquiry and since then in consumer lawsuits filed against the firm “despite the fact that there is no prohibition against the sale of such products.”

GNC-New York Agreement Spurs States’ Call To Tighten Supplement Industry Scrutiny

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