Dietary Supplement Regulation: The Consequences of Multilateral Administrative Actions

The quality of dietary supplements has been under increasing scrutiny as of late. A webinar presented by the Food and Drug Law Institute (FDLI)[1] highlighted recent enforcement actions on dietary supplement retailers by governmental entities other than the Food and Drug Administration (FDA), the otherwise putative regulatory agency. The webinar described enforcement activities by the New York State Attorney General (NYAG) and reviewed the implications that the judicial actions may have.

In February 2015, the NYAG issued a press release indicating that his office had conducted an investigation of the four major retailers (GNC, Walmart, Target, and Walgreens) to determine if the store branded dietary supplements contained the primary botanical displayed on the label. To verify the presence of the labeled ingredient, researchers contracted by the NYAG utilized DNA[2] barcode testing technology, which analyzed for short genetic markers of the labeled botanical substance. Based on the results of these analyses, according to the NYAG, only 21% of the tested store-brand supplements verified the presence of DNA associated with the botanical listed on the label. Per the NYAG, the remaining 79% either did not detect the labeled botanical or detected contaminants in the supplement (e.g., rice, beans, pine, citrus, asparagus, primrose, wheat, houseplant and wild carrot).[3] Letters were sent by the NYAG to each retailer, demanding that each stop the sale these popular supplements immediately.

Ultimately, GNC cooperated with the NYAG, as the AG office issued a press release on March 30, 2015, indicating that it had entered into an agreement with GNC to reform how supplements are handled by the company.[4] Under the agreement, GNC will, within 18 months, begin using DNA barcoding technology to confirm the identity of plants used in their supplements. GNC will also isolate and sequence DNA from any plant ingredient that does not yet have a barcode (and will publish this information to a publically accessible database within 24 months, including the methods used to identify the ingredient). The company will also conduct random analyses on products (on certain raw ingredients and finished products) for the eight most common allergens[5], and will require GNC’s suppliers to conduct an allergen analysis, as well. Lastly, GNC will display language in their stores and on their website providing further details on supplements, including details between supplements derived from whole herbs versus extracts.

This relatively recent action by a state agency was not an isolated incident. In May 2015, a joint letter was sent to the FDA from the New York State and Indiana Attorneys General. The letter called for the FDA to overhaul the current federal oversight of the supplement industry and to promulgate enhanced current good manufacturing practices (cGMP) for dietary supplements.[6] The AGs considered the quality and safety issues surrounding the dietary supplement industry a “grave public concern”.5 The motivation for the letter (and most likely for the actions against retailers) appears to be based on state consumer protection laws and how minimum requirements imposed by cGMP rules may be viewed by some as inadequate.

In August 2015, a response from the FDA was sent to each AG. The letter addressed the major points of the original letter from the AGs.[7] The overall message from the FDA appears to be that current regulations place the burden on the manufacturer of the supplement to ensure the integrity of a finished products and that there are already processes in place to ensure the quality of a dietary supplement.

Typically, enforcement actions against food and drug companies are orchestrated by the FDA, as federal laws and regulations typically trump state and local laws. However, there have been times where the FDA has been slow to react to a situation or it may be legislatively expedient for the state or local authorities to act.  One example given in the FDLI webinar was ephedra and its inclusion as an ingredient in supplements. Based on negative health effects following ingestion of supplements containing ephedra, and an apparent lack of immediate action by the FDA, select states (i.e., Illinois, New York, and California) banned the sale of dietary supplements containing ephedra in the early 2000s. Following the actions of the individual states, in 2004, FDA banned the sale of dietary supplements containing ephedrine alkaloids, due to the unreasonable risk of illness or injury they present.[8] The FDA action was authorized under the Dietary Supplement Health and Education Act (DSHEA) of 1994.

The recent actions by the NYAG show that local enforcement agencies are not afraid to take action when concerns are present and when the FDA appears to be slow to react. While the actions of holding manufacturers to a quality threshold above the minimum may be viewed by some as admirable, the methodology used by the NYAG (and contract researchers) for evaluating the identity of botanicals in a dietary supplement have been scrutinized and criticized.

Critics of the DNA barcoding technique say that the method does not work for extracts, the target ingredient in the supplements investigated by the NYAG. During manufacturing and extraction, most botanical DNA is denatured and, thus, is not present in the final ingredient. Many experts are not surprised that the DNA barcoding technique failed to properly identify the source plant DNA.[9] Experts suggest molecular fingerprint technology (e.g., high-performance liquid chromatography and mass spectrometry) to more accurately identify the active ingredient material, rather than plant residue.[10]

To combat situations where a governmental agency may overstate the issues surrounding a dietary supplement, the key industry experts from the FDLI webinar recommended proactive actions that industry can take. As the NYAG investigation has shown, the retailer can be held liable for the misbranding of dietary supplements. The FDLI presentation suggests that retailers should conduct their own due diligence and hold manufacturers and suppliers to a high standard. The same can be true for manufacturer’s relationships with suppliers. While there are process control requirements in the Code of Federal Regulations (CFR) for dietary supplements[11], the FDLI webinar suggested, then there should be verification up and down the supply chain. A substance’s identity should not only be verified, but testing should be continuous to ensure that the product is of high quality. While the CFR allows a manufacturer to rely on information for the other components of an ingredient on a certificate of analysis from the supplier, the presenter suggested that the manufacturer should go beyond the minimum effort and should independently verify the identity of an ingredient in addition to determining its quality; testing should also be conducted to ensure that the ingredient is not a pharmaceutical intended to have the same activity as the supplement.

The portion of the CFR (21 CFR 111) addressing cGMP does not apply to suppliers of raw ingredients for dietary supplements. However, the proposed Food Safety Modernization Act (FSMA) regulations will require ingredient suppliers to take additional safety steps.

The actions taken by the NYAG put a spotlight on the dietary supplement industry, as they provide an example for those that may want to engage manufacturers or retails in the court of law (as alluded to in the FDLI presentation). Additionally, challenges like these highlight the risk of including inaccurate information on a supplement label (although, as pointed out, there is no scientifically verified evidence that the supplements targeted by the NYAG were, in fact, mislabeled). In all cases, if any alleged inadequacies or inaccuracies result in contact by a regulatory agency, it is important to always reply to the agency and state what corrective action shall be taken. Ignoring a communication from an agency will create additional trouble in the long run.

The current reality is that dietary supplements are a target for scrutiny, by both public watchdogs and certain government agencies. While there are reforms proposed under the Food Safety Modernization Act (FSMA) that should add to the safety of supplements, these reforms should be clear, realistic, and appropriate. Analysis of botanical ingredients using unpublished and unavailable methodologies and results (the NY AG has yet to release detailed information on the DNA barcoding) is a sure way to set the industry up for failure (e.g., the DNA barcoding agreement that GNC entered into with the NYAG).  Collaboration between industry leaders, regulatory agencies, and scientific experts on how to proceed with future quality standards is the most realistic approach for bolstering the safety of dietary supplements.

References

[1] FDLI Webinar: Dietary Supplements Enforcement: The New York Attorney General Actions and Jurisdictional Lines. July 23, 2015.

[2] Deoxyribonucleic acid.

[3] http://www.ag.ny.gov/press-release/ag-schneiderman-asks-major-retailers-halt-sales-certain-herbal-supplements-dna-tests

[4] http://www.ag.ny.gov/press-release/ag-schneiderman-announces-agreement-gnc-implement-landmark-reforms-herbal-supplements

[5] Per the FDA: milk, eggs, fish, crustaceans, tree nuts, peanuts, wheat, and soybeans.

[6] http://www.ag.ny.gov/pdfs/Letter_to_FDA_5_26_2015.pdf

[7] Letter from Jeremy Sharp, Deputy Commissioner, Policy, planning, Legislation & Analysis, Food and Drug Administration to Greg Zoeller, Indiana Attorney General, date stamped 080715.

[8] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108242.htm

[9] http://www.nytimes.com/aponline/2015/02/08/us/ap-us-herbal-supplements-investigation.html?_r=0

[10] http://www.forbes.com/sites/alexmorrell/2015/03/14/did-the-ny-ag-flub-its-testing-in-herbal-supplement-smackdown/

[11] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm

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