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HerbalEGram: Volume 6, Number 1, January 2009
Class Action Lawsuit Filed Against Bayer after FDA Sends Warning Letters for Combination Dietary Supplement-OTC
Drug Products
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Two warning letters from the US Food and Drug Administration (FDA) object to Bayer HealthCare LLC's (Morristown, NJ) marketing of 2 products combining low-dose aspirin with dietary supplement ingredients (DSIs).1 At least one law firm has since filed a class action lawsuit against Bayer2,3 in relation to these products based on what the FDA called “misbranded” products and “new drug[s that are] not the subject of ... approved new drug application[s]."1
The October 27, 2008, warning letters from Debra M. Autor, Director of the FDA's Office of Compliance, to Gary Balkema, President of Bayer, demand immediate changes for Women's Low-Dose Aspirin + Calcium™ (hereinafter referred to as WLDA+C), containing 81 mg aspirin and 300 mg elemental calcium, and Aspirin with Heart Advantage™ (AHA), with 81 mg aspirin and 400 mg phytosterols.1 (Phytosterols are plant-derived sterol compounds with cholesterol-lowering properties demonstrated in controlled clinical trials.4) The combination products (CPs), labeled as over-the counter (OTC) analgesics, are also labeled for use in reducing risks of heart disease through aspirin's blood-thinning effects, a disease-prevention consumer self-care use FDA says must be professionally diagnosed and supervised.
The products also carry labeling as dietary supplements (DS). In AHA, an "analgesic phytosterol supplement,"5 reduced heart attack risk is attributed to the plant sterols that "help lower bad cholesterol," along with aspirin's effects. WLDA+C is labeled as "fighting osteoporosis" through its calcium content. WLDA+C was introduced in the US in 2002;6 AHA was introduced in spring 2008.
Pharmaceutical and DS manufacturers have long expressed interest in combining some OTC medicines with DSIs, but no legal path to do so has been defined. In 1994, when the Dietary Supplement Health and Education Act (DSHEA) was passed, the FDA stated only that it did "not believe it would be appropriate to preclude [combined health claims for a DS and OTC drug labeling] under all circumstances. Such [dual] claims may be permissible if... [they] neither misbrand the product nor create a safety problem."5,7
The October warnings accuse Bayer of both misbranding and creating safety issues. Neither of the recently-cited CPs is approved by the FDA for labeled uses. The agency writes that disease-treatment uses claimed for both CPs render developing appropriate language for direct consumer use "impossible." The letters cite specific deficiencies for each product, including contradictory, misleading, and inadequate labeling, and take issue with the efficacy of their ingredients, if taken according to labeled directions, for all indications.1
FDA did not request immediate recall of the products, giving Bayer 15 days to respond. [Editor’s Note: To date, December 17, 2008, Bayer does not appear to have done so.) Concerning AHA, the FDA suggested its phytosterols could be sold separately as a DS, as long as no health-related claims for cholesterol-lowering were made, "except as part of an explanation of [how] phytosterols reduce the risk of heart disease," but appeared to leave no room for AHA as currently formulated to be marketed.
However, while stating that calcium carbonate in the aspirin-calcium CP could be sold separately as a DS, if no osteoporosis-related treatment claims were made other than authorized as a health claim for calcium under the terms of the Nutrition Labeling and Education Act of 1990 for calcium and reduced osteoporosis risk, FDA adds, "calcium carbonate could be combined as a buffering agent with aspirin as long as no osteoporosis-related claims were made." However, both FDA letters state, "[W]hen... a drug and a dietary ingredient are combined into a single dosage form, the combination becomes a 'drug.'"1
The AHA warning also responds to an August, 2008, letter from Bayer's Balkema to FDA Chief Counsel Gerald F. Masoudi, wherein Balkema reportedly argued that the FDA and Federal Trade Commission encourage public education on cardiovascular benefits of aspirin, and that barring AHA's cardiovascular claims would violate Bayer's First Amendment rights. The FDA disagrees on both points.1 No similar reference appears in the WL-DA+C letter, and it remains unclear how this CP, after being marketed for 6 years, came to the FDA's belated attention. The agency acknowledges that there have been no reports of adverse events for either CP.8
At least one legal complaint now claims Bayer violated FDA regulations and New Jersey's Consumer Fraud Act.2 Kris Gerhard v. Bayer (08-cv-05660), filed in US District Court, District of New Jersey by attorneys Hagens Berman (Seattle, WA), seeks refunds for customers who bought the cited products, alleging Bayer "illegally targeted" people who feared heart disease and women worried about osteoporosis.3
"We stand behind both products and all marketing claims made in their support," Bayer said in a statement, adding that its product advertising tells buyers to talk with their doctors before taking the CPs. AHA labels also say the drug does not replace cholesterol-lowering drugs.9 The American Botanical Council’s calls to Bayer seeking further comment for this article were not returned, and no public statements were found on the company's Web site.*
DSHEA does not provide a regulatory category for combined DS-OTC products. In fact, one of the major tenets of DSHEA is that DS are not drugs. No rule-making process has addressed DS-OTC products. In 2000 then-FDA Associate Commissioner for Policy Margaret Dotzel told industry attorneys that CPs "raised significant public health and policy issues" requiring agency resolution, adding, "The number of inquiries ... has made ... these issues a priority." Pending resolution, however, the FDA strongly recommended against marketing CPs.10
In 2002, the FDA told the US House of Representatives' Committee on Government Reform it was "looking at creating a policy to consider issues"11 with co-packaging DS and OTC drugs. The committee chair noted that some firms had received warning letters for CPs, "despite the fact that there has been no official guidance."12 The agency said it "might ultimately determine that it is appropriate to issue guidance or regulations on co-packaging."11
Michael McGuffin, President, American Herbal Products Association, asked Jeffrey E. Shuren, FDA Assistant Commissioner for Policy, for clarification on the status of CPs in May, 2008,4 citing warning letters sent in 200113 to manufacturers that introduced acetaminophen-containing CPs,† and noting AHA's debut. Hearing of the Bayer warning letters, McGuffin said the FDA, with its limited resources, had taken "the simplest and least creative approach ... by enforcing the current rules without any modification. FDA could have developed a streamlined science-based policy to control the introduction of health promoting products, rather than forbid all [CPs]."7 The warning letters do not, in fact, forbid all such products, but find Bayer's 2 offerings fail to pass muster.
Steve Mister, President and CEO of the Council for Responsible Nutrition (CRN), of which Bayer is a member,6 said the 2001 warnings addressed specific combinations of DS and acetaminophen, but the FDA has never publicly reversed its 1994 statement that combined DS health claims and OTC labeling might be achievable.6,13,14 CRN has long advocated for allowing CPs, and reiterated its support following the Bayer warnings.15
Mark Blumenthal, founder and executive director of the American Botanical Council, commented that various people in the herbal community and beyond were "astonished" at Bayer's significant and potentially costly risk in the highly-publicized launch of its aspirin-phytosterol combination. Regardless of the regulatory outcome, he said, "one of the impacts of the product introduction is its underscoring of the legitimacy of plant sterols as a safe, effective ingredient to help lower elevated cholesterol levels. This is a positive message to the public about the benefits of a plant-based dietary supplement ingredient" (E-mail to M Garner-Wizard, October 31, 2008).
The FDA letters came 2 weeks after the House Committee on Energy and Commerce's Subcommittee on Oversight and Investigations asked Bayer and Health and Human Services Secretary Michael Leavitt, whose department includes the FDA, about AHA's legality.16 The Committee, then chaired by Rep. John Dingell (D-MI), began investigating whether Bayer erred by marketing AHA directly to consumers.9 Rep. Dingell said on October 28 that the investigation would continue.16 He was ousted from the chairmanship of the powerful Committee in December;17 potential effects of this change on the Bayer investigation, and other matters of interest to the herbal and DS communities, are as yet unknown.
Meanwhile, another drug maker has taken the plunge into the CP market: Vicks (Procter & Gamble, Cincinnati, OH) has introduced new versions of its OTC Nyquil™ and Dayquil™ cold products, with supplemental vitamin C and dual OTC-DS labeling. The CPs make no health-related claims for the vitamin, and advise consumers to use the products according to labeled drug-use directions.18
* At press time, no response to either warning letter had been posted on the FDA or Bayer Web site. At Bayer, Mr. Balkema’s office referred ABC’s calls to the press office, but there has been no response to those messages.
† The acetaminophen-containing products receiving warning letters were Melagesic™ (BF Ascher & Co, Inc, Lenexa, KS) with melatonin, Inholtra® Joint Pain Capsules™ (Omni Nutraceuticals, Inc., Los Angeles, CA) with glucosamine sulfate, and Omni’s IJP Plus Capsules™, adding chondroitin sulfate to the glucosamine.
—Mariann Garner-Wizard
References
1. Warning letters. October 27, 2008. FDA Web site. Available at: http://www.fda.gov/foi/warning_letters/s6991c.htm (regarding AHA) and http://www.fda.gov/foi/warning_letters/s6990c.htm (regarding WL-DA+C).
2. Voreacos D. Bayer faces suits after FDA warning on aspirin with supplements. Bloomberg.com Web site. November 19, 2008. Available at: http://www.bloomberg.com/apps/news?pid=206011278&sid=adw.oHmiBSqY.
3. Hagens Berman files class action against Bayer Healthcare over misleading marketing campaign [press release]. Seattle, WA: Hagens Berman Sobol Shapiro; November 19, 2008.
4. Moriusi KG, Oosthuizen W, Opperman AM. Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: A systematic review with meta-analysis. J Am Coll Nutr. 2006;25(1):41-8.
5. Letter from Michael McGuffin, President, American Herbal Products Association, on May 29, 2008, to Jeffrey E. Shuren, FDA Assistant Commissioner for Policy. Available at: http://www.ahpa.org/portals/0/pdfs/08_0529_AHPA_to_FDA_OTC_DS_Combination_Products.pdf.
6. Bayer warning letters reinforce FDA ban on supplement/drug combinations. The Tan Sheet. October 28, 2008.
7. Food labeling; general requirements for health claims for dietary supplements. Final rule. Filed by FDA, Department of Health and Human Services. 21 CFR Parts 20 and 101. Docket No. 85N-061D. RIN 0905-AB67. 59 Federal Register 395, 419, January 4, 1994. Available at: http://frwebgate3.access.gpo.gov/cgi-bin/TETgate.cgi?WAISdocID=41807532080+0+1+0&WAISaction=retrieve.
8. DeNoon DJ. FDA: 2 Bayer aspirin products 'unlawful.' WebMD Health News. October 28, 2008. Available at: http://www.webmd.com/heart-disease/news/20081028/fda-2-bayer-aspirin-products-unlawful.
9. Heavey S. US warns Bayer over aspirins containing supplements. Reuters, October 28, 2008. Available at: http://www.reuters.com/article/euRegulatoryNews/idUSN2838864820081028.
10. Letter from Margaret Dotzel, FDA Associate Commissioner for Policy, on May 30, 2000, to attorneys at the firm of Morgan Lewis & Brockius [as quoted in 5 above].
11. FDA responds to Burton inquiries. Natural Products Insider. March 11, 2002. Available at: http://www.naturalproductsinsider.com/hotnews/22h116128.html.
12. Burton asks FDA for answers on GMPs, combination products. Natural Products Insider. January 28, 2002. Available at: http://www.naturalproductsinsider.com/hotnews/21h28143839.html.
13. The 2001 warning letters quoted by McGuffin in 5 above are archived at PharmCast.com: http://www.pharmcast.com/WarningLetters/Yr2001/Oct2001/BFAscher1001.htm and
http://www.pharmcast.com/WarningLetters/Yr2001/Oct2001/OmniNutraceuticals1001.htm.
14. Mister S. OTC/supplement combos offer opportunity. Natural Products Insider. June 11, 2008. Available at: http://www.naturalproductsinsider.com/articles/crn-fda-encourage-supplement-otc-combos.html.
15. Council for Responsible Nutrition says that supplement-OTC drug products play important role in healthcare and wellness [press release]. Washington, DC; Council for Responsible Nutrition; October 28, 2008. Available at: http://www.crnusa.org/CRNPR08_Combo102808.html.
16. Dingell, Stupak on FDA's warning letter on Bayer Aspirin with Heart Advantage [press release]. Washington, DC; Committee on Energy and Commerce; October 28, 2008. Available at: http://energycommerce.house.gov/Press_110/110nr374.shtml.
17. Walker EP. Waxman takes gavel from Dingell as chairman of powerful house committee. MedPage Today, November 20, 2008. Available at: http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/11862.
18. Information on combination products. Available at: http://www.vicks.com/products/nyquil-plus-vitamin-c.
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