Congressional interest turns up the pressure on FDA to make a statement on Bayer Aspirin with Heart Advantage , and issue a definitive policy on any products that combine dietary supplement and OTC drug ingredients.

The House Energy and Commerce Committee, under its continuing investigation of direct-to-consumer drug marketing, sent letters Oct. 14 to FDA and Bayer inquiring about the product, which combines aspirin and plant phytosterols and carries cholesterol-lowering claims.

The product appears to violate an agency policy, expressed in a letter eight years ago, that companies should not market OTC/supplement combinations not approved through the NDA process.

However, FDA "was advised regarding Bayer's plans" for the combination product and the firm met with the agency to discuss it prior to launch, Anne Coiley, director of Global Cardio Communications for Bayer, says in an e-mail.

FDA has remained mum since the issue was raised in May in a letter from a trade group. Meanwhile, experts disagree about the legality of the product, and whether the agency's lack of enforcement action sets a precedent.

A spokeswoman with FDA's Center for Drug Evaluation and Research says "the matters raised in the letters are under review and consideration," but declined to comment further on the legality of Bayer Aspirin with Heart Advantage.

The correspondence from Committee Chairman John Dingell and Subcommittee on Oversight and Investigations Chairman Bart Stupak should raise the stakes on the issue.

Strong Recommendations, Unclear Policy

In the letter to FDA, the Michigan Democrats ask if the agency has "made any recent decisions related to the regulation of marketing such combination products."

The lawmakers refer to a May 2000 letter in which FDA recommended "that firms refrain from marketing products that combine both drug and dietary supplement ingredients," unless approved through the NDA process.

In that letter, FDA wrote to Kansas City, Mo.-based NTCO that the company's Good News Andy Pill , mixing aspirin with vitamin B12, qualifies as a combination product that raises "a number of significant public health and policy issues" (¹ Also see "OTC/Supplement Combinations "Serious Concern" For FDA" - Pink Sheet, 12 June, 2000., p. 3).

The agency also said at the time that it was unclear how a new ingredient could alter the safety and efficacy of the drug component and consumers could be misled into thinking FDA gives the same amount of scrutiny to combinations as it does for OTC drugs.

In October 2001, the agency took a stronger stance against a specific combination product, sending a warning letter to Lenexa, Kan.-based B.F. Ascher & Co., regarding its Melagesic PM Caplets containing acetaminophen and melatonin.

The Ascher letter states that the presence of acetaminophen renders the entire product a drug and the use of melatonin, which is "not identified as a monograph nighttime sleep-aid active ingredient," necessitates NDA approval for the product.

Despite a promise in the 2000 NTCO letter to make "resolution of these issues a priority," FDA has not offered guidance on combination products in the years since.

Bayer In The Woods

In their letter to Bayer HealthCare, Dingell and Stupak ask about internal deliberations, communications with FDA and studies linked to Aspirin with Heart Advantage.

The lawmakers say the company's marketing for the product "may mislead the public" given FDA's previous recommendations to other firms against marketing drug/dietary supplement combinations.

The letter asks Bayer to provide records on its communications with FDA and information on whether it submitted either a new drug application, an abbreviated NDA, or a request for an amended monograph for the product.

No Bright Line

Coiley asserts that Bayer Aspirin with Heart Advantage is a legal sum of its parts, since "aspirin is recognized in the OTC monograph and phytosterols are the subject of an FDA-approved qualified health claim."

Bayer has drawn parallels between Aspirin with Heart Advantage and its Women's Aspirin Plus Calcium , a combination product legally marketed since 2002 (² Also see "Bayer’s Aspirin/Phytosterols Combination May Draw FDA Warning" - Pink Sheet, 26 May, 2008., p. 3).

However, unlike phytosterols, calcium is approved for use as a drug individually, as well as in combination with aspirin under FDA's internal analgesics monograph.

Food and drug attorney Marc Ullman says he is "unaware of any legal theory that would allow a dietary supplement to include aspirin as an ingredient."

He says the lack of a bright line in combination product policy may leave the door open for aspirin-containing soft drinks and other disconcerting formulations that could adulterate their drug ingredients.

No Word From FDA

In May, the American Herbal Products Association requested "additional information promptly" from FDA on the status of its policy on OTC/supplement tandems, in the wake of Bayer introducing Aspirin with Heart Advantage (³ Also see "Will Bayer Supplement-Drug Combo Draw Other Firms Into New Market?" - Pink Sheet, 9 June, 2008., p. 4).

The agency's delay in acting since being alerted to the product is a "shocking failing," Ullman says.

Steve Mister, president of the Council for Responsible Nutrition - of which Bayer is a member - has said the Food, Drug and Cosmetic Act is sufficiently broad to allow for mixing drugs and dietary supplements.

In an Oct. 14 statement, Mister says he is "perplexed as to why Congress is raising questions about the appropriateness of supplement/OTC combination products," especially in light of the ongoing dialogue between FDA and the industry.

"We believe there is an appropriate place in the market for these combination products and that consumers want them," he says.

Letter Implies Rx Connection

In the Bayer letter, Dingell and Stupak suggest a connection between the discontinuation of Bayer's cholesterol drug Baycol (cerivastatin) in August 2001, and the development of Aspirin with Heart Advantage (⁴ Also see "Statin Safety Report Due Out At Year-End, National Lipid Association Says" - Pink Sheet, 25 July, 2005., p. 11).

The letter requests Bayer provide information on "internal deliberations" relating to the development and marketing of Aspirin with Heart Advantage between the discontinuation of Baycol and the launch of the combination product.

An Energy and Commerce spokesperson says the intent of the request is to know if Bayer "started the idea to market their new aspirin product after Baycol went down the tubes."

Ullman says the idea of a direct connection is "just pure speculation."

Bayer declined to comment on any link between the products.

"DTC" Probe Keeps Supplements In Its Purview

Bayer's product is not the first supplement making cholesterol claims to be targeted by the committee's direct-to-consumer advertising investigation, which by definition is more focused on prescription DTC advertising.

Wyeth is currently producing documents for the committee, defending claims for its Centrum Cardio multivitamin (which does not include an OTC drug). The committee targeted the phytosterol-containing product in a September letter seeking substantiation of claims (⁵ Also see "Science, FDA Rule Support Centrum Cardio Claims, Wyeth Will Tell Congress" - Pink Sheet, 22 September, 2008., p. 10).

Separately, the committee also issued letters the same day to FDA and a nonprofit with links to the pharmaceutical industry, investigating the agency's development of a Web site to educate consumers on DTC advertising.

[Editor's note: Read more about Congress' DTC advertising investigation in " ⁶ The Pink Sheet ," your weekly source for prescription pharmaceutical news. For more information call 1-800-332-2181.]

- Dan Schiff (d.schiff@elsevier.com)

Congress Presses FDA To Speak Up On OTC/Supplement Combo Products

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