Bayer OTC-Supplement Combo Products Draw FDA Warnings

Big Pharma has long eyed the dietary supplement market as a market ripe with opportunity, but has never discovered a way to go beyond simply competing head-to-head, supplement to supplement, with pure natural products manufacturers. Enter Bayer aspirin combined with dietary supplement ingredients—Bayer Aspirin with Heart Advantage and Bayer Women's Low-Dose Aspirin + Calcium—a marriage of a safe and heralded OTC ingredient with well researched natural ingredients approved in some way by FDA for health claims.

This consolidation of non-prescription segments often separated in a pharmacy is innovative, if not risky from a regulatory prospective. Aspirin products must have a Drug Facts panel, while natural ingredients must have a Supplement Facts panel. Bayer's line of OTC-supplement fusions has both such panels. It also has health claims for its aspirin-phytosterols and aspirin-calcium based on the claims approved by FDA for foods and supplement containing certain amounts of those ingredients.

However, longtime natural products industry foe Rep. John Dingell (D-Mich.) took exception to the aspirin products, sending a letter to Bayer execs demanding scientific evidence to back the health claims used on the labels.

Given aspirin's long history of safe use as an OTC drug, and the similarly relative benign supplements calcium and phytosterols, it is amazing the Dingell finds time in all the crises that currently face our nation and Congress to take exception with one of hundreds of product claims that come into question each year. Of course Bayer is high profile and aspirin a household staple remedy, so the opportunity for a political crusade is ripe.

In warning letters sent to Bayer, FDA says its problem with Bayer's new aspirin products is in the claims, which it says don't strictly adhere to those approved for each calcium-osteoporosis and phytosterols-heart disease. For plant sterols, foods must contain .65 g/serving; for supplements the required amount rises to 1.7 g/serving (3.4 g/day). Bayer's Heart Advantage has .4 g/serving, a total of .8 g/day according to recommended dosing.

Similarly, the FDA requires a food or supplement product to contain .4 g calcium and a label to note that more than 2 g/day conveys no added benefits. In its warning letter to Bayer, FDA notes its Women's Low-Dose Aspirin + Calcium contains an undisclosed amount of calcium carbonate but a total 300 mg elemental calcium. Otherwise, Bayer's label statement on calcium and osteoporosis appears to include the requirements of the FDA approved claim (multiple risk factors, 2,000 g/day maximum benefit, etc.).

In addition, FDA seems to be uncomfortable with the combination of drug and supplement, noting the use of both Drug and Supplement Facts Panels on the products' packaging. It said the inclusion of aspirin and the use of drug claims render the entire product a drug. It said Bayer could market the supplement ingredients separately from aspirin, provided it ensures any claims used adhere to the FDA-approved health claims under 21 CFR 101.72 (calcium) and 21 CFR 101.83 (plant sterols).

FDA seems to be wary of drug-supplement combinations because it may falsely imply both the drug and the supplement ingredients involved have been approved via the agency's drug approval process. It has taken issue with such products in the past, although it has claimed it will take a case-by-case approach, rather than one of a blanket precedent. However, Dingell challenged Bayer on its launch of these products given the FDA's past disapproval of such combinations. He said Bayer should have sought pre-market approval for these products. He added his committee will continue to investigate Bayer on this matter despite the FDA actions.

Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research argued that "...the overuse or misuse of these aspirin-containing products can put consumers at risk for internal bleeding and other adverse events." She further noted that while FDA allows caalcium-osteoporosis claims, the use of the phrase "fighting" osteoporosis would require additional approval. She said the heart product similarly oversteps approved claim language by stating an effect on cholesterol instead of just coronary heart disease.

In defense of such combo products, Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), said combination dietary supplement-OTC drug products have a useful and important role to play in integrated healthcare and wellness, although he didn't specifically address the issue of pre-market approval for such products. "Our hope is that FDA will assist companies attempting to maneuver the regulatory challenges of developing products that combine these ingredients and meet the labeling and formulation requirements of both drugs and dietary supplements, as required by the law."

Mister explained in 1994, FDA stated in the Federal Register: "FDA does not believe that it would be appropriate to preclude such claims [health claims and OTC drug labeling] under all circumstances. Such claims may be permissible if a firm can demonstrate that dual claims can be made in a manner that will neither misbrand the product nor create a safety problem’ (59 Fed. Reg. 395, 419, January 4, 1994)."

He noted that statement has never been revoked. "Since then, FDA has issued a few warning letters addressing specific combinations of supplement and OTC drug ingredients, but has never publicly reversed its view that combination products with dual labeling can be developed that would satisfy the agency’s appropriate concerns for safety," he said. "It would be unfortunate if overly formalistic interpretations of labeling regulations carried the day and kept these beneficial products from consumers."

In various public statements, Bayer has said it is reviewing the FDA warning letters, but it stands behind the marketing of these products. It contends there is adequate warning and advice on the packaging. Heart Advantage was launched earlier this year (I saw an ad for it last night on CBS), but the apirin-calcium product has been on the market since 2002.

At this time, I am still awaiting Bayer's response to my specific questions about this situation.