Federal lawyers and Bayer Corp. are squaring off in federal court over whether the giant health care company has sufficient science to back up claims that a dietary supplement can support colon health.
Last week, attorneys in the Consumer Protection Branch of the U.S. Justice Department filed a motion requesting an order to show why Bayer should not be held in contempt for violating a 2007 order. The present case dates back to an investigation FTC launched in 2011.
A probiotic supplement marketed by Bayer, Phillips’ Colon Health, claims it is effective against constipation and diarrhea, as well as gas and bloating, despite the fact that the company “fails to possess any competent and reliable scientific evidence," government lawyers contend in court papers filed in the U.S. District Court for the District of New Jersey. The government lawyers said Bayer’s unsubstantiated claims violated a 2007 order that require the company to back up any claims about dietary supplements through competent and reliable scientific evidence.
The Justice Department brought the motion on behalf of FTC, which oversees advertising claims and regulates business practices to ensure that they are not anticompetitive, deceptive or unfair to consumers.
In the 30-page motion, which was filed with FTC’s assistance, the Justice Department asks the court to hold Bayer in contempt and assess a fine of USD $25,000 per day to coerce compliance with the 2007 order.
The government estimated consumers have spent hundreds of millions of dollars on the colon supplement, “luring consumers away from available alternatives." A bottle of 30 capsules retails for approximately $18, with each capsule reportedly containing 1.5 billion cells of a special formula comprising three strains of bacteria, according to court papers.
Tricia McKernan, a spokeswoman with Bayer, said the company intends to vigorously defend itself.
“Phillips’ Colon Health is a safe and beneficial probiotic product," she said in an emailed statement. “Bayer believes that the product’s benefits for consumers are fully substantiated and supported."
At issue is whether Bayer needed to conduct randomized, double blind human clinical trials in support of its claims for the particular strains of bacteria that are contained in the supplement. The government thinks so, relying on the expert opinion of a board-certified gastroenterologist and professor at Yale University School of Medicine, Loren Laine.
Comparing Bayer’s product to a placebo would distinguish the “placebo effect" from the apparent benefit of the supplement while randomly assigning participants to take the placebo and product ensures differences in the outcomes are attributed to the product under review, according to the government. The Justice Department also cited the importance of ensuring that neither the investigators nor the participants have knowledge concerning the identity of the patients taking the placebo and the product being studied.
“Otherwise, a patient’s knowledge of whether he is taking the active product or an inactive placebo can ‘dramatically influence’ how that person rates his symptoms," government lawyers said, “and an investigator’s knowledge of the same can not only affect her rating and recording of study outcomes, but also can result in her signaling to the patient whether he’s taking the product or placebo."
Responding to the motion, Bayer declared the government is requiring a standard of clinical evidence that generally applies to drugs but is not required for dietary supplements. The Council for Responsible Nutrition (CRN), a trade organization in Washington representing the dietary supplement industry, expressed the same opinion.
The 2007 settlement with FTC related to claims Bayer made in support of a different supplement, its WeightSmart line of One-A-Day vitamins. Government lawyers said Bayer agreed to pay a civil penalty of $3.2 million and consented to a permanent injunction that prohibited the company from making implied or express representation concerning “the benefits, performance or efficacy of any dietary supplement it markets or sells unless Bayer ‘possesses and relies upon competent and reliable scientific evidence that substantiates the representation’ at the time it makes the representation."
Bayer satisfied the scientific standard in connection with Phillips’ Colon Health, McKernan said. Government lawyers acknowledged Bayer provided to FTC nearly 100 non-duplicate scientific papers and several cover letters to back up its claims. But the government’s expert, Laine—the past chair of the American Gastroenterological Association—reviewed the literature and wasn’t satisfied Bayer met the “competent and reliable scientific evidence" standard, according to the Justice Department.
Bayer is expected to retain its own expert to rebut Laine and testify that the research is adequate to substantiate its claims.
Bayer “has cutting-edge genomic research supporting our structure-function claims," McKernan said. “Bayer therefore believes that this assertion by the FTC is contrary to law, the policy of the United States Food and Drug Administration and previous FTC Guidance."
Firms marketing dietary supplements are authorized under the Dietary Supplement and Health Education Act of 1994 (DSHEA) to make statements describing the role of a dietary ingredient or nutrient that is intended to impact the normal structure or function of the body, otherwise known as structure/function claims.
“Were the court to find Bayer didn’t have adequate substantiation for its structure/function claims, the industry would have reason for grave concern," said Marc Ullman, a New York lawyer whose clients include dietary supplement firms. “It calls into question … almost everybody’s substantiation."
Although claims in connection with dietary supplements must be backed by “competent and reliable scientific evidence," FTC’s standard can be satisfied through “a variety of rigorous and robust scientific studies", said Steve Mister, president and CEO of CRN, in an emailed statement to reporters.
“Requiring these claims to be supported by multiple RCTs [randomized controlled trials], without regard for other credible methods of analysis, would hold dietary supplements to unreasonable, inflexible and pharmaceutical-like standards," Mister said, “which contradicts how dietary supplements are defined and regulated under the law."
Setting a precedent
At least two of Bayer’s peers—other widely known multinational companies selling probiotic products—capitulated to FTC, agreeing to conduct human clinical trials in support of certain claims under settlements negotiated with the agency.
Three years ago, in what was the first FTC case that challenged advertising for probiotics, FTC resolved allegations that Nestle S.A. made deceptive advertising claims in connection with BOOST Kids Essentials, a nutritional drink for children between the ages of 1 and 13. Nestle was barred from representing that the product curtailed acute diarrhea in children or reduced illness-related absences from school unless the statements were non-misleading and another requirement was satisfied: Nestle produced “at least two adequate and well-controlled human clinical studies of" BOOST Kids Essentials or an equivalent product to substantiate its claims.
Just a few weeks later, in early 2011, FTC announced finalizing an order settling charges that Dannon Company Inc. overstated the health benefits of its Activia yogurt and DanActive Dairy drink. Dannon was prohibited from representing that the yogurt “relieves temporary irregularity or helps with slow intestinal transit time, unless the representation is non-misleading and conveys that eating three servings a day is required to obtain the benefit." The order carved out an exception that would authorize Dannon to make the above claims without including the three-servings-a-day caveat. The company would need to substantiate its statements with the same research required in the Nestle case: at least two human clinical studies.
“What Bayer may have been confronting here was a settlement with the FTC where the FTC was demanding two adequate and well controlled clinical trials to support claims," said a veteran lawyer who specializes in FDA and FTC law and agreed to speak on condition of anonymity. “It wouldn’t be surprising that the FTC would be asking the same from Bayer in a probiotic case especially."
Bayer may have refused to do so, the lawyer said, prompting the government to seek judicial relief.
The Justice Department asserted Bayer must substantiate its claims “based on clinical trials of Phillips’ Colon Health or a product comprised of the same combination of the same strains of bacteria."
“Studies done using products containing a different combination of bacterial strains than Phillips’ Colon Health do not qualify as substantiation for Bayer’s claims, because different combinations of ingredients can have different effects," government lawyers said.
Bayer could have 100 studies showing that two of the three bacteria strains contained in the probiotic supplement support the health-related claims while another 100 studies demonstrate support for claims related to the third strain of bacteria; yet “once you combine the three of them, the [government’s] position is there is no evidence whatsoever to support the science," said Rick Collins, a partner with the Mineola, New York-based law firm Collins Gann, McCloskey & Barry, whose practice areas include representation of sports nutrition companies in the dietary supplement industry.
“What if another brand wants to do a similar product with the same ingredients but a slightly different ratio of those ingredients?" Collins asked. “The implication is new double blind placebo-controlled studies with appropriate population and sample size would have to be initiated."
The cost to Bayer of conducting two human clinical trials to substantiate its probiotic claims could be around $300,000, said Douglas S. Kalman, director of Nutrition & Applied Clinical Trials with Miami Research Associates, a clinical research trial center. When factoring in state and federal tax credits that the company could obtain for the research, the costs would be significantly less, he said. Kalman, however, cautioned that costs of human clinical trials vary depending on a number of factors such as the type of population that is a target for the study, its duration and the number of visits study participants must make to a research lab or other facility.
Other companies selling probiotic products have either conducted human clinical trials or agreed to do so in support of certain claims. For instance, the results of a human study of 61 subjects conducted by Miami Research Associates on behalf of Ganeden Biotech were published in 2009 in the journal, BMC Gastroenterology. The research found that subjects who took the probiotic dietary supplement enjoyed a reduction in gastrointestinal symptoms.
Laine, the government’s expert in the case against Bayer, reviewed two human studies that have not been fully published. Government lawyers said neither study was adequate. That is because one studied participants who suffered from irritable bowel syndrome. The other study was insufficient, government lawyers said, because “participants were not enrolled based on the presence or absence of symptoms of constipation, diarrhea, and gas and bloating."
In television and print advertisements and on packaging, Bayer expressly characterized its product as a “probiotic supplement" that “helps defend against" the occasional constipation, diarrhea, and gas and bloating, government lawyers said. The Justice Department considered such statements express claims that were subject to the 2007 order.
At least one lawyer specializing in FDA and FTC regulatory matters, Ullman, views the express claims as “pretty mainstream structure/function claims" that DSHEA permits.
One of the questions squarely before the court is whether the science upon which Bayer relied is adequate under FTC law to support the express claims. Ullman said it is well accepted that dietary supplement firms don’t necessarily need human clinical trials to substantiate structure/function claims and can rely on other science to back them up.
Human clinical trials in support of a structure/function claim are the “exception, not the rule," said Ullman of the law firm Ullman, Shapiro & Ullman LLP. “Reliance on ingredient-based substantiation is commonplace; it is accepted practice in the industry.
The Justice Department further alleged Bayer’s colon product impliedly claims that it “prevents, cures, or treats constipation, diarrhea, and gas and bloating."
Although dietary supplements can be marketed in the United States without preapproval from FDA, they cannot make so-called drug or disease claims that they prevent, mitigate or treat a disease. Fourteen years ago, in a final rule distinguishing disease claims from permissible structure/function claims, FDA said it is acceptable to make a claim on a product label, “For relief of occasional constipation", but such a label should specify “the product is not intended to be used to treat chronic constipation, which may be a symptom of a serious disease."
McKernan said Bayer never made disease claims about its probiotic supplement.
Ullman expressed a different opinion. “The implied claims push if not cross the outer boundaries of structure/function claims into the realm of disease treatment claims," he said.
While FDA rather than FTC is responsible for taking enforcement action against supplement firms that make unlawful disease claims, a finding by the court that Bayer made such claims would likely subject them to a higher standard of substantiation: the need for human clinical trials.
FDA treats disease claims in connection with a dietary supplement as the marketing of an unapproved new drug. Six years ago, in warning letters sent to Bayer, FDA alleged that two separate aspirins marketed as a combination over-the-counter drug and dietary supplement product contained disease claims—rendering each product a drug.