As FDA continues to inspect dietary supplement manufacturers under the new CGMP framework, it is clear that many manufacturers share similar deficiencies.  Recent FDA warning letters show that many manufacturers are still struggling with structure function claims, the required pre- and post-production qualitative and quantitative testing requirements, and strong quality control units that have the necessary authority and resources needed to comport with CGMPs.  (See, e.g., here, here, here, here, here, and here.)  When coupled with recent administrative guidance suggesting FDA may resort to reprimanding non-complying firms under the Park Doctrine, which imposes strict criminal liability for non-compliance with CGMPs, it is imperative that dietary supplement firms understand the potential consequences arising from serious CGMP violations.

Indeed, last year FDA sent a letter to Senator Charles Grassley (R-IA) explaining its intention to reintroduce the possibility of imposing criminal charges for misdemeanor violations of the Federal Food, Drug and Cosmetic Act (“FFDCA”) under the Parks Doctrine.  The Park Doctrine imposes strict liability, which means that the violating firm’s senior management need not have intent or knowledge of the violations to be found guilty.  Therefore, given FDA’s publicly stated intention of imposing harsher punishments for CGMP non-compliance, are future violations similar to those recorded thus far likely to result in criminal sanctions under the Park Doctrine?

The Park Doctrine is derived from United States v. Park, 421 U.S. 628 (1975), a landmark case decided by the Supreme Court.  In Parks, the president of Acme Markets, Inc., a large national food retailer, was convicted of violating sections of FFDCA for failing to sufficiently rectify unsanitary conditions at some of Acme’s warehouses, and for allowing adulterated food to be distributed in interstate commerce.  The Court reasoned that “[t]he requirements of foresight and vigilance imposed on responsible corporate agents are beyond question demanding, and perhaps onerous, but they are no more stringent than the public has a right to expect of those who voluntarily assume positions of authority in business enterprises whose services and products affect the health and well-being of the public that supports them.” Parks, 421 U.S. at 672.  A dietary supplement is considered adulterated if it is prepared, packed or held in conditions that do not comply with CGMPs, or if it contain poisonous or unsafe ingredients.  21 U.S.C.A. 342.

While FDA has enumerated several “serious” violations of FFDCA during routine CGMP audits, the severity of the violations found do not necessarily pose a serious public health risk as seen in Parks.  For example, FDA’s recent warning letter to Gaspari Nutrition cites several deficiencies in the company’s customer complaint recording procedures.  While the absence of customer complaint recordation procedures may (substantially) delay the recall of an adulterated dietary supplement product that poses a public health risk, it is not aconduct that is necessarily an imminent public health risk.

In fact, the majority of violations found in dietary supplement firms—as recorded in FDA’s published warning letters—stem from a lack of documentation, validation, or pre- and post-production testing.  In Parks, however, the violations were more obviously deleterious; FDA inspectors found chronic rodent infestations in some of Acme’s warehouses.  However, this is not to say that deficiencies in documentation, validation, and testing cannot result in the manufacture or distribution of dietary supplements that pose a public health risk.  On the contrary, such deficiencies may simply be telltale indicators of more substantive public health risks.  For example, if a dietary supplement firm cannot confirm the identity or purity of an ingredient through documentation, it is logically plausible to conclude that the dietary supplement may contain ingredients that are injurious to public health.

Dietary supplements that are processed in operations that do not comport with CGMPs are more likely to be contaminated by virtue of the fact that such operations lack the necessary infrastructure and procedural controls necessary to prevent cross-contamination and adulteration.  Smaller dietary supplement firms are less likely to have made the necessary investments in air handling and water purification systems, both of which are potential sources of adulteration.  If a cleaning procedure is not validated though quantitative testing, how can the manufacturer verify that the equipment has been sufficiently cleaned to prevent potential microbial growth or product cross-contamination?  To be sure, firms that lack validated operating procedures risk improperly cleaning equipment and facilities without sufficiently eliminating the potential for adulteration.

Despite these deficiencies, anecdotal consensus suggests that any future Parks Doctrine enforcement will stem from gross violations of FFDCA and CGMPs that are so pervasive that they pose a substantial and imminent risk to public health.  And, using Parks’ factual circumstances as a guide, habitual or repeated violations will likely be a prerequisite for a Parks Doctrine prosecution.  From a procedural vantage, if FDA intends to pursue criminal sanctions under the Park Doctrine, it must notify its Office of Criminal Investigations accordingly, which is then required to conduct further due diligence.  Unfortunately, FDA has not supplied a bright-line rule articulating what kinds of violations will warrant criminal sanctions.  Instead, firms are left with a series of factors, which includes repeated violations and illegal conduct, inter alia.

Although the likelihood of FDA imposing criminal sanctions to owners and senior decision-makers of dietary supplement firms for minor violations of CGMPs is unlikely, repeated violations that engender public health risks will certainly be candidates for the draconian consequences that arise from the Parks Doctrine.  Accordingly, it is in the dietary supplement industry’s best interest to adopt super-adequate quality control and quality assurance protocols.  Instead of waiting for FDA’s inexorable audit, dietary supplement firms should be conducting regular internal audits to ensure compliance with CGMPs and other relevant regulatory rules.  Such measures will engender good will with consumers of dietary supplement products as well as government agencies.

Shafiel A. Karim earned a B.A. from California State University, Fullerton and an M.A. from California State University, Long Beach.  He is currently a J.D./M.B.A. candidate at Southwestern University School of Law and the Peter F. Drucker and Masatoshi Ito School of Management at Claremont Graduate University.

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The purpose of the letter is stated as to “address the significant public health problems posed by products that are marketed as dietary supplements but that contain the same active ingredients as FDA-approved drugs, analogs of the active ingredients in FDA-approved drugs, or other compounds, such as novel synthetic steroids, that do not qualify as dietary ingredients.”

The letter states that the FDA has received numerous reports of serious adverse events associated with consumer use of those FDA-approved ingredients, which are generally undeclared in the labeling, that are being included in dietary supplements without warning to consumers. These adverse events include strokes, acute liver injury, kidney failure, pulmonary embolisms and death.

The FDA has been investigating supplements in order to discover whether or not they include ingredients that are deemed to be FDA-approved drugs. The areas in which the FDA found the highest rate of products marketed as dietary supplements but containing hidden ingredients include products for weight loss, sexual enhancement and body building. This includes a recall of more than 70 products marketed for sexual enhancement, 40 products marketed for weight loss and more than 80 products marketed for body building.

Although warning letters and recalls have been the primary source of action by the FDA, the letter states that the government may initiate criminal investigations to hold accountable those who violate the Federal Food, Drug, and Cosmetic Act and endanger the public. The letter makes sure to point out that individuals, not just companies, can also be brought up on charges when it states “Responsible individuals, even if the individual did not participate in, encourage, or have personal knowledge of the violation, can be criminally prosecuted under the Act.”

The FDA’s recommendation in this letter is that all firms that manufacture, import, distribute, or sell dietary supplements understand and investigate their full supply chain and review their manufacturing and quality assurance activities to ensure the lawfulness, quality and safety of their products. The FDA also encourages the industry to report any suspected tainted supplements and has offered an anonymous reporting method.

The FDA is hoping that this letter is spread widely throughout the industry in order to eradicate the use of chemicals regulated as drugs in nutritional supplements. It is also seeking continued input from people within the industry to help strategize a way to combat this problem.

To read the letter, click here.

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Peter Quinter of Becker & Poliakoff

Guest Post from The Customs and International Trade Law Blog

The U.S. Food and Drug Administration recently issued several warning letters to prominent food and drink companies regarding false claims displayed on their food and drink products, including those marketed to children.  Some food products brazenly claim to increase a person’s immune system, reduce the chance of getting a cold, or even cure cancer.  Are they really believable?

The Obama Administration has taken a more aggressive posture to attempt to reduce the obesity of Americans, especially children.  There is a direct connection between what we eat and our health.  Remember the saying ”You are what you eat”?   Dr. Margaret Hamburg, the new FDA Commissioner, announced in a March 3, 2010 letter to food companies:

I have made improving the scientific accuracy and usefulness of food labeling one of my priorities…It is clear to me as a working mother that the use of front of pack nutrition symbols and other claims can be helpful to busyy shoppers who are often pressed for time in making their food selections.

In a typical Warning Letter to one of the worlds’ largest food companies, Nestle, in a December 4, 2009, the FDA complained about Juicy Juice All Natural 100% Juice Grape products.  The FDA alleged that the product was misbranded because the lables were misleading in that the label was designed to imply that the producct is 100% grape juice when it truly was not.

The FDA regulations regarding food, including drinks, are complex.  True and accurate health claims are allowed on certain food products under specific circumstances, according to the FDA guidance.  Hopefully, the food industry will be more responsible, and if not, I encourage Commissioner Hamburg to pursue civil penalties against companies and the corporate officers of those companies who deceive the public. 

A discussion about health claims on food products and how to respond to FDA Warning Letters will take place on June 3, 2010 in Miami, at a seminar entitled “Importing Food Products in Compliance with FDA and U.S. Customs Rules“. 

In solidarity with FDA Commissioner Hamburg, I am a working Dad, and I don’t like to be lied to either!

Thanks Peter!  -Ed.

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Don Witters of the FDA Center for Devices and Radiological Health (CDRH) said the agency’s goal is to achieve safe, secure, and reliable deployments of wireless technology in health care.  As a result, the FDA more interested in the iPhone use by licensed medical professionals.  Mobihealthnews.com reports that Witters has defined a medical device as:

“…an implementation, product, apparatus or other component or accessory, which is used in the diagnosis, cure, mitigation, treatment, prevention of disease or effects any structure of the body–that could actually include some information technologies and performance technologies–but usually something that is performed on the patient, touches the patient or is performed between physician and patient.”

Can an iPhone achieve many or all of these uses and purposes?  Yes. It appears that an iPhone loaded with the proper apps is indeed a medical device of some sort.

If that’s the case, how should the FDA get involved in regulating the device? Witters said the FDA’s role is “to provide some reasonable assurance of safety and effectiveness in medical devices marketed in the U.S.”

mHealth apps developers as well as wireless medical device makers should contact the FDA to provide their views about how this emerging industry should be regulated.  For questions on this subject, or to provide an opinion, contact the FDA’s CDRH.  As regulations and roles are defined and categorized, so too will laws emerge regarding mobile devices and their medical use.

This post courtesy of The AppsLawBlog.  Come visit us here.

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To understand why Sen. John McCain introduced a bill on dietary supplements, read the press releases. The legislation announced Feb. 3  addresses public safety, but mostly it’s about the reputation and revenue of professional and Olympic sports.

The evidence: McCain says in the release that “a little over a year ago the NFL suspended six players, including two players from one of the teams competing this Sunday, for violating the league’s anti-doping policy.  Several of the players were surprised that they tested positive for a banned substance because they used a dietary supplement they believed to be safe and legal.”

McCain ends the release, “It is my hope that this legislation will ensure that all Americans, including athletes, have all the information necessary to make informed decision when choosing whether to use a dietary supplement, and that the FDA has the ability to remove any harmful dietary supplements from the market.”

What organization was first to endorse the legislation? Major League Baseball. Commissioner Bud Selig issued a statement supporting the bill and MLB.com reported on McCain’s announcement of the legislation.

Next on board: The U.S. Anti-Doping Agency, which issued a press release with an affiliated group, Supplement Safety Now. Its members include Major League Baseball, NFL, NBA, NHL, PGA, NCAA and other national sports organizations. All are powerful organizations inside and outside Washington. And they share a complaint: Their athletes have been unwitting victims of mislabeled supplements that caused disqualifications and suspensions.

In other words, the products were bad for business. The groups want to arm the FDA with the data to monitor supplements and the power to yank immediately the detrimental ones off the shelf. They found an ally in McCain, whose 2008 presidential campaign received substantial financial support from athletes and others in pro sports, ESPN reports.

The initial response from groups representing supplement makers and marketers was tepid. “Though we have not yet examined this bill completely, it places new burdens on dietary supplements that are not required for any other class of food,” Michael McGuffin, president of the American Herbal Products Association said the third paragraph of a press release.

The last sentence of the third paragraph of a press release from the Council for Responsible Nutrition quotes CEO Steve Mister as saying, “The best way to help consumers is through collaborative efforts with industry, government and other stakeholders, such as USADA, to implement the current laws, to provide more resources and funding to FDA, and to pass the food safety bill, which already includes many of these provisions.”

As the bill moves from the headlines to the sidelines, look for an intense lobbying effort by sports organizations. Supplement-related scandals have hurt their reputations and wallets. They see a solution in increased federal action and will push hard for that.

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Marketers of nutritional supplements often complain that they do not know what the FDA wants. Even after the agency sends a warning letter about misleading claims and advertising, its staff does not explain what would fall within the rules. That’s the reality; the FDA will tell you what’s wrong, not what’s right.

Through warning letters, the agency provides insight into how a marketer can fall afoul of the rules. Companies that examine why their competitors get chastised can apply the lessons to their Web sites, catalogs, labels and the like.  Washington attorney Ivan Wasserman looked at the 73 letters issued in 2009 (way, way up from 44 in 2008) and found that 72 related to claims on Web sites. Six involved claims made in metatags.

Lesson #1: The FDA is surfing the Web, checking not just product descriptions and benefits, but Googling for questionable SEO/SEM.

Wasserman’s list would rank the letters by claim problems in this order:

• Drug and disease claims: 72
• H1N1 virus claims: 37
• Other drug and disease claims: 20
• Heart disease and cardiovascular claims: 11
• Diabetes claims: 8
• Cold and flu claims (not H1N1): 8
• Cancer claims: 8

Lesson #2: The medical emergency that makes the most headlines gets the greatest scrutiny. In 2009, that was H1N1.

The FDA also sent 12 warnings letters related to claims made on labels and product labeling. Some of these may have echoed what was published on Web sites as manufacturers compounded their marketing errors.

Lesson#3: The FDA reads labels in the stores and on packages sent by mail. Adding an asterisked disclaimer to language on a label is no protection.

The FDA lived up to its announced commitment of greater enforcement and more scrutiny of the supplement industry. The agency could top the century mark in warning letters this year. Companies that have not recently reviewed their sites and labels would be wise to do so now before the mail carrier brings bad news.

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Jin Hua Qing Gan Fang made in lab.

The rules are different here in the United States. Hyde Park Holistic Center in Cincinnati recently received a warning letter from the Food & Drug Administration that read like many others having to do with nutritional supplements and the H1N1 virus. In China, though, the same admonishment could not be heard.

First, the FDA’s message to Hyde Park, which operates the Web site drdahlman.com: “The FDA has determined that your website offers a product for sale that is intended to diagnose, mitigate, prevent, treat or cure the H1N1 Flu Virus in people. This product has not been approved, cleared, or otherwise authorized by FDA for use in the diagnosis, mitigation. prevention, treatment, or cure of the H1N1 Flu Virus.”

The product in question is “4 Life Transfer Factor Plus Tri Factor,” which is sold in a password-protected store on the site. The product apparently supports immune system health or, as the FDA quotes Dr. Dahlman on one of his Web pages, “I firmly believe that use of this product will sufficiently upregulate your immune system and should be a primary part of your strategy to avoid the dangers of swine flu (H1N1 virus).”

It’s worth noting that Dr. Dahlman is not an M.D. His online biography says he is “a Chiropractic Physician with a degree in Nutrition, is Director of The Hyde Park Holistic Center in Cincinnati, Ohio and specializes in treatment of chronic health problems using nutritional, herbal and homeopathic therapies.”

If Dr. Dahlman were in China, he might have gotten praise rather than criticism. On Dec. 16, Chinese medical specialists said they had developed a Chinese herbal medication to treat H1N1. An article from the official Chinese news agency, Xinhua, quotes Wang Chen, president of Beijing’s Chaoyang Hospital, as saying the medication “can shorten patients’ fever period and improve their respiratory systems. Doctors have found no negative effects on patients who were treated in this way.”

The article adds that the herbal formula, called “Jin Hua Qing Gan Fang,” had been tested at 11 hospitals on 410 people who exhibited mild symptoms of H1N1. With success in treatment over a five-month period, the makers were seeking international patents.

The herbal medication is being positioned as a lower-cost alternative to Tamiflu, which WHO recommends for the treatment of H1N1.
Interestingly, the article quotes Cris Tunon, a senior officer at the WHO office in China, as saying that “WHO welcomes the clinical results.”

It’s unlikely the herbal medication would get the same greeting in the United States. The FDA has warned a number of companies with herbal products to stop making H1N1-related claims. Twice in 2009, the AHPA has advised against the use of dietary supplements to prevent or treat the flu. What happens when “Jin Hua” is marketed on American shores?

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The DEA’s actions are the equivalent of the carnival game, “Gopher Bash,” in which you take a soft, oversized mallet and bop gophers on the head when they emerge through holes in a playing surface. Even though you might strike all the gophers on the head, they keep popping up.

The DEA, FDA, nutritional supplement make, retailers and some athletes are all prisoners of this game. The DEA is trying to keep up with companies that synthesize new forms of steroids. In this instance, the agency declared off the shelves the following — Madol, boldione and 19-nor-4,9(10)-Androstadienedione. Because they are now considered anabolic steroids, retailers run the risk of arrest if they sell supplements containing those substances. Manufacturers and marketers have to find another way to market the substances, which may be available by prescription.

And as more substances make their way onto the DEA list, makers, distributors and stores will have to keep a close eye on what they should — and should not — be producing and stocking. And athletes have to watch what they keep on their shelves; they do not want to accidentally take a substance that was banned after they bought it.

Rather than notify the DEA of a problem substance, Travis Tygart, the head of the United States Anti-Doping Agency, said in a statement that, “We need a regulatory system capable of managing the magnitude of this problem, and that can stop those rogue supplement manufacturers who are meanwhile profiting.”

Who might that regulator be? The logical choice would be the federal  agency that oversees drugs and nutritional supplements. Whether the FDA wants the full responsibility is yet to be seen.

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As we have written before, makers of nutritional supplements should pay close attention to comments submitted to the FDA before February 2010. There will likely be advocates for warnings on all products that make a claim to support good health. The agency’s rules on search-based advertising for health products could encompass non-prescription items such as vitamins and muscle-building powders.

The ruckus in Washington on Nov. 12 and 13 stemmed from FDA warnings in March to drug makers that their search-based ads did not contain proper product warnings. Drug makers backed off their advertising, and the search-engine companies saw revenues plunge. Everyone hurried to Washington to ask the FDA for clarification.

Google presented a solution. It told the agency that sponsored links are now less transparent and relevant. Google then proposed a standard for product-claim sponsored links:

1. A headline that links to a product landing or home page.
2. A first line with the Web address for that page, followed by an information message.
3. A second line containing a safety warning that cannot be altered, followed by a link to a Web page with more details on the warning.

You can see sample Web pages by Google at Scribd. Other companies and public advocacy groups will likely have ideas on how to balance sales messages and product warnings. There may be software solutions such as pop-ups or Flash that could be integrated in order to present more information in an ad, but an elegant solution seems unlikely. Thus, the FDA could write rules that force makers and marketers of nutritional supplements to alter their sponsored links in ways they never wanted.

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Ever since receiving FDA notices about their advertising generated from Google and similar searches, drugmakers have toned down their language and sought clarity on what is allowed. The discussion has ramifications for makers of nutritional supplements, because they could be next to face agency scrutiny for every ad created in response to a search for acai, reseveratrol and the like.

On Nov. 12, drugmakers and search-engine advertising agencies participated in about 30 presentations before the FDA. The hearing room was so crowded that most people seeking an audience seat were turned away. Here are two media takes:

(Yahoo’s David) Zinman testified that this shift to generic ads that don’t mention a brand name has created “a world where users have less transparency” because the ads deprive searchers of critical information about the landing pages. (MediaPost)

“We don’t think companies should be responsible for policing the entire Internet for information about their products,” said Johnson & Johnson executive Elizabeth Forminard.  (Reuters)

The key word is transparency, but Yahoo’s Zinman has it backwards. The FDA’s criticism was based on a lack of transparency in the form of who could take the drugs and what warnings should consumers receive before they clicked on the link. The FDA sent the warning letters because there was not enough information in the search-generated ads.

Forminard should walk down to FTC offices and read the new rules on Web marketing that take effect on Dec. 1; J&J will be responsible for a significant portion of what is posted on the Internet about its products.

There is more testimony today (Nov. 13) and the FDA will continue listening through February 2010. Nutritional supplement makers should watch for when they get dragged into the discussion. We all know that some vitamins are contraindicated for some people; will that fact have to be disclosed in your Google ad?

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