Sen. Dick Durbin (D-IL) plans to introduce legislation to regulate dietary supplements more strictly. Seems the Senate has been unable to do much of anything. Maybe they can agree on some supplement bashing?

Food and drug attorney Justin Prochnow (Greenberg Traurig, Denver) comments on the issue:

Once again, Senator Durbin has taken a run at introducing legislation designed to restrict dietary supplements. The amount of inaccuracies and lack of knowledge in the press release is shocking. Durbin lumps 2 oz energy shots, which are clearly supplements, with other products. Does he really think 2 oz replaces a normal serving? He indicates that dietary supplements contain potentially unsafe additives right next to beverages that have undergone FDA approval. FDA approval? Is that a new regulation I am unaware of? While additives in foods and beverages must be approved food additives or GRAS [generally recognized as safe], there is no requirement for FDA approval and many ingredients are self-affirmed GRAS without specifically FDA approval.

As I see it, the issue is not the need for more regulations — the FDA just needs to enforce the regulations that are already on the books.

I would like to believe Durbin really has public health and safety in mind, but frankly, I don’t. The press release (as usual) says the bill is “Designed to Protect Consumers of Dietary Supplements.” FYI, Senator, proper use of pharmaceutical drugs kills around 300,000 Americans each year and injures two million more. (“proper use” meaning this doesn’t include the additional numerous cases of overdose, suicides and accidents such as pharmacy or physician error). By comparison, supplements are responsible for fewer deaths, meaning ZERO, Senator. Of course, the Senator should know this. It’s hardly new. In 1971 (!) the cost of caring for victims of drug toxicity accounted for 1/7 of hospital stays at a cost of $300 million a year. In 1998 the Journal of the AMA reported that over 2 million patients had a serious adverse drug reaction (ADR) and the 106,000 deaths put drug reactions between the 4th and 6th leading causes of death among all Americans. It seems obvious that drug toxicity, not supplement labeling, is a serious problem we need to address. Instead, Durbin is again demonizing supplements, especially “energy drinks” and “shots.”

Ironically, the specific supplements he takes aim at are energy products, which owe their activity to the most often-consumed and most socially sanctioned drug in the world — caffeine.

Durbin’s press release is HERE

This isn’t a first for the good (for business) doctor. The peer-reviewed (and shame on the reviewers) journal Anesthesia and Analesia had to retract 10 papers authored by Reuben. Another 21 Reuben articles were apparently also fabricated according to London’s The Day. Reuben received nearly a half million from Pfizer, which I guess he has to give back, and possibly pay a $250,000 fine on top of that. Maybe even jail time.

But for Pfizer and the other companies that got rave reviews from “ethical research,” nothing. Bextra and Vioxx were also beneficiaries of Reuben’s fairy tale “research.” But these drug companies are not treated as conspirators. They’re “victims” of this fraud. Coverage in The Day fills in the details.

Reuben’s studies, five of which were funded by Pfizer, had bolstered claims about the post-surgery effectiveness of such painkillers as Pfizer’s Celebrex and Merck’s Vioxx.

Reuben’s attorneys said a bipolar disorder with “alternating periods of mania and depression fueled his misconduct.”

Oh poor guy. I’m sure we can all understand how depression could make someone want to fake dozens of scientific articles. No, we can’t. That’s a BS defense.

Meanwhile, these bogus “research studies” have been used to bolster claims of effectiveness for Celebrex and other drugs, as the public is fed the fiction that we have the best research in the world and the safest and most effective drugs. Yes, we have the best research results money can buy, and the best “approving for dollars” system too.

This corporate medical/scientific corruption hurts us all, and the media is only too happy to trot out the results of these “studies” while lapping up billions in pharma advertising.

And it’s not like this is new. Before this “biggest drug research fraud case in history,” there was the former biggest in 1989 when NJ physician Robert Fogari pled guilty to taking $2 million from drug companies for investigational new drug research that he never conducted. Fogari “investigated” new drugs for nine drug companies including Ciba-Geigy, Johnson & Johnson, Warner-Lambert, Pfizer, Upjohn, Syntex, and Merck, Sharp & Dohme. Fogari had his employees list persons who were not in the study and make up patients. He failed to do the urine, stool and blood tests and forged signatures of radiologists and others. The doctor also failed to report the deaths of two
patients in the “study” in order to “maintain a favorable impression” with the drug companies who hired him. At least the deaths were presumably not caused by the drugs they didn’t take as a part of the study they weren’t in that never took place.

Fogari admits he did not conduct any legitimate research during the whole eight year period.

A year earlier, Constantine Kostas admitted that of the 85 subjects in his clinical trial of Cipro, only 15 had actually been given Cipro. I suppose it hardly matters, since Kostas also faked the results of lab tests and examinations that never took place.

All of this is especially irksome to those of us who have endured Big Pharma’s war on herbs and supplements. How many of the so-called “research studies” on herbs funded by big pharma are also bogus? It’s easy to find such “studies” in which the patients chosen were inappropriate, or the protocol designed in ways that appear destined to fail. Indeed, “failure” of an alternative medicine is exactly what the drug companies want to see.

In a recent BBC article (hat tip to Ed Smith of Herb Pharm for noting this) Prince Charles is quoted as saying “herbal medicine must be regulated.” Here in the United States, we often hear legislators and especially FDA officials calling for stricter regulation of herbal products and other dietary supplements. So my first reaction to the BBC article was “oh, no! The orthodox medical establishment has gotten to Prince Charles.” I even wondered if his opinion was colored by the fact that he is now in the herbal medicine business with his own herbal product line.

Prince Charles has been a consistent supporter of alternative medicine, and made a special appearance by video at the Columbia medical school course on botanical medicine. The Prince has been a consistent supporter of homeopathy and traditional herbal remedies. So this seemed like a bit of a betrayal of his former position.

On further thought, though, I had to reflect on the drama surrounding regulation of herbal products and nutritional products by the European Union. The “drama” featured a clash of different regulatory approaches employed by Great Britain and Germany. In Germany, nutritional and herbal products are regulated as drugs, and the German position has been adamantly in support of the entire world treating these products as such.

The British approach on the other hand, has been to allow truthful claims about those products that have been used as “traditional remedies” for medicinal purposes. So, for example, the herb feverfew, when sold in the UK, could bear labeling that stated “traditionally used for fever” or “traditionally used for headache.” Whether or not modern scientists or doctors agree that a particular herb has scientific merit for a specific condition, the UK approach was to allow claims based on historical use and experiential evidence (as long as the product is considered safe).

The German approach, much closer to the sentiments of American medical authorities and regulators, is that a substance must be proven to government officials as being safe and effective before it can be marketed with claims for particular purpose.

That may sound like a fine idea but there are a number of problems with it. The most commonly cited problem is that nutritional products are not patentable, which makes it virtually impossible to spend possibly hundreds of millions of dollars to prove their effectiveness. Furthermore, almost none of the current over-the-counter drugs, like aspirin, acetaminophen, cough syrups, astringents etc, have been subjected to that much scrutiny. Plus, many herbs and nutrients are best suited as preventive medicines for maintaining optimal health. This is exceedingly difficult to prove in clinical trials, because humans don’t have standardized diets or lifestyles. Finally, current regulations and most of the world discriminate against complex medicinal agents, preferring the simplicity of a mono substance synthetic chemical.

We’re still looking for something directly from Prince Charles explaining his position in calling for increased regulation and how that fits with his support for alternative medicine. Stay tuned.

Safety of Green Tea Extracts : A Systematic Review by the US Pharmacopeia.
Drug Saf. 2008;31(6):469-84.. Sarma DN, Barrett ML, Chavez ML, Gardiner P, Ko R, Mahady GB, Marles RJ, Pellicore LS, Giancaspro GI, Low Dog T.

Green tea [Camellia sinensis (L.) Kuntze] is the fourth most commonly used dietary supplement in the US. Recently, regulatory agencies in France and Spain suspended market authorization of a weight-loss product containing green tea extract because of hepatotoxicity concerns. This was followed by publication of adverse event case reports involving green tea products. In response, the US Pharmacopeia (USP) Dietary Supplement Information Expert Committee (DSI EC) systematically reviewed the safety information for green tea products in order to re-evaluate the current safety class to which these products are assigned. DSI EC searched PubMed (January 1966-June 2007) and EMBASE (January 1988-June 2007) for clinical case reports and animal pharmacological or toxicological information. Reports were also obtained from a diverse range of other sources, including published reviews, the US FDA MedWatch programme, USP’s MEDMARX((R)) adverse event reporting system, the Australian Therapeutic Goods Administration, the UK Medicines and Healthcare products Regulatory Agency, and Health Canada’s Canadian Adverse Drug Reaction Monitoring Program. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. In addition, the Committee analysed information concerning historical use, regulatory status, and current extent of use of green tea products. A total of 216 case reports on green tea products were analysed, including 34 reports concerning liver damage. Twenty-seven reports pertaining to liver damage were categorized as possible causality and seven as probable causality. Clinical pharmacokinetic and animal toxicological information indicated that consumption of green tea concentrated extracts on an empty stomach is more likely to lead to adverse effects than consumption in the fed state. Based on this safety review, the DSI EC determined that when dietary supplement products containing green tea extracts are used and formulated appropriately the Committee is unaware of significant safety issues that would prohibit monograph development, provided a caution statement is included in the labelling section. Following this decision, USP’s DSI ECs may develop monographs for green tea extracts, and USP may offer its verification programmes related to that dietary ingredient.

the health minister of the South American nation of Guyana is becoming concerned about the “growing power and influence of alternative medical practitioners” and is seeking to rein in some of the “more exaggerated claims.” The Guyana Association of Alternative Medicine shares some of those concerns, and official medical institutions have they “uneasy coexistence with this relatively new branch.”

Health Minister Leslie Ramsammy said the time has come not only
to sit down with the subsector and look at it holistically, but
also to draft modern laws to ensure that it operates in the
public’s interest. That is not exactly the case right now.
“Some of the herbalists have invoked a divine right to practice
and heal people. Others have had two weeks’ training or have read
some literature and started to practice, but it is obvious that we
have to do better than that,” he said.

[J]oint teams from the association and the ministry are
working on draft laws to go before parliament. One requirement
would stipulate that herbalists selling medicine must clearly list
the ingredients in much the same way that conventional
pharmaceutical firms are mandated to do.

A framework for self-regulation is also being worked out and a
lobby is emerging from the health faculty of the University of
Guyana to design courses that would properly train and certify
alternative practitioners, mostly to satisfy the anxieties of the
public.

The CGMPs for dietary supplements do not apply to dietary ingredient manufacturers, labelers, packers and those who hold dietary ingredients unless and only if a dietary ingredient is sold in bulk and then repackaged and, without further processing, is sold as a single component dietary supplement. If the latter occurs, the dietary ingredient supplier, whether in the United States or not, is subject to these cGMPs. Therefore, an ingredient supplier has a duty to find out from its purchaser the intended use of the dietary ingredient. The term “dietary ingredient” has been replaced by “component” throughout the final regulation , also called a Final Rule. The preamble (discussion) of the 70 page regulation is about 750 pages.

The cGMP for dietary supplements will be legally binding on those involved as manufacturers, packers, labelers and holders no sooner than 12 months after the federal regulation is published in the Federal Register. The federal regulation is expected to be published in the Federal Register tomorrow, Monday, June 25, 2007. For most dietary supplement companies, the compliance date will be June 25, 2009.

The Final Rule for CGMPS for dietary supplements was published today in the Federal Register at page 34, 712. The preamble (discussion of the Final Rule which is the actual federal regulation) is found at pages 34, 712 through 34,942 which is 230 pages. The actual regulation is only 16 pages in length and will be cited as 21 CFR Part 111. For very small companies, i.e. those with 20 employees or less, the compliance date is June 25, 2010.
The new cGMPs for dietary supplements will constitute Part 111 of 21 CFR. A violation of Part 111 is an act of adulteration by the person who is responsible for the act in question.

The FDA , by Interim Final Regulation published in the Federal Register on Monday, June 25, 2007, established a procedure for an industry company to request an exemption from the newly issued federal cGMP regulation for dietary supplements.,21 CFR 111..75 (a)(1 ) that compels a manufacturer to conduct at least one test to verify the identity of 100% of alls incoming dietary ingredient ( now called a component). Of course, the exemption does not apply until the Compliance Date for all of the cGMPs with respect to your company.

21 CFR 111.1 (b) clearly states that the cGMPs that apply to the “holding” (i.e. storage) of dietary supplements do NOT apply if “you are holding those dietary supplements at a retail establishment for the sole purpose of direct retail sale to individual consumers.” “Holding ” is not defined by these regulations.

(June 22, 2007) — The U.S. Food and Drug Administration (FDA) has posted its final rule on current good manufacturing practice (cGMP) for dietary supplements at its website and will soon publish the rule in the Federal Register. The agency has simultaneously posted a related interim final rule that allows for submission to, and review by, FDA of an alternative to required 100-percent identity testing of dietary ingredient, as discussed within the cGMP itself, provided certain conditions are met. These documents are on the FDA’s website HERE and HERE

Additional information is at FDA’s home page.

Since the Dietary Supplement Health and Education Act (DSHEA) was passed in 1994, companies that manufacture, pack, label or hold dietary supplements have been required to conform to conventional food cGMP. The American Herbal Products Association (AHPA) and its members in 1995 joined with numerous other industry groups to request that FDA establish a higher standard for the dietary supplement industry. In the intervening years AHPA has maintained an active role in communicating with FDA to ensure that cGMP for supplements are “appropriate and necessary,” and has expressed concerns that FDA has often lapsed in its responsibility to enforce the existing cGMP.

FDA’s announcement of the completion of its rulemaking process came this morning during a teleconference with industry stakeholders, including AHPA. FDA representatives on the call included Dr. Robert Brackett, Director of the Center for Food Safety and Applied Nutrition; Dr. Vasilios Frankos, Director of the Division of Dietary Supplements Programs; Dr. Mary Poos, a Senior Science Policy Analyst in FDA’s Office of External Relations; Brad Williams, also of the Division of Dietary Supplements Programs; and Jarilyn Dupont, Directory of Regulatory Policy in FDA’s Office of Policy and Planning.

Dr. Brackett noted that the publication of this rule is a “significant accomplishment” in FDA’s food safety efforts, and that “consumers should have greater confidence” in the quality of dietary supplements in the U.S. market. Dr. Frankos added that the final rule is written in a manner that is intended to provide flexibility to manufacturers without lessening their ultimate responsibility to meet all label claims and prevent product adulteration.

Key elements of the final rule include:

• The final rule is relevant only to dietary supplements, and not to dietary ingredients. This is a more narrow scope than was addressed in FDA’s proposed rule in 2003.
• The rule is relevant to all dietary supplements sold or offered for sale in the United States, so that even foreign firms will be required to meet the new manufacturing standards.
• Very small companies (with less than 20 employees) will have three years to come into compliance with the rule while small companies (less than 500 employees) will have two years and larger firms must comply within one year
•   Every dietary ingredient used in a dietary supplement will be required to meet “100-percent identity testing,” such that manufacturers will be required to “conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient.” Manufacturers will also be required to “confirm the identity of other components.”
• There will be no requirement for providing an expiration date on dietary supplements, but companies that use such dating will need to have supporting data.
• FDA will “exercise enforcement discretion” with regard to products made by practitioners, such as acupuncturists and herbalists, who are “adequately trained in their profession,” and who use the products that they make in a “one-on-one consultation.”
• The final rule is not applicable to retailers of dietary supplements.

“It is too soon to know how well FDA incorporated the comments submitted by industry to the 2003 proposed rule, or to completely understand the economic implications of the final rule,” commented AHPA’s president, Michael McGuffin. Noting that AHPA’s staff will be studying the rule in great detail, McGuffin also stated, “I encourage all AHPA members to review the rule promptly and to communicate your thoughts to me at your earliest opportunity.” McGuffin can be reached at mmcguffin@ahpa.org.

Besides, a supplement manufacturer has no right to ask for a customer’s medical records, to see if she already had a health condition or risk factor that might explain the apparent reaction to a supplement. Marketers of supplements simply can’t fully investigate complaints, which may or may not be related in any way to the supplement. I’m reminded of the infamous case of a fatality attributed by the Texas Health Department to an ephedra supplement. Yes, the ephedra supplement user died, but the coroner blamed the knife wound. In another “ephedra fatality” it was probably the extreme blood alcohol coupled with the head on auto collision. Chaparral was said to be so dangerous it had caused a rash of liver failures. There have been none before or since. Same with kava. And scullcap, that turned out to be germander, itself probably innocent. Again, no problems before or since.

Maury Silverman, a literature researcher and staunch supporter of supplements argued unsuccessfully to have the language of the new law require the disclosure of simultaneous drug use, which may better explain the “adverse event”. For example, if someone takes an herbal supplement and a Tylenol, seriously, which one is more likely to have caused that liver toxicity?