CENTER FOR Science IN THE Public Interest The nonprofit publisher of Nutrition Action Healthletter
April 26, 2016
The Honorable Robert Califf, M.D. Commissioner Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Dear Commissioner Califf:
Re: Docket No. FDA-2015-P-0059-0003, Petition to Ban the Retail Distribution of Pure and Highly Concentrated Caffeine Sold in Powder Form as a Dietary Supplement.
The Center for Science in the Public Interest writes to supplement the Citizen Petition we submitted on December 9, 2014, seeking an immediate ban on the retail sale and distribution of pure caffeine products as dietary supplements. 1
In May 2014, 18-year-old Logan Stiner of Ohio died from an accidental overdose of powdered caffeine.2 In July 2014, 24-year-old Wade Sweatt died after ingesting caffeine powder the first time he used it. 3 A third death occurred in 2014 when a 39-year-old man ingested 12 grams of pure anhydrous caffeine.4 Just a teaspoon of powdered caffeine is equivalent to toughly 28 cups of coffee, 5 and the suggested "safe" dose is a scant 1132 to 1/16 of a teaspoon. 6 In December 2014 parents of both young men met with officials at the FDA's Center for Food Safety and Applied Nutrition. Senators Blumenthal, Brown, Durbin, Gillibrand, Markey, and Schumer, and later Senator Casey, also called on FDA to ban bulk sales of caffeine. 7
1 CSPI Petition to ban the retail distribution of pure and highly concentrated caffeine in powder form as a dietary supplement. Dec. 9, 2014. http://cspinet.org/new/Caffeine-petition-CSPI-12-9-2014.pdf. 2 Death of Teen Logan Stiner Puts Focus on Caffeine Powder Dangers (July 19, 2014), Associated Press, http://www .huffingtonpost. com/20 14/07 I 19 /logan-stiner-caffeine-pow n 5 60 177 5 .html (accessed Dec. 5, 2014). 3 National Public Radio. Potent powdered caffeine raises safety concerns. Jan. 2, 2015. http://www.npr.org/sections/health-shots/20 14112/31/371692640/potent-powdered-caffeine-raises-safety worries. 4 Seema B. Jabbar & Mark G. Hanly, Fatal Caffeine Overdose: A Case Report and Review of Literature, Am. J Forensic. Med. Pathol. 34:321-24 (2013). 5 The USDA nutrition database reports that one cup (8 oz.) of ground coffee contains 95 mg of caffeine: https :/ /ndb .nal. usda.gov /ndb/foods/showI 4 2 77. 6 See CSPI petition at 8 7 Comment from CSPI to FDA Docket No. FDA-2015-P-0059-0003. July 21, 2015. http://www.regulations.gov/#!documentDetail:D=FDA-2015-P-0059-0005. Teresa Bonner. "Sen. Casey to FDA: Ban sale ofpowdered caffeine," Feb. 2, 2015. http://www .pennlive.com/midstate/index.ssf/20 15/02/sen casey to fda ban sale of p.html
Litigation Office • The "t-.kadows Building • 5646 Milton Street, Suite 211 • Dallas, TX 75206 • tel2l4 827 2774 • h1x 214 827 2787 • W\Vw.cspinet.org Page2
In lieu of issuing a ban, in September 2015 FDA sent warning letters to five dietary supplement companies stating that higrJy concentrated caffeine has been associated with dangerous side effects in consumers, including deaths. 8 Those companies voluntarily removed pure powdered caffeine from their retail sites.
But pure caffeine in powdered (PPC), liquid (PLC), and now inhalable (I C) forms is still widely available for purchase online. CSPI recently conducted a basic internet search for pure caffeine products and found that at least fifteen online suppliers-a short list is below-are still selling products identical or similar to those that killed Logan Stiner, Wade Sweatt, and others.9 Thus, FDA's actions thus far are sorely inadequate to ensure consumer safety and prevent future deaths or other serious harm from highly concentrated (and inadequately labeled) forms of caffeine.
Through a simple (and non-exhaustive) Internet search for PPC, CSPI found five domestic suppliers that still sell PPC to retail consumers and ten international suppliers (based in Canada, the United Kingdom, India, and China) that ship to the United States. Through these suppliers, which areboth international and domestic, consumers have access to quantities of PPC ranging from 1Og to 1OOOkg. Packages containing 1Okg include enough caffeine to kill 500 people at a lethal dose of lOg-which is 25 times the level FDA cites for daily adult caffeine consumption to avoid "dangerous, negative effects"10-and cost less than $120. 11 Of the products we ordered, only a single company included a means by which consumers could measure a "safe" (1/32 tsp) dose ofPPC (not that simply enclosing a measuring spoon is an appropriate solution to the problem, as such spoons can be misplaced); nor do the labels sufficiently warn consumers that exceeding this extraordinarily small dose can result in death.
PPC is also available through online marketplace platforms, such as Ebay and its counterparts abroad, which is additional cause for concern, because accountability through these platforms is difficult to achieve. In contrast, a ban would clearly indicate to Ebay and other platform hosts that such products are illegal.
In sum, FDA's five letters appear to have ceased the sale of powdered caffeine at only the companies to which the agency addressed its letters. In the larger marketplace, sales of PPC remain commonplace, and the substance is still widely available. This compelling evidence demonstrates why a ban is the only step that will protect consumers from the hazards ofPPC. Moreover, a ban would prevent legal importation of this dangerous substance into the country from foreign suppliers.
8 U.S. Food and Drug Administration (FDA). Pure Powdered Caffeine. Sept. 9, 2015. http://www. fda. gov /food/ dietarysupplements/productsingredients/ucm46009 5 .htm. 9 It appears there may have been three additional known fatalities. See Sarah Kerrigan & Tania Lindsey, Fatal caffeine overdose: two case reports, Forensic Sci. Int. 153(1): 67-69 (Oct. 3, 2005); Seema B. Jabbar and Mark G. Hanly, Fatal Caffeine Overdose: A Case Report and Review of Literature, 34 Am J Forensic Med Pathol 321 (2013). 1°FDA Consumer Health Information. FDA to investigate added caffeine. May 2013. http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM350740.pdf. 11 Jabbar & Hanly, id. Page 3
Adding to the risks, PLC (which FDA did not address in its warning letters to companies selling powdered caffeine) is also marketed as a healthier, and even safer, alternative to energy drinks or regular coffee, with "no sugar, no added chemicals, no gut rot ... [and] without the "crash" or ups and downs caused by typical energy drinks." (Liquid Caffeine. com, see reference below). 12 Additionally, the product's label recommends a serving size in "pumps," but the product CSPI received was a pour-cap, which makes a recommended serving in pumps meaningless and thereby reduces a consumer's ability to measure a safe serving of the product.
From a supplier in Minnesota, we were able to obtain Purecaf, a gallon jug of caffeine in liquid form, which looks surprisingly like water, yet a single full measuring cup of the substance would be more than a lethal dose. The label indicates only that consumers should use it "sparingly." And from a supplier in South Korea came three small bottles of CafeDrops, a shockingly concentrated liquid caffeine-the largest, which is the size of small shampoo bottle, indicates it contains 9,000 mgs of caffeine, and has no serving size information on the label whatsoever except the instruction to drop some "amout'' [sic] and not to "overuse it."
Another PLC product, Kaffn8, markets itself to health-conscious people through its website, which mimics the hip aesthetic of an outdoor sporting-goods store. The home page of Ka:ffn8 shows a man kayaking on a calm lake in the early morning, and an entire section of its website called "Get Inspired," features a photo collage of happy people exercising, taking photos, playing music, etc. Nowhere does the website warn consumers that overdosing on the product can be lethal.
Kaffn8 comes with an "EZ-Dose" measuring bottle, which measures "one serving" of PLC to be 240 milliliters, or roughly equal to the caffeine in about 2-3 cups of coffee. This measurement and method is worrisome, because consumers are most familiar with dosing cups from taking cold medicines or cough syrups, where precision in serving size is not the difference between life and death. Many people take two or three times the recommended serving of such over-the-counter products to relieve symptoms. Some consumers might well misunderstand the suggested 240 milliliters of PLC to mean a minimum dose that could be increased two or three times without risk of harm.
12 CSPI purchased a bottle of Liquid Caffeine (pictures enclosed with this comment) that was advertised online to be I6 ounces, but had no net volume label on the actual product, which likely violates 2I C.F.R. § I Ol.I05(a), requiring that the principal display panel of a dietary supplement declare the net quantity of its contents. If"Liquid Caffeine" does not meet the exception for small businesses that have less than $50,000 in gross sales or less than $500,000 in gross business done (See 2I C.F.R. I01.36(h)(l)), it appears to violate these additional regulations: • 2I C.F.R. § I 0 I.36(b)(1 )(i) (requiring that the serving size of a dietary supplement be indicated under the heading "Supplement Facts" on its label); • 2I C.F .R. § I 0 I.3 6(b )(I )(ii) (requiring that a dietary supplement indicate the amount of servings per container); • 2I C.F.R. § I01.36(b)(2)(i) (requiring that a dietary supplement list the RDIIDRV for specific dietary ingredients (e.g., total calories, sugars, etc.)); • 2I C.F.R. § IOI.36(e) (providing the formatting requirements for the "Supplement Facts" table). Page4
Similarly, another PLC product, Cafe Drops, features a promotional video on its homepage, which shows two extremely tired people indiscriminately pouring (without measuring) PLC into water to wake up. Elsewhere on the website it recommends a serving size of200ml and a warning not to exceed 600ml in a day, which exceeds FDA's recommendation that adults consume no more than 400ml per day. More importantly, a dosing instrument to measure a 200ml serving is not included with the product, which increases the likelihood that consumers could improperly measure a safe dose.
IC is also emerging as a trendy way for young people to ingest pure caffeine. Yet FDA has sent warning letters to companies marketing inhalable caffeine indicating that the product has not been shown to be safe, as the safety data describes hazards from ingestion, not inhalation. 13
CSPI' s investigation produced the following, non-exhaustive list of current suppliers of PPC, PLC, and IC. (Hardcopy screen shots of the companies' products are enclosed.)
• Powder City, LLC. (American Company; PPC available in lOg, 50g, lOOg, 500g, lkg, 5kg) • NutriVita Shop- (American Company; PPC available in 50g, lOOg, 250g, 500g, lkg,2kg,5kg, 8kg, 10kg,25kg) • PureCaffeine.org- (American Company; PPC available in 1Og, 30g, 90g, 500g, 1 kg) • LuxNaturesSuppliers via Etsy.com- (American Company; PPC available in 1 oz) • Transcendence Nootropics- (American Company; PPC available; server down at time of access) • Flavor West- (American Company, PPC available in 1OOg, 250g, 500g, lkg) • TJM Resale's Synaptik Supplements & Ligand Solutions- (American Company; PPC available in lOOg, 250g, lkg, 5kg, lOkg, 25kg) • MyProtein.com- (UK Company, ships to USA; PPC available in 1OOg, 500g) • Bulk Powders- (UK Company, ships to USA; PPC available in lOOg, 500g, lkg) • Blackburn Distributions- (UK Company, ships to USA; PPC available in 1OOg, 250g,500g, lkg,2kg,5kg, lOkg, 15kg,20kg,40kg, 100kg,250kg, 500kg, lOOOkg) • Buy Caffeine- (UK Company, ships to USA; PPC available in 500g, lkg, 2kg, 5kg, lOkg, 15kg) • Durachem Distribution- (Canadian Company, ships to USA; PPC available in 250g,500g, lkg,2kg) • PureCaffeinePowder.com- (Canadian Company, ships to USA; PPC available in 250g, 500g, lkg, 2kg, and larger custom orders) • GBY.uk Supplements- (UK Company, ships to USA; PPC available at 250g, 500g, lkg, 5kg, 1Okg) • PureCaffeine.info- (UK Company, ships to USA; PPC available in 250 g, 500g, lkg,2kg,5kg, lOkg)
13 FDA Warning Letter to Breathable Foods, Inc. CEO, Thomas Hadfield. Mar. 5, 2012. http://www.fda.gov/ICECI/EnforcementActions/WamingLetters/2012/ucm294774.htm. in
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which FDA worked out solutions to reduce dosage errors in over-the-counter (OTC) pediatric cough/cold medicines: "Despite dosage instructions on packaging, the agency raised legitimate concerns that many consumers couldn 't determine the appropriate dose for children of various ages and weights and that the measuring devices provided with many of those products only contributed to confusion. So OTC manufacturers collaborated with FDA to develop clearer instructions, new measuring devices that accompany the products, and consumer education to teach parents how to appropriately medicate their children. That's what a responsible industry does. Similarly, marketers of pure powdered caffeine could develop packaging for their purified caffeine in single serve dosages if they want to sell it directly to consumers." (Emphasis added).
Thank you for your urgent consideration of further agency action, including a ban on sales of pure powdered caffeine and other appropriate restrictions on highly concentrated forms of caffeine that pose a risk to consumers of an unintentional, harmful overdose.
Sincerely,
Michael Jacobson, President
Laura MacCleery, Directory of Regulatory Affairs FDLI'S
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Pure Powdered Caffeine: Stakeholders Take Measure of FDA's Warning Letters
Brenda Seidman Seidman Regulatory Toxicology
Jay Sirois Consumer Healthcare Products Association
Rend AI-Mondhiry Council for Responsible Nutrition
Duffy MacKay Council for Responsible Nutrition
Laura MacC/eery Center for Science in the Public Interest
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0 0 0 0 Pure Powdered Caffeine: StakeholdersTake Measure of FDA'sWarning Letters By Brenda Seidman, Seidman Regulatory Toxicology, Jay Sirois, Consumer Healthcare Products Association, RendAI-Mondhiry, Council for ResponsibleNutrition, Duffy MacKay, Council for Responsible Nutrition and Laura Mace/eery, Center for Sciencein the Public Interest
I. INTRODUCTION TO THE COMPENDIUM
On August 27, 2015, the US Food and Drug Administration (FDA) issued Warning Letters to five companies 1 2 3 5 selling pure powdered bulk caffeine to consumers as a dietary supplement. • • A Each letter stated that the agency considers their product to be: "adulterated within the meaning of section 402(f)(l)(A)(i) of the Federal Food, Drug, and CosmeticAct (the Act) [2 1U.S. C.§ 342(f)(l )(A)(i)] becausethey are dietary supplements that present a significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling."
6 8 9 While this is not FDA's first caffeine action .7 or its first demonstration of concern, • it does highlight the agency's continuing concerns about this stimulatory substance, particularly when caffeine's use as a food product is promoted for use at levels it considers unsafe and/or promoted to vulnerable populations, such as
children and adolescents. Its concerns have related to caffeine-containing dietary supplements ~mdenergy 10 11 12 drinks (a group of products that are marketed both as supplements and conventional food) • • as well as 13 14 to other conventional food, including caffeine-containing confectionary. • 1 To promote discussion of the best approach to regulating powdered bulk caffeine, the volunteer editor of this compendium invited a number of stakeholders to share their views on the August 2015 action.
Participants in this issue of Policy Forum were asked if they believed FDA was justified in issuing the Warning Letterson pure powdered caffeine and, more broadly, to address FDA'sand their own roles in assuring the safety of dietary supplement products on the market.
This compendium begins with an overview of the regulatory and legal underpinnings of dietary supplements, including a brief discussion of the 1994 amendment to the Federal Food Drug & Cosmetic Act (FFDCA), the Dietary Supplement Health and Education Act (OSHEA), which provided a legal definition of these products, and established a new regulatory framework. The introductory overview also provides background on caffeine, including how much Americans consume daily, differences in how individuals respond to caffeine, how the body processes caffeine, and what is known about its toxicity. This is followed by the contributions from participating stakeholders (trade associations and a consumer group) outlining their perspectives on the risks posed by pure powdered bulk caffeine and their responses to this regulatory challenge.
Invited stakeholders included: Center for Science in the Public Interest (CSPI),Consumer Healthcare Products Association (CHPA), Council for Responsible Nutrition (CRN), FDA, Natural Products Association (NPA), and United Natural Products Alliance (UNPA). Although FDA, NPA, and UNPA chose not to participate, each has made their position known. UNPA issued a fact sheet on pure powdered bulk caffeine, which, although preceding FDA's action, suggests support for it, since UNPA has a retail"no-sale" policy of pure powdered
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FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOF THE FOOD AND DRUG LAW INSTITUTE II FDA's pure powdered bulk caffeine Warning Letters do not object to caffeine's use in dietary supplements or to use of pure powdered caffeine itself. However, the letters do object to the marketing of pure powdered bulk caffeine products.22 Judging from users' comments on at least one of the enforcement letters recipients' websites, it appears that it is common practice among such users to add caffeine to gel capsules or to beverages of their own making.23 Therefore, FDA's concerns seem largely related to an interplay between human factors and toxicity issues, specifically, consumers' difficulty following label directions in "separating out a safe serving from a potential lethal amount:'24 The bulk packaging of these pure caffeine products, which have been sold in quantities as large as 25 kg, is integral to this problem. FDA therefore, concluded that these contributing factors comprise an "unreasonable risk:'25 Perhaps unstated is concern about the young consumers to whom high dose/pure caffeine dietary supplements are marketed, as well as the 26 27 unfortunate human tendency to think that if something is good for us, then "more is better:' •
B. What is Caffeine?
Caffeine (1,3)-trimethylxanthine)?8 a white, bitter crystalline solid, is a central nervous system stimulant, and is found in botanical sources that include coffee beans, tea leaves, cola nuts, and cocoa pods.29 It can be isolated from these sources by solvent extraction, providing pure caffeine as a byproduct. It can also be chemically synthesized. It is generally recognized for its ability to prevent or relieve drowsiness and to boost energy and focus. Crystalline caffeine (pure anhydrous powder) has historically been sold in bulk, mostly for use as a food additive (e.g., in colas and other beverages) and for the manufacture of caffeine containing prescription and over-the-counter pharmaceuticals (e.g., Fioricet®, Excedrin Migraine, and No Doz). The marketing of pure crystalline (powdered) caffeine targeted to consumers, mostly via the Internet, is a relatively new development. FDA apparently first became aware of the marketing of these products to consumers in 2014, after the report of the death of a user of pure powdered bulk caffeine.30
C. How Much Caffeine Do Americans Consume Daily? 4 Caffeine is widely consumed in a range of food products, although almost 90 percent of adults in the US consume caffeine in the form of coffee or tea.31 Not surprisingly, caffeine consumption (from multiple sources) varies among individuals, as well as age groups. Data analyzed using the National Health and Nutrition Examination Survey (NHANES) from 2007-2010 (N=17,387), indicates that caffeine intake by Americans during this period was primarily in the form of beverages (coffee, tea, soda, and energy drinks), and was highest among those between the ages of 50-59, who had an average caffeine consumption of approximately 250 mg/day32 (the equivalent of approximately 2.5 cups of coffee/day33).1n the 50-59 year-old age group, the 90th percentile intake from beverages was 515 mg/day (approximately five cups of coffee/ day).34 FDA requires that added caffeine in a food product, including dietary supplements, be noted on the label; however, there is no requirement that the amount of caffeine in that product be ·identified.35 Some have noted that the lack of information on amounts of caffeine, both that added and naturally present in conventional food products, makes it difficult for consumers to estimate how much caffeine they are ingesting.36
D. Why Do Some People Tolerate Caffeine Better Than Others? The ability of individuals to respond to the same amount of caffeine differs for a number of reasons, including body weight; time or frequency of caffeine ingestion during the day; health and smoking status; genetic variations in enzymes responsible for caffeine's metabolism and adions, and; medications. Since children weigh less, they receive a higher effective dose on a body weight basis, compared to an adult consuming the same amount. Consequently, a specific amount of caffeine consumed by a child or adolescent may have a greater effect on younger individuals than on adults. Also, we all process (absorb, metabolize, and
FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOF THE FOOD AND DRUGLAW INSTITUTE II eliminate) caffeine differently, despite some common features. Caffeine is nearly entirely absorbed by the gastrointestinal tract after we consume it, and is then quickly transferred to the blood, metabolized in the liver, and excreted (primarily in the urine). Peak blood (plasma) concentrations are reached between only 15 minutes to two hours after ingestion.37 All things being equal, a slow metabolizer's caffeine blood level will be higher than a fast metabolizer's. This depends on the nature of an individual's metabolizing enzymes; pregnancy or smoking status; whether or not the individual has liver disease and; interactions of caffeine with medications or St. John's Wort. 38•39A0A1A2A3•44AsA6.4?A8A9.so Individual caffeine consumption patterns also influence caffeine's actions and peak blood caffeine levels. For example, a single, very high dose of caffeine during the day can result in a higher caffeine blood level at a single point in the day relative to multiple, moderate doses of caffeine. This is because a specific amount of caffeine that is broken up into smaller
amounts and ingested during the day is incremen~allymetabolized and excreted, resulting in lower caffeine blood levels than that expected after ingestion ofthat same amount all at one time. In addition to metabolic differences among individuals, there are differences in various receptors that affect individuals' sensitivity 51 52 53 54 to the effects of caffeine. • • • All of these factors influence caffeine's desired stimulatory effects in an individual, as well as its toxicity.
E. What Levels of Caffeine Are Generally Considered Safe?
The US Department of Agriculture (USDA) states that the daily intake of <400 mg/day"is not associated with increased risk of chronic diseases, such as cardiovascular disease (CVD) and cancer and premature death in healthy adults"55 and FDA has concurred.56 For caffeine added to cola, FDA considers acceptable a caffeine level of< 200 ppm (0.02%), equivalent to 71 mg of caffeine in a 12-oz serving of cola 57-a little less than that contained in a cup (eight ounces) of most coffees.58 However, this determination for cola does not apply to levels of caffeine that might be used in other products, or total caffeine intake per day. Some who ingest caffeine on a daily basis at levels that are considered safe experience sleep disturbances,59 headaches or heart palpitations,60 and other effects, such as jitteriness. Others experience symptoms of withdrawal with a decrease or cessation in caffeine consumption.61 However, none of these effects from moderate doses 5 of caffeine are considered safety risks in healthy individuals. On the other hand, not many would dispute that large doses of caffeine can be extremely toxic, as well as fatal,62 and that the dose ranges related to its adverse effects can be expected to significantly differ among individuals.
It is possible that consumers' familiarity and comfort with caffeine moderates possible concerns about excessive consumption.63 Still, overdosing on caffeine is rare. Sometimes overdosing is intentional, such as with suicide attempts. However, it has also been known to occur as a result of an apparent lack of awareness of safety risks or dose estimation errors,64 such as when taking high, single doses, or an excessive number of doses (especially if there is a misperception that bulk quantities should be handled with no greater care than protein powder), or due to a lack of understanding of the inherent variability in sensitivity to caffeine in the general population.
F. What Level of Caffeine Is Toxic or Lethal? Due to the great variability in how individuals respond to caffeine, there appears to be no bright line between a safe and a toxic dose, although, as noted above,< 400 mg of caffeine per day is generally considered safe for healthy adults. Toxicity may occur at doses greater than 400 mg of caffeine per day, resulting in hypertension, hypotension, tachycardia, and vomiting,65 and death may occur if 10 g of caffeine is ingested (roughly
666768 equivalent to 100 cups of strong coffee), or if blood caffeine levels reach 100 ~g/ml,•• although cardiac arrest has been reported with a consumption of"only" 15-20 cups of coffee/day.69 Fatalities from high doses of caffeine, some of which have been attributed to caffeine-containing energy drinks, have been reported. These appear to have been from a single and very high dose of caffeine, or from several sufficiently high
FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOFTHE FOOD AND DRUGLAW INSTITUTE II doses within perhaps a relatively short period. A non-exhaustive list of documented fatalities appears below. Note that isolated fatalities, which can sometimes be related to exposure to several substances, are generally published as case reports in the scientific literature, filed as cases with poison control centers, or reported to FDA as adverse events?0 As with pharmaceuticals, adverse event reporting for dietary supplements can be problematic and is also associated with incomplete information and under-reporting?1
• A 39-year old man died from the ingestion of approximately 12 g of pure powdered caffeine; his autopsy blood caffeine level was 350 mg/liter (or 350 1Jg/ml).72
• A 22-year old woman died of cardiac arrest after ingesting mail order diet pills containing caffeine as the only active ingredient. Her blood serum caffeine level was 1560 1Jg/ml.73 [Note that a single cup of coffee, which provides a dose of 0.4-2.5 mg of caffeine/kg of body weight and which is considered safe, may yield apeak blood concentration of< 4 2 mg caffeine/liter (or 21Jg caffeine/ml blood).l ]
• A 38-year old woman on an anti-depressant that caused dry mouth, drank up to eight liters/day of Pepsi Max (equivalent to 1555 mg caffeine/dayf5 to alleviate the drug's side effect. A post-mortem examination determined that her death was due to "excessive consumption" of both caffeine and the anti-depressant drug's active ingredient?6
• An 18-year old male died as a result of taking pure powdered caffeine?7
• A 24-year old male died as a result of taking pure powdered caffeine?8
• A 14-year old girl (with a pre-existing cardiac defect) died of cardiac arrhythmia, which her family attributed to a caffeine-containing energy drink (Monster), of which she 6 drank two 24-oz cans (equivalent to 480 mg of caffeine) within a 24-hour period before 9 80 her death? •
In summary, FDA issued Warning Letters to distributors of pure powdered bulk caffeine sold to consumers as a dietary supplement. The agency stated that its actions were related to caffeine's lethal properties at very high doses, but also cited the potential for users ofthe products to make seemingly trivial, but deadly, measurement errors. Caffeine is considered safe at daily doses of <400 mg, but high single or multiple doses, such as those that appear to be related to fatalities attributed to caffeine, are a risk.
FDLI and this novice volunteer editor are grateful to the organizations contributing to this compendium in the following pages, providing the reader with a chance to learn of their reactions to FDA's action on pure, powdered bulk caffeine and to gain an understanding of what each organization is doing to assure the safety of all dietary supplements marketed in the US.
II. CONSUMER HEALTHCARE PRODUCTS ASSOCIATION (CHPA) STATEMENT
FDA Actions on Powdered Caffeine and the Role of Responsible Industry
Caffeine (1,3)-trimethylxanthine), widely considered the most commonly used psychoactive drug in the world,81 is a naturally-occurring mild central nervous stimulant found in the leaves, seeds and fruits of several
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a a 7 7 Dietary Ingredient Notifications. Thus, nearly all aspects of dietary supplement manufacturing, advertising, and labeling are covered by extensive regulations issued and enforced by FDA Moreover, the Federal Trade Commission (FTC) reg.ulates advertising of dietary supplements and requires that health claims be based on "competent and reliable scientific" evidence.
Dietary supplement manufacturers must perform identity testing for each dietary ingredient they use and must establish specifications for the identity, purity, and strength of all dietary ingredients used to manufacture dietary supplements. Manufacturers must also verify a dietary ingredient supplier's compliance with GMPs and periodically update these qualifications. Industry-funded trade associations and independent GMP auditors have helped responsible companies to address concerns associated with ingredient quality or identity. Along with the Council for Responsible Nutrition (CRN) and the United Natural Products Alliance (UNPA), CHPA participates in the Standardized Information on Dietary Ingredients (SIDI) Workgroup, which has developed voluntary guidelines intended to assist dietary supplement companies with supplier qualification activities as part of complying with the GMP regulations.
CHPA believes that the current regulatory framework for dietary supplements, defined under OSHEA, is adequate. We have voiced our support for increased agency action against manufacturers marketing illegal products containing active pharmaceutical ingredients or undeclared substances masquerading as dietary supplements. Along with the other dietary supplement trade associations, we have also expressed a willingness to work with the agency in helping it in this regard.
Periodically, accusations of an "unregulated" dietary supplement industry are published in the mainstream media implying that the entire industry operates in a "wild-west" type of environment. Of course, this is simply not true and such statements fail to recognize the long-standing differences in the regulatory structures 8 governing drugs and dietary supplements. This often results in consumer confusion about these beneficial health products that millions of Americans rely on to support their overall health and wellness.
The dietary supplement industry has grown considerably since the passage of the OSHEA Although the vast majority of dietary supplement manufacturers responsibly adhere to all aspects of GMPs, there are unfortunately those who do illegally spike their products with active pharmaceutical ingredients or undeclared substances with similar structural or pharmacological properties. CHPA member companies are committed to manufacturing and marketing their dietary supplement products in a responsible fashion, and we support increased efforts by the agency to remove illegal products sold as supplements from the market. Along with the other supplement trade associations, we believe that FDA would be better able to perform its functions if it had increased funding and we are supportive of the elevation of the Division of Dietary Supplements to an Office.96
Concerns have been expressed about FDA's issuance of Warning letters to marketers of pure powdered caffeine, noting that these were based on anecdotal evidence.97 CHPA believes that the potential for caffeine overdose and the ensuing serious consequences that could result provide sufficient basis for the FDA action. In this instance, pure powdered caffeine presents a unique risk-consumers are required to accurately measure out an appropriate and very low dose using measures (1/16 to 1/32 teaspoon) that are not commonly employed or likely recognized by the average consumer.
CHPA believes that the dietary supplement industry can help to keep illegal and/or unsafe products sold as dietary supplements from reaching the marketplace. Just as FDA has a role in exercising a more rigorous enforcement of the current laws in an effort to prevent the marketing of illegal products, industry trade
FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOF THE FOOD AND DRUG LAW INSTITUTE II www.fdli.org associations can help by increasing consumer awareness of safe dietary supplement use. In 2013, CHPA developed voluntary guidelines for industry addressing the labeling, packaging, and promotion of dietary supplements containing caffeine.98
CHPA recently updated the guidelines to include an agreement that the Association's members will not market pure powdered caffeine to consumers; CHPA's members are also expected to comply with other significant aspects of the guidelines. These include: 1. disclosure of the total caffeine content per serving in a dietary supplement (a disclosure that is not required by FDA); 2. inclusion of a statement on the label of any supplement containing more than 100 mg total caffeine per serving noting that the product is not intended/ recommended for children less than 18 years of age, or those sensitive to caffeine; 3. inclusion of information on labeling that notes the serving size and safe daily intake recommendations; 4. a commitment to "not advertise, market, or otherwise promote the use of caffeine-containing dietary supplements in combination with alcohoL or to counter the acute or immediate effects of alcohol:'
In collaboration with CRN, we have published articles in journals targeted to convenience store owners stressing the need to adequately monitor the products sold in these and other similar type stores (e.g., 99 10 gas stations). • °CHPA provides consumers with easy to understand information on the safe use of dietary supplements. These tips stress the need for consumers to share information with their healthcare provider regarding the types of supplements they are taking, to avoid purchasing supplements promising "miracle" effects, and to only purchase supplements from companies that consumers know and trust. Dietary supplement trade associations also hold regular meetings to discuss current events regarding supplements, including ways to support educational efforts and how best to work with FDA to ensure that dietary supplement manufacturers are compliant with all applicable regulations.
CHPA has a long history of working with partners to promote and enhance the safe and effective use of 9 OTC products. The CHPA Educational Foundation, established in 2004, educates consumers on how to use, store, and dispose of OTC medicines and dietary supplements. Information and materials representing the latest medical and scientific thinking and research address specific areas identified by CHPA as those for which consumers need guidance and support. The CHPA Educational Foundation developed and launched KnowYourOTCs.org, a website providing facts and education'al tools geared to consumers, and presented in a user-friendly format that is intended to help them take charge of their own healthcare. This includes examples of dietary supplement products, an explanation of dietary supplement health claims, important tips for safe use, and commonly asked questions about dietary supplements.
CHPA believes that educating consumers on the best practices for choosing dietary supplement products manufactured and marketed in a responsible fashion can make a difference in consumer understanding and public health. CHPA is committed to working with FDA in whatever capacity necessary to ensure the public's continued access to safe, beneficial dietary supplement products, and to working with FDA to prevent the marketing of illegal or potentially unsafe products.
FOODAND DRUGLAW POLICY FORUM II A PUBLICATIONOFTHE FOOD AND DRUGLAW INSTITUTE II Ill. COUNCIL FOR RESPONSIBLE NUTRITION (CRN) STATEMENT
Preventing Consumer Accessto Pure Powdered Caffeine: The Role of FDA and Industry Self-Regulation
A. Introduction
CRN's mission is to sustain and enhance a climate for our members to responsibly develop, manufacture, and market dietary supplements and nutritional ingredients. CRN supports a comprehensive regulatory framework that provides consumers with access to a wide variety of affordable, high quality, safe, and beneficial dietary supplement products, while also encouraging innovation, research, and product development based on sound science.
B. Summary of CRN's Position
CRN supports FDA's issuance ofWarning Letters to distributors of pure powdered caffeine. The Federal Food, Drug, and Cosmetic Act (FFDCA) authorizes the agency to take enforcement action if a dietary supplement presents a significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling.101 In the present case, although pure powdered caffeine is a legal dietary ingredient, when sold in bulk form it presents an unreasonable risk to consumers because the margin between the recommended serving size and a toxic amount is miniscule. A simple mistake in accurately measuring a safe dose of the product could result in a serious adverse event or possibly death. Because the hazards associated with caffeine overdose are significant, CRN supports restrictions on the sale of bulk pure powdered caffeine (PPC) directly to consumers.
C. Role for Industry and FDA Industry and FDA have unique but complementary roles in ensuring the safety of dietary supplements. 10 Many dietary supplements and the ingredients used in these products, including caffeine, have a long and established history of safe use. Therefore, the FFDCA does not require FDA's approval of dietary supplements or their ingredients. However, manufacturers intending to market new dietary ingredients (NDis) must notify the FDA at least 75 days before marketing an NDI.102 Whether or not an ingredient is an NDI, the FFDCA requires companies intending to market them to assure the safety of products before they are marketed. In addition, companies must comply with various FDA laws and regulations, including current Good Manufacturing Practices (GMPs), Adverse Event Reporting (AER) requirements, as well as with the more recent Food Safety Modernization Act (FSMA).103 The purpose of the FSMA is to ensure safety in the US food supply by shifting the focus from responding to contamination to preventing it. Under the FFDCA as amended by FSMA, companies that manufacture, process, pack, or hold human food, including dietary ingredient suppliers, must identify food-safety hazards and implement preventive controls.104 Certain provisions, such as facility registration,105 administrative detention,106 and mandatory recall authority,107 also apply to dietary supplement manufacturers.
The FFDCA also addresses requirements for structure/function claims. 108 These claims may describe the role of a nutrient or dietary ingredient intended to affect the normal structure or function of the human body, e.g.,"calcium builds strong bones;' or may characterize the means by which a nutrient or dietary ingredient acts to maintain such structure orfunction.ln 2000, FDA issued a final rule/'Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body;' 109 which establishes the types of statements that may be used on a dietary supplement's immediate product label or packaging, as well as statements that are placed physically apart from the product's container, such as promotional material including that on websites. Unlike health claims or qualified health claims, structure/
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of of 1 1 1 Finally, the nature of this action is not unique for FDA For example, FDA has taken similar action with over the-counter (OTC) pediatric liquid acetaminophen and liquid vitamin D. In 2011, the agency raised concerns regarding dosage instructions for pediatric liquid acetaminophen after receiving reports of accidental overdoses.117 OTC manufacturers worked with FDA to develop clearer instructions, new measuring devices to accompany the products, and a consumer education campaign to raise awareness among parents and caregivers. 118 Also, in 2010, FDA alerted parents and consumers that some liquid vitamin D dietary supplements were sold with droppers that could allow for excessive dosing of vitamin D to infants. Manufacturers of these products were advised by FDA to modify droppers so that they hold no more than the recommended dose and that the dose is clearly marked on the dro.pper. 119 Likewise, FDA has an obligation to warn consumers about the potentially serious hazards associated with products such as pure powdered caffeine/ especially when there are documented cases of adverse events and deaths. Without a doubt, caffeine is a safe and legal dietary ingredient; however, similar to the issue with liquid acetaminophen and liquid vitamin D, this safe ingredient becomes a potential hazard when measuring or dispensing a safe dose is not a simple process. Thus, makers of pure powdered caffeine could consider working with FDA to reformulate their products or packaging their products in a way that promotes safe use of caffeine.
E. CRN's Objectives and Actions in Contributing to the Goal of Keeping Unsafe Products from Entering the US Market
A key component of CRN's mission and strategic objectives is promoting responsible industry practices. CRN's Code of Ethics requires its members' compliance with all federal and state regulations governing dietary supplements and food in the areas of manufacturing, marketing, quality control, and safety. CRN's members also agree to adhere to additional voluntary guidelines that go beyond federal requirements. CRN has a robust self-regulatory program that includes labeling guidelines for caffeine, among others.12° CRN approved its caffeine guidelines in 2013 to help consumers make informed decisions about caffeine in the dietary supplements they purchase.121 The guidelines address disclosure of caffeine content and set forth consumer advisories to promote the safe, responsible use of dietary supplements. They also specifically 12 recognize that caffeine, whether natural or synthetic, is a safe and legal dietary ingredient. The guidelines call on manufacturers to disclose on the product label the total amount of caffeine, from both natural sources like green tea extract; coffee bean extract; guarana or yerba mate; as well as added caffeine. In addition to the recommendation for label disclosure of total caffeine content, the guidelines recommend that products with a total caffeine content of more than 100 mg per serving include label advisories for children, those sensitive to caffeine, pregnant or nursing women, and those with a medical condition or taking medication. The guidelines also discourage companies from marketing or promoting the use of caffeine-containing dietary supplements in combination with alcohol, or to counter the acute or immediate effects of alcohol.
Immediately after FDA issued its consumer advisory on pure powdered caffeine, CRN amended its guidelines to include restrictions on the bulk sale of pure powdered caffeine directly to consumers. The guidelines do, however, recognize the legitimate sale of bulk pure powdered caffeine as part of business-to-business transactions (i.e., ingredient suppliers selling directly to finished product manufacturers). CRN also issued press statements supporting the FDA Warning Letters on pure powdered caffeine.122
Additional CRN self-regulatory efforts include the following guidelines:"Recommended Guidelines: Labeling and formulation of melatonin-containing dietary supplements for sleep support;"123 "Recommended Guidelines: Iodine Quantity in Multivitamin/Mineral Supplements for Pregnancy and Lactation;"124 "Best Practices Guide for Enzyme Dietary Supplement Products;"125and,"CRN Guidelines for Labeling of Protein in Dietary Supplements and Functional Foods:'126 CRN also issued a guideline on the dosage and labeling of DHEA, kava, and ephedra in supplement products:"CRN Safety Considerations for Dosage Recommendations
FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOF THE FOOD AND DRUG LAW INSTITUTE II www.fdli.org and Labeling:'127 Finally, in 2006 CRN partnered with the National Advertising Division (NAD) 128 on an initiative to increase monitoring of advertising for dietary supplements. This program targets deceptive, false, and misleading dietary supplement advertising which is then reviewed by the NAD to determine whether the claims are truthful and supported by competent and reliable scientific evidence. The program enhances the marketplace for dietary supplements by increasing consumer confidence in the truth and accuracy of advertising claims for dietary supplement products and encourages fair competition within the industry.129 CRN will continue to implement such programs that go above and beyond the legal requirements and support appropriate FDA enforcement actions targeting unsafe products.
IV. CENTER FOR SCIENCE IN THE PUBLIC INTEREST (CSPI) STATEMENT
The Case of Powdered Caffeine and the Need to Fix Dietary Supplements Oversight
On May 27, 2014, 18-year-old Logan Stiner was discovered on the floor of his family's home by his brother. Logan, an Ohio high school athlete and scholar with a bright future, died of an accidental overdose of powdered caffeine.130 In June 2014, James Wade Sweatt, a 23-year-old engineer, died after repeatedly going into cardiac arrest, despite multiple attempts to revive him. "That powder is making me sick;' Wade told his wife, before collapsing.
CSPI, a non-profit organization that works to improve nutrition and public health, filed a Citizen Petition with FDA in December 2014131 asking the agency to ban the sale of pure powdered caffeine and highly concentrated caffeinated powders and liquids. CSPI argued that pure powdered caffeine and other highly concentrated forms of caffeine present"a significant or unreasonable risk of illness or injury under conditions of use suggested or recommended in the labeling;'m and are thus "adulterated or misbranded"133 and 13 cannot be sold. CSPI also proposed that a ban on caffeine sold in a highly concentrated form to consumers is justified because it"pose[s] an imminent hazard to public health or safety:' 134 Lastly, CSPI encouraged FDA to impose requirements for clearer labeling and potency restrictions to minimize risk of an accidental overdose.
A single teaspoon of pure, powdered caffeine is the equivalent of drinking 25 8-ounce cups of coffee.135 It is so concentrated that the suggested serving size-generally between 1/32 and 1/16 of a teaspoon-is beyond the measurement capabilities of a typical consumer.
In August 2015, FDA issued five enforcement letters to companies selling powdered bulk caffeine directly . to the public. Shortly thereafter, CSPI renewed its call for FDA to ban all highly concentrated powdered and liquid caffeine products to prevent harm to consumers.136 While the companies to which FDA addressed enforcement actions appear to have suspended sales of the products named in the Warning Letters, the sale of such a hazardous product highlights the extent to which the current regulatory scheme for dietary supplements fails to protect consumers. A recent study published by FDA and the Centers for Disease Control and Prevention underscores that conclusion. Based on surveillance data from 63 emergency departments from 2004 through 2013, the authors found that supplements cause, on average, an estimated 23,000 emergency room visits per year.137 Adverse-event reports (AERs) from 2008-2015 describe 2,100 incidents involving serious outcomes, including life-threatening illnesses and deaths. 138
There are considerable gaps in reporting. In the case of powdered caffeine, for example, in addition to the two deaths, news reports indicate there were 30 cases of overdoses of pure caffeine reported to poison
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Under current law, FDA may remove products from the market only after they pose a "significant or unreasonable risk of harm" or an //imminent hazard" to the public.159 It is clear from the numerous failures described herein that this post-market, ad hoc approach inflicts unacceptable risks on the public.
Reforms of dietary supplement oversight should include:
Mandatory third-party premarket oversight of safety and efficacy, with attention to classes of products posing a particular threat because oftheir ingredients, contaminants, or susceptibility to being adulterated;
More meaningful product labeling, including changes to the clarity, prominence, and font size of disclaimers, and warning labels for hazardous products;
A requirement for manufacturers, ingredient suppliers, and distributors to register marketed dietary supplements with FDA, including annual sales data;
More stable funding for FDA through modest user fees, and improved mechanisms for obtaining and disseminating adverse event and related health information from 15 emergency rooms, poison control centers, consumers, and other sources; 160
FDA should finalize its draft NDI guidance through a binding rulemaking process. The final rule should specify the quantity and quality of evidence for safety determinations and excise the exemption from the NDI notification requirement for self-affirmed GRAS food ingredients;
• To address efficacy, Congress should require the agency to develop a process for evaluating evidence for all dietary supplement claims and develop sensible standards for review of new claims; 161
FTC should continue its ongoing efforts to police dietary supplements for unsupported claims of efficacy and DOJ should bring criminal and civil prosecutions where supported by evidence.162
FOOD AND DRUGLAW POLICYFORUM II A PUBLICATIONOF THE FOOD AND DRUGLAW INSTITUTE II Images of Bulk Caffeine Powder
ENDNOTES 16
1. SeeWilliam A. Correll, FooD& DRuGADMIN. FDA Warning Letter to Bridge City LLC August 27,2015, available at http://www.fda.gov/iceci/enforcementactions/warningletters/2015/ucm460203. htm, last access Nov. 25, 2015.
2. SeeWilliam A. Correll, FooD& DRuGADMIN. FDA Warning Letter to Hard Eight Nutrition LLC August 27, 2015, available at http://www.fda.gov/iceci/enforcementactions/warningletters/2015/ ucm460200.htm, last access Nov. 25, 2015.
3. See William A. Correll, FooD& DRuGADMIN. FDA Warning Letter to Kreativ Health Inc Dba Natural Food Supplements. August 27,2015, available at http://www.fda.gov/iceci/enforcementactions/ warningletters/2015/ucm460208.htm, last access Nov. 25, 2015.
4. SeeWilliam A. Correll, FooD&DRuG ADMIN. FDA Warning LettertoPureBulk.August27,2015, available at http://www.fda.gov/ICECI/EnforcementActions/Warningletters/2015/ucm460204.htm, last access Nov. 25, 2015
5. See William A. Correll, FooD & DRuGADMIN. FDA Warning Letter to Smartpowders. August 27, 2015, available at http://www.fda.gov/ICECI/EnforcementActions/Warningletters/2015/ ucm460201.htm, last access Nov. 25,2015
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17. Dietary Supplement Health and Education Act of 1994, Pub. L., No. 103-417, 108 Stat. 4325 (1994); 21 U.S.C.§321.
18. FDA appears to have tentatively taken the position that synthesized herbal/botanical constituents, including caffeine, do not qualify as dietary ingredients. See FooD & DRUG
ADMIN.,DRAFT GUIDANCE FOR INDUSTRY: DIETARY SUPPLEMENTS: NEW DIETARY INGREDIENT NOTIFICATIONS AND RELATEDIssuEs (July 2011 ), available at: http://www.fda.gov/Food/GuidanceRegulation/ GuidanceDocumentsRegulatorylnformation/DietarySupplements/ucm257563.htm, last access Nov. 23, 2015.
19. Although such products do not require approval from FDA before marketing, dietary supplement manufacturers are expected to notify the agency, or risk the product being deemed adulterated, if they intend to market a supplement containing an ingredient that was not marketed as a dietary ingredient before October 15, 1994 (or if the dietary supplement itself was not marketed before this date), i.e., a //a new dietary ingrediene 21 U.S.C.§350b.
20. Caffeine-containing energy drinks can be marketed as either a conventional food or dietary supplement, a determination that is based on a numberoffactors.See FooD&DRuG ADMIN., GUIDANCE FORINDUSTRY. DISTlNGUISHING LIQUID DIETARY SuPPLEMENTS FROM BEVERAGES, (January 2014), available at http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/ ucm381189.htm, last access Nov. 24, 2015. 18 21. /d.
22. FooD& DRUGADMIN. FDA TakesAction on Bulk Pure Powdered Caffeine Products. Constituent Update (Sept. 1, 2015), available at: http://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ ucm460097.htm, last access Jan. 15, 2015.
11 23. For example, on the bulksupplements.com website, on Aug. 27, 2014,'john//wrote, 1 filled the
11 capsules with 300 mg .. . and on Mar. 2, 2015, 'james// wrote, //1 purchased this to add to my home made [sic] preworkout:'Others commented positively on its miscibility, which suggests they mixed the powder with a liquid and ingested it in beverage form BuLKSUPPLEMENTs.coM, http://www.bulksupplements.com/caffeine-powder-anhydrous.html, last visited Nov. 6, 2015.
24. Correll, supra note 2. Note: Identical or similar language appears in the other Warning Letters.
25. Per 21 U.SC.§342(f)(1 )(A), an //unreasonable risk//causes a dietary supplement to be considered //adulterated:' Also, 21 U.SC.§342(f)(1)(A)(i) specifically states that such an unreasonable risk includes// conditions of use recommended or suggested in labeling:'[emphasis added]
26. P.Mason. One Is Okay, More Is Better? 66 PRocNUTR Soc no. 4, 494 (2007).
FOODAND DRUG LAW POLICY FORUM II APUBLICATION OFTHE FOOD AND DRUG LAW INSTITUTE II 27. AMER.CANCER Soc., DIETARYSuPPLEMENTS: WHAT Is SAFE?Megadosing: The 'More is Better' Myth, available at http://www.cancer.org/treatment/treatmentsandsideeffects/ complementaryandalternativemedicine/dietarysupplements/dietary-supplements-toc, last access Nov. 23, 2015.
28. Uniquely identified by its Chemical Abstract Service Number: 58-08-2. Also known by other names: 3}-Dihydro-1,3}-trimethyl-1 H-purine-2,6-dione (9CI); Anhydrous caffeine, Caffeine, Coffeinum, Guaranine, Methyltheobromine, Methylxanthine theophylline, Thein, Theine, 1,3}-Trimethyl-2,6-dioxopurine [NATIONALLIBRARY OF MEDICINE.CHEMIDPLUS, http://chem.sis.nlm. nih.gov/chemidplus/rn/startswith/58-08-2, last access Nov. 6, 2015.
29. See INsT. OF Mm., CAFFEINEINFooD AND DIETARY SuPPLEMENTS: ExAMINING SAFETY: WoRKSHOP SuMMARY (20 14).
30. Personal communication, Siobhan Delancey, FooD& DRUGADMIN. (Oct. 30, 2015).
31. Bill J. Gurley et al., Multi-ingredient Caffeine-containing Dietary Supplements: History, Safety, and Efficacy 37 CLINICALTHERAPEUTICS no. 2, 275 (2015).
32. INST.oF Mm., supra note 29.
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134. 21 U.S.C. 342(f)(1 )(C).
135. Food and Drug Admin., FDA CoNSUMERADVICE ON PowDERED PuRE CAFFEINE (last updated Sept. 1,2015), available at http://www.fda.gov /Food/Reca llsOutbrea ksEmergencies/Safety AlertsAdvisories/ ucm405787.htm, last access Dec. 5, 2014.
FOODAND DRUG LAW POLICY FORUM II APUBLICATION OFTHE FOOD AND DRUG LAW INSTITUTE II www.fdli.org 136. CSPI'sletter to FDA (included in FDA Regulatory Docket FDA-2015-P-0059) noted the agency neglected to send a warning letter to at least one other company also marketing powdered caffeine to consumers, and should take action against a closely related product one of the cited companies is also marketing to consumers. Available at http://www.regulations.gov/# !docketBrowser;rpp=25;po=O;dct=N%252BFR%252BPR%252BO;D=FDA-2015-P-0059. As of December 3, 2015, the letter has not yet been posted on the regulatory docket at regulations. gov.
137. Andrew I. Geller, et a!., Emergency Department Visits for Adverse Events Related to Dietary Supplements,373 N.ENGL.J.Mm.1531 (Oct.15,2015). ·
138. Jennifer Weeks, Dietary Supplements: Is Regulation of the Industry Too Lax? 25 CQ RESEARCHERno. 39, (2015) at 916.
139. Laura Ungar, Caffeine Powder RaisesOverdose Concerns, THECoURIER-JouRNAL (Sept. 12, 2014), http://www.courier-journal.com/story/life/wellness/health/2014/09/12/caffeine-powder raises-overdose-concerns/15512267 /,last access Nov. 25,2015.
140. Ctr. for Food Safety & Applied Nutrition, FooD& DRuGADMIN., CAERS Reports Allegedly Related to PureCaffeine, as of Nov. 13,2014 (obtained byCSPI via FOIA request); Seema B.Jabbar and Mark G. Hanly, Fatal Caffeine Overdose:A CaseReport and Review of Literature, 34 AM. J. FoRENSIC.Mm. PATHOL.321 (20 13).
141. Whats Behind our Dietary Supplements Coverage, CoNSUMERREPORTS, available at http://www. consu m erreports.o rg/c ro/20 12/04/what-s-beh in d-o u r-d ieta ry-s up plements-fcoverage/ 27 index.htm (noting that more than half of respondents to a national Harris poll in 2002 said they believed that supplements must be approved by a government agency before they can be sold to the public); 2002 Harris poll no longer publicly available for reference.
142. CA Morris & J Avorn.lnternet Marketing of Herbal Products. JAMA 2003 Sep 17; 290(11 ):1505-9.
143. See 21 C.F.R.1 01.93(f).
144. Dietary Supplement: Structure/Function Claims Fail to Meet Federal Requirements, Office of Inspector General, U.S.Department of Health and Human Services, Report (OEI-01-11-00210), Oct. 2012 at 12 and 16, available at http:!/oig.hhs.gov/oei/reports/oei-01-11-0021 O.pdf, last · accessed on Dec. 3, 2015.
145. U.S. Government Accountability Office, Food Labeling: FDA Needs to ReassessIts Approach to Protecting Consumers from False or Misleading Claims, Jan. 2011, available at http://www.gao. gov/assets/320/314473.pdf, last accessed on Dec. 3, 2015.
146. Chung-Tung Jordin Lin, How Do ConsumersInterpret Health Messageson Food Labels? NuTRITION ToDAY,43, no. 6 (2008). The study found that consumers rate the level of scientific evidence and other attributes associated with structure/function claims as similar to those of health
FOODAND DRUG LAW POLICY FORUM II APUBLICATION OFTHE FOOD AND DRUG LAW INSTITUTE II claims, and that structure/function claims are the most popular of all claims-consumers prefer them to health claims, which they saw as wordy and disease-specific.
147. A. Kapoor &J.M.Sharfstein, Breaking the Gridlock: Regulation of Dietary Supplements in the United States. DRuGTEST. ANALYSIS (2015), citing Josh Long, FDA Date: SupplementcGMPCompliance Rates Show Modest Improvement, NATURALPRODUCTs INSIDER (2014), available at http://onlinelibrary. wiley.com/doi/1 0.1002/dta.1892/abstract, last accessed Dec. 3, 2015.
148. CTR.FoR DRUG EvALUATION & RESEARCH, FooD & DRUGADMIN., Tainted Products Marketed as Dietary Supplements, COER, available at http://www.accessdata.fda.gov/scripts/sda/sdNavigation. cfm?sd=tainted_supplements_cder. Last updated Dec. 3, 2015, last access Dec 3, 2015.
149. Josh Long, FDA GMP Inspectors Cite 70% of Dietary Supplement Firms. NATURALPRoDuCTs INSIDER (2013), available at http://www.naturalproductsinsider.com/news/2013/05/fda-gmp inspectors-cite-70-of-dietary-supplement.aspx, last access Dec. 3, 2015; Josh Long, More supplement manufacturers complying with FDA GMP regulations, but room for improvement. NATURALPRODUCTS INSIDER (2015), available at http://www.naturalproductsinsider.com/blogs/ insider-law/2015/03/more-supplement-manufacturers-complying-with-fda.aspx, last access Dec. 3, 2015.
150. Alison Young, Supplement Shell Game, USA ToDAY(Dec. 20, 2013), available at http://www. usatoday.com/topic/a6a2541 c-Ob71-46bf-81 a5-c3d21 ba55b2d/supplement-shell-game/, last accessed Dec. 3, 2015.
151. Dep't. of Justice Press Release, Justice Department and Federal Partners Announce 2 8 Enforcement Actions of Dietary Supplement Cases, Nov. 17, 2015, http://www.justice.gov/ opa/pr/justice-department-a nd-federa 1-partners-a n nou nce-enforcement-actions-dieta ry supplement-cases, last access Dec. 3, 2015.
152. An NDI is one not marketed in the United States before 1994. See21 U.S.C.§ 350b.
153. /d.
154. FooD AND DRUG ADMIN.,Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues,July 2011, available at http://www.fda.gov/food/ guidanceregulation/guidancedocumentsregulatoryinformation/ucm257563.htm
155. OSHEA was enacted in 1994, prior to changes at the FDA that substantially diminished its oversight of food ingredients. SeeComments by CSPI,the Natural Resources Defense Council and others to the docket for Substances that Are Generally Recognized as Safe, April 15, 2015, available at; http://cspinet.org/new/201504151.html, last access Dec. 3, 2015.
156. 21 U.S.C.350b(a)(1 ).
157. SeeDietary Supplements, Draft Guidance for Industry, IV.B. 2, citing 21 U.S.C.350b(a)(1 ). (FDA's draft guidance compounds the problem by providing that if a substance is merely"marketed"
FOODAND DRUG LAW POLICY FORUM II APUBLICATION OFTHE FOOD AND DRUG LAW INSTITUTE II www.fdli.org for use in food in the U.S. or abroad(without chemical alteration, the exemption from NDI notification applies).
158. T. Neltner & M. Maffini, Generally Recognized as Secret: Chemicals Added to Food in the United States, Natural Resources Defense Council, April 2014, at 8, available at: http://www.nrdc.org/ food/files/safety-loophole-for-chemicals-in-food-report.pdf, last access 11.29.2015 (noting that"[s]everal dietary supplement manufacturers appear to be making a GRAS determination to avoid having to notify the FDA under both OSHEA and the Food Additives Amendment of 1958:')
159. 21 u.s.c.§ 342(f)(1 ).
160. FDA should report this information publicly annually and labels should be required to include a toll-free telephone number and Web address for incidents to be reported. Congress should also require reporting of mild and moderate adverse events.
161. For example, Congress could ask the National Academy of Medicine (NAM) to use existing evidence from the National institutes of Health, the U.S. Preventive Services Task Force, and other sources, and prepare a list of allowed claims for products, as in Europe and Canada. Congress should require FDA to review claims for products prior to market to assure there is an evidentiary basis for them consistent with NAM's guidelines.
ABOUT THE CONTRIBUTING ORGANIZATIONS AND AUTHORS 29 Brenda Seidman, M.S., Ph.D. RAC is a regulatory toxicologist and Principal Consultant of Seidman Regulatory Toxicology, LLC in the Washington, D.C. metropolitan area. She served as a volunteer editor of this issue and one of its contributors, and thanks Ms. Judy Rein, Policy Forum's Editor, for giving her this opportunity, and for her guidance and patience. Seidman also thanks Ms. Jeanne Faubell for generously donating her time and expertise in assisting Seidman with the preliminary formatting of this issue's endnotes, and to each of the participants, not only for their willingness to participate, but also for their hard work and professionalism.
Consumer Healthcare Products Association The Consumer Healthcare Products Association (CHPA) is the 134-year-old national trade association representing the leading manufacturers and marketers of over-the-counter (OTC) medicines and dietary supplements. CHPA is committed to empowering consumer self-care by preserving and expanding choice and availability of consumer healthcare products.
~JaySirois, Ph.D. is responsible for regulatory and scientific affairs activities, including cooperative programs with the U.S. Food and Drug Administration, ingredient safety, and dietary supplement programs at CHPA.
He is experienced in pharmaceutical, medical device, and dietary supplement regulatory affairs, pharmacovigilance, Rx-to-OTC switch, product safety, and clinical research. Sirois is a member of the Regulatory Affairs Professionals Society and is an ad hoc reviewer for the Neurotoxicology journal.
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By Steve Mister, President & CEO, Council for Responsible Nutrition , 09-Sep- 1 comment 2015 ·~ Last updated on 09-Sep-2015 at 15:43 GMT Heat-killed • • ~ F. o.r stability, • "-.~·'0 3 Times ...... Potentiated • .. . For Immunity. • ci§> The clinically pn.wen !mmunt}biotic " benefft of the HK-L1371actobacillus Improves by a factor t;){ thni>e;
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Related tags: Pure powdered caffeine, Caffeine, CRN, Dietary supplements NPA sues 10 current and former board members who allegedly sought to 'undermine' organization Once again the dietary supplement industry finds itself having to make tough decisions. Today the issue is pure powdered caffeine being sold directly to consumers. And the NBTY sells Vitamin World to Centre Lane Partners options are a lot more momentous than merely "would you like cream and sugar with that?"
Recently FDA issued warning letters to several marketers of pure powdered caffeine declaring that the bulk sale of this substance to consumers violates the Food, Drug & Cosmetic Act because, when sold in bulk, pure powdered caffeine presents a serious risk of illness or injury despite the suggested serving level on the labeling. At issue is whether consumers can appropriately dose themselves when the ingredient is sold in its purified form in large quantities.
Pure powdered caffeine is a white powder that is essentially 100 percent synthetic caffeine without any of the binders and fillers that might be added to finished products to "cut" its potency. In that form, anywhere from 1/32 to 1/14 of a teaspoon can provide about 200 milligrams of caffeine-the same amount as one would expect to find
in two cups of coffee. It is being sold in bulk bags of anywhere from 25 grams (about 125 servings) to 25 kilograms (about 125,000 servings!).
The problem is not the ingredient as much as it is the concentration of pure powdered caffeine and the fact that so little carries so much of a punch. Even if the bulk bags provide directions that 1/16 of a teaspoon equals a serving, can average consumers use the product according to those directions? And will they? Can a consumer population accustomed to measuring sports nutrition products with 1/8 cup scoops appreciate the risks of exceeding 1/16 teaspoon? Even if consumers have a 1/16 measuring device (often called a "pinch" measuring spoon) or a milligram scale in their kitchen, it's too easy to make a mistake. Add a little too much salt or pepper to your pot roast and you change the taste; but add a little too much of pure powdered caffeine in your post-workout smoothie and you might never be able to taste-or do anything else-again.
FDA has already documented two cases in which young, otherwise healthy men overdosed themselves (apparently unintentionally) with pure powdered caffeine and died.
Which brings us back to the industry's moment of decision: Will supplement manufacturers and marketers support FDA's action and join the call to remove pure powdered caffeine from the consumer marketplace, or will they dig in and defend a few companies' ability to sell a potentially dangerous product under the banner of OSHEA? Visit Us of Engredea: .. Booth #317
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MCT powder, an excellent choice for a healthy lifestyle INNOBIO Limited One teaspoon of pure powdered caffeine is equivalent to the amount of caffeine in about28 cups of regular coffee. Image© iStockPhoto I Ozgur Coskun What Is the Most Bioavailable, Organic We decided to support FDA's call for the removal of this product Form of Magnesium? Albion At CRN, that decision was easy. We decided to support FDA's call for the removal of this product from the consu~ermarketplace. Do consumers really need to buy five kilogram bags? The safety An ultra-pure, science-backed L-Citrulline risks of mismeasuring or overdosing outweigh the benefits. Moreover, hunkering down to protect a for Nitric Oxide support Kyowa Hakko hypothetical "right" to sell a dietary ingredient in bulk would put the industry on the wrong side of consumer safety and cultivate the impression that we are defending the right of a few marketers to View All Products peddle a dangerous substance.
So CRN amended its existing Recommended Guidelines Caffeine-Containing Dietary S_upplements On demand Supplier Webinars
to include a recommendation against selling pure powdered caffeine in bulk to consumers Transparency in dietary supplements - by Nutralngredients-USA (legitimate business-to-business transactions are permitted). Further, CRN has supported FDA's William Reed Business Media action by calling for non-CRN members to stop selling this product as well as urging FDA to act swiftly, using the full extent of the enforcement tools the law provides to remove it from the market. Inflammation: opportunities and challenges William Reed Business Media
FDA has already persuaded industry action with All supplier webinars regard to over-the-counter (OTC) pediatric cough/cold medicines. Despite dosage instructions on packaging, TODAY'S HEADLINES the agency raised legitimate concerns that many NBTY 01: Strong brand consumers couldn't determine the appropriate dose performance offsets contract for children of various ages and weights and that the manufacturing exit measuring devices provided with many of those products only contributed to the confusion. So OTC GNC ends tumultuous 2015 with year-over-year net income dip manufacturers collaborated with FDA to develop clearer instructions, new measuring devices that accompany the products, and consumer education to Whole Foods explores promotions as way to shake "whole paycheck" teach parents how to appropriately medicate their moniker children. That's what a responsible industry does. Similarly, marketers of pure powdered caffeine could Traders pound USANA's stock over Steve Mister, CRN slowdown in China sales develop packaging for their purified caffeine in single serve dosages if they want to sell it directly to consumers. That would certainly make the "conditions of use" described in their labeling more feasible and realistic. NPA grassroots voices support for Some have suggested that to acquiesce to FDA and to remove, or even repackage, these products The Health Savings Act would lead to the metaphoric slippery slope, and before we know it, FDA would be alleging vitamin
C isn't safe. Sometimes the "slippery slope" is no slope at all, and a clear demarcation exists. Is Gut microbes' protective effects pure powdered caffeine an ingredient for which we want to fall on our proverbial swords? Does the compromised by alcohol industry think that any dietary ingredient potent enough that a teaspoon of it could kill someone should be available to consumers in bulk form-whether it's ephedrine or caffeine or the purified form of an herbal extract? Consumers don't need access to purified ingredients that are sold in a manner that turns a blind eye to, if not invites, accidental and intentional misuse.
CRN has taken the right path here. We are protecting our consumers from a safe ingredient that becomes dangerous when sold in a bulk pure powdered form directly to consumers. CRN has chosen to put public safety first and we urge other companies to demonstrate that ours is a responsible, mature industry that self-polices as well as knows when to work with our regulators. It's time to wake up and smell the coffee.
Copyright- Unless otherwise stated all contents of this web site are© 2016- William Reed Business Media SAS- All Rights Reserved- Full details for the use of materials on this site can be found in the Terms & Conditions RELATED NEWS: FDA sends warning letters to five marketers of bulk powdered caffeine
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1 COMMENT (COMMENTS ARE NOW CLOSED) This should be classified as hazardous If you ship products in bulk, it should have a hazardous marking on the product if it can cause injury to a person. We work in the bulk bag industry and this applies to any chemical that is being transported in bulk, so caffeine should be no different.