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Vaping, Slurping, & Spitting: Vexing Regulatory Issues for the FDA

    

Guest Post by Jennifer K. Wagner, JD, PhD
jennifer.kristin.wagner@gmail.com

Summary

This post highlights discussions from the April 2, 2014 Science & Society Journal Club and provides a brief overview of the FDA policies related to regulation of e-cigarettes, partially hydrogenated oils, and DTC personal genomics. This is intended to be a conversation starter rather than a final word on the matter.

Introduction

The FDA is on a mission to protect you from yourself. Consideration of the FDA’s handling of three distinct regulatory issues—e-cigarettes (or electronic nicotine delivery systems), junk food (including trans-fats, sugar, and salty food), and the direct-to-consumer personal genomics industry–provides us with a better understanding about why so many people are enraged by (and perhaps eager to rage against) the FDA regulatory machine. A look at how the FDA is trying to regulate these three areas forces us to think about serious questions, such as the following:

  • Who holds the relevant expertise to develop and enforce rules to promote safety and ensure efficacy/effectiveness (i.e., the former referring to whether an article or intervention of interest produces desired results under ideal conditions and the latter referring to whether an article or intervention of interest produces those desired results under typical conditions)?
  • How safe is safe enough?
  • What amount of evidence is necessary and sufficient to prove safety and effectiveness?
  • What should be the default: to allow an item until actual harms surface that are not adequately remedied using existing mechanisms or to restrict an item until speculated harms are demonstrated to be adequately mitigated or avoided altogether?
  • Upon whom should the burden of proof be placed (e.g., the government trying to restrict access, the manufacturers/retailers trying to provide access, or the customer/consumer/end-user)?
  • In what ways is the FDA stretching or exceeding its constitutionally delegated authority from Congress to regulate these areas?
  • In what instances must (or should) the FDA defer to other agencies, such as the FTC, CMS, and CDC?

1. Vaping: E-Cigarettes or Electronic Nicotine Delivery Systems (ENDS)

The “vaping industry” is currently an estimated $2 billion market with projections to grow to a $10 billion industry by 2017. Roughly 200 companies serve this market, with three companies (Lorillard, Inc., NJOY, and LOGIC Technology) dominating 80% of the market. The products offered are diverse in shape and content but generally consist of a battery-operated item that vaporizes a liquid containing nicotine. The liquid is often flavored and, accordingly, is often referred to as a “juice” cartridge. E-cigarettes reportedly deliver nicotine doses in the range 0.025mg – 0.77mg while traditional tobacco cigarettes deliver nicotine doses in the range of 1.54mg- 2.6mg.

There is a continued need for high quality scientific studies on e-cigarettes. The current literature is unclear about their health risks and safety as tobacco products or their efficacy and effectiveness as smoking cessation aids. A 2013 Lancet study suggested e-cigarettes are as effective as nicotine patches in helping smokers quit. A 2013 PLoS One study indicated that e-cigarettes might help reduce nicotine consumption and help heavy smokers quit even when they switch to e-cigarettes with no intention of quitting. A 2014 JAMA study indicated that users of e-cigarettes did not show higher rates of quitting than those smokers who did not use e-cigarettes; however, the study has been criticized as “an example of bogus or junk science.” In 2013 the World Health Organization concluded, “Until such time as a given ENDS is deemed safe and effective and of acceptable quality by a competent national regulatory body, consumers should be strongly advised not to use any of these products, including electronic cigarettes.”

Localities are responding to vaping trends. A number of cities, including Boston, New York, Chicago, and Los Angeles, have now brought vaping in line with smoking and have public bans. States are responding, too. At least four states consider vaping to be synonymous with smoking in the context of indoor smoking bans. Nine states lump e-cigarettes into “tobacco products.” Seven states exclude e-cigarettes from policies for tobacco products (including North Carolina, which explicitly defined them as “vapor products” and not “tobacco products”). There are considerable tax implications on how these products are defined. Minnesota, for example, has passed legislation to collect tax on e-cigarettes at an even greater rate than it does for traditional cigarettes.

The FDA has not yet issued rules and regulations specifically for the vaping industry, though it is collecting data on adverse events and suggested as early as 2011 (see p.8) it planned to regulate the industry. The delay in FDA regulatory action has been called “disgraceful.” The fundamental question of the FDA’s regulatory oversight of vaping is not whether the FDA has the authority to do so, but, rather, under which statutory scheme the FDA should exercise that authority. In other words, are e-cigarettes, aka electronic nicotine delivery systems, tobacco products or a drug/device combination product?

From a public policy perspective, the question as to which statutory scheme applies is an important one. Are e-cigarettes a means for “healthier” smoking and useful harm reduction tools to which American consumers should have broad access? Alternatively, are e-cigarettes gateway products (drug/devices) that should be banned before they undermine de-normalization of efforts? Potential benefits and concerns about e-cigarettes have been summarized at JAMA.

In 2010 in Smoking Everywhere, Inc. and Sottera, Inc. d/b/a NJOY v. FDA, a federal district court in DC issued an injunction blocking the FDA’s regulation of e-cigarettes as a drug-medical device combination product unless the product is provided with a claim regarding its “intended use” as a drug-medical device combination product. The DC Circuit Court of Appeals upheld the decision in 2011. So basically, unless the e-cigarettes are being marketed in a way that suggests their “intended use” is to help people overcome nicotine addictions, the products are not drug/medical devices. Instead, they are to be considered akin to tobacco products. The court explained that the scope of FDA authority here is clear in light of the U.S. Supreme Court’s decision in FDA v. Brown & Williamson and the FSPTCA: (1) the FDCA drug/device provisions cannot be applied to items “customarily marketed” as tobacco products but can be applied to items marketed for therapeutic purposes and (2) items that are “customarily marketed” as tobacco products can be regulated as per the FSPTCA.

The statutory language of the FSPTCA is clear: it defined “tobacco product” as “any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product.” The statute provided the FDA with immediate authority to regulate only cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco, and it mandated the FDA to issue prior notice before exercising regulatory authority over any other products (which would include hookahs and e-cigarettes).  At least 40 US Attorneys General called on the FDA to act quickly to regulate the industry as a tobacco product. The Tobacco Control Legal Consortium is in agreement and filed a Citizen Petition in 2013 also urging the FDA to regulate hookahs, e-cigarettes, and other items as tobacco products. With the CDC’s recent release of the dangerous of e-cigarette poisoning (noting the proportion of monthly poison center calls involving e-cigarettes and traditional cigarettes has jumped from 0.3% to 41.7% from September 2010 to February 2014), the FDA will be under increased pressure to take action. 

Relevant Statutes to Consult:
  • Family Smoking Prevention and Tobacco Control Act (FSPTCA)
  • Food, Drug, & Cosmetic Act of 1938, as amended (FDCA)
Recent FDA Activity:

 

Additional Reading

2. Slurping: Partially Hydrogenated Oils (PHOs) and Junk Food Generally

Food safety and security are bipartisan priorities. Roughly 48 million Americans get sick and 3000 die each year from food-borne illnesses, costing $152 billion/yr. Food safety issues include crop safety (e.g. genetically modified corn and soybeans), animal welfare given “healthy animals help produce safer food” (e.g. antibiotics in feeder animals, humane livestock stewardship, and cultured meats as animal substitutes), presence of contaminants (e.g. salmonella in raw poultry, E. coli in ground beef and spinach bags, Listeria on cantaloupes, and arsenic in apple juice), safety of food additives (e.g. azodicarbonamide in bread and ammonia-treated beef), and food substitutes (e.g. toxic pufferfish mislabeled as monkfish, farmed salmon mislabeled as wild salmon obscuring PCB risks, pangasius imported under alternative names to avoid duties, horsemeat in beef products). Food security issues range from food deserts (inaccessibility of healthy foods) to dangers of drive-thrus and other societal (rather than physical) determinants of food security. Food safety and security responsibilities are shared among 15 federal agencies overseeing >30 related laws (e.g., the FDA oversees 80% of the food supply, receives only 24% of food safety budget funds, and lacks funds to implement FSMA).

A number of policy approaches have been proposed for lowering the consumption of junk food, including labeling (to inform, educate, and warn), taxation (to deter consumption and also to generate revenue for use in combating the resulting healthcare costs arising from that consumption), bans (such as in hospitals and schools) on sales and marketing, and limits on consumption. Some have pointed out that our nutrition policy has been an epic fail. Winkler, for example, has argued that we need to rely not only on the traditional bag of policy tricks (education, taxation, and regulation) but also that we need to make nutritionally improved foods more available and incentivize the purchase of those nutritionally improved foods (in other words, reward good behavior rather than punishing bad behavior). Generally anti-junk food policies have limited political support (a recent Cornell internet study found higher levels of support for policies on calorie labeling and removal of sugar-sweetened drinks from schools than for policies taxing soda or limiting portions).

One of the fundamental questions facing the FDA is upon what lens food safety policies should be focused. Should regulations be based on what government knows individuals, on average, to be doing (e.g., current over-consumption levels)? Should regulations be based on what government prefers individuals to be doing (e.g., minimum or maximum thresholds or targeted nutritional recommendations)? Or should regulations be based on what government knows from scientific studies to be safe or effective (at a level safe for one-time consumption or at a level safe for cumulative consumption or lifetime exposure)?

The industry had been voluntarily reducing trans fats, apparently lowering the trans fat levels in their products by 73% since 2005. The World Health Organization (WHO) had called for a full removal of trans fats from the global food supply. A number of cities (including Baltimore, Seattle, Philadelphia, New York City, and Boston) have placed local bans on trans fats.

In November 2013, the FDA announced that it was making the preliminary determination that partially hydrogenated oils were not “generally recognized as safe.” PHOs (like vegetable oil) were in the food supply since at least 1911, decades before the regulations ushered in by the FDCA of 1938 or FAA of 1958. There never was an official, explicit determination by the FDA that PHOs were “generally recognized as safe,” the FDA never approved PHOs as a food additive. PHOs were simply assumed to be safe because they had been in use so widely in the food industry for so long. Prior to the FDA’s move on PHOs, the FDA focused food safety inquiries on whether the food item caused death or acute injuries. With PHOs, however, the FDA is now addressing food safety also on whether the food item causes chronic illness. The decision effectively means that PHOs are considered food additives and cannot be placed in the food supply unless the manufacturer gets pre-market approval from the FDA. While it is estimated that the phasing out of PHOs from the food supply will cost the industry $12-14 billion over 20 years, the projected benefits are estimated to be $117-242 billion in healthcare costs and deaths avoided.

Trans fat is just one additive though, and it is perhaps an easy one for the FDA because trans fat has no known nutritional value and has been pegged as the culprit of chronic illnesses. In 2010 the Institute of Medicine urged the FDA to regulate sodium levels in food. Yet sodium is an essential element. So the approach used for trans fats is not a viable option. The FDA has also been urged to regulate sugar in drinks. As Jeffrey Senger has explained, “Sugar isn’t the same thing as arsenic. It’s not a food that’s inherently unsafe.” Yet a Citizen Petition filed in February 2013 (signed by dozens of nutrition researchers and public health departments) argued just that: there is scientific consensus that added sugars are unsafe at current consumption levels. WHO (not without its own critics) recently reiterated its 2002 recommendations that sugar intake be less than 10% of total energy intake per day is reiterated and indicated that a further sugar intake reduction to 5% of total energy intake per day would provide additional benefits (i.e., 25g or 6tsp per day for an adult of normal BMI). WHO specifically warned that much consumption of added sugars is done unknowingly, as added sugar consumption is a “hidden” ingredient.

In February 2014, the FDA announced it also will update nutrition labels. The labels will distinguish added sugars from the total sugar content, update serving sizes to reflect “what people actually eat, not on what people ‘should’ be eating,” and add potassium and vitamin D to the required nutrient declarations.

Labeling may be protectionism (using politics to increase marketshare), “falsely alarm” consumers if disclosures are ultimately for safe products, cause consumer fatigue if extensive, and simply be ignored. When discussing labeling, it is necessary to keep in perspective that labeling is a form of compelled speech, a policy approach that is distinguishable from restrictions on speech and government speech.

Getting Americans to eat more healthful foods is not the delegated mission of the FDA. It involves other players as well. The FTC noted that $150 million was spent in 2009 on advertising junk food (i.e., foods high in fat, salt, and sugar) to kids in school. The USDA has announced it will, at First Lady Michelle Obama’s prompting, begin to eliminate such advertising and improve nutritional content in school lunches, vending machines, and fundraisers. The DHHS generally plays an important role in promoting healthier population, and the CDC plays an important role in food safety too. Healthy People 2020 is an initiative devoted to science-based policies to improve our nation’s health in 10 years.

Rage against the FDA with regards to this issue of food safety is aimed at the substance of the rules and regulations rather than questioning the agency’s authority to do something or under which statutory scheme. The scientific evidence is in flux and contradictory (see, e.g., Katz and Meller 2014 and Chowdhury et al. 2014), which makes the FDA’s job challenging. What evidence is necessary and sufficient to show “generally recognized as safe”?  How does that differ from demonstrating an item’s nutritional value? How does the FDA assess risks of foods and food additives?

Relevant Statutes to Consult:
  • Food, Drug, & Cosmetic Act of 1938, as amended (FDCA)
  • Food Additives Amendment of 1958 (FAA)
  • Nutrition Labeling and Education Act (NLEA)
  • FDA Food Safety Modernization Act (FSMA)
Recent FDA Activity:

 

  • Tentative Determination Regarding Partially Hydrogenated Oils; Request for Comments and for Scientific Data and Information (78 FR 67169)
  • Food Labeling: Revision of the Nutrition and Supplement Facts Labels; Proposed Rule (2012-N-1210). Deadline for comments: June 2, 2014
  • Food Labeling: Serving Sizes of Foods That Can Reasonably Be Consumed at One-Eating Occasion; Dual-Column Labeling…Proposed Rule (2004-N-0258). Deadline for comments: June 2, 2014
  • FDA 2011-F-0171, 0910-AG56 (food labeling in vending machines)
  • FDA 2011-F-0172, 0910-AG57 (food labeling in chain restaurants)
Additional Reading:

3. Spitting/Swabbing: Direct-to-Consumer (DTC) Personal Genomics

Rage against the FDA regarding vaping is that it hasn’t been using the right statutory authority to act. Rage against the FDA regarding food safety is either that it has been using an inappropriate focus risk assessment (e.g., safe for one-time consumption versus lifetime exposure; acute harms versus contributions to chronic illness). Rage against the FDA regarding Direct-to-Consumer (DTC) personal genomics is that it lacks the authority to do so, the agency expects industry to follow rules that have not been announced, and/or the agency’s most recent approach is an infringement on First Amendment freedoms of speech.

As early as 1992 the FDA planned to impose premarket requirements on LDTs but instead backed off and chose to regulate the analyte specific reagents (ASRs). As I noted on the Genomics Law Report a few months ago:

For years the FDA has been trying to figure out just what to do with genetic and genomic technologies. The FDA’s proposed efforts in 2006 to regulate in vitro diagnostic multivariate index assays (or IVDMIAs) in 2007 failed, and, in 2010, the FDA signaled its interest in abandoning narrow regulation of IVDMIAs in favor of broadly regulating LDTs. Congressional hearings were held in July 2010, but little tangible policy progress has been made. (See Jeffrey Gibbs’ discussion of the costs of FDA regulation of LDTs.) In March 2011, the FDA held a two-day public meeting to discuss DTC tests, such as the PGS provided by 23andMe. No formal rulemaking has yet been provided to let entrepreneurs know just what game the regulatory agency wants scientific entrepreneurs to play. As Hank Greely aptly blogged, “We’ve all been waiting . . . and waiting . . . and waiting . . . for long-promised draft FDA guidance (or regulations) on regulating genetic tests. Rumor has it that the FDA thought they were done in mid-2012.” In 2011 RUO/IUO draft guidance was issued for research use only and investigation use only in vitro diagnostics (IVDs). In August 2013—the same month that 23andMe launched is new ad campaign—members of Congress pressured the Obama administration to release draft guidance for the regulation of LDTs. There has not yet been a response. The only word we’ve received thus far is the notice from the FDA published in the Federal Register on November 25, 2013 about the distribution of in vitro diagnostic products labeled RUO/IUO “to remind manufacturers that RUO and IUO labeling must be consistent with the manufacturer’s intended use of the device.” (Coincidentally, it is a useful reminder that 23andMe uses such an RUO/IUO IVD provided by Illumina in its service.)

What we know is that the FDA put DTC Genetic Testing: IVDs on its “B List” when it reported to Congress its agenda for fiscal year 2014. This effectively means that the FDA will get to this item only if and when it has accomplished its stated goals on the A List. And we know from the FDA’s previous notices and from the recent cease and desist letter issued to 23andMe, Inc. that the FDA will seek to regulate DTC genetic tests as “medical devices.” Let’s keep in mind the definition of medical device within which the FDA must confine its actions: “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is…intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in many or other animals, or …intended to affect the structure or any function of the body of man or other animals.” The focus is on regulation of an object (something tangible, physical) rather than interpretations of results or information gleaned from that object.

With the approval of MiSeqDx platform, the FDA notes that it is not aiming to prevent access to raw genomic data. The agency is focusing on the interpretation of the data. And if it is the interpretation, how does “know how” or an information service fit under the regulation of a device? Moreover, how many devices would there be? For a whole genome sequencing company, would that provision of a sequence be one medical device (i.e., a genome) or 3.17 billion or perhaps even 6.34 billion “devices” (i.e., taking into consideration the number of base pairs in a human haploid and diploid genome)? Would 23andMe’s PGS be one device or perhaps ~254 (the approximate number of traits and conditions which had been reported prior to the November 2013 cease and desist letter)? The FTC, the agency charged with enforcement of consumer protection laws (including the Federal Trade Commission Act) to stop “unfair and deceptive trade practices,” has indicated in a recent proposed settlement with GeneLink, Inc. that any claims must be “true and based on competent and reliable scientific evidence,” which necessitates two adequate and well-controlled studies per claim (i.e., randomized clinical trials, double-blind and placebo controlled).

If it is information that is being regulated by the FDA rather than the legal fiction used to make a “service” under the statutory guise of a “device,” there is a serious First Amendment question. For example, as the U.S. Supreme Court explained in Sorrell v IMS Health, 131 S.Ct. 2653 (2011), “Speech remains protected even when it may ‘stir people to action,’ ‘move them to tears,’ or ‘inflict great pain.’” So the fact that there is potential, speculated harm arising from access to genomic information that may prompt customers to act (or refrain from acting) is not a strong legal argument. The creation and dissemination of information is speech deserving of First Amendment protection. Green and Farahany (2014) noted, “The FDA now claims jurisdiction over companies that provide health-related interpretations with genomic data (but not those that provide genomic data alone)… The FDA cannot reasonably regulate all such indirect information as medical devices” (emphasis added). Contrastingly, Zettler, Sherkow, and Greely (2014) noted, “23andMe provides this [SNPs and health consequence] information directly…if the FDA does not require any evidence of clinical validity, it would invite chaos-and quacks” (emphasis added). Moreover, what remains to be determined is who decides the intended use of a service when there is disagreement?

The FDA recently announced its proposal to reformat the three-tier risk classification structure required by statute into a five-tier structure and to control access to mobile health information technology. Specifically, FDASIA required the FDA to submit a proposed strategy for health information technology by January 9, 2014 (i.e., the FDA was two months late in submitting its homework to Congress). FDASIA, which was designed to prevent FDA from stifling innovation, requires the FDA to notify Congress at least 60 days in advance of any issuance of draft or final guidance. This proposed rule would redefine Class III medical devices (the class into which the FDA has been arguing that 23andMe’s Personal Genome Service® falls). Interestingly, FDASIA seems to have required the FDA to clarify a “least burdensome” standard that specifies what scientific information is the minimum required for premarket clearances (an attempt by Congress to prevent FDA from requesting information that, while perhaps medically or scientifically interesting and relevant is not necessary for the threshold determination of safety and effectiveness).

Relevant Statutes to Consult:
  • Food, Drug, & Cosmetic Act of 1938, as amended (FDCA)
  • Medical Device Amendments of 1976 (MDA)
  • Food and Drug Administration Safety and Innovation Act (FDASIA)
Recent FDA Activity:

 

Additional Reading:

Concluding remarks

When it comes to FDA action and inaction, there is something for everyone to criticize.

With vaping and e-cigarettes or electronic nicotine delivery systems, criticism is focused on the FDA having clear regulatory authority (FSPTCA) but not exercising that authority quickly enough and not exercising the appropriate authority (trying to force the products through premarket approval processes as drugs/medical devices rather than “other tobacco products”).

With junk food, criticism is focused squarely on (1) the FDA lacking sufficient resources to handle its workload, (2) the FDA’s unwillingness or practical inability to revisit the safety of food additives once they have been determined to be “generally recognized as safe,” even when mounting scientific evidence suggests negative health consequences, and (3) the FDA’s mission creep (i.e., safety and nutrition are not synonymous).

With DTC personal genomics, criticism is aimed at the FDA on the one hand for being too slow to develop broad policies for laboratory developed tests (LDTs) or, on the other hand, for exceeding its congressionally delegated authority, usurping other agencies’ roles (such as the FTC and the CMS), and infringing on the freedom of speech guaranteed by the First Amendment.

There is good reason why the FDA handles different products in different realms differently. Regardless of what action the FDA takes (or actions the FDA doesn’t take), the ground rules the FDA must follow are clear. When the FDA is engaged in rulemaking (i.e., acting as a substitute for Congress) and when the FDA is engaged in adjudications (i.e., acting as a substitute for the Judiciary), the FDA’s actions are subject to challenge for being arbitrary, capricious, an abuse of discretion, or not in accordance with law. The Administrative Procedure Act, the specific statute(s) upon which the rule or order was based, and the U.S. Constitution’s Due Process clause set requirements on what the FDA can and cannot do.

It doesn’t seem like many people are satisfied with business-as-usual. Let’s take a step back and ask what our goals are and what scientific evidence we need to make intelligent, effective policies. If we think the FDA is going rogue and regulating areas it never was authorized by Congress to regulate, we have the ability to challenge those actions. Similarly, if we think the FDA is the right agency for a new problem, Congress has the ability to delegate that new legislative task to that agency (and the people have the ability to pressure Congress to do so).