FDA admits that it could start processing e-cig applications in 10 months; it should stop fighting the health groups and just do it

On May 15, 2019, a federal court ruled that the FDA was abrogating its responsibility and set aside FDA’s August 2017 Guidance that gave e-cigarette companies until 2022 (and companies selling other newly-deemed combustible products until 2021) to file premarket applications (PMTAs) to sell their products. Another problem with the FDA’s current policy is that it would allow products to remain on the market while the FDA considered their applications, regardless of how long FDA spent thinking about it.

The court gave the health groups and the FDA two weeks to file their suggested remedies.

The health groups proposed that the judge order the FDA to give the tobacco companies 120 days to file their PMTA applications and give the FDA 1 year to act on the applications, during which time the products could stay on the market.  After that 1 year window, any products that did not have a marketing order would be subject to enforcement and could be pulled from the market. They also called on the judge to require quarterly reports from the FDA on progress it is making in processing the applications.

Other than the effective date (which would be October 2019 rather than the August 2018 deadline in the original deeming rule), this is the process, including the one-year window, that was in the original deeming rule.

The FDA has made its counter-proposal to the judge. 

The FDA opens with a vigorous argument that the court does not have the power to order a specific schedule. 

But, if they lose the argument that the judge should leave the agency alone, the FDA admits that it could get the job done if the deadline for submitting applications was set 10 months from now (around April 2020).

That’s a lot better than 2022.

But the FDA also wants the judge to allow it to permit specific products to stay on the market for more than a year if the FDA is still thinking about what to do with their applications.

That’s bad; FDA should be required to stick with the policy in the original deeming rule.

The FDA justifies the longer time before the deadline on the grounds that it could receive a flood of from 5,424 to 6,724 PMTA applications, including 1,610 to 2,950 from e-cigarettes alone, and that it is likely that a lot of these applications will be poorly done and inadequate. 

While the FDA is probably right that all the applications will be dumped on it at the last minute – they note that in March 2011, manufacturers submitted 3,000 of the total 3,600 provisional substantial equivalence applications within the last several days before the deadline – the fact is that the FDA (and the companies) have known that the deeming rule was coming since the Family Smoking Prevention and Tobacco Control Act passed in 2009, even if the FDA didn’t get around to issuing the rule until 2016.

Even then, both the FDA and companies could have been getting ready for the original 2018 deadline.  (The FDA reports that not a single e-cig company has submitted a PMTA even though they could have done so for the last three years.) As Judge Paul Grimm concluded in his Memorandum Opinion, “manufacturers long have been on notice that they will have to file premarket approval applications, substantial equivalence reports, and exemption requests, and if they have chosen to delay their preparations to do so, then any hardship occasioned by their now having to comply is of their own making.”

Given that everyone will do everything at the last minute anyway, that is no reason for delay.

Moreover, it is not the FDA’s responsibility to prepare the applications for the companies any more than it is NIH’s job to write grant proposals for me.  The FDA has been going to great lengths to advise industry, and if a company can’t put together a decent application, they have no business selling a product as toxic as an e-cigarette.

So, here’s our proposal:

The FDA and health groups split the difference at 7 months with the original provision that no product can stay on the market more than a year after the application has been submitted unless the FDA has issued a marketing order, the process FDA announced in the original deeming rule.

Regardless of the specific deadline set, manufacturers will submit their PMTAs within a few days of the deadline. If FDA or the court set a compliance date for 10 years from today, all of the applications would almost certainly be submitted within a few days of that date in 2029. 

This problem could be resolved by setting up a staggered system so that PMTAs are submitted over a period of time, thus not creating an “undue administrative burden” on the FDA. Amici’s brief at p. 6 states that “ENDS manufacturers come in different shapes and sizes, with vastly different levels of resources.”  The court can consider that fact when setting up a compliance timetable, allowing smaller manufacturers with fewer resources another 6 months to submit PMTAs than larger manufacturers (like Juul, Philip Morris, and other multi-billion dollar companies) who have almost certainly begun, if not completed, most of the tests necessary for a PMTA to meet the shortest deadline.  These are, after all, the companies with the most sales, too.

That would avoid more litigation, represent a tremendous improvement over the status quo, and a big win for public health.

Here are more details for people who want them:

The FDA needs to stop making over-optimistic assumptions about e-cigarettes

One of the troubling arguments that the FDA made several times in its brief was this: “And Plaintiffs’ [the health groups’] proposed timeframe could adversely affect the public health by abruptly clearing the market of e-cigarette products, creating a genuine risk that former smokers addicted to nicotine could migrate back to conventional cigarettes.”

There are several problems with this argument:

• It ignores the fact that most smokers who use e-cigs do not “switch,” but rather become dual users where they continue to use both products.
• Dual use carries higher risks for heart and lung disease than just continuing to smoke.  .
• Even “switching” does not confer any benefit in terms of heart attacks because the risks of being a current e-cig user add to the risks of being a former smoker.
• We don’t know that these former smokers would go back to cigarettes; they might just quit all tobacco use.
• While some smokers do successfully use e-cigarettes to stop smoking cigarettes, for the population as a whole, smokers who use e-cigs are less not more likely to quit smoking, i.e., for most people, e-cigs keep smokers smoking.

While the FDA gives lip service to the epidemic of youth vaping, they still don’t take it seriously.  The best study of the trade-off between e-cig’s helping adults quit and promoting youth initiation found that for every adult who quit 80 kids started.  And even that 80-1 ratio is overly optimistic for two reasons: (1) the estimates of the value for e-cigs helping people quit was based on the most optimistic randomize clinical trial showing of the use of e-cigs for quitting while, as noted above, in the real-world population, e-cigs make it harder for most smokers to quit, and (2) the data on youth initiation was collected before Juul took off, so grossly underestimates youth e-cig initiation. 

The FDA’s argument also prejudges the PMTAs that the companies are required to submit in a way that takes the companies’ likely arguments as established, rather than requiring the manufacturers to provide affirmative evidence that the statements that the FDA makes are, in fact, valid for the products in question.  In particular , to obtain a marketing order from FDA, the manufacturers would have to demonstrate in their PMTAs that their products are “appropriate for the protection of the public health” by presenting scientific evidence showing the likelihood that non-smokers and former smokers will not start smoking cigarettes.  FDA’s contention that e-cigarettes “may be less harmful” than cigarettes is as yet unsubstantiated conjecture, and FDA’s statements presuppose the outcome of future PMTA submissions.  And even if as a general rule, ENDS products could be shown to be less harmful than combustible cigarettes, the burden is on each manufacturer to demonstrate in their PMTA that their particular product is appropriate for the public health. 

FDA should focus on the public health concerns inherent in allowing products to be marketed that have not undergone any agency review.

FDA should ban flavors, as they tried to do under Obama

FDA also argues that setting the deadline for submission of premarket applications to no sooner than 10 months would also allow the agency to finalize its March 2019 draft guidance setting forth its enforcement priorities in the interim, stating FDA plans to do so within 120 days. 

The original Deeming Rule called for a complete ban of flavors – including menthol and mint – in newly deemed products unless a company could make a specific case for a specific flavor in a specific product, but Obama’s Office of Management and Budget deleted that part of the deeming rule. 

FDA made a strong public health case for this strict regulation of flavors in the 17 pages OMB deleted.  Instead of following its own experts’ preferred approach, FDA’s March 2019 draft guidance calls for prioritizing enforcement of flavored e-cigarette products – except tobacco, mint, and menthol flavors – offered for sale in stores after August 2021 if the manufacturer has not submitted a premarket application and offered for sale online without “heightened age verification.”  This is exceptionally weak and is simply what the companies want.  This approach relies on some incorrect assumptions, including that youth and young adults are not attracted to mint and menthol-flavored e-cigarettes, that online age verification systems effectively block youth from purchasing contraband products online, and that adult smokers who switch to e-cigarettes would “migrate back” to using combustible tobacco products if bubble-gum, mint, and menthol-flavored e-cigarettes weren’t available.

Rather than focusing on this weak youth access control, FDA should implement its original well-justified plan to regulate the product and ban flavors – including mint and menthol -- in e-cigarettes unless manufacturers could make a specific case that including a specific flavor in a specific product would be “appropriate for public health.”

The excuses for further delay are not valid

Both the FDA (in Mitch Zeller’s declaration) and the tobacco companies (in their amicus brief) say that the companies won’t have time to prepare proper applications because the FDA just issued an updated guidance document on how to prepare a Premarket Authorization Application for e-cigarettes.  In fact, the draft of this document was issued over three years ago, in May 2016.  The FDA just (June 2019) finalized the guidance. 

While we have not done a line-by-line comparison of the May 2016 and June 2019 guidances, we only saw a few differences:

• There are several definitions that are different or new.  For example, "e-cigarette" is defined in the new final guidance as either "open" (refillable) or "closed" (e.g., e-liquid is contained in cartridges or pods, which would include Juul and similar e-cigs).
• The final June 2019 guidance has a section on "comparison products" (p. 13-14) that recommends comparing applicant's new tobacco product to products of both similar and different categories and subcategories. This is probably a good idea. For example, a big problem with PMI's PMTA for IQOS is that PMI compared IQOS to cigarettes, but not to e-cigarettes, which would have made it harder for the FDA to conclude that allowing marketing of IQOS was “appropriate for the protection of the public health.”  (More on this later.)
• While neither the draft nor the final guidance pay enough attention to dual use, the final guidance may be a bit better on this.
• Both guidances use a lot of space to discuss batteries, but pay little attention to chips and other software and technologies, such as the ability for companies to track how individuals use e-cigs (Juul is planning this and PMI IQOS already does it), a technology that companies could use to “tune” the e-cigarettes to make them even more addictive for every person who used them.  (More addiction = more pod and heet stick sales.  The new final guidance mentions software, but not in the context of measuring puffing behaviors, or things like two-way communications being used to encourage consumers to buy more refills.

The other key points we identified in the guidance are all sensible and things that the companies should have been thinking about for years:

• p. 13 - recommends that applicants compare the health risks of its product to both products within the same category (e.g., ENDS) and subcategory (e.g., e-liquid, closed e-cigarette, pre-filled open e-cigarette) as well as products in different categories (e.g., cigarettes, cigars).
• p. 14 - last sentence of section on Comparison Products (an afterthought?): "Polytobacco use risks should also be considered."
• p. 14 - recommends that companies include "nicotine exposure warnings" on labels. E.g., "WARNING: Contains nicotine, which can be poisonous. Avoid contact with skin and eyes. Do not drink. Keep out of reach of children and pets. In case of accidental contact, seek medical help." or "WARNING: Contains nicotine. Do not get on skin or in eyes. Do not drink. Store in original container and keep away from children and pets. In case of accidental contact, call the Poison Control Center a 1-800-222-1222."
• p. 14 - "Nicotine exposure warnings" are in addition to the required warning statement regarding the addictiveness of nicotine.
• p. 20-22 - Lays out "descriptive information" required.  List of required information does not appear to include software or chips, and does not include pH (although these factors are mentioned later in Guidance)
• p. 28-29 - Lists 33 constituents or chemicals plus "other constituents as appropriate for your particular product" (including, for example, flavorants that can be respiratory irritants such as benzaldehyde, vanillin, and cinnamaldehyde) that FDA recommends should be considered.  This list notably includes "nicotine salts" under the category "nicotine from any source."
• p. 30 - Recommends that companies report the pH of the e-liquids tests and the resulting aerosol, in addition to the constituents.
• p. 37 - recommends submitting data and considerations addressing the human health impact of the new tobacco product, including biomarkers of exposure, biomarkers of harm, health outcomes, looking at users and nonusers, dual users, users who opt to use new product instead of FDA-approved cessation medication, youth, never users, former users, etc.
• p. 38 - says consumer perceptions and intentions evaluations should address nonuser populations and vulnerable populations such as youth and young adults.
• p. 41 - recommends including potential impact of flavors on product toxicity and appeal to youth and young adults. Points out that since e-liquid is not food or intended or oral ingestion, the fact that some substances have been designated generally recognized as safe (GRAS) for food does not mean that they are safe for inhalation.
• p. 42 - recommends examining adult appeal of flavors in their decisions to initiate use, cease use of more harmful products, or dual use.
• p. 42-43 - e-cig design factors to consider - includes "capabilities to monitor product performance (e.g., temperature sensing, voltage sensing, battery life detection), but doesn't mention puffing behavior, level of e-juice or messages to buy more that could be generated by devices that communicate back to the manufacturers.
• p. 46 - recommends that "if e-cig is software-driven," should include "the function(s) for which the software is used (e.g., controlling temperature, nicotine content, flavor delivery)."  These are all functions internal to the e-cig; the FDA ignores two-way communication with the company or other third parties.

FDA’s and Amici’s (the tobacco companies’ and allied advocacy groups’) central argument that Plaintiffs’ timetable would jeopardize public heath presupposes the outcome

• FDA argues at p. 6 that clearing the market of thousands of e-cigarette products would “rais[e] the risk that some former smokers addicted to nicotine might migrate back to conventional cigarettes.”
• FDA argues at p. 7 that for “cigarette smokers who completely switch to ENDS, these products may be less harmful at an individual level than combustible tobacco products” and the “mass market exit: of e-cigarettes “would limit the availability of a potentially less harmful alternative for adult smokers seeking to transition or stay away from combustible tobacco products,” and this “could present a serious risk that adults, especially former smokers, who currently use ENDS products and are addicted to nicotine would migrate to combustible tobacco products…”
• Amici argue at p. 15 that “wiping out” the ENDS industry and driving ENDS products off the market “would endanger public health, risking a significant reversal in the historic downward trend of cancer-causing cigarette consumption.  Many of the roughly 14 million ENDS users have switched, or are transitioning, from very harmful cigarettes to ENDS products.”

As noted above, these arguments presume that if PMTAs were submitted and evaluated for particular ENDS products, the manufacturers would prove the truth of these statements.  Indeed, evidence that these statements are true would be necessary for the manufacturers to demonstrate that their products are “appropriate for the protection of the public health” by showing that current smokers would be less likely to use cigarettes, and that the subject products are indeed less harmful than combustible cigarettes (not that they “may be less harmful,” which is as yet unsubstantiated conjecture).

These arguments also assume as true a “genuine risk of migration” (FDA, p. 12-13) by adults from ENDS back to combustible cigarettes, and that “many of the roughly 14 million ENDS users have switched, or are transitioning, from very harmful cigarettes to ENDS products” (Amici, p. 15).  Once again, these statements are assuming the conclusions the manufacturers need to demonstrate in their PMTAs; namely, that some number (how many of the roughly 14 million ENDS users?) are using ENDS because they quit smoking, and how many of these former cigarette smokers have “switched completely,” and that these numbers trump the 3.6 million and counting of youth who have initiated nicotine use with ENDS.

And even if as a general rule, ENDS products can be shown to be less harmful to combustible cigarettes, the burden is on each manufacturer to demonstrate that their particular product is appropriate for the public health.  Even Amici’s brief admits this point at page 11.  It says that when commenters to the Deeming Rule emphasized the public health benefits of ENDS and argued that restrictions on their access would be detrimental to public health, “FDA responded that its “ ‘consideration of [the] public health benefits’ of the products ‘will be included in FDA’s review of PMTAs based on the evidence.’ [81 FR at 28,995/1].” 

FDA and the tobacco companies and their allies (the Amici) cannot use an assumption of public health benefits as the basis of an argument that the court or FDA should not set a timetable for requiring manufacturers to submit PMTAs. Rather, the court should focus on the public health concerns inherent in allowing products to be marketed that have not undergone any agency review.  In addition to the perhaps more subtle questions of whether ENDS products in general are less harmful than combustible cigarettes, what about simpler concerns of whether a particular product is tainted in some way, uses toxic additives, or is otherwise unsafe, adulterated, or misbranded?

FDA’s and Amici’s (the tobacco companies and their allies) arguments that Plaintiff’s proposed remedy violates the Administrative Procedures Act (APA) seem flawed

• FDA argues at p. 5 that the court should not substitute its judgment for the scientific expertise of the FDA, and should instead remand to the FDA to permit it to choose a new course of action, and cites TCA section 2(44) to support this point. However, FDA’s expertise in evaluating “scientific studies supporting claims about the safety of products” has nothing to do with the agency’s ability to make a policy decision about setting a timetable for reviewing those scientific studies and safety claims.  “Scientific expertise” is not at issue on this particular point.
• FDA argues at p. 3 that “absent unusual circumstances not present here, it is inappropriate to issue an injunction imposing specific duties on the agency.” Although I have not read the cases cited in footnote 2 on page 3, even FDA’s brief one-line statements of the holdings of those cases seem to show similar, rather than unusual, circumstances that are, in fact, present here.  The cases cited seem to rely on a failure of the agency in question to enforce the very laws they were mandated to uphold, resulting in the public not being protected by the very agency tasked with protecting them. The court in the present case accepted similar arguments made by Plaintiffs that by extending the compliance date for submitting and reviewing PMTAs, the FDA violated its mandate and failed to protect the public health.  As Micah Berman’s recent paper “The Faltering Promise of FDA Tobacco Regulation” highlights, FDA has a history of repeatedly failing to meet its mandates and protect the public health since the TCA was enacted in 2009 and shows a similar “pattern of actions” that perpetuate the public health crisis it was tasked to address.
• FDA’s “separation of powers” argument at p. 14 seems similarly flawed.  If an agency fails to meet its statutory mandate to enforce laws under its authority, it is violating the law and courts can and should address these failures.
• The tobacco companies and their allies (Amici) argue at p. 9 that the court should not set aside the August 2017 Guidance, but should instead instruct FDA to determine what are the necessary next steps. However, in this case, setting aside unlawful agency action without also imposing a remedy would put Defendants in a better position and Plaintiffs in a worse position than before the lawsuit was filed, because then the manufacturers would have absolutely no required deadlines or compliance dates, and therefore their products would remain on the market indefinitely without any agency review.
• Amici cite the Deeming Rule at 81 FR p. 28977 for the proposition that agencies are “not subject to the requirements that govern notice-and-comment rulemaking.”  However, they left out a key point that is stated in the very next sentence: “a compliance policy guide is not a substantive rule and is not subject to the Administrative Procedure Act’s (APA) notice-and-comment rulemaking.”  Wouldn’t this mean that FDA’s and Amici’s argument that Plaintiffs’ proposal violates the APA falls on its face, because a compliance policy is not subject to the APA?

Lauren Lempert collaborated with me to prepare this blog post.