Company News

September 28, 2023

This week, Juul Labs Chief Regulatory Officer, Joe Murillo, delivered remarks at the 76th Tobacco Science Research Conference, where he discussed the current state of regulation of vapor products in the United States and the uncertainty facing the category. 

Read the full remarks below as prepared for delivery:

Good morning. I’m Joe Murillo, Chief Regulatory Officer at Juul Labs. 

From the Institute of Medicine’s 2001 report to the passage of the Tobacco Control Act in 2009, to FDA’s Comprehensive Plan for Tobacco & Nicotine in 2017 – the path to introducing less harmful alternatives to cigarettes has been arduous. 

But I have always believed it is essential to pursue a path to transform the marketplace through regulation and innovation. Product technologies and innovations have facilitated products that offer a compelling choice to adults who smoke. Concurrently, other advancements in technology now allow for focused marketing with little or no reach to unintended audiences. Innovations at the product level and retail level have created meaningful controls which can effectively limit access to unintended audiences, particularly those underage. And, important for this audience, significant scientific advances have demonstrated the efficacy of biomarkers of risk and potential harm.

What’s not working? 15 years after the TCA we do not have a clear understanding of the rules of the road for PMTAs. It is still not clear what is needed to introduce new, potentially less harmful tobacco products to the market. Therefore, we do not have a robust, regulated marketplace with alternatives to smoking for adults who can’t or won’t stop using nicotine.

We find ourselves in a world where the vast majority of ENDS products fall into one of three precarious scenarios: One, those being sold illegally. Two, those awaiting a marketing decision from FDA after years of review. Or three, those stuck in a highly opaque administrative process. One that’s subject to shifting requirements and unpredictable timelines.

The market is flooded with illegal disposable ENDS … pouring into the US from China. The illicit market has tripled since 2020, representing more than 40% of the tracked ENDS market. Government data show illicit disposables are driving underage use. None of these products were on the market in 2016. None have been authorized. Some may have submitted PMTAs, but that’s irrelevant – none should be on the market. 

PMTAs, which by statute must be reviewed in 180 days, languish in review for years. ENDS PMTAs submitted in 2020 have been in review for over 3 years. Even post-bolus, applications take at least a year to enter scientific review. The interminable review process has consequences: State-of-the-art innovation will likely be obsolete by the time it navigates the multi-year PMTA process.

For example, In the UK, we have sold JUUL2 for two years and behavioral data show that it is reaching – and switching – smokers. This summer, we submitted a PMTA for that product and we hope it will be taken into review quickly. Should the US be years behind its peers in allowing adult smokers access to innovative, likely less harmful, products?

How is this consistent with what Congress intended when creating the PMTA pathway? A pathway intended to enable innovative, potentially less harmful, tobacco products to reach US smokers. 

The PMTA pathway is not functioning as it should. In the seven years since the Deeming Rule and more than three years after the deadline for PMTAs for on-market products, FDA has issued only 23 MGOs for ENDS, which make 7 distinct products – all tobacco-flavored. FDA has not authorized a single ENDS product in the last 15 months. Adult smokers have tried – and largely rejected – these 7 products, which represent less than 4% of the legal ENDS market. The illegal marketplace dwarfs the market for FDA-authorized ENDS.

This process does not benefit the nearly 16 million adult vapers, who are predominantly former smokers, as well as the millions of adult smokers interested in non-combustible alternatives. The PMTA pathway stands in stark contrast to the Substantial Equivalence pathway, where combustible cigarettes are regularly authorized. It should not be easier to get the most harmful products to market than to get authorization for less harmful alternatives. This system benefits the incumbent cigarette industry which can harvest cigarette profits to provide financial stability as independent ENDS manufacturers struggle for survival waiting for agency action.

The options for being a successful business in this space should not be limited to either 1) relying on your cigarette portfolio to weather regulatory uncertainty or 2) flouting the laws and selling illegal products. We need an efficient and consistent PMTA pathway to ensure a fully regulated marketplace of innovative tobacco products as alternatives for the 28 million Americans who smoke. We have the products – less harmful products that smokers actually want to use, as shown in our purchaser studies. And we have the regulatory architecture to make this work, but we’re all stuck. 

No one wants the agency to get this right as much as my company and me. I want to offer – what I hope – is constructive feedback on how we can improve this process. I have always believed – and still believe – that regulation is the way forward for tobacco products. So please take my remarks in that spirit. 

So – as I’ve said – the PMTA process is not working as Congress intended. In a report commissioned by Dr. Califf, one of the Reagan-Udall Foundation’s strongest recommendations was to set review standards. A key issue is that FDA has still not defined the appropriate for the protection of public health, or APPH, standard. It’s been 15 years since Congress passed the Tobacco Control Act, and we still do not have a shared understanding of the most basic aspect of the PMTA process: the standard under which these applications are reviewed.

Without a clear definition of APPH, FDA’s review of applications has become ad hoc and falls short of the holistic review of the science required by the TCA.Without a clear definition of APPH, FDA’s expectations for PMTAs are unclear. We piece together applications based on our understanding of what the standard might be. Without a clear definition of APPH, FDA’s standards can shift, resulting in inconsistent requirements across applications, and even within the same application.

Defining APPH will help FDA – as the Reagan-Udall evaluation recommended – do a better job of explaining how and why it weighs the evidence, explicitly quantify the trade-offs it is willing to accept, and distinguish policy judgments from scientific information and determinations. Since FDA has not defined APPH or been clear on its expectations of applicants and the data necessary to support a finding of APPH, we’re stuck with the current approach: case-by-case adjudications.

This lack of clarity presents challenges. An obvious example is that the foundational rules for PMTAs post-dated the requirement to submit PMTAs.  FDA has been similarly unclear on what data are needed to support an APPH determination. We’ve learned – again after the submission of ENDS PMTAs – that non-tobacco flavored ENDS must have an outsized benefit among adult smokers. But we have no guidance or precedent on how to establish this outsized benefit or how much of an outsized benefit is sufficient.

Look – I know that some of this mess was outside of the agency’s control. What is within the agency’s control is following the statute and its own guidance. These issues have resulted in challenges to FDA’s review of PMTAs and has led the agency into legal quagmire.

The Courts have criticized FDA for failing to conduct holistic reviews, as the law requires. Most recently, in striking down certain MDOs, the DC Circuit made clear that FDA must conduct an “all-things-considered” review to make an APPH determination. But many in industry have experienced exactly this issue – with their applications denied without a full review against the public health standard.

Courts have also called out the Agency for denying applications on “narrow technical grounds” —  without explaining how these relate to the overall public health consequences of the product. Even FDA recognized in the Final Rule on PMTAs that its decision must be “based on all of the contents of an application.”

We’re not seeing this consistently. For some PMTAs, FDA has completed a holistic review and balanced potential concerns against other data — coming to a determination of APPH. For example, in one review, FDA weighed signals of toxicological concern against substantial reductions in HPHCs compared to cigarettes to support authorization. However, in other reviews, the Agency applied a “do-not-pass-go” approach, relying on discreet issues as a basis to truncate review and reach a negative decision — without considering the entirety of the application. FDA did not evaluate whether data from one area of the application outweighed concerns raised in another.

In some applications, the Agency has not followed established guidance on study conduct and interpretation; something my colleague Dr. Mike Oldham will be discussing tomorrow.

The courts have called out additional issues with FDA’s review of PMTAs outside the scope of the TCA.  Recently, the DC Circuit decided FDA acted arbitrarily and capriciously, in violation of the Administrative Procedures Act, when it moved the regulatory goalposts by denying Fontem’s applications on grounds not raised in its sole deficiency letter – which the court described as an unlawful “surprise switcheroo.”

Regulated industry has a reasonable expectation that FDA’s application process will be consistent and fair. Inconsistent review standards and departing from established guidance is neither consistent nor fair. Clearly, FDA is not evaluating PMTAs appropriately. It’s a different standard than used in other Centers at FDA.  I know acknowledging a tobacco product could have a public health benefit may be difficult. However, it is what the law requires. 

The standard for judging these products is not safe and effective – it’s based on weighing risks and benefits to the population as a whole. And it’s only possible through holistic review of an application. 

Many of these issues with review could be resolved by better communication with applicants during the review process. This engagement is critical for successful applications. FDA has said it expects a minimum of 2-4 deficiency letters per application. But here again, FDA has one process for some manufacturers and a less collaborative process for others. Many applicants received a single deficiency letter followed by an MDO.

But others had many opportunities to engage with the agency –  through advice/information letters, meetings, calls, and amendments. For instance, one company had 18 engagements with FDA during the two-year review of its initial PMTA.  FDA ultimately authorized the product and has since authorized new iterations of that product, additional flavors, and even a modified exposure claim through the MRTPA pathway.   

Iterative engagement with the agency benefits everyone. It enables applicants to answer FDA’s questions and provide data from ongoing research, providing valuable learnings for subsequent applications. I understand that FDA was under enormous pressure during the ‘bolus’ of ENDS PMTAs. Nonetheless, the Agency has a responsibility to engage with applicants to ensure fair and complete application review. The one-strike process has backfired and created less efficiency.

We need to forge a path forward in a post-bolus world. We need to create regular order. 

The Agency’s approach to PMTA review raises another issue: timeliness. The Agency has yet to meet the 180-day review period laid out in the TCA as to any application. I believe that if FDA addressed the issues I raised above – consistent review standards, clear expectations, better engagement with applicants – regular order would naturally flow. Then we can turn to enhancing the process, such as the streamlined reviews advocated for by the Reagan-Udall evaluation. And establishing product standards to make this process even more clear. 

After reviewing millions of ENDS PMTAs, the Agency certainly has the data it needs to pursue this approach, which would be less burdensome for applicants and help CTP more efficiently manage its workload. So where does that leave us?

The process is not functioning, and the market is suffering. As I said at the beginning, I wholeheartedly support FDA and believe in the regulation of tobacco products. While frustrating, I do not believe these issues are insurmountable. To get to a better place requires leadership, vision, and engagement with regulated industry to mold a PMTA process that functions for both applicants and the agency. Only then, can we realize a marketplace of noncombustible products that effectively compete with cigarettes. 

FDA’s public meeting on the PMTA process next month is an encouraging step in the right direction. We expect this to be a meaningful engagement with back-and-forth dialogue between FDA, industry, and other stakeholders. 

We can make this process simpler without sacrificing scientific integrity while still protecting public health. Over the last century, we have seen this market shift incredibly quickly. Now is our opportunity to make that shift beneficial to public health. 

I’d like to remind you of the opportunity that ENDS present. ENDS provide less harmful alternatives to cigarettes that smokers can and do switch to in large numbers. US market data show accelerated declines in cigarette sales following the growth of ENDS. Population-level data show adult smokers transitioning and completely switching from cigarettes to ENDS. Behavioral and economic data show ENDS are substitutes for cigarettes. Population models show ENDS not only accelerate the decline of cigarette smoking – they likely translate to reduced smoking related morbidity and mortality

Imagine how much progress could be made for the 28 million American adults who smoke if we can get this process right. We owe it to them to work with FDA to finally establish the rules of the road and finally provide a marketplace of satisfying alternatives to combustible cigarettes. 

The Tobacco Control Act requires industry and FDA to work together in this process. And we stand ready to work with FDA toward a functioning PMTA pathway. Our shared commitment to making the regulatory process work will help us make significant progress towards ending smoking.