Challenges Faced by FDA's Tobacco Product Center Review

Recently, Robert Califf, the commissioner for the United States Food and Drug Administration (FDA), announced an external evaluation of the Center for Tobacco Products (CTP). According to an FDA press release, the evaluation aims to address complex policy issues, develop more enforcement activities, and prepare for future challenges related to new products that may have a significant impact on public health. The review is expected to drive the organization to improve its performance.

Califf is right - the CTP clearly needs help. The purpose of this article is to review how the CTP can achieve its goals in this untenable situation and identify key areas for review.

"Our starting point

Without a doubt, the FDA's Center for Tobacco Products (CTP) finds itself in a highly scrutinized position, with no regulatory approach able to please everyone. The anti-tobacco/e-cigarette groups will never be satisfied until all tobacco products disappear, thus harm reduction proposals will always face opposition. As the CTP attempts to develop an efficiency-driven review strategy, many in the industry claim to be "complete prohibitionists," disregarding the human and economic consequences of harm reduction decisions.

Recently, several court opinions and CTP actions have significantly strengthened the challenges faced by CTP.

West Virginia sues the US Environmental Protection Agency. Although it is not directly related to the Clean Power Plan, the Supreme Court's decision in West Virginia's case against the EPA raises questions about the future limitations of regulatory agency management. The court appears to be preparing to restrict the power of regulatory agencies and return decision-making authority to the legislative branch.

The US Cigar Association sues the FDA. The US Cigar Association has recently filed a lawsuit against the FDA, with Judge Amit Mehta overseeing the trial. The District of Columbia Court reviewed whether the FDA's rules for defining high-quality cigars were arbitrary and capricious. The court ultimately found that the FDA had ignored evidence in the development of the rules and ruled in favor of the Cigar Association, finding the FDA to be in violation.

E-cigarette company Juul has filed a lawsuit against the US Food and Drug Administration (FDA) after it discovered that the FDA's Center for Tobacco Products (CTP) had identified toxicological issues with its products and issued a marketing denial order (MDO). Juul responded by requesting an emergency hold on the MDO in Washington, D.C., which was granted. The CTP stated that it will continue to maintain the MDO and investigate further, citing "unique scientific issues" with Juul's products. Some critics have questioned the CTP's decision to re-examine Juul's application, suggesting it indicates inadequate scrutiny or a lack of confidence in the CTP's decision-making. The entire sequence of events has raised questions about the CTP's review process.

The Center for Tobacco Products (CTP) is still under pressure to make a decision regarding pre-market tobacco product applications (PMTAs) for companies involved in a Maryland court ruling. The CTP states that this ruling will not be completed until next summer. Additionally, the center is faced with the challenge of reviewing approximately 1 million synthetic nicotine PMTAs after the July 13th congressional marketing decision deadline in 2022. It remains to be seen how the CTP will handle this pressure. So far, the CTP appears to be proceeding at its own pace while trying to comply with the Maryland court order.

These external and internal factors indicate a significant conclusion - CTP seems to be struggling and needs some changes. Considering the aforementioned situation, here are a few recommendations for the external (and internal) review of CTP in several areas.

Operational Changes

In terms of its operations, CTP appears to have the resources (staff and budget) to effectively regulate tobacco products. However, certain policy choices and administrative actions seem to hinder the center's ability to manage its space effectively. It's important to note that the complexity of the US tobacco regulation program, along with the lack of clear product testing and approval standards and a murky application process, obstructs effective oversight.

One of the most challenging operational issues stems from the current regulatory framework, which is overly complex for tobacco products. While the Tobacco Control Act sets parameters and requirements, the Center for Tobacco Products (CTP) has some leeway in how they implement these processes. The comprehensive PMTA guidance and strict final rulings demand an excessive level of scientific depth. The question remains: are all the scientific data required to determine if a product is appropriate for protecting public health truly necessary?

Compared to combustible cigarettes, most electronic nicotine delivery products (ENDPs) appear to be easier to determine based solely on chemistry. However, currently, the costs of materials and reviews are compounded by toxicology, human factors, pharmacodynamics, and behavioral research. It is no wonder that the review process takes so long.

If there are no clear standards, CTP and the industry rely on guesswork and speculation to make decisions. While APPH doesn't have a simple formula to understand, clear expectations would be beneficial and effective. For example, which equipment features really need testing? How deep should stability testing be? What constitutes sufficient pharmacokinetic studies? Although initial meetings with scientific offices can help answer such questions, defining specific product standards and minimum requirements will greatly simplify the approval process.

The related reviews also lack transparency, although people can view the technical project reviews and some review standards posted on CTP's website, but few PMTA applicants know the progress of their applications. Apart from the initial pre-PMTA meeting and the sole review result, applicants have little knowledge of the status of their applications. Take Juul as an example, reports show that Juul provided thousands of pages of data related to toxicological issues raised by CTP in MDO, and these issues should be resolved as soon as possible following the court's ruling.

Policy Shift

It's no secret that the policies of the United States government are subject to change. Developing and maintaining long-term policies is difficult, especially given the turnover of each new administration. However, policies aimed at reducing harm should be the cornerstone of tobacco regulation. If reducing harm is a top priority, regulatory agencies should prioritize avenues to reduce harmful products entering the market, encourage innovation, and focus on providing more options for traditional tobacco users seeking to quit.

Harm reduction policy. During former FDA commissioner Gottlieb's tenure, many in the industry believed harm reduction was gaining ground and that everyone recognized vaping products as safer alternatives to combustible cigarettes. Unfortunately, youth usage of several types of vape has significantly increased, putting CTP in a difficult position. Public health groups are dissatisfied with CTP's progress and have resorted to lawsuits to hold them accountable.

Assuming the goal of the Tobacco Control Act remains to lower smoking-related illness and death rates, harm reduction strategies are key to achieving this objective. It is important that all stakeholders accept harm reduction strategies. While the CTP has made some strides forward, is there a plan in place specifically to transition smokers to safer alternative products? Such efforts to move smokers to lower-risk alternatives are futile when these products cannot pass PMTA. Harm reduction efforts are commonly accepted in areas like drug use and sexually transmitted diseases, but we are still searching for the right balance when it comes to tobacco.

Given all the challenges facing CTP, it seems that partnering with non-governmental groups and industry to develop harm reduction policies may not be the best use of time. When CTP was first established, scientific meetings were frequently held to address various issues, such as harmful and potentially harmful constituents. In recent years, these meetings have decreased, partly due to COVID-19 and possibly because of CTP's heavy review workload. Prioritizing sincere and open dialogue between CTP, industry, and tobacco control groups is crucial for developing robust harm reduction policies. Holding scientific meetings on harm reduction plans and policies (through CTP or the Tobacco Products Scientific Advisory Committee) will enhance transparency and allow for all ideas to be put forward.

When considering reducing harm from products, the FDA should not aim for perfection. Currently, PMTA appears to be seeking a perfect solution, focusing on the smallest details that may pose a risk, while neglecting to compare APPH against traditional tobacco products, which are known to contain 70 carcinogens and result in 480,000 annual deaths. APPH does not mean it is risk-free—it means the risk is lower than the deadliest consumer product in history, which is traditional cigarettes. Reconsidering how to assess APPH would be an excellent first step in combating smoking-related illnesses and deaths.

It is necessary to encourage harm reduction. For electronic cigarette companies looking to develop and sell new products, time will be their biggest cost. The product development alone takes one year, followed by a three-year PMTA testing process (including two years for stability and time to plan, conduct, and write research) and then up to three years for CTP review before they can even enter the market. This sounds like a pretty bad investment. The PMTA process needs to change to more quickly bring low-risk products to market.

Society cannot forget about traditional smokers. While the issue of youth tobacco use is important, it is also crucial to address the 1,300 smokers who die every day. There is a need for a balanced harm reduction policy that controls access and exposure for young people, while also encouraging traditional cigarette smokers to quit or transition to lower-risk products.

Advance" or "Move forward" - this is not a complete sentence and does not make sense on its own in standard journalistic English.

It is hoped that an external review will be an effective exercise in providing CTP with strong alternative solutions. If the review addresses the key issues, it can ultimately lead to a reasonable and harm-reducing world for tobacco regulation, giving smokers hope for the future.

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