The chief research officer of the US research organization ARAC interprets PMTAs and the regulatory environment: Age verification is useful but still requires scientific benefit assessment, and companies should proactively adapt to the new FDA requirements

The chief research officer of the US research organization ARAC interprets PMTAs and the regulatory environment: Age verification is useful but still requires scientific benefit assessment, and companies should proactively adapt to the new FDA requirements

In response to the FDA's memorandum on PMTA applications for non-tobacco flavored e-cigarettes, 2Firsts contacted Dr. Jessica Zdinak, chief research officer of the US research institute ARAC. She explained the challenges and necessity of the FDA review process. For age verification technology, she believes that it is useful but still requires scientific evaluation. She also called on companies to increase investment in scientific research to meet FDA requirements.

Disclaimer:

1. The content of this article only represents the personal views of the interviewees and does not represent the position of 2Firsts.

2. This article does not constitute any legal, investment or business advice.

3. The Chinese is translated from the English, so please refer to the English content. Click here to read the English version.

 

The U.S. Food and Drug Administration (FDA) recently issued 13 memoranda outlining its review policy for premarket tobacco product applications (PMTA) for non-tobacco flavored e-cigarettes. These documents clarify the FDA's methods and standards for evaluating e-cigarette products. To further explore these developments, 2Firsts spoke with Dr. Jessica Zdinak, Chief Research Officer and CEO of Applied Research and Analysis Company (ARAC).

 

In the interview, Dr. Zdinak discussed her perspective on emerging age-verification technologies and the challenges facing the FDA in the PMTA process based on her extensive experience in government and industry settings. She noted that while age-verification technology can help reduce the likelihood of underage access to e-cigarettes, it is not a substitute for strong scientific research. She emphasized that manufacturers must continue to conduct evidence-based research to evaluate the effectiveness of age-verification and its role in reducing the use of tobacco products by non-target populations.

 

Here are Dr. Zdinak's key points:

The FDA's "fatally flawed" review process is designed to handle a large number of applications with limited resources, which is scientifically sound but needs clearer communication.

 

All PMTA applications for non-tobacco flavored e-cigarettes are still required to provide strong research, especially randomized controlled trials (RCTs) or cohort studies to demonstrate their substitution benefits.

While age verification technology can reduce risk, it is not a substitute for a thorough scientific evaluation to determine its actual benefit to public health.
The FDA has clarified the review requirements through memorandums and other forms, and manufacturers should proactively meet these standards to increase the success rate of their applications.

DR. JESSICA ZDINAK, ARAC CRO | Source: ARAC

 

Below is the full interview:

2Firsts: How would you rate the fatal flaw in the FDA's internal substantive review process for non-tobacco flavored products, which dates back to July 2021? Can you give us more detailed background?

 

Dr. Zdinak: My understanding of the FDA review memo is that they have to strategize "in real time" to handle the large number of review applications submitted at the same time (or even on the same day).

 

This strategy seems to take into account several factors:

1) The progress of the application in the review process;

2) The time of submission of the application;

3) Whether the application contains specific alternative data;

4) Determining the order of review of the application through randomization.

 

I think that the FDA Center for Tobacco Products (CTP) is a young agency, and these memos are the only way for it to advance its review work in a short period of time. This perspective stems from my years of working with the federal government, and I know that public sector decision-making processes require lengthy coordination and are often more complex than those in the private sector.

 

In addition, at the time some of the memos were issued, the federal government and other public health and tobacco control organizations had begun to take notice of the increasing use of flavored electronic cigarette (ENDS) products by youth. It seems that for this reason, the FDA's Center for Tobacco Products (CTP) established a "threshold" for scientific reviewers to determine whether sufficient evidence was provided in an application. Sufficient evidence was then further defined as "reliable and robust" data presented in the form of an experimental design or longitudinal cohort study. As behavioral science experts, we at ARAC knew that these were the two best ways to demonstrate that flavored e-cigarettes have an additional public health benefit compared to tobacco-flavored e-cigarettes. These types of study designs allow the FDA to directly compare the effects of flavored e-cigarettes to tobacco-flavored e-cigarettes while indirectly assessing the risk to public health. In this case, the risk is primarily from the increasing use of flavored e-cigarettes by youth.

 

As research psychologists, we are scientifically trained to understand that randomized experimental studies are necessary to fully assess the effect of a variable on an outcome and establish causality. However, longitudinal cohort studies can also clearly demonstrate evidence of strong associations by considering multiple variables in analyses and models.

 

We are unable to comment on these memos from a manufacturer's perspective, as we are an independent third-party research organization and are largely unaffected by the FDA's position in these memos. Our focus is to provide manufacturers with the scientific research methods we believe best meet the needs of the FDA. Our experience and success in the US FDA regulatory environment give us great confidence that this scientific background and experience are highly consistent with the needs of the FDA, whether or not it involves the "fatally flawed" process.

 

2Firsts: If non-tobacco products have already applied for PMTAs with age-verification technology, do non-tobacco flavored products still need to undergo RCTs or longitudinal studies during the PMTA process?

 

Dr. Zdinak: Yes, I think all applications seeking to obtain authorization for non-tobacco flavored electronic cigarette (ENDS) products will need to conduct these studies. First, the past cannot be erased overnight. The growth trend of youth use of flavored e-cigarettes a few years ago will not be forgotten in the short term. This phenomenon affects many relevant groups, including parents, school systems, teachers, health care providers, and public health and tobacco control organizations.

 

Based on the data we have seen recently in the 2024 National Youth Tobacco Survey (NYTS), there are some encouraging results showing a significant decline in the use of flavored e-cigarettes by youth. However, this does not mean that there will be less concern about protecting youth from such products.

 

In addition, age verification technology may be a way to reduce youth access to e-cigarettes, but I think it remains to be seen whether it can actually reduce youth use. We have seen a variety of different age verification technologies, but industry cannot assume that as long as a certain technology is implemented in a product, it no longer needs to prove the risk-benefit ratio in the application.

 

I can imagine that the FDA would be interested in evaluating the likelihood that these technologies can be "cracked" or how effective these technologies are in preventing product purchase, first use, and each use. From a regulator's perspective, they may find it difficult to understand why manufacturers are willing to invest tens of millions of dollars in product development, technology innovation, software systems, and other scientific research for PMTAs, but are unwilling to spend an additional approximately $1 million on the research that the FDA continues to require to prove the "benefit" of the product to public health.

 

Age verification technology may well be a mechanism for risk reduction, but the level of "benefit" to smokers will still need to be assessed in a robust, generally applicable, and well-designed surrogate study.

 

One of the maxims I often quote in life is, "When I know better, I do better."

 

I think that applies here as well. Before the "fatally flawed" process was made public, I could understand why companies were not able to understand exactly what the FDA was looking for, and I could understand and sympathize with their frustrations at not having the opportunity to provide these studies to the FDA.

 

However, now that the industry has a clearer understanding of the requirements, most manufacturers are indeed making improvements. But it is still hard for some companies to believe that these studies are necessary, especially with the large number of applications still in the FDA review and decision stage.

 

I hope that things will progress quickly and that the FDA will make many long-awaited decisions. Only then, I think, can manufacturers and industry representatives move forward from the current "freeze or flight" mentality.