Electronic cigarettes are the “poster child” for FDA considering new nicotine-delivery products as treatments to help smokers quit using combustible tobacco, says Center for Tobacco Products Director Mitch Zeller.

CTP is working with FDA’s drug and medical device centers on “some sort of jurisdictional policy” to “determine how to evolve the regulation of therapeutic nicotine products, whether they are prescription drugs, over-the-counter drugs, etcetera,” Zeller said Oct. 21 at a Food and Drug Law Institute conference in Washington.

“E-cigarettes, in my mind, are really the poster child for the questions if not the debate that needs to take place on the societal level about nicotine,” he added.

FDA Center for Tobacco Products Director Mitch Zeller

A jurisdictional policy will establish a comprehensive approach that regulates nicotine-containing products along a continuum that acknowledges different types of nicotine-delivery products, which include cigarettes and other combustible products in addition to newer products that vaporize rather than burn nicotine for inhalation, impact individual and public health at different levels.

“It’s a public health opportunity using the tools of regulation to shift people down that continuum. It starts with becoming tobacco-free, and what can we do to move down the continuum where if they continue to need nicotine-containing products, the products they are using are cleaner, safer and less harmful,” Zeller said.

Zeller did not estimate when FDA will issue a jurisdictional policy on nicotine products but said “look for” its publication.

The cross-center discussions are “not public but there is some active and productive internal dialogue going on between the centers on these issues related to nicotine,” Zeller said.

“We need to look at nicotine differently because the very same drug has been regulated by [FDA] for over 30 years as a safe and effective medicine. Nicotine as a medicinal product is so safe and effective that when it’s sold in the form of gum, patch or lozenge, the agency hasn’t even required a prescription for close to 20 years.”

“For FDA that means creating and putting into place an integrated agency-wide policy based on principles of public health for the products that the agency regulates that contain nicotine. This has implications for regulatory policy across the board.”

FDA currently regulates e-cigarettes and other novel nicotine-delivery products as medical products when a therapeutic claim is made. CTP in April published a proposed regulation that adds e-cigarettes as well as other novel nicotine-delivery products, cigars and pipe tobacco to its oversight, but currently the products are not subject to FDA tobacco regulations (see box below).

Some of the devices, which could be called traditional e-cigarettes, provide nicotine in closed, disposable cartridges, most of which will work only with battery devices bearing the same brand, while others – the faster growing part of the market – employ open containers that users can re-fill and use repeatedly and most often are compatible with battery devices from multiple manufacturers.

Following a 2010 federal court ruling that limits FDA to regulating e-cigarettes as medical products, the Center for Drug Evaluation and Research encouraged manufacturers of novel nicotine-delivery products to submit new drug applications as nicotine replacement therapies Also see "In Brief" - Pink Sheet, 13 December, 2010..

However, while sales of e-cigarettes and other novel nicotine-delivery products are soaring, no NDAs have been submitted to FDA seeking approval of novel nicotine-delivery products as medical devices.

For its comment on the development of a jurisdictional policy for nicotine-containing therapeutic products, CDER referred to FDA’s 2012 report to Congress describing the available pathways to market. The report, required by the 2009 Family Smoking Prevention and Tobacco Control Act, states the agency has doubts about the safety of indefinite nicotine use.

Comment In-Box Passes 135,000

FDA is “hard at work at reviewing” the more-than 135,000 comments submitted on the April 2014 proposed rule that deems additional products subject to the agency’s oversight authorized by the 2009 Family Smoking Prevention and Tobacco Control Act, according to Center for Tobacco Products Director Mitch Zeller.

“I’m the first to admit it took us too long to get the proposed rule. I hope to go final a lot quicker than it took us to get the proposed rule out,” Zeller said.

The proposed rule allows e-cigarettes and other products that would become FDA-regulated, as well as products yet to be launched, to remain available for sale in the U.S. without approval by the agency until two years after the proposal becomes a final rule.

Before the end of the two-year period firms must submit for each product an application to remain available, which the agency will review to determine whether a product will remain on the market, and after the grace period, FDA could order an e-cigarette or other product off the market Also see "Turning Back Calendar Could Keep E-Cigarettes Available Without Approval" - Pink Sheet, 6 June, 2014..

FDA said it is unclear “whether individuals who quit smoking but continue to use nicotine (and likely remain addicted to nicotine) are at higher risk for returning to cigarettes, or initiating use of other tobacco products. These potential risks, including the risk of ‘dual use’ of nicotine and cigarettes, raise important public health concerns over and above the specific health risks that may be associated with any particular tobacco product. FDA will take these issues into account while encouraging innovation in the development of new products and treatments to promote abstinence from tobacco use.”

However, the agency in April 2013 liberalized its nicotine replacement therapy labeling evaluations, saying that some risk information for NRT products was outdated and expressing a willingness to work with sponsors to update labeling through the supplement NDA process. The first changes for NRT labeling came in October 2013 with Nicorette and NicoDerm CQ cleared to drop duration-of-use limits and some warnings about risk ([A#05131118005]).

Nicotine Not Without Problems

FDA approval of nicotine-containing products that would be indicated for indefinite use remains a contentious issue in the public health sector, as speakers at the FDLI conference stated. Additionally, some advocates argue that with widespread sales of e-cigarettes, frequently to minors despite state and local age restrictions, the products will initiate children into nicotine use and lead many to combustible tobacco use.

The Legacy smoking-cessation advocacy organization, for instance, opposes allowing e-cigarettes or other novel forms of nicotine delivery to remain available unless approved as therapeutic products. “If [smokers] are recommended by their physicians to use the products to quit, we certainly support that,” said Andrea Villanti, associate director for regulatory science and policy at Legacy’s Schroeder Institute.

Legacy and other smoking-cessation advocates also recommend banning the use of characterizing flavors in e-cigarettes, as the Tobacco Control Act required for cigarettes and loose and smokeless tobacco products.

Villanti acknowledged Legacy’s stance on flavors runs counter to arguments that more smokers will switch to less-harmful products if manufacturers are allowed to continue to use flavors. Research has yet to determine whether including flavors is beneficial, and whether electronic nicotine delivery has detrimental effects in addition to addiction.

“Our recommendation for a ban on flavors comes from what evidence we had,” Villanti said, adding, “We don’t know a lot about the new products out there.”

Tobacco Free Kids senior consultant Mark Greenwold, an attorney who also represents states in litigation with the tobacco industry, is critical of the existing oversight of e-cigarettes by federal, state and local agencies and of FDA’s proposed rule that brings the products under CTP regulation.

E-cigarette displays, Greenwold said, “are right next to the candy” in some stores. “So, pick it up, kids.”

FDA’s proposed rule would prohibit sales of e-cigarettes to consumers under 18 and in vending machines in venues accessible to minors and would require a label warning that nicotine is addictive, but does not ban online sales or establish limits on advertising for novel nicotine-delivery products. Those regulations, and other more-detailed rules for manufacturing and marketing the products, would have to come through a separate rulemaking after the agency establishes oversight of the products in its currently proposed rule.

“Basically, in the absence of regulation under the Tobacco Control Act, there’s no effective regulation on advertising, promotion and marketing of e-cigarettes at the federal level. E-cigarettes are being aggressively advertised, promoted and marketed to kids and the proposed FDA regulations don’t do much about that,” Greenwold said.

Zeller emphasized that prohibiting sales of combustible tobacco and other nicotine-delivery products to minors is crucial, but he also explained that FDA’s regulatory approach must acknowledge that although nicotine is addictive, other ingredients in tobacco products are the causes of cancer, lung disease and other conditions for users.

“Tobacco use remains the leading of cause or preventable death and disease. A disproportionate toll comes from combustible products, but at the end of the day it’s not the nicotine that kills half of all long-term smokers,” he said.

“I’m not saying that nicotine is completely safe … especially when it comes to initiation with nicotine-containing products by kids. Any initiation by kids of any nicotine-containing product, combustible or not, is not good for public health. It’s not good for the still-developing adolescent brain. But at a population level, e-cigarettes, I think, really pose some profound questions that we all need to be asking and thinking about when it comes to nicotine,” Zeller added.

“For FDA as the regulator, what are the implications from those questions for regulatory policy across the board, regardless of the standard for the different categories of nicotine-delivery products that we regulate, whether its tobacco products under the public health standard or nicotine-containing drugs and/or devices under the safety and efficacy standard?”

E-Cigarettes Spark Evolution Of FDA’s Nicotine-Containing Medical Product Regulation

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