U.K. Packages All Electronic Cigarettes Under Medical Regulation

The U.K. pharma regulator requires all electronic cigarettes to be licensed as nonprescription medicines beginning in 2016, noting concerns about product quality. Meanwhile, FDA considers allowing e-cigarettes to be marketed as nicotine replacement therapy on a case-by-case basis.

The U.K. decision to regulate all electronic cigarettes as drugs highlights a distinction from the U.S. regulatory system, which will consider nicotine replacement therapy proposals for e-cigarettes while allowing sales of the products marketed without a drug claim.

The U.K. Medicines and Healthcare products Regulatory Agency June 12 announced it will regulate e-cigarettes as nonprescription medicines beginning in 2016 regardless of whether they make drug claims. The U.K. also will ask that the European Union recognize nicotine-containing products as medicines.

MHRA said delaying enforcement gives manufacturers time to comply with the safety, quality and efficacy requirements of a medicine. Until then, MHRA encourages “those manufacturers with unlicensed products currently on the market to apply for a medicine license.”

The agency said the quality of e-cigarettes and other non-tobacco, nicotine-containing products not licensed as drugs “can vary considerably” and “licensing them as medicines will allow people to have the confidence that they are safe, are of the right quality and work.” E-cigarettes, battery-operated devices with cartridges to allow users to inhale vaporized nicotine, flavor and other chemicals, currently are regulated as consumer products in the U.K., where an estimated 1.3 million people use them.

The U.K. National Institute for Health and Care Excellence recently published a health guidance supporting the use of licensed nicotine products – such as gums, transdermal patches and lozenges – to help people to reduce or stop smoking, the agency adds.

MHRA said its 2010 proposal to make the change generated “widespread support for medicines regulation from the public health community,” according to a release (Also see "Chart: E-Cigarettes Headed For U.K. Drug Regulation?" - Pink Sheet, 15 Feb, 2010.).

MHRA Chief Medical Officer Sally Davies pointed out that e-cigarette use is surging despite the absence of regulatory standards. “More and more people are using e-cigarettes, so it’s only right these products are properly regulated to be safe and work effectively,” she said in the release.

Jeremy Mean, MHRA’s manager of vigilance and risk management of medicines, said the agency will not evaluate the efficacy of e-cigarettes for smoking cessation, but will require manufacturers to provide data on product quality, nicotine delivery and on how they compare with approved NRTs.

The rule is “not about banning products that some people find useful, it’s about making sure that smokers have an effective alternative that they can rely on to meet their needs," Mean said.

The move comes with U.K. firms already showing interest in gaining indications of harm reduction and smoking cessation for e-cigarettes. For instance, CN Creative Ltd., based in Manchester University’s Bioscience Incubator, submitted an application to MHRA for its Nicadex e-cigarette as a drug and a medical device (Also see "E-Cigarette Firm Targets Harm Reduction In Therapeutic Claim" - Pink Sheet, 5 Mar, 2012.).

CN Creative, which also markets EVOlution e-cigarettes in Europe and the U.S. through its Intellicig business, plans to launch Nicadex first in the U.K. and later in other European Union markets before seeking U.S. approval as a nicotine replacement therapy.

FDA Open, But Guarded

In the U.S., FDA says it is open to receiving new drug applications from sponsors interested in marketing e-cigarettes as NRTs and is not enforcing against those or other nicotine products, such as lozenges, that do not make violative drug or medical device claims. The agency in 2010 set ground rules for regulating e-cigarettes in warning letters to firms about unapproved smoking cessation claims and a summary letter to an industry trade group (Also see "Smoking Cessation Claims For E-Cigarettes Draw FDA Warnings" - Pink Sheet, 13 Sep, 2010.).

However, the agency’s introduction to the e-cigarette industry came in 2009 with an order to stop shipments of e-cigarettes entering the U.S. because tested lots contained toxic materials. A federal court later ordered the ban lifted and agreed with e-cigarette firms that because tobacco is not banned, nicotine delivery devices such as their products should not need FDA approval to be on the market (Also see "In Brief" - Pink Sheet, 13 Dec, 2010.).

Like MHRA, FDA considers quality control a problem in the e-cigarette space. Agency attorney Grail Sipes, speaking at the Food and Drug Law Institute Conference April 23 in Washington, noted that e-cigarettes “vary quite considerably” in quality.

“At this point in time, there still is a great deal that we do not know” about e-cigarettes, said Sipes, senior regulatory counsel in the Center for Drug Evaluation and Research’s Office of Regulatory Policy.

Although e-cigarettes marketed without smoking cessation or harm reduction claims are not under CDER’s oversight, the products are currently not acknowledged as tobacco products by FDA.

Sipes reminded pharma and tobacco industry stakeholders, however, that gaining approval as a medical product requires proof of safety and efficacy.

“If you want to get that product legally marketed for therapeutic purpose you have to prove … in a clinical trial that it’s effective and safe for that use,” she said.

Potential Meets Regulatory Roadblocks

The same concerns the U.K. and U.S. regulators have about e-cigarettes keep the American Cancer Society from endorsing the products as safer alternatives to smoking.

Tom Glynn, director of International Cancer Control for ACS, says quality control varies greatly among the more than 200 companies currently making e-cigarettes. Not only do products vary on the quality of nicotine used, with some containing unidentified contaminants, but also on delivery of nicotine at specific levels.

“For the moment, the ACS still regards them as intriguing, but still is concerned that we don’t have enough data on … what’s in e-cigs across the board. We’re not talking about one product, we’re talking about many products,” Glynn said in an interview.

Consolidation in the sector, though, could weed out low-quality products, he added. “I suspect over the next few years as they consolidate and the weaker companies start to go away or be absorbed, we’ll start to see much better quality control.”

Sipes pointed out e-cigarettes could be brought under the Center for Tobacco Products’ oversight. The center has authority under the Family Smoking Prevention and Tobacco Control Act to identify products in addition to cigarettes, roll-your-own tobacco and smokeless tobacco that it will regulate. Cigars and pipe tobacco also could be added to the center’s oversight.

CTP has yet to publish regulations and guidances for applications to approve for sale in the U.S. tobacco and nicotine products that were not grandfathered in under the Family Smoking Prevention and Tobacco Control Act of 2010.

However, although approval through CTP as a nicotine product would not come without costs for manufacturers, stakeholders predict few firms will choose to submit a new drug application to CDER to approve an e-cigarette as an NRT.

Until CTP determines whether it will regulate e-cigarettes, those products face no pre-market approval.

“Am I going to go the CDER route and jump through the hoops and make a claim, or am I just going to go the other route and just put it out there?” said smoking cessation researcher Jonathan Foulds at the FDLI conference

“Even if I think it helps people quit smoking, even if I have data to show it helps people quit smoking … I’m not sure that I would be persuaded to go the tough route. I might just put it out there and not make the claims,” said Foulds, a public health sciences and psychiatric professor at Pennsylvania State University’s College of Medicine Cancer Institute.

Large e-cigarette firms could find the drug approval route as daunting as smaller firms.

The leading tobacco product manufacturers are entering the e-cigarette space, including Altria Group –parent firm of the largest global producer – saying June 11 its Nu Mark LLC business will launch MarkTen e-cigarettes in August at retail stores in Indiana. However, Altria executives said Nu Mark does not plan to make health claims for MarkTen.

The second and third largest tobacco firms entered the e-cigarette space in 2012. Reynolds American Inc. launched its Vuse brand in limited markets, and Lorillard Inc.’s Lorillard Tobacco Co. business acquired Charlotte, N.C.-based manufacturer blu ecigs.