Electronic cigarettes (e-cigarettes), battery-operated products designed to deliver nicotine, flavor and other chemicals to the user, have been marketed for some time as a safe alternative to traditional ciagarette smoking. E-cigarettes turn nicotine and other chemicals into a vapor that is inhaled by the user. However, since their safety and efficacy has not been fully studied, there is no way of knowing whether they are safe for their intended use, how much nicotine or other potentially harmful chemicals are being inhaled during use, or if there are any benefits associated with using these products. In addition, e-cigarettes may lead young people to try other tobacco products, such as conventional cigarettes, which are known to cause disease and premature death.
FDA Warning Letters
In September 2010, the FDA published notice that it had issued a number of warning letters to five e-cigarette distributors for various violations of the Federal Food, Drug & Cosmetic Act (FDCA), including violations of good manufacturing practices, making unsubstantiated drug claims, and using the devices as delivery mechanisms for active pharmaceutical ingredients. The distributors were E-CigaretteDirect LLC, Ruyan America Inc., Gamucci America (Smokey Bayou Inc.), E-Cig Technology Inc., and Johnson’s Creek Enterprises LLC. The FDA determined that the e-cigarette products addressed in the warning letters were subject to FDA regulation as drugs. As such, the distributors could not claim that their drug products could treat or mitigate a disease, such as nicotine addiction, unless the drug’s safety and effectiveness had been proven. Despite this, and without FDA review of relevant evidence, all five distributors claimed that their products helped users quit smoking cigarettes.
Industry Association Letter
At the same time, the FDA also sent letter to the Electronic Cigarette Association outlining the regulatory pathway for marketing drug products in compliance with the FDCA. In the association letter, the FDA indicated that it had determined that the e-cigarette products addressed in the warning letters, and similar products, met the definitions of both a drug and device under the FDCA and the definition of a combination product in 21 C.F.R. Part 3.2(e), with a drug the primary mode of action. According to the FDA, firms which introduced these products into the marketplace would have to comply with the FDCA, including the new drug application (NDA) process.
The NDA process would require an applicant to provide (1) a description of the chemistry of the drug substance and drug product; (2) their manufacturing processes (compliance with FDA Good Manufacturing Practices) and their controls (including in process and end product specifications); (3) a description and characterization of the device; (4) a characterization of the pharmacokinetic delivery of nicotine, including site of absorption and pharmacokinetic parameters associated with use at the recommended dosing level; (5) non-clinical toxicology studies to support the safety of the proposed route of administration (note that the pulmonary route is considered a novel route of administration); (6) any novel excipients and drug substance/drug product impurities; and (7) data from adequate and well-controlled clinical trials to support the safety and efficacy of the product for the intended use.
In addition, if a firm proposes its e-cigarette product for over-the-counter (OTC) use, it may need to perform consumer studies (label comprehension and actual use studies) in addition to the above-mentioned efficacy studies in order to demonstrate that consumers can use these products without a physician.
The Family Smoking Prevention and Tobacco Control Act of 2009 (Tobacco Control Act) (P.L. 111-31), which amended the FDCA, provided the FDA with the authority to regulate “tobacco products.” The FDCA, as amended by the Tobacco Control Act, defines the term “tobacco product,” in part, as any product “made or derived from tobacco” that is not a “drug,” “device,” or combination product.
Under the FDCA, the definition of “drug” (21 U.S.C. sec. 321(g)(1)) includes articles intended: (1) for use in the diagnosis, cure, mitigation, treatment or prevention of disease, or (2) to affect the structure or any function of the body. Similarly, “device” is defined in 21 U.S.C. sec. 321(h) to include articles intended: (1) for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or (2) to affect the structure or any function of the body.
As a consequence, between 2008 and 2010, the FDA determined that certain e-cigarettes were unapproved drug/device combination products and detained and/or refused admission to those offered for import by Sottera, Inc. and other manufacturers. Sottera, Inc. challenged that determination in court.
In 2010, the U.S. Court of Appeals for the D.C. Circuit, in Sottera, Inc. v. FDA, issued a decision with regard to e-cigarettes and other products “made or derived from tobacco” and the jurisdictional line that should be drawn between “tobacco products” and “drugs,” “devices,” and combination products, as those terms are defined in the FDCA. The D.C. Circuit held that e-cigarettes and other products made or derived from tobacco can be regulated as “tobacco products” under the Act and are not drugs/devices unless they are marketed for therapeutic purposes. As a result, the court ordered the FDA to stop blocking the importation of e-cigarettes from China. The FDA decided not to seek further review of this decision.
E-cigarettes marketed for therapeutic purposes are currently regulated by the FDA Center for Drug Evaluation and Research (CDER). The FDA Center for Tobacco Products (CTP) currently regulates cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco. In the future, the CTP intends to regulate other nicotine-containing products, including e-cigarette products that do not make a therapeutic claim.