We do not routinely cover enforcement actions by the Center for Tobacco Products, but we do address notable first of a kind action.

Most warning letters from this Center are issued to outlets that sell cigarettes and tobacco products to underage individuals. This warning letter is different and worth addressing because the product type is covered in the news almost every day with current CDC and FDA investigations ongoing into serious pulmonary adverse events including death.

The Warning Letter

Juul Labs (San Francisco, CA) received a warning letter on September 9, 2019 from the Center for Tobacco Products. This warning letter is based on information provided during a July 24 and 25, 2019 Congressional hearing that addressed “Examining JUUL’s Role in the Youth Nicotine Epidemic”, a four day site inspection in September 2018 (yes, a year ago), JUUL’s submission of information to the agency, and the content of their website.

FDA Cites Congressional Testimony

This is the first time I can remember seeing a warning letter cite the content of Congressional testimony as a source of information for enforcement action. The content of the warning letter focuses almost exclusively on the content of the testimony.

In this warning letter, the FDA describes their authority over this product type, particularly for “modified risk tobacco products.” The FDA determined that the JUUL products are “electronic nicotine delivery system products” and are deemed adulterated because the firm is “selling or distributing them as modified risk tobacco products without an FDA order in effect that permits such sale or distribution.” The warning letter states that adulterated and misbranded tobacco products may be subject to refusal of admission if made outside the US and imported to this country.

It’s worth reading the letter to see the FDA logic here. My question is what took them so long; did they really need to wait for a Congressional hearing to make this decision?

The warning letter does not provide any examples of the product being ‘adulterated’ as we use the term with drugs, and no mention is made of observations identified during the inspection in September 2018. Overall, the comparison here would be to a firm that distributes an unapproved new drug with labeling that is not scientifically sound or adequate.

The Congressional testimony focused on the JUUL representative statements and evidence that the product is safer than cigarettes. In addition, during their educational and outreach efforts, JUUL mentions that FDA would be approving the product very soon.

Perhaps I’m naive here, but this appears they are almost bragging about selling a product that is not supported by an “appropriate FDA order in effect.” This appears in direct conflict with a 2012 FDA draft guidance, Modified Risk Tobacco Product Applications which states on page 10 that introducing a modified risk tobacco product into interstate comment without an Exposure Modification Order (FD&C Act section 911(a)) is a ‘prohibited act.’ Further, unlike drugs or devices, the decision supporting the Order is valid for no more than five years, and the applicant must file for renewal.

The JUUL approach also does not appear to be consistent with Investigational Use of Tobacco Products as described on page 43 of the above-mentioned guidance. It is worth noting that in 2016 FDA published a final rule that extended its authority to e-cigarettes which were out of scope of the original FD&C Act amendment addressing tobacco. E-cigarette makers must submit their products to FDA for review by May 2020.

FDA’s Extensive Requests

In addition to the warning letter, the FDA also sent a 12-page multi-item heavily footnoted letter to JUUL Labs, requesting additional documents and information. The requests focus on topics raised at the Congressional hearing as well as additional documents that have been requested but not yet provided. The following outlines these requests.

Educational Engagement and Outreach

The focus of the request is on JUUL’s ‘educational engagement and outreach” where FDA requests “any instructions, training materials, and any other material…provided to those conducting such engagement and outreach.”

FDA expanded the request to include engagement and outreach to Native American groups, particularly identifying the Cheyenne River Sioux Tribe. Additional outreach included those to health insurers and employers with the intent to assist employees to stop smoking, and as a result health coverage costs would decrease.

Nicotine Salt E-Liquids

In addition to documentation supporting educational engagement and outreach to the variety of organizations mentioned above, FDA also requests information on JUUL’s use of nicotine salt e-liquids in its product designed to reduce the bitterness of nicotine. It also triples the nicotine content so that these are now the “most potent e-cigarette on the market” according to text in the letter.

Product Formulation

With regard to product formulation, FDA requests technical information regarding aerosol particle size as compared to combustible cigarettes, design and data from pK studies on the e-liquid product compared to combustible cigarettes, and data on how the design and performance of the device impact the addictive potential of the product. Further, the firm is asked to explain why they use nicotine salt e-liquids and why they use a nicotine concentration of 5% in their products.

Documents Provided to Congress

And finally, FDA asks that JUUL provides previously requested documents including the complete set of documents that were provided to Congress but not provided to the FDA.

I expect potential additional actions; the story is certainly not over regarding this product type. We will monitor this and keep you all informed.