“Substantial Equivalence”: Massive Backlog at the FDA Center for Tobacco Products

by Micah Berman — Wednesday, Sept. 16, 2015

The key compromise at the heart of the 2009 Tobacco Control Act was this: Tobacco products that were already on the market would be “grandfathered,” but any new tobacco products would have to undergo premarket review and demonstrate that allowing them to be sold would be “appropriate for the protection of public health”—a tough standard to meet, if you’re a cigarette. (Initially, this requirement applies only to cigarettes, smokeless tobacco, and role-your-own tobacco. A “deeming rule” that would extend the FDA’s jurisdiction to other types of tobacco products, including e-cigarettes, is currently being finalized.)

In the grey area between grandfathered and new tobacco products stood “substantially equivalent” (SE) products—products that differ from grandfathered products, but only in very minor ways. The Tobacco Control Act split the difference for these products. A form of premarket review was required for SE products, but not if the manufacturer filed an SE application (referred to as an SE report) by March 22, 2011. Products for which an SE report was filed by that deadline are not fully “grandfathered”—if the FDA concludes that they are not, in fact, substantially equivalent to grandfathered products, they can be pulled from the market—but they can continue to be sold pending FDA review.

Congress perhaps should have, but apparently did not, anticipate what happened next. In short, tobacco companies tried to place as many products as possible on the market by March 22, 2011, and they filed a boatload of SE reports with the FDA at the last possible minute. Between the enactment of the Tobacco Control Act and February 2011, the FDA received only 26 SE reports. But in March of 2011, it received 3,491. To put it mildly, this created a mountain of paperwork for the FDA.

It has now been four and a half years since March 2011, and the FDA has barely made a dent in the massive backlog of SE report. Of those filed by March 22, 2011 (referred to as “provisional SE reports”), the FDA has made final determinations on only 23 of them. (All 23 were determined to benot substantially equivalent, meaning that their manufacturers had to discontinue their sale.) [Update: The current number is now 27; see the update at the end of this post.]

At this rate, it will take the FDA at least another 500 years to clear the backlog of provisional SE applications. And that is not counting the new avalanche of filings that will likely come when the “deeming rule” expands the FDA’s jurisdiction to new types of tobacco products.

Why has the FDA been moving so slowly? For one, it has chosen to prioritize the review new SE reports (those filed after March 22, 2011) over provisional SE reports. Unlike provisional SE products, new SE products cannot be sold without first obtaining a marketing order from the FDA. Therefore, reviewing new SE reports firsts serves the industry’s interest in getting these new products to market as quickly as possible. But this prioritization makes no sense at all from a public health perspective. In delaying the review of provisional SE reports, the FDA is undoubtedly allowing products that the Tobacco Control Act meant to remove from the marketplace to remain available for years.

Secondly, though it is hard to know what the FDA is doing internally, it appears to be conducting the substantial equivalence reviews quite inefficiently. The FDA should be able to quickly conduct an initial review of all provisional SE reports and reject those that are incomplete or plainly fail the statutory standard. Instead, the FDA has been issuing multiple request letters to manufacturers, asking for additional information and clarifications. It is the manufacturer’s burden to submit complete reports and demonstrate compliance with the statutory requirements—not the FDA’s job to help them make their case.

The FDA has said that it is prioritizing the review of provisional SE reports that have “the greatest potential to raise different question of public health” (and are therefore most likely to be found notsubstantially equivalent), but it has not been transparent about how it is doing so. The FDA could, with the help of the public health research community, develop a long list of product changes that “raise different questions of public health,” and reject SE reports that contain any such changes. Taking such an approach, the FDA should be able to address its backlog more speedily. Critically, if a product raises “different questions of public health,” the review process should stop; there is no reason for the FDA to waste its time by continuing to conduct a comprehensive review of a product that has already failed the relevant test.

In sum, the “substantial equivalence” pathway was intended to be a narrow exception to the rule that new tobacco products must undergo a thorough review by the FDA before they can be sold. The tobacco industry has abused this pathway, and in the process, it has stuck with the FDA with a huge backlog of regulatory paperwork. In order to protect public health, the FDA must act much more quickly to ensure that “new” tobacco products are not masquerading as “substantially equivalent” ones.

Update: As I was preparing this blog post, the FDA announced that it had issued “not substantially equivalent (NSE) orders” for four products manufactured by R.J. Reynolds (RJR), including Camel Crush Bold. The order means that RJR can no longer sell these products unless and until they undergo premarket review as new tobacco products. This action is significant, because it is the first time that the FDA has issued NSE orders to one of the major tobacco manufacturers.

Although the FDA is receiving plaudits from the public health community for this action, the FDA’s decision memo also highlights some of the problems discussed above. Focusing on Camel Crush Bold, RJR submitted its SE report on March 18, 2011 (just before the March 22, 2011 deadline). The report failed to identify a “grandfathered” product to which it was supposedly substantially equivalent—the most basic step in an SE report. FDA identified this deficiency almost immediately and alerted RJR. The FDA could have rejected the SE application at this point, but it instead engaged in protracted correspondence with the company. Finally, the FDA told RJR that it would begin its scientific review on May 14, 2013—more than two years after the application was filed—and that RJR would have until then to name a predicate product. RJR complied and named a predicate product on May 14, 2013: Kool Filters King Box. The distinguishing feature of Camel Crush Bold is a crushable pellet that releases menthol flavoring when squeezed; by contrast, the Kool Filters are a menthol cigarette without a flavored pellet. Thus, it should have been obvious that the addition of a flavored pellet raised “different questions of public health,” making the substantial equivalence pathway inappropriate for this product. But instead of issuing an NSE order, even after concluding that the two products were not, in fact, “substantially equivalent,” the FDA engaged in further correspondence with RJR about whether RJR could now name a different product instead of the Kool Filters as the predicate product for comparison (the FDA ultimately said no). The final NSE order was not issued until September 15, 2015—four and a half years after the initial SE report was filed. In short, the FDA ultimately came to the right conclusion, but it took far too long to do so.

This entry was tagged , , .

Cite As: Author Name, Title, Yale J. on Reg.: Notice & Comment (date), URL.

Leave a Reply

Your email address will not be published. Required fields are marked *