FDA Deadline Clarification: Hitting the Snooze Button

Posted by Mitch Clarke on 14th Dec 2016

On Dec. 9th, the FDA released a second revision to the requirements outlining the deadline for US manufacturers of tobacco products to register their establishment as well as provide extensive listings for any and all products they manufacture and wish to register for market approval; coming just weeks before the official deadline, the reasoning behind such a move is leaving observers scratching their heads and questioning their best next move.

Applying only to manufacturers that were in business both before and after the August 8th, 2016 cut-offany organizations established after that date need to immediately file for registration before being able to enter the marketplacethe initial previous revision issued last July set the final day for submissions as the 31 st of December, leaving many small business owners with mere months remaining as they scrambled to complete a collection of submissions detailing the many products and countless variations they sell, as well as come up with the associated fees for each product which could quickly compound until a small manufacturer is left to pay a price tag more appropriately attached to a large mansion or European sports car. However, as we approach this dreaded deadline, the FDA released a clarification to their updated requirements: while all applications are technically due in December, the FDA would not be enforcing this deadline, only so long as the applications are received by June 30 th, 2017.

The vibration from thousands of fists simultaneously unclenching was felt around the globe.

While this does provide many manufacturers with a little more leeway to complete their applications, why did the FDA decide at the last minute to delay their enforcement of their policy? Well, to get a good idea of exactly how the FDA tends to handle a sudden influx of applications, we’ll take a look at how the FDA has handled such an event in the past, why this event occurred, and what about it the FDA would like to avoid in the future by remaining lenient with their policy enforcement:

Will History Repeat Itself?

In order for a tobacco product to be approved by the FDA and released onto the market for user consumption, the manufacturer must submit an extensive collection of information pertaining to each individual product. There are many different types of applications, of which the Provisional Substantial Equivalence (Prov. SE) Report, the Regular Substantial Equivalence (Reg. SE) Report, and the PMTA are the most relevant and commonly used.

The two types of SE reports, Provisional and Regular, are the most easily completed for both the FDA and manufacturers, as these reference an existing “predicate” tobacco product as being very similar and therefore comparable in the impact it will have on public health. Eligible for submission any time before March 22, 2011, Provisional SE reports were applicable only to products already on the market between February 2007 and March 22, 2011. As long as the report for such a product also correctly references a very similar "predicate”, the product is allowed to remain on the market until further notice from the FDA. Any Substantial Equivalence reports that don't follow these guidelines cannot earn the Provisional status allowing the product to stay on the market, but will continue as a Regular SE report for (apparently) expedited approval.

Despite having a deadline for submission that has long since passed, Prov. SE reports are by far the most prevalent form of tobacco product submission: over 3100 Provisional SE reports were submitted by major tobacco companies a mere three weeks before the March deadline, creating a massive backlog of applications – one obvious reason why the FDA would speak up to extend their deadline just three weeks before this year’s December deadline. In comparison, as of January 2016, five years after the March 2011 cut-off, only 1917 Regular SE reports have been submitted. And yet, flying in the face of such an early submission date, the FDA has been reviewing these Provisional SE’s at a snail’s pace: as of June 2013, of the 3788 total SE reports they received (3165 of which are reported as Prov. SE’s), the FDA had completed a whopping total of six reports. That’s right, between March 2011 and June 2013, a period of over two years, only six reports had been reviewed to completion.

In April 2013, hearing a growing grumble from the public, FDA staff (credited as Cristi Stark, M.S and Matthew Holman, Ph.D.) compiled a presentation promising:

“In order to protect public health, [Provisional SE] products with the greatest potential to raise different questions of public health are being given higher priority in the review queue.”

However, according to Greg Connolly, DDS, of the Harvard School of Public Health:

“To date [January 16, 2014], with the exception of Newport Gold, all denials and approvals have to date been for niche products with deminimus market share and, in reality, no or extremely limited public health impact…One has to wade through thousands of pages of materials on Newport Gold to realize that some[thing] is wrong in the State of DC. This is not how social democracies work.”

Such slow work may have garnered the approval of the FDA's gastropodous-minded upper management, but for other quick-footed observers, such a clear abuse of authority was enough to accumulate vicious backlash. At least one article—written by three members of the Tobacco Control Legal Consortium and published in the May 2016 issue of Tobacco Control, a highly regarded medical journal covering all facets of tobacco research—identified the FDA’s process as heavily biased in favor of these Provisional SE reports and outlined the dramatic difference between the number of Regular SE and Provisional SE reports completed. The ever-prominent anti-nicotine poster child Stanton GlANTZ, a mechanical engineer whose position at the highly controversial Truth Initiative coalition bought him a seat amongst UCSF's Faculty as Professor of Tobacco Control, had his own various choice words for the FDA.

Criticism for the FDA’s process grew so great, in fact, that the Government Accountability Office (GAO) was sent in 2013 to complete an internal review and, after investigating established procedures and interviewing employees, quickly found severe efficiency issues in need of immediate correction. By October, 2014, performance guidelines were drafted outlining a steady rise in the FDA's completion percentage rate for the years to follow, but these suggestions applied only to Regular SE reports, not the Provisional reports keeping unapproved analogue tobacco products on the market. So, if not made part of these fairly vague performance standards, what steps will the FDA take to ensure that these Provisional reports are completed fairly, accurately, and in a timely manner? The FDA had this riveting statement to put our qualms to rest.

“As FDA gains more experience with reviewing provisional SE Reports, we intend to identify and implement performance standards for these submissions as well.”


Incorrect/Incomplete Submissions

All three types of tobacco applications, the Prov. SE, Reg. SE, and especially the PMTA, require massive amounts of information to be carefully compiled and submitted. This collection of data is wide-reaching and encompasses every aspect of the product, from manufacturing methods to advertising to a complete list of ingredients, not to mention a reference to a “tobacco product standard” as most recently defined by the Secretary of HHS.

With the PMTA being the most complex and least common method of approval thus far, and the FDA's track record for aversion towards pushing progress into the double digits, the FDA has given a Final Notice on only 8 of these reports—all filed by a single Snus manufacturer through GlobalSubmit, a third-party eCTD publisher, and all approved without a hitch. However, in stark contrast to the 100% approval rate it's set thus far, as of Sept 2016, the FDA has refused to even accept the other 98% of PMTAs that have been filed—many compiled by eager spirited, but ill-informed small business owners—and rightly so, because for every single one of these rejected applicants, their lack of success comes from their own doing (or lack thereof). In FDA-Track, the Agency's online data monitoring system, the FDA lists the same reason for every refusal: an incomplete or incorrectly completed application. Given the complex and subtly ambiguous nature of the data required to complete a PMTA, it's only inevitable there would be some screwups. However, when faced with such a high rate of failureespecially when most manufacturers are most likely receiving guidance from experienced law professionals along the waythe fault seems to fall not on the incompetency of the students, but on the inadequacies of the tutors tasked with educating the public about navigating the confusing and needlessly complicated requirements of the PMTA filing system.

In spite of such a high standard of submission quality that falls just short of impossible to achieve, the PMTA is essentially the only path small e-cigarette manufacturers can use to provide their products with market approval; because e-cigarette technology has advanced at such breakneck speeds, the few basic e-cigarette products on the market before 2012 have long since fallen out of favor with a majority of users. An overwhelming majority of modern vape devices often come with recently developed technologies such as high-wattage limits and temperature control capabilities that leave vape manufacturers with no relevant “predicate” product to reference in a SE report.

Only large tobacco companies like R.J.Reynolds, Altria, and British American Tobacco rolling forward with Substantial Equivalence applications (most likely of the Provisional variety) for their late-to-the-game products (e.g. Vuse, Vype, MarkTen, etc.) will be able to use these the outdated models of e-cigarettes (e.g. cigalikes, closed system e-cigs, etc.), which, considering the extremely high fees inevitably assessed with each application, gives them yet another advantage over smaller independent e-cigarette manufacturers.

For many of the small manufacturers and start-ups in the US, gathering the necessary documentation is an extremely confusing and murky procedure; thankfully, FDA has acknowledged this uniquely cumbersome process, providing this inspirational quote for manufacturers losing sight of the proverbial light at the tunnel’s end:

However, FDA recognizes that the forms developed by FDA are new to some manufacturers of newly deemed products and may require additional time to complete accurately. In addition, we are aware that product listing for newly deemed products may result in multiple submissions that the manufacturer must prepare and submit.”

Well, not exactly a message that strikes hope into the hearts of the weary, especially for manufacturers stressfully double-checking their applications to ensure they only need to fill it out the once, but at the very least, giving some sort of notice is most likely a wise move on the FDA’s part, as over 1300 letters have been sent out by December 2012 to manufacturers who submitted incomplete applications. Manufacturers are given a specified amount of time to respond to these letters: this period used to be 60 days long, but because many of these letter recipients took as long as possible to respond in order to further extend their product’s time to remain on the market, this time frame has been reduced to only 30 days in an attempt to speed along the process.

Given the track record of such applications, notwithstanding the 97.9% of PMTA applications refused outright, delaying the deadline for e-cigarette manufacturers to submit their best chance at market approval, a PMTA, is a wise decision. If the FDA estimates creating a single application will take even as little as 500 hours (3 rd party estimates are closer to 1600 hours), the FDA is ill-equipped to handle reviewing thousands upon thousands of incoming PMTAs, especially while tasked with clearing their existing and equally daunting SE backlog.

Why so many applications were sent in despite being incomplete may also be due to the sudden influx of Provisional SE applications that were submitted just before the March 22, 2011 deadline. What mattered to early submitters wasn’t accuracy or efficiency; only allowing their products to remain on the market while the application undergoes review was the driving motivator for many early applicants. These applications could be sent in tons of missing information, but such mistakes are unlikely to be discovered any time in the near future—the FDA’s requests for additional corrected information can come as late as two years after the submission date—let alone require a timely response.

Examples of such bureaucratic inadequacies are readily found by perusing what few SE reports and applications the FDA has actually completed so far: one such report, submitted by R. J. Reynolds (RJR), a major tobacco company behind brands like Newport, Camel, and Pall Mall, is truly eye-opening and gives a glimpse of the sticky bureaucratic mess driving the FDA's actions.

Like many other large and prominent tobacco companies, RJR submitted all of their SE applications well before the March 22, 2011 deadline, earning each of their applications a Provisional status and allowing RJR to keep their products on the market. However, it wasn’t until late October, 2012 – two years later – that the FDA finally noticed something odd about RJR’s applications: in every single one of the SE applications, where each product is designated an existing and comparable “predicate” product, RJR identified the predicate product as “a composite of all cigarettes commercially marketed in the United States as of February 15, 2007.” While an appropriately devious move for a major tobacco company, the FDA requested that, instead of using a hypothetical composite of all cigarettes in existence, RJR identify unique predicates for each submitted application. In November, 2012, RJR refused to edit their applications, reaffirming that the imaginary predicate was indeed accurate and totally applicable to this process.

But was this enough for the FDA to recognize when they were being spun a yarn? Of course not! The FDA took this wildly appropriated evidence and prepared to process the rest of the application; it wasn’t until March of the following year that RJR would be notified of their applications’ continuation to the scientific review portion. RJR was given until May 15 th to submit any amendments to their applications, or else it would be completed as is. On May 14 th, RJR submitted amended SE reports, complete with corrected and unique predicates for each product, but in the end, the FDA didn’t approve RJR’s reports, even in spite of drawn-out extension requests. RJR may have known from before 2011 that they wouldn’t have their applications approved, but because of their efforts, their products stayed on the market for four years longer than they could have otherwise.

Yet another example of the FDA's laughable inefficiency when processing applications comes from an internal review of the Provisional SE report filed by the now (and long since) defunct Pacific Stanford Manufacturing Company.

On December 10th, 2010, PSMC filed a Provisional SE report -- perfectly normal procedure so far, to be honest, it's hard to see what could go wrong. The FDA, never one to call the very next day, waits eleven months before alerting the PSMC via Acknowledgment Letter that their application had been received. But we've learned that with the FDA, an extremely slow yet steadily single-minded pace is to be expected, so we can't even really blame them for what they did next.

A full year later--after (and this is what I can only imagine as the most logical explanation) an absent-minded intern misplaced the only key to the application file closet and the FDA didn't have enough left in the budget that year for a locksmith--the FDA sent a fax to PSMC requesting some various additional information they had neglected to include in their application. Because this is no longer the 20 th century, their fax went unanswered. After letting a month pass, presumably to give PSMC time to fish their fax machine out of storage, the FDA decided to utilize modern technology by emailing their information request to PSMC. As most could've guessed, this attempt iteration did finally garner a response: PSMC quickly replied, informing the FDA that since filing their application over two years ago, they had unfortunately gone out of business and closed their doors for good.

This was certainly an acceptable explanation for their lack of communication and an excellent indication of their intentions for their application. The FDA apologized for not doing their due diligence, immediately closed PSMC’s application, and wished the former owners the best of luck in their future business endeavors.

…at least, in a perfectly sane and logical world, that’s what would have happened. But in our perfectly irrational world, the FDA runs on rails made of red tape, not ridiculous hindrances like reason, so naturally, the FDA remind ed the PSMC to submit a formal withdrawal of their now totally irrelevant and completely inapplicable report, and continued processing the application as normal. A month later, the FDA sent an additional information request to PSMC, this time through paper mail, which, to the dismay of about a third of the office betting pool, went without a response. In September 2013, eight months later, an email reminding PSMC to submit their formal withdrawal was sent out – this, too, garnered no response. Almost a year goes by after this email. At this point, the FDA was starting to think that the PSMC was no different from all the other applicants, no matter what it said. It talked a big talk when it wanted and knew how to play hard to get, but when it came down to it, it just wasn't ready to stick around for the long haul. Well, too bad, its loss.

But...it couldn't hurt to call again. Just to see how it's holding up. And, just maybe, it's changed for the better this time... 

In August of 2014, the FDA informed the PSMC of the upcoming deadline to submit any application amendments before their scientific review, which began on September 26 th. Again, this could not coax a reply from the PSMC. The FDA then put all of the PSMC's stuff in a box and threw it over the side of a bridge.

On April 15th, 2015, after a few too many glasses of wine, the FDA compiled the results of their review and issued a Preliminary Findings letter, instructing PSMC that a response was necessary before May 1 st if they wanted to continue with their application, and they meant it this time. No response was received. On May 8 th, the FDA tried calling the PSMC offices—maybe it was still staying where it grew up, though it seemed more likely that it had gotten its own place by now.

What few phones were remaining in the abandoned office building rang with all their might, but like the hypothetical tree, went unheard. Eleven days later, the FDA gave one last attempt  to reach someone, anyone representing PSMC. This time around, finally, contact was made. However, the PSMC's representative on the other end informed the FDA that they had not yet received the Preliminary Findings letter, but to be fair, nor will they at any point in the future, seeing as by that point the PSMC had been out of business for over four years. The final report review from the FDA says best how they gracefully and maturely handled this newly provided information:

“To date, the applicant has not responded to the Preliminary Finding letter.”


Insufficient/Inefficient Staffing

In early 2011, the FDA saw a massive flood of applications submitted. Equipped with a paltry team of 225 staff members, most of whom were not assigned to reviewing applications, the FDA was largely unprepared to handle the extensive and time-consuming process of sorting through thousands of incoming applications, approving and rejecting each one individually based on an initial inspection, contacting manufacturers through telephone, email, paper notices, and so on. As the years passed and the FDA was allocated more and more employees by Congress through the annual allocations, you would think that at least most of the 426 FDA employees working full-time in 2013—346 of whom were employed in the Center for Tobacco Products—that received salaries supported solely by the quarterly collected tobacco fees would be able to assist in processing incoming applications, but the GAO found in 2013 that in the only office of the FDA actually processing applications, only 102 staff members were actually part of the review process— and only 61 of these staff members spent even a majority of their time on applications. Alone, this shortage of working staff is reason enough for the massive backlog of applications plaguing the FDA as it is; it’s no wonder why the FDA would want to delay receiving the latest wave of PMTAs, given the extensive complexity of these applications and reoccurring inaccuracies that caused the FDA to refuse nearly 98% (366) of all previously submitted PMTAs.

Considering that the FDA’s sparsely-filled staff list is barely enough to process the existing backlog of applications at a rate difficult to regard as acceptable, not to mention undergoing the time-consuming process of reviewing the inevitably incoming influx of inaccurate and incomplete applications, and navigating the murky sludge of bureaucracy surrounding the FDA’s methods of subsequent applicant correspondence, it’s not hard to imagine that the FDA will not only continue to postpone their final deadline until the very last minute, but once they do open their gates to the unprecedented flood of PMTAs, they will let a vast majority of these applications sit to gather dust for years to come.