by Willie McKinney, Ph.D., DABT

Looking ahead after the PMTA submission deadline

Although it’s well outside of their purview, the US Coast Guard motto “Semper Paratus” (always ready) best articulates how to succeed with a Premarket Tobacco Application (PMTA) submitted to the FDA. One key to that success while saving a considerable amount of both money and effort is to plan for the next stages while completing your application. You need to know what’s coming and what your options are.

The first two phases of the post-submission review process are what some regulatory experts might call exclusion tests: measures designed to prevent the FDA from becoming overwhelmed by inappropriate or incomplete applications. Luckily, these prioritization gateways are essentially administrative and easily overcome by thorough preparation and guidance.

The first two responses to your application by the FDA should be predictable. If you’ve submitted all of the mandated documents, which is a straightforward administrative matter, you should receive an acceptance letter. If you receive a refuse to accept (RTA) letter, that suggests you overlooked something in your stack of papers, or you missed a deadline.

The next letter you receive should be a filing letter, which means that you’ve included (ideally with an accompanying checklist to make things easy for the reviewers) all of the items mandated in the Food, Drug, and Cosmetics Act as amended by the Family Smoking Prevention and Tobacco Control Act and specified in the FDA’s industry guidance.[1] If you receive a refuse to file (RTF) letter, you might have missed an item on the list or an item is stuck in the electronic portal.

The real challenge comes with the questions the FDA is likely to have based on the specifics of your application.

Your response to those questions, especially if you disagree with the FDA’s premise or interpretation of data, is more likely to be effective and successful if you focus not only on data but also on tone. Remember that the FDA has considerable flexibility in these matters. For example, it can decide whether to begin enforcement action against a particular product as the one-year period for review comes to an end in September 2021.[2]

Questions about your application at this point are likely to be in the form of a deficiency letter, an environmental information request letter or an advice/information (A/I) request letter. The deficiency letter indicates that the FDA needs additional information to make an authorization decision. The environmental information letter means that the FDA has made a preliminary decision to support a marketing order, but needs more data related to environmental considerations. The A/I request letter means that the FDA needs additional or clarifying information.

For perspective, remember that receiving one of these letters should be considered a good thing. Your application is moving through the system. You’ve shifted the conversation from “SHOULD we consider this application?” to “HOW should we consider this application?”

Don’t fall into the trap of simply trying to provide clarifying information in response to the FDA’s. deficiency and environmental information request letters. That could be misinterpreted as either (1) you think that the reviewers didn’t understand what you’d said, or (2) you didn’t give the FDA all your relevant data as part of your application package. Both responses are tone-deaf. Instead, you’ll be expected to conduct new studies that address these questions before receiving authorization. Be sure to consult the agency about new study designs and request enough time to conduct and analyze those new studies without appearing to stall.

It is very exciting to receive an A/I letter from the FDA because their questions provide insight on the status of your application. However, make sure that you understand those questions. If your answer appears the slightest bit evasive–even if that’s not your intent–it can lead to increased suspicion and additional probing. If you’re unclear about what they’re asking, don’t guess; contact them for clarification.

Additional post-submission steps:

  • The FDA will likely inspect both your manufacturing facility and the clinical/nonclinical laboratories you used for your supporting data. Proactively collect documents that are typically requested during inspections (e.g., Certificates of Analysis). They may also request samples of your product so that they can conduct their own tests.
  • The FDA may refer your application to the Tobacco Product Scientific Advisory Committee (TPSAC). These TPSAC evaluations can be very detailed and complex; expect to spend a lot of time preparing for one. We’ll deal with TPSAC in future articles.

Learn more about how to navigate the PMTA process.

[1] Section V of the FDA Guidance for Industry: Applications for Premarket Review of New Tobacco Products (September 2011). Accessed September, 9, 2020.

[2] Individual Requests for Extensions of Sept. 9 Premarket Application Deadline. Accessed September 9, 2020.