3 FDA CTP Memos to Assist in Building Premarket Applications

The Substantial Equivalence and Premarket Tobacco Product Application final rules were both issued in late 2021 and are two of the most commonly used pathways through which a manufacturer can seek marketing authorization for a new tobacco product from the FDA CTP. They are both very comprehensive documents with specific direction for required submission data to be included. Even with these guidelines there can be confusion as to what is actually required to be included for a successful application. Here are 3 CTP memoranda which may help manufacturers further refine their science plans in advance of submission. These memos are in some cases several years old but I believe they are still relevant and useful despite the current regulatory stalemate.

1️⃣ CTP interpretation of requirements for filing under 910(b)(1)(A) as it pertains to information that is not generally necessary for a substantive determination on a premarket tobacco product application. November 17, 2017

The purpose of the filing review is to determine the basic adequacy of the information submitted in the application such that CTP is able to proceed with substantive scientific review of the PMTA. Based upon CTP’s review experience to date, we have identified certain types of scientific data and information that generally do not contribute to CTP’s substantive scientific review and are not required for filing an application.

• Case report forms (CRFs) from clinical studies.

• Raw chromatograms/spectra/mass spectra arising from analytical chemistry testing (except those needed as representative to demonstrate the adequacy of separations/specificity, standard solutions,and sample solutions); and,

• Raw (meaning no integration of the data) output from high-throughput (e.g., genomic) studies.

2️⃣ PMTA Review: Evidence to Demonstrate Benefit of Flavored ENDS to Adult Smokers. August 17, 2021

• The purpose of this memo is to describe our findings with respect to the type of evidence that may support a finding that the marketing of a flavored ENDS is appropriate for the protection of the public health (APPH), in light of the significant concerns that flavored ENDS present with respect to youth appeal, uptake, and use. Specifically, FDA has determined that the known and substantial risk to youth posed by flavored ENDS establishes a high burden for applicants seeking to demonstrate a potential benefit to adult smokers that could justify that risk.Based on existing scientific evidence and our experiences in conducting premarket review employing the APPH standard over the last several years, FDA has determined that, to effectively demonstrate this benefit in terms of product use behavior, the strongest types of evidence should be submitted—most likely product specific evidence from a (1) randomized controlled trial (RCT) or (2) longitudinal cohort study.

3️⃣ Scientific Review Job Aids. February 18, 2021

PMTA Process Flow