This is the second post in our multipart series evaluating the Food and Drug Administration’s response to the Regan-Udall Foundation report on the operations of the Center for Tobacco Products. If you missed our first post, check it out here.
There is a common refrain that appears throughout the Reagan-Udall Foundation report on the Center for Tobacco Products (CTP) at the Food and Drug Administration (FDA) — lack of transparency. The report found that stakeholders generally perceived premarket tobacco product applications (PMTAs) — required for all electronic nicotine delivery systems (ENDS) on the market — as “ineffective and problematic” due in part to a “lack of adequate guidance and transparency regarding CTP expectations,” as well as a “lack of clarity regarding review standards.”
In this segment of our multipart series evaluating FDA’s response to the Reagan-Udall report, we examine a subset of the report’s recommendations forwarded to FDA’s Science and Application Review Task Force for consideration regarding the premarket review process. Although the agency’s response makes general commitments to conduct additional outreach with external stakeholders, the response is light on details. Moreover, the response lacks an express commitment to publishing clearer guidance on the premarket application and review process, as recommended by the Reagan-Udall report, although, it indicates the agency will do so “as appropriate.”
For context, the December 2022 Reagan-Udall report came in the wake of a deluge of marketing denial orders for PMTAs for ENDS — many of which had been pending for years — based on reasons that could and arguably should have been disclosed to applicants ahead of time. Chief among these was FDA’s request that applicants with nontobacco-flavored ENDS submit proof that their products will help adult smokers of combustible cigarettes to completely switch away from or significantly reduce their smoking at rates greater than tobacco-flavored ENDS because FDA had found tobacco-flavored ENDS did not pose the same risk to youth as nontobacco-flavored ENDS. Nowhere in prior PMTA guidance had FDA signaled that this specific comparison was required or that FDA had determined that nontobacco flavors, as a category, were disfavored. In short, for external stakeholders, the premarket review process has lacked transparency.
The lack of transparency has also made some marketing denial orders feel arbitrary. For example, FDA has issued PMTA denials, only to later backtrack and say the applications warranted additional consideration based on information that was evidently overlooked by the reviewers. Moreover, CTP internal memorandum indicates that CTP leadership has had an unusual level of influence in decisions ordinarily made by the Office of Science.
To develop a “clear and predictable framework” for high-quality PMTA and modified risk tobacco product (MRTP) application submissions, the Reagan-Udall report recommended that CTP:
- Prioritize timely development and completion of policies and scientific standards necessary for high-quality submissions;
- Simplify, standardize, document, and publicly disseminate review procedures;
- Further develop operations management capabilities;
- Clarify supervisory roles and responsibilities for ensuring review quality and develop a process for the review team to timely identify novel or complex scientific issues that merit senior management attention or consultation with specialized subject matter experts; and
- Provide more details in public summaries of marketing granted orders, and provide summaries at regular intervals of deidentified reasons why marketing denial orders were issued to provide applicants more insight into CTP’s regulatory decision-making process.
The report also invited CTP to clarify in formal policy the center’s plans for triaging its substantive reviews to conserve resources when there are certain critical sections of the application that can be indicative of whether all sections of the application merit review.
Lastly, to aid FDA in developing and publishing this guidance transparently, the Reagan-Udall report invited CTP to meet more frequently with the Tobacco Products Scientific Advisory Committee (TPSAC). TPSAC has statutory authority to advise FDA on a wide variety of tobacco products’ safety, health, and scientific issues, as well as to provide reports and recommendations on specific premarket review applications. See 21 U.S.C. §§ 387q(c), 387j(b)(2). Because TPSAC’s 12 members are drawn from the health community, government, the general public, and industry, greater reliance and use of TPSAC would not only provide external expertise to FDA, but also facilitate transparency for all stakeholders.
How did FDA respond? It made general commitments to conduct more outreach, convene TPSAC meetings once per year, and dedicate more resources to internal application review and deliberation, but did not expressly commit to revising or making public its premarket review standards and review procedures.
First, the agency committed to conducting more outreach generally. Effective immediately, the response noted that CTP would work internally and through engagement with external stakeholders to better communicate on scientific issues and practices to support efficiency, effectiveness, and transparency, including efforts to streamline review. In spring 2023, CTP will provide additional information regarding the premarket review process in symposiums, conferences, and meetings. By the end of 2023, CTP will conduct a public meeting to explain the current review process and solicit external feedback.
Our Takeaway. This is a positive development, as there should be more opportunities for engagement for stakeholders with FDA moving forward, including in at least one public meeting this year.
Second, with respect to TPSAC, CTP indicated it would hold one or more TPSAC meetings per year. The response noted that FDA may also broaden the committee’s focus to also include discussion of premarket evaluation and individual product applications.
Our Takeaways. This step could also help increase transparency on tobacco products regulation. Many TPSAC meetings are conducted in the public eye, so greater use of TPSAC will provide yet another channel for input from stakeholders. We note, however, that the role of industry on the TPSAC membership is limited, as there are only three nonvoting membership roles for industry representatives who serve as consultants for the nine voting members — seven of whom are drawn from medical fields. (TPSAC’s next meeting is on May 18, 2023, and will focus on FDA’s proposed rule for tobacco product manufacturing standards.)
Third, CTP suggested it would dedicate more resources internally to scientific review. The response noted that CTP will hire additional dedicated personnel to enhance program management and implementation, including for application review, and increase internal communication to improve mechanisms for scientific engagement and deliberation.
Our Takeaways. Hiring additional personnel will not help to streamline, standardize, or simplify the premarket review process. It instead suggests that FDA believes its current approach is working and it simply needs more staff, which is not consistent with the findings of the Reagan-Udall report that suggest substantive changes are needed to the premarket review process. In addition, additional internal communication is all well and good, but it does not address the threat of arbitrariness that could result from CTP leadership overruling the decisions of its Office of Science.
Lastly, although CTP indicated that it would continue to publish PMTA guidance documents “as appropriate,” CTP did not expressly commit to developing and publishing clearer guidance on premarket tobacco product applications and the review process. The response notes that in spring 2023, CTP will resume the posting of scientific policy memos and reviewer guides, “when appropriate.” And, moving forward, CTP will explore options for more transparent and timely dissemination of information, “as appropriate,” as well as convene webinars and issue guidance to industry.
Our Takeaway. The posting of scientific memos, reviewer guides, webinars, and additional guidance are welcome, but it remains to be seen what FDA will deem “appropriate.” It’s disappointing that FDA did not take this opportunity to commit to revising its premarket application and review procedures to simplify, standardize, and document the agency’s expectations, as recommended by the Reagan-Udall report. Although FDA has published guidance and rules on the premarket review process, there are few clues as to FDA’s ultimate standards for authorization, other than heavily redacted decision summaries. Stakeholders are therefore often left guessing at the ultimate evidentiary showing required for marketing authorization, and in many cases, have learned of new standards only after FDA has acted on their applications.
For stakeholders hoping for an overhaul of the premarket review process following the Reagan-Udall report, FDA’s response leaves much to be desired. That said, the response signals the agency is prepared to conduct more outreach, which will hopefully provide greater transparency to a premarket review process that desperately needs it.
