The following statement from Dr. Scott Gottlieb was issued today via an FDA Press Release which deals with substantial equivalence among other things.
Our comprehensive plan on tobacco and nicotine regulation, unveiled in July 2017, aims to tackle the leading cause of preventable death in the U.S. by focusing on two key areas: reducing the nicotine levels in combustible cigarettes to render them minimally or nonaddictive; and harnessing new forms of nicotine delivery that could allow currently addicted adult smokers to get access to nicotine without all the risks associated with using combustible tobacco products.
In order to secure these goals, and to advance our efforts to protect kids from the harms of tobacco products, we’re committed to issuing foundational rules to make the science-based regulatory review process more efficient, predictable, and transparent for manufacturers, while upholding the agency’s public health mission. In particular, it’s critical we have a strong, science-based application review process that ensures new products meet public health standards by evaluating important factors such as ingredients, product design and health risks.
One way we can help achieve this is by developing new guidance and regulations to further clarify the rules of the road for what information the FDA needs in order to review and potentially allow new tobacco products to come to market.
We’ve already made progress toward putting into place the proper scientific and regulatory foundation to efficiently and effectively implement the Family Smoking Prevention and Tobacco Control Act, including updating some of our product application review processes, gathering input from stakeholders on that process and taking steps to provide additional information about the FDA’s science-based review and decisions to manufacturers.
Today, we’re announcing several new actions as part of our commitment to ensure sound regulatory oversight of tobacco products and an effective application review process that considers the impact on public health.
First, we’re issuing a proposed rule (to be released April 2nd, 2019) that would establish requirements for the content and format of reports manufacturers must send to the agency to demonstrate the substantial equivalence (SE) of a new tobacco product. This proposed rule, which will be open for public comment, will also provide information as to how the agency intends to evaluate these submissions.
The SE pathway is one way in which a manufacturer can seek marketing authorization for a new tobacco product. In order for a new tobacco product to be substantially equivalent, the FDA must find that it either has the same characteristics as a valid predicate tobacco product; or that it has different characteristics than the predicate tobacco product but the information submitted demonstrates that the new product does not raise different questions of public health. Examples of disciplines that may evaluate whether the new products can raise different questions of public health include engineering, chemistry, microbiology, toxicology, behavioral and clinical pharmacology and social science. For example, different product characteristics in those areas may impact initiation, cessation, frequency of use, patterns of use, and perceptions of harm or addictiveness among both youth and adults, and may result in a not substantially equivalent decision.
Given the important factors the agency must consider in reviewing these products, it’s critical that manufacturers provide high-quality submissions to allow the FDA to make a determination. Over the past few years, the quality of SE Reports sent to the FDA has improved, but the reports submitted to the agency still range widely in the level of detail included. For example, some have very little information on the comparison of the new tobacco product with a predicate tobacco product while other SE Reports are much more detailed in describing how the new tobacco product compares to the identified predicate tobacco product and provide supporting information. Our experience reviewing this wide range of SE Reports has been helpful in developing this proposed rule, which describes in detail the information that an applicant would be required to include in an SE Report. Once finalized, the SE rule would formally set the minimum requirements for submitting SE Reports, allowing for greater predictability and efficiency for all stakeholders. Some of this information is currently outlined in agency guidance. We hope the proposed rule will bring greater uniformity to the consistency and completeness of SE Reports, and make the tobacco product review process more effective and efficient.
Secondly, we’re providing additional information and resources on our website regarding several improvements to the tobacco product application process. Specifically, the FDA recently posted six SE Report Appendices on our website to assist manufacturers preparing SE Reports. These appendices, which are broken down by product type, highlight common deficiencies that may result in an unfavorable SE decision.
Additionally, as the proposed rule was being developed, we continued to receive input from stakeholders on the SE review process through their SE Report submissions, and FDA meetings and listening sessions with industry. Based on that input, the agency has already implemented additional improvements to the SE application process over the past several months, as mentioned during the October 2018 public meeting on the tobacco product application review process. In the interim, we expect these changes will provide industry more predictability on timelines for their review as we continue to work toward finalizing a rule. In particular, we’ve increased the time manufacturers have to respond to a deficiency letter and provided applicants with more time to amend their applications prior to scientific review. These improvements will allow manufacturers to develop and submit higher quality and more complete applications in a timely manner. As a result of these improvements, the agency recently announced it no longer intends to grant requests for extensions in response to deficiency letters. We’ve already implemented these improvements, but we’re also seeking input from industry on the appropriate timelines for this process as part of the public comment period for the proposed rule.
Lastly, we’re releasing the latest results of internal performance measures the FDA has had in place for several years to help improve the timeliness and predictability of the review of certain applications. The data show we surpassed a majority of our performance goals in fiscal year 2018. For example, the FDA reviewed and acted on 95 percent of regular SE Reports within 90 days—better than the goal of 80 percent. This is also marked improvement from the 73 percent achieved in the previous fiscal year.
These are just some of the steps we’re taking to lay a solid foundation that will continue to allow the FDA to protect the public health by regulating the manufacture, distribution and marketing of tobacco products. Among other things, we also intend to issue regulations outlining what information the agency expects to be included in Premarket Tobacco Product Applications (PMTA) and Modified Risk Tobacco Product (MRTP) applications. We also intend to explore product standards for electronic nicotine delivery systems (ENDS, including e-cigarettes) and other tobacco products, as well as to propose rulemaking requiring manufacturers to establish tobacco product manufacturing practices. Additionally, we plan to finalize guidance on how we intend to review PMTAs for ENDS, and we will continue our efforts to assist industry in complying with federal tobacco laws through online information, meetings, webinars and guidance documents.
We also continue to give guidance to individual manufacturers who are considering filing PMTA and MRTP applications with the agency. We have expressed a lot of concern around the tragic rise in youth use of e-cigarettes. Some of the leading manufacturers of these products have likewise made public commitments to address these trends. We would welcome the opportunity to engage a manufacturer on the filing of an application for one of these e-cigarette products. The application review process provides a foundational vehicle for properly weighing the public health tradeoffs of these products. To date, no manufacturer has submitted a complete application with the FDA seeking a PMTA or MRTP authorization for an e-cigarette.
We’re committed to using all the tools at our disposal to ensure our comprehensive plan on tobacco and nicotine regulation meets its objectives to significantly reduce tobacco-related disease and death, including a particular emphasis on protecting kids from the dangers of tobacco products. Protection of the public health is paramount and it’s critical we put tobacco products through an appropriate series of regulatory gates to ensure they meet the standards under the law.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
