Amendment 1_Notice of Intent to Award a Sole Source –ENDS Toxicological Studies

The U.S. Food and Drug Administration (FDA) intends to solicit a 2-year, sole source, firm-fixed-price type contract from Lovelace Biomedical Research Institute; 2425 Ridgecrest Dr. SE; Albuquerque, NM 87108, in accordance with the authority under Federal Acquisition Regulation (FAR) 6.302-1 – Only one responsible source and no other supplies or services will satisfy agency requirements, and 15.101 Contracting by Negotiation. The North American Industry Classification System (NAICS) code is 541380 – Testing Laboratories. The anticipated period of performance consists of a 2-year base contract.

On June 22, 2009, President Barack Obama signed the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) into law (Public Law 111-31). The Tobacco Control Act amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) and granted the FDA authority to regulate the manufacture, marketing, and distribution of tobacco products to protect the public health and to reduce tobacco use by minors.

Premarket tobacco product applications (PMTAs) are submitted for any new tobacco product seeking an FDA marketing order under the FD&C Act. A PMTA is required to provide sufficient scientific evidence demonstrating that marketing of the new product is appropriate for the protection of public health (APPH). Scientific data must address, among other things, any health risks and benefits of the new product to the US population as a whole. This requirement includes a thorough toxicological assessment that directly addresses the health risks associated with a product. The final PMTA rule emphasizes detailed assessment of the toxicological profile from the use of or exposure to a new tobacco product. Electronic cigarettes are very recent additions to the United States tobacco market compared to conventional cigarettes. Sufficient time has not yet passed to directly assess the effects of electronic cigarettes in humans and yet there are many constituents in electronic cigarette vapor, such as aldehydes like formaldehyde and metals like nickel, that raise concerns about the long-term effects of e-cigarette use. Moreover, unlike conventional cigarettes, e-cigarettes are wholly manufactured consumer products that have different electrochemical components. In order to fully evaluate e-cigarettes that come in for pre-market review, FDA needs to have some understanding of the toxicological effects of different kinds of e-cigarettes. In lieu of long-term data epidemiological data, FDA initiated this contract to understand the effects of longer-term exposures to e-cigarettes in rodents. While the data that comes in with applications can be useful, currently available in vivo data for electronic cigarettes is limited and the in-depth toxicological study necessary to understand these necessary details of e-cigarette toxicity relevant to long-term e-cigarette exposure in humans is not available. Therefore, the outcome of this project will be CTP mission-relevant in better understanding and addressing potential in vivo toxicological risks, including pathology, biomarkers of harm associated with repeated use of electronic cigarettes that can be used to inform tobacco product regulations, regulatory application reviews, and to continue CTP’s mission of protecting public health.

In Fiscal Year 2019 (FY19), FDA awarded contract 75F40119C10161 to Lovelace Biomedical Research Institute. Under this contract, a comprehensive, large multi-faceted, and repeated chronic exposures of ENDS aerosols with pharmacokinetic study, including dose-range finding, 28-day, 90-day and 180-day with 45-day recovery of Products A and B; and pharmacokinetic study, including dose-range finding, 28-day and 90-day with 45 day recovery of Product C in vivo toxicological studies, were performed to address unique toxicological issues that cannot be addressed by alternative computational or in vitro culture approaches.

The repeated chronic exposure studies (28-day, 90-day, and 180-day studies) are progressive, with increases in the length of exposure with each subsequent study. To inform the selection of doses for the proposed sequential studies, a baseline toxicity evaluation and a thorough assessment of tissue histopathology, clinical observations, and bioanalysis of blood, urine, and bronchoalveolar lavage fluid is required. The 28-day and 90-day studies set benchmark doses for the 90-day and 180-day studies, respectively, based on the impact of longer exposure duration on the toxicity endpoints as well as other biomarkers. Therefore, before beginning the large, 90-day, an evaluation of a portion of the findings of foundational 28-day study needed to be completed. This delay was necessary to ensure that the planned 90-day study design and dosing were appropriate for the increased length of exposure, to avoid a potentially failed experiment, animal mortality, loss of time and funding, and to ensure meaningful scientific results. Similarly, the 180-day study relies on the findings of the 90-day study and required the completion of that study. The review of the preliminary histopathology data from each time points prior to completion of the next step in the studies (i.e., 90-day and 180-day) rendered a delay in the study timeline and subsequently, an extension of the period-of-performance.

For toxicological studies, a maximum tolerated dose (MTD) is used in assessing toxicological effects at the highest level of exposure without causing substantial toxicity, which would be critical for toxicological assessment from use of the products. In the original contract, for each flavor, 3-dose groups were proposed; high, mid, and low-dose groups. These doses were accommodated with 6h exposure (high), 3h exposure (mid), and 1h exposure (low). The exposure module was able to generate the No-Observed-Adverse-Effect-Level (NOAEL) and Low-Observed-Adverse-Effect-Level (LOAEL) responses but could not produce the MTD. To attain the MTD exposure required the contractor to re-structure the inhalation exposure unit so that the highest dose could be exposed. This new configuration allowed the contractor to include a highest dose group; however, all the original proposed dose groups, including the highest dose, could not be exposed at the same time. Therefore, the studies were conducted in a staggered format, increasing (doubling) the overall time that it takes to perform the study. This was not defined in the original contract and has created additional delays to the program.

The original contract proposed a tank device for Product C. The ENDS tank devices used in the dose-range finding and pharmacokinetics studies were no longer commercially available for the 28-day and 90-day studies. Additionally, the e-liquids originally selected for the ENDS tank device were also commercially not available. Therefore, the change/replacement of the ENDS tank devices and e-liquids, and the preliminary assessment studies before the long-exposure study rendered additional delays to the program.

Additionally, in order to initiate the biomarker studies proposed in the contract, lead time on receiving many reagents (e.g., kits for Luminex and ELISA) was significantly extended due to supply chain issues from COVID, which delayed the completion of the proposed studies.

The contractor has completed all in-life experiments associated with the contract, but there was not sufficient time to complete the data analysis, generating interim reports and final reports. The FDA is seeking to award a sole source contract to Lovelace Biomedical Research Institute to complete the data analysis, interim reports and final reports for the work started under contract 75F40119C10161.

Nature of the acquisition and proposed unique qualifications of the contractor(s).

Lovelace Biomedical Research Institute is the contractor who performed the experiments conducted under contract 75F40119C10161. The in-life experiments have been completed, the data analysis and interim reports were being generated. Currently, one of the reports is at the stage of final signature; the remainder are in various stages of completion. However, the contract 75F40119C10161 has expired. It would be impractical for a new contractor to complete the data analysis of these studies without having conducted them. This study will provide valuable information regarding the toxicity of e-cigarette aerosols, but the results of the scientific study need to stand up to the scrutiny of scientific peer review. Having a contractor perform the data analysis who did not conduct the experiment would not stand up to peer review scrutiny. Moreover, in order for a new contractor to successfully provide FDA with usable data, they would have to repeat the experiments that have already been completed. This would essentially double the investment FDA has made in time and money to get usable results from this study. Additionally, there would be great risks in transporting the samples, including freeze-thaw of the biological samples, from one contractor to another for data analysis to occur. If one of the samples were to be damaged, the study would have to be repeated again. Furthermore, as the contractor is in various stages of completion of data analysis and generating the interim reports, Lovelace Biomedical Research Institute would be able to finalize the deliverables at a faster pace. Therefore, a sole source contract award to Lovelace Biomedical Research Institute to complete the study work they have started will allow FDA to get the results of this study in a more timely and cost-effective manner.

This notice is not a request for competitive proposals. However, any party that believes it is capable of meeting the requirements as stated herein may submit a written response which clearly supports and demonstrates its ability to perform the requirements. Any response must be received by the response date and time set forth in this notice. Any response will undergo a review to determine whether the respondent can meet the contract requirements. A determination by the Government whether to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government.

Response Date and Time: 4:00 p.m. ET on August 1, 2025. Responses must be emailed to Kimberly Pennix at Kimberly.pennix@fda.hhs.gov, with a CC: to Ian Weiss at Ian.weiss@fda.hhs.gov.