Request for Information (RFI) 2 NAICS Code: 541714 - Research and Development in Biotechnology (except Nanobiotechnology) HHS BARDA

1. SUMMARY: The Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), is issuing this Research & Development Request for Information (RFI) to collect feedback from current and potential biopharmaceutical partners. Information collected from this notice will serve as continued market research for a possible program where BARDA would partner with one or more organizations to achieve target preparedness and response goals. The development and licensure of mRNA vaccines for COVID-19 has enabled the creation of novel interventions for seasonal influenza, pandemic influenza, and other public health emergencies. If proven safe and effective to merit regulatory approval, these vaccines are poised to transform pandemic preparedness strategies moving forward. BARDA plans to continue to make a range of investments in platforms and other technologies to improve pandemic and outbreak response capabilities to novel and/or emerging viral pathogens. As part of this effort, BARDA plans to solicit partnerships to access platform technologies that can rapidly pivot between threats. BARDA has assessed that currently, mRNA technology offers the fastest time from original sequence identification to cGMP vaccine, coupled with proven efficacy. In this RFI, BARDA seeks to: (a) understand if there are other flexible and scalable platform technologies used in a licensed vaccine that can generate a final container product starting from a new sequence in less than 5-6 weeks, as has been seen with mRNA platforms; and (b) receive feedback from mRNA and other manufacturers on how the proposed partnership could be structured to ensure the development of a sustained capability. This partnership(s) will serve as a core component of BARDA's rapid response capabilities. The number, size, and scope of awards will be driven primarily by funding availability. 2. DISCLAIMER: Pursuant to Federal Acquisition Regulation (FAR) Part 10, the intent for this RFI is to conduct market research. This is NOT a solicitation for proposals, proposal abstracts, or quotation. This announcement does not constitute an Invitation for Bids (IFB), Request for Quote (RFQ), or a Request for Proposal (RFP), and it should not be construed as a commitment of any kind by the Government to issue a formal solicitation or ultimately award a contract. Responses to this notice cannot be accepted as offers. The sole purpose of the RFI is to assist the Agency in crafting the appropriate solicitation and shall be used for information purposes only. Any proprietary information will be protected if appropriately marked. The information provided is voluntary and will not impact the ability to submit on future requirements. 3. BACKGROUND: A bedrock to BARDA's success over the past 15 years in responding to public health emergencies (e.g., H1N1 influenza, Zika, Ebola, COVID-19) has been its diverse public-private partnerships. BARDA's investments in these partnerships have yielded 69 FDA-cleared, licensed, and/or approved medical countermeasures (MCMs), as well as supported development and manufacturing capability for platform technologies to rapidly address other emerging infectious diseases. For example, certain technologies supported by BARDA for pandemic influenza and other existing threats'mRNA, monoclonal antibody platforms, adenovirus 26-based vectors, and recombinant protein'were adapted for SARS-CoV-2 with support from the U.S. government (USG). Although these approaches have primarily focused on developing a licensed product for a single threat, they have the potential ability to rapidly pivot to new and emerging threats. While filling critical gaps in the nation's preparedness and response capabilities, one lesson learned from COVID-19 is the need to be able to pivot these platform technologies to new threats even faster, and for this capability to be regularly exercised. Further, sustainability will require a combination of appropriate risk sharing as well as achieving licensure of a commercially viable vaccine(s) (or USG sustainment funding for those emerging infectious disease products that are unlikely to have sufficient commercial interest). 4. THE POTENTIAL PROMISE OF mRNA VACCINE PLATFORMS: As BARDA develops and licenses MCMs based on true - plug-and-play manufacturing platform capabilities that can meet the requirements outlined in various strategy documents, including the American Pandemic Preparedness Plan (APPP)[1], the mRNA-based platform stands out due to its proven speed of manufacturing, safety and efficacy profile, and ability to rapidly pivot to new strains and the potential to address additional viruses. This includes the proven ability to produce and release clinical trial material in less than 40 days from sequence identification to support rapid immunogenicity testing, with a manufacturing process short enough and footprint small enough to enable sustainable domestic production capacity for vaccinating the US population within 130 days. Viral vectors and recombinant protein approaches not only require longer timelines for testing at multiple stages of development, but also the expression and/or purification process development can vary significantly even between strains within the same viral family, posing significant risk to expedited development and achieving the goals outlined in the APPP. Similarly, inactivated vaccines have barriers in terms of time needed to determine optimal growth properties, the potential for requiring either selection/creation of attenuated strains, and/or high-level containment, all of which can slow development. For these reasons, BARDA plans to prioritize mRNA vaccines as one of its first deployable vaccine technologies for novel threats for the next pandemic. 5. BARDA's VISION FOR NEW PARTNERSHIP MODEL: BARDA seeks a 15- to 25-year partnership that shares similarities with the current pandemic influenza model, which includes shared risk, reliance on the commercial market for a significant portion of sustainment, with agreed-upon USG sustainment funding to support pandemic readiness and agreed-upon pricing for pandemic responses. The partnership is expected to initially strive to license a seasonal and a pre-pandemic influenza vaccine as part of this effort, in alignment with the HHS pandemic influenza preparedness plan[2]. However, based on challenges with the COVID-19 and other responses, three significant changes will be incorporated to enhance response capabilities: (1) active and ongoing development of vaccines against current and new threats as a way to exercise the rapid response capability as well as support responses globally; (2) ongoing efforts to improve access by improving physical properties of the vaccine, such as reducing the amount of antigen and/or number of doses required, improved stability, reducing/eliminating cold-chain requirements, or improved labeling approaches to enhance tracking/tracing; and (3) willingness to partner with third parties to support development, particularly against emerging infectious diseases internationally. These partnerships could include non-governmental organizations (NGOs) or non-USG Governments to support outbreak response and international clinical trials, or developers of new technologies that could further improve on the safety/efficacy of, or access to the vaccines. To support the breadth of activities and requirements for enhancing response capabilities, BARDA envisions that a new partnership(s) will be predicated on (1) long-term collaboration and (2) commitment to develop multiple products using a single, flexible platform capability. Commercial development would not be limited by BARDA funding, but rather BARDA support would be limited to those areas in its current threat space. BARDA envisions the key to sustaining a long-term partnership will be a combination of the developer's commercialization plan, coupled with significant USG investment in this platform capability in the next 1-2 years, focusing on licensing 1-2 products in pre-pandemic influenza and/or other biological threat space. The specific approach, scale, and breadth will depend, in part, on what type of funding, if any, is available in addition to BARDA's limited annual appropriations. BARDA envisions sustainment funding would support a combination of base-level vaccine development work with the ability to rapidly scale, if needed. Base-level sustainment would include partnerships with technology developers to improve characteristics of the - platform, and generation, characterization, and manufacturing of vaccines against known threats'and partnerships to take those vaccines to licensure. BARDA envisions some aspects of this effort to be structured as cost plus and/or incentive-based, while the larger scale efforts would be firm fixed price options. 6.0 ATTRIBUTES OF A SUCCESSFUL PARTNERSHIP & RESPONSE CAPABILITY: Based on lessons learned from numerous outbreaks over the last 20 years, BARDA believes the following components will be critical to a successful, rapid response approach: As described in BARDA's strategic plan[3], as well as lessons learned from COVID-19[4], vaccine licensure is critical to ensure a rapid response to existing or new infectious disease threats. As such, any new partnership will focus on obtaining product licensure. Proven developer with a flexible platform in advanced clinical development with clinical data against influenza. A well-defined commercialization plan, funding, and manufacturing capability (or access to domestic, commercial-scale manufacturing to ensure appropriate support for rapid, large-scale manufacturing). BARDA is interested in an approach where the capability to rapidly pivot to new threats is being constantly exercised through development of vaccines to known threats. To ensure the platform stays as relevant as possible, and to constantly strive to improve access, ongoing efforts to incorporate new technologies to improve the underlying response capabilities and characteristics of the platform'such as incorporation of new formulations that address storage challenges. Strong ability to work internationally across multiple partners, given that the best approach to preventing a pandemic is to stop the spread at its source, wherever it may occur. An upfront understanding of vaccine cost per dose, including ensuring access in endemic regions as relevant. Upfront alignment on sustainment costs to be provided by USG 7. INSTRUCTIONS FOR SUBMITTING A RESPONSE: BARDA is interested in understanding potential partnership structures, with an emphasis on understanding the challenges faced by commercial developers when supporting vaccine development efforts in the biothreat and emerging infectious disease space, and out-of-the-box proposals for how a partnership could be structured to address those risks. Referring to the Vision for New Partnership Model and Attributes of a Successful Partnership & Response Capability sections, please provide your organization's perspective and experience by responding to any or all of the following questions (responses not to exceed 10 pages). 1. What is your perspective on vaccine platflorms that can meet the 100-day goal outlined in the APP? a. If the capability to use these platforms exists within your organization, please provide a timeline/Gantt chart showing how long it would take to complete the key activities to design, test, and release a vaccine against a new sequence/viral strain. b.Explain your ability to: (a) incorporate enhancements to improve access (e.g., optimize formulation to minimize cold storage requirements), and (b) rapidly pivot during a public health emergency and gain access to population-scale manufacturing capability. 2. What is your perspective on structuring contracts with a cost-plus base agreement to sustain a commercial market outside of a public health emergency and with firm-fixed-price options in the event of a public health emergency to ensure the USG can provide vaccines free of charge to the entire U.S. population? 3. Are there any Attributes of a Successful Partnership & Response Capability that may present challenges for your organization? a. How might these challenges be addressed by your organization? By BARDA? 4. Are there additional Attributes of Successful Partnership & Response Capability not captured in the above that you would like to highlight? Respondents shall provide the requested information in Microsoft Office or Adobe Acrobat format and furnish responses electronically (via email) to the individual(s) listed in Section 8 below. Respondents shall mark all copyrighted information, data, and materials with appropriate restrictive legends (i.e., confidential, privileged, proprietary, trade-secret). Please note that non-federal BARDA personnel performing advisory and assistance services will have access to any submission under this RFI. All non-federal BARDA personnel are required to sign a non-disclosure agreement prior to accessing the RFI responses. 8. SUBMISSION: Interested parties are requested to submit responses to the following individuals: Lavivian Peasant, Contracting Officer Division of Contracts Management and Acquisition (DCMA) Biomedical Advanced Research and Development Authority (BARDA) E-mail: Lavivian.Peasant@hhs.gov and Bria Andrews, Contract Specialist Division of Contracts Management and Acquisition (DCMA) Biomedical Advanced Research and Development Authority (BARDA) E-mail: Bria.Andrews@hhs.gov Please include RFI No. HHS-23-BARDA-RFI-mRNA-001 in the subject of all correspondence. BARDA intends to use electronic mail for all correspondence regarding this RFI. Paper copies will not be accepted. Questions and comments must be received no later than 5:00 PM ET on Friday, 10 March 2023. Electronic responses to this RFI are due no later than 5:00 PM ET on Friday, 7 April 2023. 9. REFERENCES [1] https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf [2] https://www.medicalcountermeasures.gov/BARDA/Documents/pan-flu-report-2017v2.pdf [3] https://medicalcountermeasures.gov/barda/strategic-plan/ [4] Johnson RA, White RC, and Disbrow GL. Hum Vaccin Immunother. 2022 Nov 30;18(6):2129930.doi: https://doi.org/10.1080/21645515.2022.2129930.