BAA-18-100-SOL-00003_Amendment_1_Changes_List.pdf

Change History Table

BARDA BAA-18-100-SOL-00003 List of Changes: Original -- Amendment 1

Original (Nov 6, 2018) Amendment 1 (Jun 15, 2018)

1. Revised the “Background” section to update BARDA’s priority for influenza vaccines.

Vaccines, therapeutics, diagnostics, ventilators, and respiratory protective devices are essential for protecting all segments of the civilian population from pandemic influenza and other emerging infectious diseases. This BAA will support advanced development activities of medical countermeasures for influenza and other emerging respiratory viruses to be specified by BARDA. BARDA priorities for influenza vaccines are focused on those vaccines that induce long-lasting and broad (heterotypic and/or heterosubtypic) immunity in all populations compared to currently licensed influenza vaccines. In addition, BARDA will prioritize support for vaccines that induce broad immunity so as to prime the population against newly emerging influenza viruses or other respiratory viruses of pandemic potential. BARDA is also prioritizing broadly reactive immunotherapeutics, such as monoclonal antibodies, that will be effective in treating severely ill, hospitalized patients of all ages who are infected with influenza or other emerging infectious diseases.

Such therapeutics will demonstrate effectiveness when given later than 48 hours after onset of symptoms. Additional focus will be placed on MCM and devices suitable for use in at-risk populations such as children, pregnant women, the elderly, and persons with compromised immune systems. BARDA will endeavor to

Vaccines, therapeutics, diagnostics, ventilators, and respiratory protective devices are essential for protecting all segments of the civilian population from pandemic influenza and other emerging infectious diseases. This BAA will support advanced development activities of medical countermeasures for influenza and other emerging respiratory viruses to be specified by BARDA. BARDA’s priority for influenza vaccines is sustainable, cost effective approaches that improve pandemic influenza preparedness and rapid response capabilities. BARDA’s strategy to address this priority includes 1) improve vaccine effectiveness; 2) modernize production processes to decrease response time; 3) increase and diversify the sustainable domestic vaccine manufacturing infrastructure; 4) develop new adjuvants, delivery approaches, and other strategies that can provide a priming and protective response with a single vaccine dose and are more amenable to mass vaccinations in a response event. BARDA is also prioritizing broadly reactive immunotherapeutics, such as monoclonal antibodies, that will be effective in treating severely ill, hospitalized patients of all ages who are infected with influenza or in specific cases as described in subsequent sections, other emerging infectious diseases. Such therapeutics will demonstrate effectiveness when given later than 48 hours after onset of symptoms. Additional focus will be placed on MCM and devices suitable for use in at-risk populations such as children, pregnant women, the elderly, and persons with compromised immune systems. BARDA will prioritize projects that provide benefits to all populations, while also allowing for focused development projects or studies for at-risk populations where necessary.

endeavor to prioritize projects that provide benefits to all populations, while also allowing for focused development projects or studies for at-risk populations where necessary.

2. Updated Area of Interest 1:

CBRN Vaccines to add sub-Area of Interest 1.4 Vaccines against Burkholderia pseudomallei and Burkholderia mallei

[None] [Addition sub-area of interest]:

1.4 Vaccines against Burkholderia pseudomallei

and Burkholderia mallei. BARDA is interested in advanced development projects for vaccines against B.

pseudomallei and B. mallei. The proposed vaccine candidate must have demonstrated protection from lethal challenge in mouse and non-human primate studies. The following characteristics provide information regarding BARDA’s preferred profile:

• Vaccines against B. pseudomallei will be acceptable, but those that would target B. mallei in addition are preferred.

• Vaccines showing protection against aerosolized infection, or protection against multiple routes of exposure, are preferred.

• Timeline to Investigational New Drug (IND) submission of less than two years is preferred.

• Vaccines with preliminary formulation ready to be transitioned to GMP manufacturing are preferred.

• Vaccine candidates that offer sterilizing immunity in addition to protection are preferred, but not required.

The objective of this program is to advance projects through the end of Phase 1 clinical development. The following activities are expected to be included:

• Development of any necessary assay(s) for lot release

• Establishment of animal models acceptable to FDA, if necessary

• Development of small scale GMP manufacturing process

• GLP toxicology studies

• Nonhuman primate efficacy studies to include pre-exposure prophylaxis and post-exposure prophylaxis (in conjunction with antibiotic treatment)

• Development and qualification of necessary immunoassays

• Conduct of a Phase 1 clinical trial

3. Revised Area of Interest 2:

CBRN Antitoxins and Therapeutic Proteins to revise priorities.

2.1 Development of peptide or small

molecule antitoxins, and other novel compounds, with innovative formulations offering enhanced long-term stability. The candidate must be at TRL-6 (active IND and human safety data).

2.2 Development of antibody treatments

and other therapeutic agents for viral hemorrhagic fevers viruses. Programs must be at TRL-5 with a lead candidate identified.

2.3 Development of antibody treatments

and other therapeutic agents against smallpox.

Programs must have evidence for antiviral activity against orthopoxviruses. Programs at higher TRLs will be given priority.

2.1 Anthrax Antitoxins. Candidates for funding

under this BAA must be at TRL-6 or higher and either expand current response capabilities through product type (e.g., peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.).

2.2 Botulism Antitoxins. Candidates for funding

under this BAA must either expand current response capabilities through product type (e.g., monoclonal antibodies, peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.). Candidates at TRL-5 or higher are preferred; however, candidates earlier in development may be considered based on the significance of potential improvement upon existing capabilities.

2.3 Smallpox Antiviral. Programs must have

evidence of antiviral activity against orthopoxviruses.

Programs at higher TRLs (above TRL 5) will be given priority.

2.4 Viral Hemorrhagic Fevers Antiviral. Candidates

for funding under this BAA must be at TRL-5 (lead identified) or higher and either expand current response capabilities through product type (e.g., single mAbs, peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.).

4. Revised Area of Interest 5:

Chemical Threat Medical Countermeasures to include Opiods sub-Area of Interest

[None] 5.2 Opioids: Development of MCMs to treat life-threatening respiratory depression caused by exposure to opioids during a large-scale event. These products should be fast acting, long lasting, and effective against a variety of opioids, including synthetic opioids such as Fentanyl and should preferably have a mechanism of action different from existing opioid receptor antagonists.

5. Revised Area of Interest 7:

added language to clarify “propose activities to advance to TRL 4-5” for sub-Area of Interest 7.1 Diagnostics Innovations.

7.1 Diagnostic Innovations

This section encourages innovative technologies that will provide capabilities for novel diagnostics with improved performance, as well as for their expedited development, manufacturing, and use for existing and emerging threats. Projects may be at an earlier stage of development (TRL 3).

7.3 Antibiotic Resistance Diagnostics for

priority bacterial pathogens BARDA is providing support to advance innovative rapid and improved diagnostics to detect drug resistant urgent and serious priority public health pathogens* and to characterize their resistance profiles, both for biological

7.1 Diagnostic Innovations

This section encourages innovative technologies that will provide capabilities for novel diagnostics with improved performance, as well as for their expedited development, manufacturing, and use for existing and emerging threats. Projects may be at an earlier stage of development (TRL 3), and propose activities to advance to TRL 4-5.

7.3 Antibiotic Resistance Diagnostics for priority

bacterial pathogens BARDA is providing support to advance innovative rapid and improved diagnostics to detect drug resistant urgent and serious priority public health bacterial pathogens* and to characterize their resistance profiles, for threats and routine healthcare conditions.

biological threats and/or routine healthcare conditions.

6. Revised Area of Interest 8:

Influenza and Emerging Infectious Diseases (IEID) Vaccines

Under this Area of Interest, BARDA is seeking technologies that will improve preparedness against influenza and emerging infectious diseases with pandemic potential. Successful Offerors will provide evidence that the proposed vaccine product represents a transformative improvement in key vaccine attributes as compared to currently licensed products.

8.1 Advanced development of more

effective vaccines. Candidates, which have achieved TRL 6 or greater, and that will improve preparedness against influenza and emerging infectious diseases with pandemic potential are desired. Specifically for influenza, support for advanced development of new influenza vaccine candidates with the potential to stimulate broader (across influenza subtypes and/or within influenza subtypes), durable and more effective immunity than currently licensed products. The Offeror should provide data or a plan for validation of vaccine potency and release assays that are specific for the new influenza vaccine candidate. The Offeror should provide a regulatory strategy for FDA approval of the vaccine candidate and data demonstrating transformative improvements in immunogenicity/efficacy as compared to existing FDA licensed vaccines. Proposed clinical activities (Phase 1b/Phase 2 studies) should support development toward FDA licensure and evaluate

Under this Area of Interest, BARDA is seeking technologies and approaches that will improve preparedness and response against pandemic influenza and emerging infectious diseases with pandemic potential. Successful Offerors will discuss and provide evidence that the proposed effort substantially enhances pandemic influenza preparedness and response, and describe plans and requirements for long-term sustainability.

8.1 Advanced development of more effective

vaccines. Candidates and approaches, which have achieved TRL 6 or greater, and that will improve preparedness and response against pandemic influenza are requested. Vaccine candidates and approaches that provide one or more of the following are of particular interest: a) licensure of domestically manufactured vaccines amenable to both rapid production from time of strain identification to release of bulk product, and rapid scale up and manufacturing technology transfer to new facilities; b) clinical trials to expand the age range on the label of currently licensed vaccines; c) decrease response time, such as adjuvants or other technologies that allow a priming and protective response with a single vaccine dose; or d) improve the stability, sustainability and/or utility of stockpiled vaccines. All Offerors should provide commercialization and life cycle planning approaches and any sustainability costs that would be requested to maintain the capability. Proposed clinical activities should support development toward FDA licensure or additional label claims. Offerors key vaccine attributes, such as dose schedule, mechanism of action, time to onset of protection, broader cross- protection across influenza A virus subtypes, induction of priming immunity against viruses of pandemic potential, efficacy in multiple age groups, and multiyear duration of protection.

Efforts might include development, qualification and validation of correlates of protection assays used to evaluate the immune response to the new influenza vaccine candidate. BARDA may request responses to this BAA for vaccine against specific emerging pathogens of pandemic potential. BARDA will prioritize vaccine candidates against specified emerging infectious diseases that have reached the TRL6 level, however, earlier stage candidates may be considered.

8.2 Innovative vaccine production

enhancements. Support for improvements in vaccine production and platform technologies that accelerate the availability of vaccines against viruses with pandemic potential.

[None. Administration] proposing to develop vaccines not yet licensed by FDA should provide data supporting proposed vaccine potency and release assays that are specific for the influenza vaccine candidate, and clinical data supporting dose, schedule, mechanism of action, and safety of the vaccine candidate, as well as immunogenicity against pandemic strains of influenza. The Offeror should provide a regulatory strategy for FDA approval of the vaccine candidate and data demonstrating the proposed improvements to pandemic influenza response/preparedness. Proposed efforts might include qualification and validation of correlates of protection and other assays used to evaluate the immune response to the vaccine.

8.2 Innovative vaccine production enhancements.

Support for improvements in vaccine production and administration that accelerate the availability of pandemic influenza vaccines.

4. Administration:

a. Improved approaches to route of vaccine delivery that are more amenable to large scale vaccination campaigns in a short period of time.

7. Revised Area of Interest 12:

MCM Production Platform Systems

[In 12.2 Vaccine Production Platform] Technologies will be evaluated by criteria that address the rapid response goal (time to human clinical testing, manufacturing scalability and capacity, cost to develop and manufacture, current development and regulatory status), and the applicability of the technology to a range of threats as a platform (categories of pathogens

[In 12.2 Vaccine Production Platform] Technologies are sought that address the rapid response goal. Attributes related to this goal include:

completeness of the technology from candidate generation to full manufacturing; use without variation for each new application; applicability of the technology to a range of threats as a platform (categories of pathogens covered); time to human clinical testing and covered, completeness of the technology from candidate generation to full manufacturing, use without variation for each new application).

Additional criteria that relate to the use of the technology for public health vaccines as well as the capabilities of the Offeror will also be considered.

cost to develop and manufacture (compared to current technologies); manufacturing scalability and capacity, current development and regulatory status (TRL 6 or greater), other commercial applications of the technology, and any additional attributes that relate to the use of the technology for public health vaccines (e.g., route and ease of administration).

8. Incorporated under AOI #8: Note: White Paper and Full Proposal submissions under AOI #8 are suspended until October 1, 2018.

9. Incorporated under AOI #9: Note: White Paper and Full Proposal submissions under AOI #9 are suspended until October 1, 2018.

10. Incorporated under AOI #12: Note: White Paper and Full Proposal submissions under AOI #12 are suspended until further notice.

11. Incorporated under AOI #13: Note: White Paper and Full Proposal submissions under AOI #13 are suspended until further notice.

12. Incorporated under AOI #14: Note: White Paper and Full Proposal submissions under AOI #14 are suspended until further notice.