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

Office of Biomedical Advanced Research and Development Authority

(BARDA)

Special Instructions Issuance for Broad Agency Announcement 18-

100-SOL-00003

BAA-18-100-SOL-00003)

Title: Special Instructions – BARDA’s Division of Research, Innovation & Ventures (DRIVe)

Contracting Office 200 C Street SW

Washington, DC 20201

I. INTRODUCTION AND OVERVIEW INFORMATION

A. Development Opportunity Objective:

B. Eligible Respondents & Scope Parameters:

C. Number of Awards:

D. Overview of Special Instructions Application Process:

E. Submission Deadlines and Government Response Time F. Contact and Submission Information:

II. Research and Development Areas of Interest A. Special Instructions Area of Interest #15 for DRIVe: Solving Sepsis B. Special Instructions Area of Interest #16 for DRIVe: Early Notification to

Act, Control and Treat (ENACT) III. BARDA DRIVe Initial Outreach Instructions IV. Stage 1: White Paper/Quad Chart Instructions A. Stage 1 Package Preparation B. Stage 1 Package Submission

V. Stage 2: Full Proposal Instructions

I. INTRODUCTION AND OVERVIEW INFORMATION

A. Development Opportunity Objective:

These Special Instructions under BARDA BAA [BAA‐18‐100‐SOL‐00003] specifically aim to accelerate the research, development, and availability of transformative technologies, approaches and products to protect Americans from natural and intentional health security threats by soliciting revolutionary technologies and innovations for Solving Sepsis and ENACT.

The projects awarded under these Special Instructions might be at varying stages of technological readiness and development. DRIVe is interested in projects that span the entire development spectrum and are hyper‐focused on the specific areas of interest described in these Special Instructions. Respondents may propose feasibility demonstration, non‐clinical research and development, model and process development, formulation, engineering, model development, data science and development of novel algorithms, descriptive clinical studies, regulatory activities, etc. Respondents should consider building a team across disparate areas and organizations (industry, academia, and others) in order to develop tailored solutions critical for these Special Instructions. It is anticipated that these interactions may be outside current established collaborations.

BARDA DRIVe seeks unconventional approaches that are outside the mainstream, challenge assumptions, and have the potential to radically change established practice, lead to extraordinary outcomes, and create entirely new fields in health security that will protect Americans from 21st Century Health Threats. These DRIVe Special Instructions will support projects that span Technology Readiness Levels from 3 to 9 (TRL 3‐9), with a targeted focused of TRL 3‐6. Later stage product may be funded in areas of diagnostic, devices and technologies where the time cost to market is feasible in the target award range.

Under DRIVe, these Special Instructions consist only of the following two areas of interest

(AOI):

15. “Special Instructions Area of Interest #15 for DRIVe: Solving Sepsis;” and

16. “Special Instructions Area of Interest #16 for DRIVe: Early Notification to Act, Control and Treat (ENACT)”

Additional information regarding DRIVe can be found below and at https://drive.hhs.gov

The terms of these Special Instructions supplement BAA‐18‐100‐SOL‐00003 (“BAA”). Any apparent conflict of terms of the original BAA, the terms of these Special Instructions will control. Proposals that do not conform to the requirements outlined in these Special Instructions, the BAA, or the instructions provided in the invitation letter may be considered non‐responsive and considered for review.

B. Eligible Respondents & Scope Parameters:

These Special Instructions are open to ALL responsible sources as described in the BAA.

Preliminarily, a call with the relevant BARDA DRIVe technical team is strongly encouraged prior to any submission. Target award(s) expected to be made under these special instructions will range from $750,000 to $8 Million in total government cost, but may make award(s) which differ from this range.

C. Number of Awards:

Multiple awards are anticipated and are dependent upon the program priorities, proposals’ scientific/technical merits, how well the proposals fit DRIVe’s areas of interest, and available funds. Anticipated funding for the program is subject to congressional appropriations. The program funding is subject to change due to government discretion and funding availability.

D. Overview of Special Instructions Application Process:

For complete details on this submission process, please read the full Special Instructions.

However, the following provides a general overview of the process:

1. Requirement for Preliminary Engagement with Relevant BARDA DRIVe Program

Prior to submitting a White Paper/Quad Chard, it is strongly encouraged that interested parties participate in a call with the relevant area of interest to ensure your proposed idea is within the mission space. Please see Part III of these Special Instructions “BARDA DRIVe Initial Outreach Instructions” for further details.

2. White Paper/Quad Chart Submission (Stage 1)

A White Paper/Quad Chart (“Stage 1 Package”) may be prepared and submitted, which initiates Stage I of the process. Before preparing a Stage 1 Package, prospective respondents are advised to read these Special Instructions in full and to visit the DRIVe website (https://drive.hhs.gov) for more information on the DRIVe mission, solicitations and program manager contact information.

White Paper Submission: As continued market research, respondents should submit a Stage 1 Package before they submit a full proposal. The Stage 1 Package should describe the effort in succinct but sufficient detail to allow a review of the concept's technical merit and its potential contribution to the BARDA DRIVe mission, pursuant to the page limits defined below.

Respondents whose Stage 1 Package receive a favorable review may be invited to submit a Full Proposal. Respondents whose Stage 1 Package do not receive an Acceptable rating will be provided with feedback on technical issues and concerns that DRIVe has regarding the proposed effort. This written feedback is the only response that will be provided in response to Stage 1 Packages.

3. Full Proposal (Stage 2)

After invited to submit a Full Proposal (“Stage 2 Package”), the Stage 2 Package must be submitted in accordance with the instructions provided in the invitation notice, which will be substantively similar to instructions in Part VI of this BAA.

Contents of Stage 2 Package:

o Volume I ‐ Technical Proposal

Written Submission o Volume II ‐ Cost Proposal

NOTE: Pursuant to FAR 37.203(d), input on any submission to BARDA DRIVe may be provided by non‐federal consultants /subject matter experts who are strictly bound by appropriate non‐ disclosure requirements.

E. Submission Deadlines and Government Response Time

Table 1: Submission Deadlines and Government Response Time

Proposal Stage Deadline for Submission* Government Response

Stage 1: White Paper/Quad Chart

A Stage 1 Package may be submitted on any day during the open period of these Special Instructions.

Stage 1 Package will be reviewed as they are received. However, white paper submissions may be held for review as a batch for administrative purposes.

The due date for Stage 1 submissions under these Special Instructions is:

3:00 PM ET on May 28, 2019.

A confirmation will be sent upon receipt.

A decision will be made within 45 calendar days of the submission deadline.

Stage 2: Full Proposal As defined in the Invitation Letter.

A confirmation will be sent upon receipt.

A response will be provided within 120 calendar days of receipt of submission.

F. Contact and Submission Information:

All Stage 1 Package submissions and contractual / administrative inquiries, must be submitted to DRIVeContracting@HHS.GOV with “DRIVe Special Instructions: Sepsis / ENACT (as appropriate)” as the first words of the email subject line, followed by company name and title of project.

II. Research and Development Areas of Interest

Major challenges with addressing 21st Century health security threats, require breakthrough solutions. ASPR under HHS has charged BARDA with launching a new Division for Research, Innovation and Ventures (DRIVe) to accelerate the research, development, and availability of transformative technologies, approaches and products to protect Americans from natural and intentional health security threats.

Pursuant to addressing these challenges , the contracting office on behalf of BARDA DRIVe is soliciting proposals for advanced research and development of revolutionary health security products, technologies and innovations in order to increase our capability and capacity to respond to national security health threats, with an emphasis on the research areas of interest described herein. BARDA DRIVe anticipates that R&D activities supported under these Special Instructions will be at various stages of maturity (TRL 3‐9), with a targeted focused of TRL 3‐6.

Later stage product may be funded in areas of diagnostic, devices and technologies where the time cost to market is feasible in the target award range. Some candidates may be more advanced and an award under this BAA will serve to continue the candidate product or technology toward ultimate licensure or approval by the U.S. Food and Drug Administration (FDA). For other candidates, an award might provide support in the early stages of research or development (e.g. biomarker discovery, biosensor development, etc)). These Special Instructions will also serve to advance the knowledge and scientific understanding of candidates’ research, platform technologies, inventions, modeling and forecasting, and visual analytics.

Proposed research should investigate leading edge approaches that enable revolutionary advances in medical science, health security technologies, products or systems. DRIVe wants to emphasize revolutionary approaches that are hyper‐focused on the areas of interest described below. DRIVe seeks novel approaches that may not have been applied to the field previously, which could include approaches that are outside the mainstream, and could help populate the health security innovations development pipeline.

A. Special Instructions Area of Interest #15 for DRIVe: Solving Sepsis

At least 1.7 million Americans develop sepsis each year and nearly 270,000 Americans die annually as a result1. Sepsis occurs when an infection leads to a dysregulated host response and organ dysfunction. In addition to the toll on health, sepsis incurs a large economic burden and is ranked first in total aggregate hospital costs in the US. Sepsis survivors also sustain additional chronic illnesses and associated care expenses.

BARDA’s mission is to develop medical countermeasures that target Chemical, Biological, Radiological and Nuclear (CBRN) threats, seasonal or pandemic influenza and emerging infectious diseases. A complication to these threats is sepsis, which has a very high potential to arise consequent to any of these threats. In order to fully protect Americans and save lives, 1 https://www.cdc.gov/sepsis/index.html

BARDA is investing in technologies and products to start Solving Sepsis.

The Division of Research Innovation and Ventures (DRIVe) within BARDA launched a program dedicated to Solving Sepsis. DRIVe is interested in a suite of approaches in two specific sepsis topic areas. Proposals should respond to a single topic area only. If technologies or products touch both of the listed topics, then respondents should select and respond to the most relevant topic. Novel and revolutionary technologies are desired over incremental approaches to existing research efforts. Please consider the following with your application:

Solving Sepsis is interested in medical countermeasures that address sepsis of any etiology (e.g. bacterial, viral) versus approaches that are limited to sepsis induced by a subset of pathogens.

Proposed approaches must include demonstration of effectiveness in sepsis relevant models (e.g. utilizing sepsis patient samples, sepsis patient data).

Solving Sepsis aims to mitigate the adverse host response to sepsis and therefore is only interested in host‐based approaches when considering development of diagnostics or devices. BARDA has existing programs (outside of these special instructions) for pathogen‐ targeted approaches.

Solving sepsis is interested in funding translational science, not exploring fundamental research questions.

The FDA regulatory path for approval/clearance (if appropriate) should be addressed and evidence of initial engagement with Regulatory authorities should be provided.

A commercialization strategy is required. This may include establishment of partnerships with appropriate device fabricators/manufacturers, addressing the potential to scale, intellectual property and the means to address adoption in hospitals (considering costs/unit, reimbursement strategy as well as hospital and physician desire to use).

Focus Area 15.1: Advanced Research and Development of Sepsis Diagnostics and Devices

Host‐response diagnostics and devices are crucial for early detection of sepsis. Currently, there is no marketed, FDA approved host‐based diagnostic for prediction or identification of sepsis. The ability to easily obtain a sample from a patient (aligning with traditional workflows) and provide rapid results (<1

hr) would enable sufficiently timely intervention to transform care. Research has focused primarily on detecting infection, but there are few technologies in advanced development that can specifically distinguish sepsis (the adverse host response) from infection.

BARDA DRIVe is therefore seeking devices and diagnostics that will accurately diagnose sepsis through a focus on host pathophysiology and biomarkers; distinct from diagnosing infection. These devices should incorporate factors that would promote adoption in clinical settings including ease of use, simple training required for use, rapid result turnaround with minimal sample manipulation, and unambiguous results that are easily interpretable and actionable.

For this solicitation, Solving Sepsis is interested in diagnostics or devices that are at least TRL5 stage of development and seek funding for advanced research and development to support device clearance.

Proposers should have engaged appropriate regulatory authorities and have held pre‐submission or pre‐IDE meetings as appropriate. Candidate technologies will need to have been initially assessed with clinical sepsis patient samples and been able to distinguish sepsis from other types of inflammatory response and infection. It is desirable to have diagnostics that are not restricted to a specific clinical setting (i.e. hospital laboratory) but rather can be utilized in multiple clinical settings (nursing facilities, outpatient clinics, austere environments, etc.).

Specifically the diagnostic (or device that implements the diagnostic) should:

Detect/measure a specific biomarker, biomarker set, analytes, etc. that collectively can accurately identify and distinguish among patients who are already septic, patients who are becoming septic, patients with infection who are not septic, and patients who have non‐infectious inflammation

Require minimal sample preparation, and require not more than routine minimally invasive clinical procedures (i.e., blood draw) and/or non‐invasive sensing.

Have been validated using samples from sepsis patients compared with infected, non‐septic patients as well as non‐infected, non‐septic patients; and shown to correctly classify patients as septic, pre‐septic, or non‐septic with accuracy and speed.

Focus Area 15.2: Post‐sepsis Monitoring

Sepsis survivors commonly experience reduced life spans and reductions in quality of life. Survivors incur additional health care costs owing to their high likelihood for re‐admission to the hospital. It is important for these patients to be informed of potential signs of deterioration, as early care can be sought to prevent and mitigate severe adverse events and, if possible, hospital readmission. However, patients are often not capable of self‐diagnosis due to physical limitations, confusion, lack of clinical understanding, or wariness of prior health care experiences.

Despite technological advances in smart and personal devices, including those that are capable of capturing health data, there remains a lack of integrated strategies to detect post sepsis deterioration. DRIVe wants to leverage technologies to solve these problems and provide mobile and home‐based solutions to monitor complications post sepsis, including post‐sepsis syndrome. These technologies should be able to reliably monitor sepsis survivors, provide information and recommend actions for the patient if health status veers “off trajectory” and the patient deteriorates.

Candidate technologies should provide information in a timely manner, be evidenced‐based, reliable and be cost‐effective such that they can easily be adopted for use by the patient and provider. These technologies should not be obtrusive, such that individuals can be frequently monitored, yet not adversely affect lifestyle. Proposals could include demonstration of product in post‐sepsis patients or at‐risk clinical cohorts, demonstrate ability to scale in terms of manufacture, and a commercialization plan to facilitate adoption of such technologies. Proposers must include a method to evaluate success of their intervention and specifically include metrics to measure success in correctly alerting a patient of symptoms being “off‐ trajectory” post‐sepsis.

As mentioned above, prior to submitting a white paper, it is strongly encouraged to learn more or submit inquiries to the Solving Sepsis program team.

B. Special Instructions Area of Interest #16 for DRIVe: Early Notification to Act, Control and Treat (ENACT)

The goal of the Early Notification to Act, Control and Treat (ENACT) program is to establish proactive technologies to stay ahead of health threats, known and unknown, that negatively impact American lives.

The purpose of the DRIVe ENACT program is to enable the early detection, notification and prevention of illness to transform health care from a reactive to proactive system.

The vision of this program is to empower people with technology that can turn them into their own first responders. The overall goal and vision of the program is to provide early, actionable information to alert end users of potential pathogen exposures prior to the user being aware that they are ill.

ENACT seeks to identify, characterize, and broadly adapt biological, biometric, behavioral and health (physiological) signatures that can determine the health status of healthy and/or unexposed vs infected and pre‐symptomatic individuals.

Focus Area within ENACT Area of Interest:

**Note – it is the goal of BARDA DRIVe to encourage respondents to develop and demonstrate the capability to sense, monitor, and predict healthy and ill health statuses for individuals while also being able to prognosticate the outcome of exposure, e.g., recovery and/or progression to severe disease.

Ideally, respondents would be able to demonstrate this in a proof of concept field study or appropriate surrogate model.

Focus Area 16.1: On‐Person, Wearable, and Biosensing Devices (Host Response and Direct Pathogen Detection):

Applicants should be currently developing wearables, biosensors, patches, and other sensing technologies that can collect, process and interpret biological, biometric, behavioral, physiological, and/or biochemical health signatures to establish a healthy baseline, alert of pre‐symptomatic exposure, and predict symptomatic/asymptomatic illness aiming to prognosticate different outcomes including recovery or cascading effects that lead to severe disease or death. For technologies using a direct pathogen sampling methodology, applicants should provide a business use case that shows potential market need and demand for such a device. Ideally, direct pathogen wearables or sensing technologies should be able to test for multiple pathogens and feature a use case that will allow for repeated and intermittent testing. All applicants must be able to provide data and address the criteria that support the following features:

For All Applicants in Focus Area 16.1:

Ideally in the first 12 months:

Ability to demonstrate a working prototype that can measure and establish signatures that represent a “healthy” baseline, e.g., one who has not been exposed/ infected

Ability to demonstrate either through the use of in silico modeling and analysis (host‐ based) and/or in vivo on animal models (direct pathogen and host‐based) the ability to detect changes to the “healthy” baseline while being sensitive and accurate enough to distinguish between normal and altered health functions, e.g., one who has been exposed/infected

Ideally within the period of performance:

Near final design build including all components, reagents, materials

Reduce and optimize process development activities for large scale transfer and/or economically feasible demonstration at scale

Provide business use case and feature set of final design product for transition into advanced development and manufacturing (including near and far‐field communication capability and other features)

For programs developing Indirect/Host‐based monitors:

Ideally a false positive alert rate <10%, comparable to gold standard diagnostic/sampling methodologies with a >50% sensitivity rate

Device sensor should feature either a continuous monitoring sampling method and/or an on‐demand sampling method that is sufficiently sensitive to detect pre‐symptomatic illness

Devices s measuring, monitoring, and distinguishing between health baseline signatures and pre‐symptomatic, exposed signatures.

Devices that can be operated without extensive levels of training

Ability to interface with algorithms and data analytics to enhance monitoring and sensing

Data communication and networking capabilities

Capabilities to support cross‐sensor, cross‐location data integration (timing, GPS, etc.)

Security considerations as it relates to safeguarding data transmission

Privacy, security and other considerations as it relates to FISMA, PII and HIPAA

For programs developing Direct Pathogen Detection monitors:

Ideally be comparable to current gold standard diagnostic/sampling methodologies (>85%

PPA)

Sampling technologies must be minimally invasive or non‐invasive

Describe the business case, target product profile, and use case for direct pathogen detections including list of risks and challenges predicted once product is in the market. It is important for respondents to outline the use case as it pertains to the risk‐benefit ratio of the technology.

Ability to interface with predictive algorithms and data processing/analytics tools to enhance monitoring and sensing

Data communication and networking capabilities

Capabilities to support cross‐sensor, cross‐location data integration (timing, GPS, etc.)

Security considerations as it relates to safeguarding data transmission

Privacy, security and other considerations as it relates to FISMA, PII and HIPAA

III. BARDA DRIVe Initial Outreach Instructions

The Government realizes that the preparation of white papers and proposals often represents a substantial investment of time and effort by an interested party. In an attempt to minimize this burden, BARDA DRIVe strongly encourages organizations and individuals interested in submitting proposals to make preliminary inquiry in the form of scheduling a market research call with the general need for the type of R&D effort contemplated before expending extensive effort in preparing a detailed proposal or submitting proprietary information.

Requests to schedule these calls (in addition to any general technical inquiries prior to a White Paper submission) may be submitted at any time while these Special Instructions are open to the individual mailboxes for the applicable areas of interest:

Special Instructions AOI #15: Solving Sepsis SolvingSepsis@hhs.gov

Special Instructions AOI #16: ENACT ENACT@hhs.gov

IV. Stage 1: White Paper/Quad Chart Instructions

A. Stage 1 Package Preparation

Following a preliminary call as described above, interested respondents may submit a Stage 1 Package in the following format outlined below, which is considered market research. The initial submission is limited to a cover page (“DRIVe Special Instruction Submission Form”), one‐page Quad Chart, White Paper not to exceed 5 pages, and an addendum not to exceed 4 pages (does not count the DRIVe Special Instruction Submission Form). This totals a Stage 1 Package that does not exceed 10 pages as noted in the page limits below. If submissions exceed these limitations, only those pages previously defined will be reviewed.

The White Paper/Quad Chart, and a Rough Order of Magnitude (ROM) estimate of costs must be submitted in accordance with the preparation guidance below. The White Paper/Quad Chart should describe the effort in succinct but sufficient detail to allow review of the concept's technical merit and its potential contribution to the BARDA mission. Respondents whose Stage 1 Package receive a favorable review will be invited by email to submit a Full Proposal (Stage 2). Respondents whose Stage 1 Package did not receive a favorable review will be notified as well by email.

IMPORTANT NOTE: Titles given to the White Papers and Full Proposals should be descriptive of the work proposed and not be merely a copy of the title of this solicitation.

1. DRIVe Special Instruction Submission Form (6 Pages, NOT counted in page total)

Please fill out and submit the “DRIVe Special Instruction Submission Form” to provide background on your company and proposed project.

2. Quad Chart Format (1 Page)

The format, information, sample, and template are located in Attachment 5 of BAA‐18‐ 100‐SOL‐00003 All Quad Charts should be laid out in landscape format. This should not include any proprietary information.

Heading: Title, BAA #, Development Area of Interest, Technical/Administrative point of contact (Name, Email, Phone), Company’s Name & Address.

Upper left: Objective, description of effort.

Lower left: Benefits of proposed technology, challenges, maturity of technology research area addressed as indicated by the TRL.

Upper right: Picture or graphic describing the effort.

Lower Right: Milestones, period of performance, ROM cost estimate.

3. White Paper Format (5 Pages)

The White Paper should provide a brief technical discussion of the respondent’s objective, approach, level of effort, and the nature and extent of the anticipated results. Specifically, the White Paper should include, at a minimum, the following core elements:

A brief discussion on how the proposed effort aligns with the objectives of the BARDA DRIVe Program and the BAA area of interest to which the submission is responding.

A transition plan that includes proposed Technology Readiness Level (TRL) maturity of the candidate product or device and how this project will continue after graduating from the DRIVe program

A high‐level schedule showing an overview of the proposed activities and timelines.

A brief description of the respondent’s intellectual property ownership of the proposed technology, approach or product. If intellectual property impediments may affect the respondent’s ability to develop the proposed technology. Respondents should briefly outline their strategy for addressing such impediments.

An overview of the respondent’s capabilities and experience (past and current) as they relate to the proposed development activities.

A description of the innovation that this technology/approach is bringing to the field compared to the state of the art. Company should discuss their commercialization strategy

4. Addendum (4 Pages)

Rough Order of Magnitude Preparation: A ROM cost estimate is required with the stage 1 submission. The ROM cost estimate is based on the top‐level task(s) or objective(s) set forth in the White Paper. It uses a top down estimating approach based on expert knowledge and/or previous experience. For the White Paper, each task (or objective) needs to have a ROM cost estimate. A total ROM cost (i.e., sum of all the tasks or objectives) should also be provided.

As an addendum to the White Paper, include biographical sketches (two pages) of the key personnel who will perform the research or management of project activities, highlighting their relevant qualifications and experience.

Any applicable references should also be cited if they are relevant to the proposed work plan.

Restrictive markings: Submissions will be protected from unauthorized disclosure in accordance with 41 U.S.C. § 2102 and applicable regulations. Please note that any Stage 1 submission submitted under this solicitation may be shared with other government agencies for non‐BARDA funding considerations and evaluation.

White Papers must be submitted in the following format:

Three PDF files as a file upload; one for Quad Chart, one for White Paper, and one for Addendum

Page Size: 8 ½ x 11” with 1” Margins

Page Size: 8 ½ x 11” with 1” Margins

Spacing – single

Font – Arial, 11 point (use of Arial or another readable font and readable smaller size point for tables and captions will be accepted)

The file should not exceed 10 Megabytes of storage space. Movie and sound file attachments, URL Links, or other additional files, will not be accepted.

Classification: All Stage 1 submissions must be UNCLASSIFIED.

B. Stage 1 Package Submission

All Stage 1 Package submissions and contractual / administrative inquiries, must be submitted to DRIVeContracting@HHS.GOV with ““DRIVe Special Instructions: Sepsis / ENACT (as appropriate)” as the first words of the email subject line, followed by company name and title of project.

The Stage 1 Package submissions WILL NOT BE ACCEPTED after 3:00 PM (Eastern Time) on the final date for the Special Instructions.

Limitation on Communication After Stage 1 Package Submission:

Be advised that after a Stage 1 (or Stage 2) Package has been submitted, all communications related to that submission must be through the Contracting Office at DRIVeContracting@hhs.gov .

Do not carbon copy (cc) or blind carbon copy (bcc) the technical POCs or any other individuals during submission of a Stage 1 or Stage 2 Package. Doing so may disqualify you from consideration.

V. Stage 2: Full Proposal Instructions

A. Stage 2 Package Preparation & Submission

Detailed instructions will be provided in an invitation letter consistent with BAA‐18‐100‐SOL‐ 00003.