HHS-NIH-NIAID-BAA2018.pdf

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2018 Omnibus Broad Agency Announcement:

No. HHS-NIH-NIAID-BAA2018

Issue Date: June 1, 2018

Participating NIAID Divisions: Division of Microbiology & Infectious Diseases (DMID)

Issuing Office: Office of Acquisitions, DEA, NIAID, NIH, 5601 Fishers Lane, Room 3D32, MSC 9821, Bethesda, MD 20892-9821

Issuing Contracting Officer: George Kennedy kennedyg@mail.nih.gov

(240) 669-5170

This solicitation contains opportunities to submit a proposal under the following distinct Research Areas, which are identified below:

* Proposals must be received before 3:00 PM Eastern Time on the date specified herein. Please see the Proposal

Submission Instructions for more information.

Offers will be valid for 240 days unless a different period is specified by the Offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043.

RESEARCH

AREA

NIAID

DIVISION

TITLE PAGE

NO.

PROPOSALS

DUE:

001 DMID

Development of Therapeutic Products for

Biodefense, Anti-Microbial Resistant (AMR)

Infections and Emerging Infectious Diseases

08/10/2018 *

002 DMID

Advanced Development of Vaccine

Candidates for Biodefense and Emerging

Infectious Diseases

08/10/2018 * mailto:kennedyg@mail.nih.gov

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2018 Omnibus Broad Agency Announcement

No. HHS-NIH-NIAID-BAA2018

TABLE OF CONTENTS

SECTION 1 - Broad Agency Announcement Information………………………………………………. p. 2

SECTION 2 - Contracting Officer Points of Contact………………………………….………………….. p. 2

SECTION 3 - Research Areas and Technical Objectives…………………………………….…………… p. 3

3.1 – Division of Microbiology and Infectious Diseases (DMID)

3.1.1 - Background…………………………………………………………………………….. p. 3

3.1.2 - Research Areas

3.1.2.1 - Research Area 001: Development of Therapeutic Products for Biodefense, Anti-

Microbial Resistant Infections (AMR) Infections and Emerging Infectious Diseases………. p. 4

3.1.2.2 - Research Area 002: Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases…………………………………………………………….. p. 7

3.1.3 - Additional Technical Proposal Instructions …………………………………… ….. p. 9

3.1.4 - Reporting Requirements and Deliverables ………………………………… ………. p. 16

SECTION 4 - Instructions, Conditions, and Notices to Offerors…………………………………………… p. 23

4.1 - General Instructions……………………………………………………………… ……….... p. 23

4.2 – General Information……………………………………………………………………… p. 26

4.3 – Instructions to Offerors …………………………………………………………………….. p. 28

4.3.1 - General Information………………………………………………………………... p. 28

4.3.2 - Technical Proposal Instructions …………………………………………………… p. 35

4.3.3 - Business Proposal Instructions …………………………………………………….. p. 65

SECTION 5 – Special Contract Requirements ………………………………………………………. p. 82

SECTION 6 - Evaluation Factors for Award ……………………………………………………….. p. 107

SECTION 7 - Attachments……………………………………………………………………………… p. 116

SECTION 1. - BROAD AGENCY ANNOUNCEMENT INFORMATION

You are invited to submit a proposal in accordance with the requirements of this BROAD AGENCY

ANNOUNCEMENT (BAA). The BAA is governed by Federal Acquisition Regulation (FAR) 6.102 and

FAR 35.016, as well as the NIH Policy Manual, Manual Chapter 6035, Broad Agency Announcements. A

BAA may be used as a solicitation mechanism for basic and applied research directed toward advancing the state-of-the-art or increasing knowledge or understanding and that part of development not related to the development of a specific system or hardware procurement. BAAs are general in nature, identifying areas of research interest, and shall only be used when meaningful proposals with varying technical/scientific approaches can be reasonably anticipated.

This solicitation contains multiple distinct Research Areas. Offerors may submit a proposal in response to one, or both, of the Research Areas contained herein. Offers submitted in response to this BAA must present separate detailed technical and business proposals designed to meet the Technical Objectives described for each Research Area proposed. The Statement of Work (SOW), including the specific technical requirements and performance specifications, shall be developed and proposed by the Offeror, not the Government.

Proposals are NOT evaluated against each other since they are not submitted in accordance with a common

Statement of Work issued by the Government. Instead, Research and Technical Objectives are provided in the BAA that describe individual Research Areas in which the Government is interested. Proposals received in response to the BAA are evaluated in accordance with the Evaluation Factors for Award specified in this announcement. The Government reserves the right to conduct discussions with all, some, one, or none of the proposals received in response to this BAA. If discussions are conducted, NIAID reserves the right to suggest modifying, adding or deleting milestones, decision points, research plans, processes, schedules, budget or product. The Government also reserves the right to make awards without discussions.

Additionally, the Government reserves the right to accept proposals in their entirety or to select only portions of proposals for award. Multiple awards are anticipated. The selection for award under this BAA will be based upon the evaluation factors, importance to the agency programs, and the availability of funds.

SECTION 2. - CONTRACTING OFFICER POINTS OF CONTACT

This BAA contains Research Areas issued by the Division of Microbiology and Infectious Diseases (DMID) within the National Institute of Allergy and Infectious Diseases. The Contracting Officer point of contact for questions related to specific Research Areas issued by the Division of Microbiology and Infectious

Diseases (DMID) is identified below:

Division of Microbiology and Infectious Diseases (DMID)

Research Area 001: Development of Therapeutic Products for Biodefense, Anti-Microbial

Resistant (AMR) Infections and Emerging Infectious Diseases

Research Area 002: Advanced Development of Vaccine Candidates for Biodefense and

Emerging Infectious Diseases

George Kennedy, J.D.

Contracting Officer

Phone: (240) 669-5170

Email: kennedyg@mail.nih.gov mailto:kennedyg@mail.nih.gov

SECTION 3. - RESEARCH AREAS AND TECHNICAL OBJECTIVES

3.1 - DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES (DMID), NIAID

3.1.1 - BACKGROUND

Research supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. NIAID also has a key role in the development of new medical countermeasures (MCMs) against potential agents of bioterrorism, drug-resistant pathogens, and emerging and re-emerging infectious diseases.

Through a variety of research grants and contracts, NIAID’s Division of Microbiology and

Infectious Diseases (DMID) supports basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics targeting multiple pathogens, including NIAID

Category A, B, and C priority pathogens (https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens).

These efforts are guided by the current NIAID Strategic Plan for Biodefense Research

(https://www.niaid.nih.gov/research/biodefense-strategic-plan), which established a strategy for developing new and improved MCMs against a broad array of relevant pathogens.

NIAID’s plan reflects the Institute’s partnerships with the HHS Public Health Emergency

Medical Countermeasures Enterprise (PHEMCE) and Department of Homeland Security.

The HHS PHEMCE coordinates interagency efforts aiming to optimize the United States’ preparedness for public health emergencies with respect to the creation, stockpiling, and use of MCMs. Led by the Assistant Secretary for Preparedness and Response (ASPR)/HHS, the

PHEMCE consists of the NIH, Food and Drug Administration (FDA), and Centers for

Disease Control and Prevention (CDC), and senior leadership from other federal agencies.

The 2016 HHS PHEMCE Strategy and Implementation Plan

(http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx) describes the current priorities for MCM development against advanced, enhanced, or emerging threats.

Further, an Executive Order released by the President of the United States in 2014

(http://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic- resistant-bacteria) highlights one of the most urgent public health threats facing us today – antibiotic resistance – and encourages the development of new and next generation antibiotics, among other goals. CDC has identified a list of antibiotic resistant pathogens in the United States due to their significant public health threat to the nation

(https://www.cdc.gov/drugresistance/threat-report-2013/index.html ). More recently, WHO published a list of antibiotic-resistant "priority pathogens" from 12 families of bacteria that pose the greatest threat to human health

(http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-

ET_NM_WHO.pdf?ua=1).

Through this solicitation, NIAID aims to advance research and development of promising new therapeutics and vaccines addressing infections caused by these pathogens, as specified in the research topics described under the two Research Areas below.

https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens https://www.niaid.nih.gov/research/biodefense-strategic-plan http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx http://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic-resistant-bacteria http://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic-resistant-bacteria http://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic-resistant-bacteria https://www.cdc.gov/drugresistance/threat-report-2013/index.html http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1

3.1.2 - RESEARCH AREAS

3.1.2.1 - Research Area 001 - Development of Therapeutic Products for

Biodefense, Anti-Microbial Resistant (AMR) Infections and Emerging

Infectious Diseases

3.1.2.1.1 - Budget and Award Information

NIAID estimates that two or more awards may be issued across Research Areas 001 and

002 for a total cost of up to $15.5 million for the non-severable base work across all contracts (direct and indirect costs combined), depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds. The total cost for each award(s) may vary depending upon the scope of the project and the technical objectives of the award(s).

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror should not exceed five (5) years.

Awards are anticipated to be made in or around May 2019.

3.1.2.1.2 - Technical Objectives

The objective of Research Area 001 is the development of therapeutics for use in post-event settings following the intentional release of select pathogens, or in response to naturally-occurring outbreaks of infectious diseases caused by pathogens listed in the

Technical Approach section below. While proposals for the development of broad-spectrum therapeutics are encouraged, candidate therapeutics or lead series with a limited spectrum that target high-priority pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern are eligible as proposed candidates/products or lead series.

Broad-spectrum activity is a characteristic that enables a particular product to mitigate biological threats across a range or class of agents. A limited number of anti-infectives with broad-spectrum activity directed at common, invariable, and essential components of different classes of microbes, or directed at host functions that are required by different classes of microbes, could potentially be effective against both traditional and non-traditional threats. This approach would allow a smaller number of drugs to replace dozens of pathogen-specific drugs for clinical use.

There are a number of threats for which effective treatments are either non-existent, of limited usefulness, or vulnerable to both naturally emerging and intentionally engineered antibacterial and antiviral resistance. Therapeutic candidates or lead series that specifically address drug-resistant pathogens or those for which no treatments exist are encouraged, even if these products have a narrow spectrum of activity.

Strategies to overcome bacterial and viral drug resistance could extend the clinical utility of existing broad-spectrum anti-infectives and have immediate benefits. Moreover, treatments directed towards host targets have the potential to be effective against one or more diseases.

For these reasons, proposals on non-traditional therapeutics are encouraged, provided they have demonstrated therapeutic activity when used alone or in combination with an existing licensed product. For the purposes of this solicitation, therapeutic activity is defined as the cure or mitigation of disease, preferably, once signs and symptoms of infection are evident. For the purposes of this solicitation, a therapeutic candidate or lead series is defined as either a drug (synthetic or natural product) or a biological product (e.g.

monoclonal antibodies, recombinant proteins), and therapeutic activity is defined as the cure or mitigation of disease, preferably once signs and symptoms of infection are evident.

Research Area 001 will support the progression of candidate therapeutics or lead series through the product development pipeline toward IND submission and early phase clinical studies and development, which includes Phase I and Phase II. To that end, therapeutic candidates or lead series must show all of the following characteristics:

• Demonstrated feasibility of manufacturing;

• In vitro and in vivo evidence of efficacy;

• In vitro and in vivo evidence of acceptable preliminary pharmacokinetic, safety and toxicology; and

• Sufficient characterization to allow the development of a draft target product profile.

Proposals that initiate with a single therapeutic candidate are encouraged and must complete evaluation in a Phase 1 or 2 clinical trial within the 5-year proposed period of performance. Phase 1 or 2 clinical trial completion is defined as completion of a Final

Clinical Study Report following International Conference on Harmonization (ICH)

Guidelines on Structure and Content of Clinical Study Reports E3.

Proposals that initiate with more than one lead compound (or lead series) also will be considered, provided clear plans are presented for selecting a single clinical candidate therapeutic by the end of the second year of funding to enable completion of IND-enabling activities and submission of the IND within a 5-year period of performance.

3.1.2.1.3 - Technical Approach

Solicited Products:

I) Antibacterial Therapeutics

Candidate antibacterial therapeutic products or lead series must address infections caused by one or more of the following bacterial pathogens:

a) One or more drug-resistant bacteria listed in the 2013 CDC Antibiotic

Resistance Threats in the United States report or in the WHO Priority

Pathogens List for R&D of New Antibiotics

AND/OR

b) One or more of the following select agents:

https://www.cdc.gov/drugresistance/threat-report-2013/index.html https://www.cdc.gov/drugresistance/threat-report-2013/index.html

• Bacillus anthracis

• Francisella tularensis

• Yersinia pestis

• Burkholderia pseudomallei

• B. mallei

II) Antiviral Therapeutics

Candidate antiviral therapeutic products or lead series must address infections caused by one or more of the viral pathogens from the following families:

• Flaviviruses (e.g. Zika and Dengue virus)

• Filoviruses (e.g. Ebola virus, Sudan, and Marburg)

• Orthopoxviruses (e.g. Variola major)

• Pathogenic Coronaviruses (e.g. MERS and SARS CoV)

• Alphaviruses (e.g. Chikungunya virus)

• Influenza (especially Influenza A seasonal and novel subtypes with pandemic potential)

III) Anti-toxin Therapeutics

Candidate anti-toxin therapeutic products or lead series must target one or more of the following toxins:

• Ricin;

• Staphylococcus enterotoxin B;

• One or more of the known serotypes of Clostridium botulinum neurotoxin

(serotype A, B, C, D, E, F, G); or

• Bacillus anthracis Protective Antigen, Lethal Factor and/or Edema Factor, for which only small-molecule therapeutics are eligible.

3.1.2.1.4 - Additional Requirements

Organizations responding to this Research Area, collectively with the proposed subcontractors and consultants where applicable, must have documented expertise in drug discovery and development, including demonstrated knowledge of regulatory guidelines, and submission processes for candidate products directed against emerging infectious diseases and/or biological threats.

3.1.2.1.5 - Contracts awarded under this Research Area will NOT support:

• Basic research and discovery of new series/candidates/products

• Hit-to-Lead optimization and studies

• Development of devices, topical products, or diagnostics

• Development of candidates/products or lead series that have not demonstrated therapeutic activity in a relevant animal model of disease

• Development of topical sanitation products, or vaccines

• Development of serum-derived products

• Development of licensed products as new formulations, or for additional clinical indications

3.1.2.2. - Research Area 002 - Advanced Development of

Vaccine Candidates for Biodefense and Emerging Infectious

Diseases

3.1.2.2.1 - Budget and Award Information

NIAID estimates that two or more awards may be issued across Research Areas 001 and

002 for a total cost of up to $15.5 million for the non-severable base work across all contracts (direct and indirect costs combined), depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds. The total cost for each award(s) may vary depending upon the scope of the project and the technical objectives of the award(s).

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror should not exceed five (5) years.

Awards are anticipated to be made in or around May 2019.

3.1.2.2.2 - Technical Objectives

The objective of Research Area 002 is the development of vaccines for scenarios associated with intentional release of a NIAID Category A, B, or C Priority Pathogen, or naturally-occurring outbreaks of infectious diseases caused by these pathogens or Zika virus (Zika virus vaccine would be included only as a component of a multivalent vaccine for other pathogens such as a vaccine for Flavivirus family). Only proposed candidate products aimed at these pathogens are eligible.

The candidate product(s) may also include an adjuvant that enhances the immune response

(i.e., enhanced immunogenicity, decreased time or reduced number of immunizations to achieve protective antibodies and/or increased efficacy). Adjuvants will be supported as components of the candidate product. Novel delivery platforms that reduce logistical requirements or provide other benefits may be components of the candidate product to be developed as well. Cross-cutting technologies applicable to more than one vaccine component are also of interest.

3.1.2.2.3 - Technical Approach

Solicited Products:

Research Area 002 will support the progression of candidate countermeasures through the product development pipeline toward licensure by the FDA. For the purposes of this

Research Area:

• Proposals should demonstrate vaccine candidate efficacy via challenge testing using natural routes of human exposure, to the extent possible.

• The scope of the product development activities to be undertaken will depend on the status of the individual candidate product, as well as regulatory requirements.

I) Technology Gaps that Slow Progression to Clinical Testing

There is a critical need for technologies that accelerate the vaccine design, development, nonclinical testing, and production process toward clinical testing.

These innovative technologies/tools would be in product development and/or regulatory models and reduce or eliminate the bottlenecks to clinical testing and increase the likelihood of success along the regulatory path. These tools/technologies could advance animal models, predict/determine human safety and efficacy, and/or improve manufacturing and processing methods and analytical tools to provide novel rapid methods of assessment and development. Other technologies could accelerate the development of vaccines for infectious diseases using technologies such as genome-to-vaccine or epitope-driven vaccine approaches.

II) Novel Vaccine “Plug-and-Play” Technologies

NIAID supports development of plug-and-play technological solutions/platforms that improve preparedness capabilities, approaches to MCM development and manufacturing against multiple, new and/or emerging threats. These technologies would increase the rapid response to, and development of, vaccines that contribute to greater biodefense preparedness and significantly improve the ability of the U.S. to protect its citizens against infectious diseases. Platform technologies could include multivalent and/or universal vaccines approaches, continuous manufacturing initiatives, process efficiencies, surge production capabilities, etc.

III) Enhanced Vaccine Performance (with special interest in simplicity and speed of delivery, rapid immune response and sterilizing immunity)

Several techniques can promote enhanced vaccine performance. These techniques may be applicable across a broad range of products and/or platforms. These include development of vaccine technologies, platforms, and/or formulations that minimize cold chain requirements and enhance stability. Of note, there is great need to develop influenza vaccine candidates/platforms designed to elicit broad and durable protection against multiple influenza viruses (e.g. broad subtype, or HA group 1 or group 2 specific vaccines). Candidate vaccines seeking to significantly improve seasonal flu vaccine efficacy or increase in durability of protective responses beyond 1-2 years are also of high interest.

IV) Vaccines Against Antimicrobial Resistance Threats

Antimicrobial resistance (AMR) is rendering many current countermeasures ineffective and increasingly challenges the development of effective new antimicrobials (antibiotics, antivirals, etc.) for many NIAID priority pathogens.

For example, antibiotic resistance represents a serious threat to public health and the economy. As more bacterial strains become resistant to an ever-increasing number of antibiotics, drug choices will become increasingly limited and expensive and, in some cases, nonexistent. For the many AMR pathogens, there are currently no licensed vaccines. The development of vaccines against AMR microorganisms is critical since vaccines reduce the need to use antimicrobials and antibiotics, and therefore reduce the threat of AMR.

3.1.2.2.4 - Additional Requirements

I) This Research Area focuses on the development of promising lead vaccine candidates/products. To that end, a lead candidate must possess all of the following characteristics:

a) demonstrated feasibility of manufacturing;

b) in vivo efficacy or in vitro efficacy if in vivo efficacy is unavailable, or if in vitro efficacy data supplements in vivo data in a meaningful way;

c) sufficient characterization to allow the development of a draft target product profile

II) Organizations responding to this Research Area, collectively with the proposed subcontractors and consultants where applicable, must have documented expertise in vaccine discovery and development, including demonstrated knowledge of regulatory guidelines and submission processes for candidate products directed against emerging infectious diseases and/or biological threats identified in the Technical Objectives.

3.1.2.2.5 - Contracts awarded under this Research Area will NOT support:

• Basic research and discovery of new series/candidates/products

• Refinement of a lead series to identify a candidate

• Development of devices or diagnostics in the absence of a companion product

• Development of candidates/products that have not demonstrated vaccine efficacy in a relevant animal model of disease, unless the disease is new or emerging and relevant models are unavailable

• Development of Anthrax vaccines

• Development of monovalent Zika vaccines

-- END OF RESEARCH AREA 002 --

3.1.3 - RESEARCH AREAS 001 and 002 - Additional Technical Proposal Instructions

The following information supplements Section 4 – Instructions, Conditions, and Notices to

Offerors of this solicitation, and should be used for preparing proposals in response to Research

Area 001 or 002. Separate and distinct proposals must be submitted for each Research Area to which you are proposing.

3.1.3.1 - CANDIDATE PRODUCT PROFILE

Provide a synopsis (suggested 10-page maximum – included in total page limitation) of the intended use of the candidate product and background information to support the further development of the candidate product as formulated/designed. Include the following information:

a. The intended use/indication of the lead product/formulation/design and the biodefense/public health gap the product is intended to fill.

b. The performance specifications and features the product/device would meet in order to provide benefit that would meet the Technical Objectives, including potential stability, dosing and safety.

c. A description of the product and its current formulation and/or device description.

d. Data to support the characterization and selection of the product for further development, including: a summary of manufacturing status, processes, scalability product stability and overall potential for commercialization, a summary of data that demonstrates efficacy using appropriate assays and animal models predictive of the human response; a description of the assays and animal models; and, the rationale for the choice of assays and animal models for the outcome/endpoints selected.

e. Meeting minutes or, if no meeting minutes are available, synopses from discussions with the FDA (CBER/CDER/CDRH), if any, that are relevant to development activities for the proposed product.

f. A description of activities that are part of the critical product development strategy through submission of a BLA or NDA.

3.1.3.2 - PRODUCT DEVELOPMENT PLAN

Technical Proposals must include a Product Development Plan that describes the critical path for the proposed candidate/product to eventual licensure and identifies the decision points/gates for progress of the candidate/product. Offerors should point out areas of significant uncertainty and propose likely alternatives.

The Product Development Plan should detail the specific tasks and stages to be performed with contract funding that can be reasonably completed within the period of performance. The

Product Development Plan should include a summary of the following:

a. A description of the candidate/product as it is currently configured.

b. The intended use/indication of the proposed candidate/product and the public health gap the product is intended to fill.

c. A Target Product Profile for the lead candidate, the performance specifications and features the candidate/product should have including potential stability, dosing and safety.

d. Data to support the characterization and selection of the candidate/product for further development. A summary of the data that demonstrates activity in an appropriate animal model.

e. Discussions with FDA, if available, that are relevant to development activities for the proposed candidate/product.

f. A description of activities that are part of the critical product development strategy through submission of a BLA or NDA.

g. As relevant, plans for the development, submission, and sponsorship of an

Investigational New Drug (IND)/combination product application, including compliance with all regulatory requirements.

h. As relevant, plans for the design, conduct, and completion of a Phase 1, Phase 1/2 and/or Phase 2 clinical trial for the candidate product.

3.1.3.3 - WORK PLAN (For the implementation of the PRODUCT DEVELOPMENT PLAN)

Technical proposals shall include a work plan detailing the specific tasks that the Offeror proposes to perform with contract funding that can reasonably be completed within the period of performance. These include milestones and gates for Go/No Go decisions with a timeline

Gantt chart that can be correlated with a task-linked budget at a level that facilitates government oversight of funded activities.

The Work Plan for the candidate/product submitted with the Technical Proposal will be subject to negotiations and if an award is made, the Statement of Work (SOW), to be developed by the

Offeror and provided with the Technical Proposal, shall provide for the updated Work Plan to be approved by the Contracting Officer’s Representative (COR) and the Contracting Officer prior to the initiation of any activities related to its execution. In addition, the SOW shall provide for annual updates of the Work Plan, and additional updates upon a change in any task, that must be approved by the COR and the contracting officer prior to the initiation of any activities related to its execution. The Work Plan shall include:

a. Milestones for key project objectives.

b. Threshold decision gates using objective, measurable criteria to enable Go/No-Go decisions for advancement into the next stage of development. For each decision gate proposed, a description of the specific qualitative and quantitative criteria, associated data elements and the process for making decisions to proceed or not proceed (Go/No-

Go), for advancement of candidates/products through each stage of the product development process.

c. Timelines for: the initiation, conduct and completion of product development activities for each stage; the analysis of outcomes and findings; and, the preparation of detailed reports summarizing the results of work completed and an analysis of the data as it relates to the qualitative and quantitative criteria established for Go/No Go decision making.

d. A Gantt chart of proposed activities that are associated with a task-linked budget at a level that facilitates Government oversight, and contractor management of those activities. A Gantt chart of proposed activities that can be correlated with a task-linked budget at a level that facilitates Government oversight of those activities.

The Gantt chart should be organized by each specific decision gate/stage of product development proposed, as well as the overall product development program. Schedules should be shown in terms of calendar months from the date of authorization to proceed or, where applicable, the date of a stated event. The timeline will identify summary tasks and subtasks, including predecessor and successor logic for all activities covering the initiation, conduct and completion of all product development activities in a base period and in subsequent option periods.

The task-linked budget should provide a breakdown of direct costs linked to each activity, task and subtask contained on a detailed chart. The timeline should identify summary tasks and subtasks, including predecessor and successor logic for all activities covering the initiation, conduct and completion of all product development activities in a base period and in subsequent option periods.

e. A detailed discussion of the proposed technical approach for each activity to be performed to achieve the key project objectives, with sufficient detail to fully explain and justify the scientific/technical rationale for the proposed approach and/or methodologies.

f. The following, as applicable for the project being proposed:

• Approach for manufacturing and CMC development of candidate/product to optimize production, formulation and delivery.

• Description of non-clinical studies, including all Investigational New Drug (IND)-enabling studies.

• Approach for development of assays and reagents needed to support product development activities.

• Development and submission of an IND and performance of clinical trials to demonstrate product safety and/or early efficacy.

g. Plans for quality control over the implementation, coordination and conduct of the activities set forth in the Work Plan, including plans to conduct regulatory audits.

h. Approaches to integrate adverse experimental or production results, new scientific findings and/or guidance from FDA into the proposed goals and timelines. A risk management and mitigation plan is required.

i. A plan for sharing data and resources, reagents, assays and animal models developed with contract funding with the scientific community.

j. A list and description of all items to be delivered to the Government at each stage in the product development process during the performance of the contract and a timeline for delivery to be determined at time of award. This includes delivery of all necessary supporting documentation and letters of cross-reference required for subsequent regulatory submissions, and clinical trials.

NOTE: Depending on the status of the individual candidate product, the Contractor may be required to deliver to the Government an amount of product for any purpose deemed necessary by the Government.

k. A Technical Proposal Cost Summary to include: a list of all subcontracts by activity

(for example, GMP manufacture, IND-enabling toxicological studies, formulation and fill, etc.) including a budget for each stage of product development proposed for funding (direct costs plus indirect costs).

l. Offerors proposing subcontracts and/or consultants to perform portions of the proposed work should clearly identify the specific tasks for which they plan to utilize subcontractors and/or consultants, as well as the method and level of integration/coordination between the prime Contractor and all proposed subcontractors and/or consultants, and the expected advantages of such an approach. Processes for subcontractor and consultant identification, selection, management and evaluation should be described. Expected deliverables associated with consulting services should be clearly delineated.

m. The technical proposal should include direct cost and resources information, such as labor-hours and categories and applicable rates, materials, subcontracts, travel, etc., and associated costs so that the Offeror's understanding of the project may be evaluated

(http://oamp.od.nih.gov/DGS/FORMS/Tech-Prop-Cost-Summ.pdf). However, the technical proposal should not include pricing data relating to individual salary information, indirect cost rates or amounts, fee amounts (if any), and total costs.

The Product Development Plan will be subject to negotiations, and if an award is made, the resulting contract shall provide for continuing revision of the Product Development Plan following periodic input and approval from the Government.

3.1.3.4 - CLINICAL TRIAL PROTOCOL DEVELOPMENT AND IMPLEMENTATION

Human subjects research may be carried out under this contract with the approval of DMID.

Describe experience in the conduct of human subjects research in accordance with DMID, NIAID, and NIH policies and guidelines and provide a statement acknowledging willingness to conduct clinical research according to these policies and in accordance with applicable ICH and

U.S. FDA regulations and guidance.

Provide a Protocol Synopsis for each proposed clinical trial, including a brief description of all of the following:

• Study objectives and endpoints

• Human subjects protection

• Provisions for data monitoring and safety reports

• Draft inclusion/exclusion criteria and recruitment, and retention of study participants

• Informed consent

• Quality management plan

• Clinical monitoring plan

• Summary of statistical approach

• Plan for management of subcontractor activities

Document experience of the Offeror and any proposed subcontractor(s) and consultant(s) experience with designing early phase clinical trials, executing early phase clinical trials and managing early phase clinical trials in compliance with regulatory requirements and GCP.

Provide a plan that specifies at which points in the Statement of Work (SOW) it will be critical to engage in communications with the FDA and the means by which NIAID will be kept apprised of such communications.

3.1.3.5 - REGULATORY COMPLIANCE, QUALITY CONTROL & ASSURANCE, and

DATA MANAGEMENT

• Describe the data management and quality control systems/procedures that will be used for all studies and procedures for data entry and validation, documentation of data corrections, routine maintenance and backup, transmission of data, data reporting and exporting system, access control and confidentiality, and data retrieval and disaster recovery in accordance with 21 CFR 11.

• Describe the statistical design and analysis resources that will be used to support contract activities.

• Provide a plan to develop and maintain quality assurance documentation to support adherence to FDA regulatory standards and guidance that bear on the conduct of assays under GLP, manufacturing under GMP, and performance of clinical trials under GCP standards, as relevant to the Product Development Plan.

• Document experience of the Offeror and any proposed subcontractors and consultants experience with performing regulated studies in accordance with FDA regulations and guidance, including GLP, cGMP, and/or GCP guidelines as appropriate to their proposed SOW.

• Describe a plan to determine when audits need to be performed, timely scheduling of audits, performance of audits, and responding to audit reports.

• Provide an audit history of the facilities proposed for use in carrying out contract activities that will be performed under GLP, cGMP and/or GCP.

• Provide letters signed by the appropriate authority allowing for pre-award site visits to the Offeror’s facility and proposed subcontractors’ facilities. Site visits may include

GLP, cGMP, or GCP audits (as appropriate) performed by independent auditors contracted by the NIAID.

3.1.3.6 - UNIFORM COST ASSUMPTIONS

Offerors should use the following assumptions for the purposes of estimating costs and preparing the technical proposal:

a. Audits: Assume three (3) independent QA audits per year for the duration of the contract period of performance.

b. Purchase of Equipment: Cost will NOT be allowed for the purchase of any equipment, hardware, or software under this contract.

c. Alterations and Renovations: Cost will NOT be allowed for any facility construction, alterations, or renovations under this contract.

d. Programmatic Presentations and Meetings: Assume attendance at the following meetings:

1) Post Award Contract Initiation Meeting

The Contractor shall be responsible for arranging a one-day meeting at the contractor site. Attendees should include all Key Personnel and Key Subcontractor personnel.

2) Annual Contract Review Meetings

For each year of performance, the Contractor shall attend an Annual Contract

Review meeting. The meetings will be held at the Contractor’s facility, and a location at or near Washington D.C., on an alternating-year basis. Each meeting will be one-day in length. Attendees should include all Key Personnel, members of the External Advisory Group, and Key Subcontractor personnel.

3) External Advisory Group Meetings

After contract award and in consultation with the Contracting Officer’s

Representative (COR) and the Contracting Officer, the Contractor shall establish an

External Advisory Group with the relevant expertise to critically evaluate technical progress in achieving product development objectives and established timelines. It is anticipated that the External Advisory Group will consist of at least 2 members.

The membership of the External Advisory Group will be proposed by the

Contractor and approved by the COR and Contracting Officer post-award.

Compensation for this role will be provided by the Contractor with contract funds as approved by the Contracting Officer and will be commensurate with the specific roles and duties assigned to the members.

NOTE: DO NOT identify or propose External Advisory Group members in the technical or business proposal. Do not contact specific individuals regarding service on the External Advisory Group in advance of contract award.

3.1.3.7 - POST-AWARD REQUIREMENTS

The following POST-AWARD requirements will apply to all awards made under Research

Areas 001 and 002 of this BAA.

Offerors are instructed to address responsibility for complying with these requirements in the proposed Statement of Work for the Technical Proposal. Offerors are NOT required to submit documentation to address these post-award requirements in their technical proposals.

Instructions for submitting documentation associated with post-award requirements will be provided during negotiations.

3.1.3.7.1 - Contractual Commitments

Upon award of a contract, the contractor shall be required to make legal commitments through acceptance of Government contract clauses contract. The outline that follows is illustrative of the types of provisions required by the Federal Acquisition Regulations that shall be included in the contract. This is not a complete list of provisions to be included in contracts, nor does it contain specific wording of these clauses. Copies of complete terms and conditions applicable to your contract will be provided during negotiations.

1) Inspection: Work performed under the contract is subject to Government inspection and evaluation at all times.

2) Termination for Convenience: The Government may terminate the contract at any time for convenience if it deems termination to be in its best interest, in which case the contractor will be compensated for work performed and for reasonable termination costs.

3) Disputes: Any dispute concerning the contract that cannot be resolved by agreement shall be decided by the contracting officer with right of appeal.

4) Equal Opportunity: The contractor will not discriminate against any employee or applicant for employment because of race, color, religion, sex, or national origin.

5) Gratuities: The Government may terminate the contract if any gratuities have been offered to any representative of the Government to secure the contract.

6) American-made Equipment and Products: When purchasing equipment or products under a contract award, the contractor shall purchase only American-made items whenever possible.

7) Default: The Government may terminate the contract for default if the contractor fails to perform the work described in the contract and such failure is not the result of excusable delays.

8) Contract Work Hours: The contractor may not require an employee to work more than eight hours a day or forty hours a week unless the employee is compensated accordingly (i.e., overtime pay).

9) Covenant Against Contingent Fees: No person or agency has been employed to solicit or secure the contract upon an understanding for compensation except bona fide employees or commercial agencies maintained by the contractor for the purpose of securing business.

10) Patent Infringement: The contractor shall report each notice or claim of patent infringement based on the performance of the contract.

3.1.4 - RESEARCH AREAS 001 and 002 – Reporting Requirements and Deliverables

3.1.4.1 - Reporting Requirements

In addition to reporting requirements and deliverables identified elsewhere in this solicitation, it is expected that awards resulting from Research Areas 001 and 002 will include the following reports and deliverables:

a. Monthly Progress Reports

This report shall include a description of the technical activities and results during the reporting period and the activities planned for the ensuing reporting period, and shall include a budget summary for costs incurred during the monthly reporting period for the base period and each option and milestone. The funding level shall be presented in correlation with percent completion of the activities under the base, option and/or milestone. Monthly Progress Reports shall not be required when the Annual Progress

Report is due.

b. Annual Progress Reports

This report shall include a summation of the technical activities and results for the entire contract period covered, and shall include a description of the technical activities and results during the reporting period, a budget summary for costs incurred during the annual reporting period for the base period and each option and milestone. The funding level shall be presented in correlation with percent completion of the activities under the base, option and/or milestone. An Annual Progress Report shall not be required for the period when the

Final Report is due.

c. Annual Technical Progress Report for Clinical Research Study Populations

The Contractor shall submit information about the inclusion of women and members of minority groups and their subpopulations for each study being performed under this contract. In addition, the NIH Policy and Guidelines on the Inclusion of Women and

Minorities as Subjects in Clinical Research, Amended, October 2001 applies. Include a description of the plans to conduct analyses, as appropriate, by sex/gender and/or racial/ethnic groups in the clinical trial protocol as approved by the IRB, and provide a description of the progress in the conduct of these analyses, as appropriate, in the annual progress report and the final report. If the analysis reveals no subset differences, a brief statement to that effect, indicating the subsets analyzed, will suffice. The Government strongly encourages inclusion of the results of subset analysis in all publication submissions. In the final report, the Contractor shall include all final analyses of the data on sex/gender and race/ethnicity.

d. Final and Draft Reports

This report includes a summation of the work performed and the results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. An annual report will not be required for the period when the Final Report is due. The Contractor shall submit, with the Final Report, a summary of salient results (not to exceed 250 words) achieved during the performance of the contract.

e. Product Development Plan and Work Plan

The Contractor shall update the Product Development Plan and create a Work Plan to incorporate the progress from the effective date of the contract. The Contractor shall submit an updated Product Development Plan (PDP) for review within thirty (30) calendar days of the effective date of the contract and prior to initiation of product development activities, http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm unless otherwise negotiated with the COR and the Contracting Officer. This updated

Product Development Plan and Work Plan shall include:

1) Clearly defined goals, product development stages and product development activities.

2) A breakdown of activities by fiscal year and non-severable stages, and applicable decision gates.

3) Quantitative and qualitative criteria and associated data elements for assessing the scientific merit and feasibility of moving to the next stage of product development.

4) A detailed timeline for each stage covering the initiation, conduct and completion of product development activities and a task-linked budget (a budget linked to each major activity). A Gantt chart should be provided to outline the proposed activities.

5) The Work Plan shall include a description of the studies to be performed within each stage of the project. The Contractor shall also be required to submit a revised Product

Development Plan and associated Work Plan when a change to the approved plans is requested by the COR.

6) Risk identification, analysis, and mitigation strategies for accomplishing the objectives of this contract within the period of performance, particularly with respect to adverse experimental or production results, new scientific findings or regulatory guidance from

FDA.

NOTE – For purposes of this BAA:

• The Product Development Plan describes the critical path for the proposed candidate/product toward eventual licensure and identifies the decision points/gates for progress of the candidate/product.

• The Work Plan describes the studies to be performed at each stage of the project within the 5 year term of award in order to implement the Product

Development Plan and advance the product through Phase 1 clinical testing.

f. Milestone Completion/Decision Gate Report

A Decision Gate Report shall be submitted when the Contractor has completed a stage of product development and has reached a decision point, as defined in the Work Plan for the

Implementation of the Staged Product Development Plan. These reports shall be in sufficient detail to explain comprehensively the results achieved. The description shall also include pertinent data and/or conclusions resulting from the analysis and scientific evaluation of data accumulated to date under the project. Offerors shall propose the timing of these reports to coincide with the decision points specified in their SOW.

Note: Contract activities shall be divided into manageable time frames with associated deliverables. Initial funding shall be for the Base Period only. Funding of subsequent deliverables shall be funded by Options. Each Option shall be fully funded when exercised and shall be dependent on successful completion of critical Milestones, including the United

States Government acceptance of associated deliverables,…