Attachment_7_-_TPI_0001.pdf

ATTACHMENT 7: ADDITIONAL TECHNICAL PROPOSAL

INSTRUCTIONS

FORMAT FOR TECHNICAL PROPOSAL, and TABLE OF CONTENTS

RATIONAL SYSTEMIC CHARACTERIZATION AND SELECTION OF

ADJUVANTS FOR HIV VACCINECANDIDATES (R-CASA)

75N93022R00017 REVISED April 20, 2023

It is strongly recommended that offerors use the following template as the format for the Technical Proposal. All information presented in the Technical Proposal should be presented in the order specified below.

These Additional Technical Proposal Instructions reflect the requirements of the BAA and provide specific instructions and formatting for the Technical Proposal. While Section L. of the BAA provides a generic set of Technical Proposal Instructions applicable to all NIH R&D solicitations, these Additional Technical Proposal Instructions are tailored to the specific requirements of the BAA. The information requested in these instructions should be used along with Section L of the BAA to format and prepare the Technical Proposal, and should be used as a Table of Contents for your Technical Proposal. Offerors should follow the instructions in Section L of the BAA, and include the information requested here.

Offerors are advised to give careful consideration to the Broad Agency Announcement Description, Background and Introduction, Research and Technical Objectives, all reference materials and attachments, the Technical Evaluation Criteria in Section M, and the BAA as a whole in the development of their Technical Proposals.

Offerors proposing subcontracts and/or consultants to perform portions of the proposed Statement of 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.

Offerors must refer to the BAA Attachment entitled “Packaging and Delivery of the Proposal,” which details strict guidelines, including page limitations, formatting and layout of proposals, and prohibits the offerors use of links to internet web site addresses (URLs) to direct readers to alternate sources of information.

TECHNICAL PROPOSAL – TABLE OF CONTENTS

SECTION 1:

1. PROPOSAL TITLE PAGE. Include BAA title and number, name of organization, UEI number, and identify if the proposal is an original or a copy. Offerors that include data in their proposals that they do not want disclosed to the public for any purpose, or used by the Government except for evaluation purposes, shall also include the legend regarding Restriction on Disclosure and Use of Data prescribed by FAR 52.215-1 (e)]

2. TABLE OF CONTENTS

SECTION 2: TECHNICAL PROPOSAL OVERVIEW (suggested 3-page maximum)

Provide a brief description of the proposed project, including:

1. 1-2 sentence summary describing the concept the offeror is proposing.

2. A summary describing the scope of the activities proposed.

3. A brief description of the activities proposed by the offeror and all proposed subcontractors, including identification of all proposed subcontractors and a list of key personnel for the offeror and the proposed subcontractors with degrees, titles and role in the project.

4. By area of expertise, provide the total number of staff, the number available to be assigned to the contract for the offeror and all proposed subcontractors, and total number of additional staff to be hired and trained.

5. A brief description of the facilities and other resources to be made available by the proposed prime contractor (offeror) and any proposed subcontractors.

SECTION 3: STATEMENT OF WORK FORMAT (suggested maximum of 5 pages)

Offeror(s) are required to provide a Statement of Work in their proposal.

The Statement of Work shall be developed by each offeror based on the information in the Attachment entitled “Research and Technical Objectives,” and shall consist of two parts: (1) Scope, and (2) Technical Requirements.

Provided below is an outline of the Statement of Work format that should be used by all offeror(s) in the preparation of their Technical Proposals. The headers and sub headers may be adjusted to match the requirements as proposed in each offeror’s individual technical proposal.

https://www.acquisition.gov/far/part-52#FAR_52_215_1

Contracts awarded as a result of this BAA will include the Statement of Work proposed by the offeror, as negotiated and accepted by the Government.

Offeror(s) will be required to perform the activities and provide the resources appropriate to the scope of their specific negotiated Statement of Work.

The opening paragraph under the Technical Requirements section of the Statement of Work shall be followed by a description of all activities that the Contractor shall perform after the award of the contract. The Technical Requirements shall include all activities required to effectively implement the project and shall include a description of all items to be delivered to the Government during performance of the contract, such as progress reports, financial reports, end products, and other deliverables, along with a timetable for their delivery.

[NOTE TO OFFEROR: Each offeror shall provide detailed specifications of the requirement utilizing the following sample outline of tasks and subtasks. Any tasks or subtasks that are not applicable to your proposed effort should be deleted. Any tasks or subtasks specific to your proposed effort not addressed below shall be added.]

SAMPLE STATEMENT OF WORK

1. SCOPE

Instruction to offerors: Provide a brief description (one to two paragraphs) of the overall project and objectives in broad terms that indicates the size and magnitude of the proposed effort.

2. TECHNICAL REQUIREMENTS

[NOTE TO OFFEROR: The Technical Requirements shall begin with the following introductory paragraph.]

Independently, and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified professional, technical, and administrative personnel, material, equipment and facilities, not otherwise provided by the Government under the terms of this contract, as needed to perform the tasks set forth below. Specifically, the Contractor shall:

A. Biochemical Characterization B. Immunological Characterization C. Data Analysis

SECTION 4: TECHNICAL DISCUSSIONS

In addition to the guidance in section l of the BAA, this section of your technical proposal should include documentation to demonstrate how you will accomplish the work detailed in your proposed Statement of Work. It is recommended that your proposal be organized in accordance with the order of your Statement of Work and the technical evaluation criteria provided in Section M.

Additionally, please ensure that your Technical Proposal addresses the following:

Organizational Experience:

In addition to the information requested under Section L, Part c.

Business Proposal Instructions, paragraph 12, Qualifications of the Offeror, all offerors are requested to include in their technical proposals a description of at least two examples of similar projects performed by your organization that are of comparable size and scope and/or related to the effort proposed in response to this BAA. The projects may be either completed or ongoing.

Technical Approach:

This solicitation provides an opportunity for the side-by-side comparison and immune characterization of HIV immunogen-adjuvant formulations to inform standardized screening and selection of the most promising formulations. Identify up to ten (10) HIV immunogens, plus reference immunogen(s) and up to ten (10) adjuvants, plus reference adjuvant(s), for initial screening. Describe the detailed scientific rationale, technical approaches, proposed methodologies and data analysis tools, and proposed plans and procedures for achieving the objectives of Sections A (Biochemical Characterization), B (Immunological Characterization), and C (Data Analysis) outlined in this solicitation. In addition, describe potential problems and proposed solutions and alternatives for each of the Sections, and plans for making the data generated publicly available.

A. Biochemical Characterization Provide a detailed description of the approach to and rationale behind the selection of proposed immunogens and adjuvants. Include a description of the processes and procedures for biochemical characterization of the immunogen-adjuvant formulations, including criteria for solubility, conformational and thermal stability, aggregation, dispersion, osmolarity, pH, degradation products, and relevant parameters according to the intended use of each formulation (mucosal, intramuscular, intradermal etc).

B. Immunological Characterization Provide a detailed discussion of the immune characterization of the innate and adaptive immune response in the periphery and relevant tissue sites triggered by the immunogen-adjuvant formulation. Specifically address the following:

1. In vitro studies using cell lines, primary animal and/or human cells, and/or organoids to characterize immune profiles;

2. The composition of the proposed immunogen-adjuvant formulations to be investigated plus formulation(s) comprising up to two immunogens and two adjuvants, that will be tested for comparison (as semi-controls).

Provide a rationale for down-selection (go-no-go criteria) of up to five (5) formulations to further investigation in animal models. Include preliminary data and/or references indicating that the immunogens and adjuvants, individually (i.e. separately) and/or in combination:

I. can elicit an immune response (e.g. antigen-specific antibodies, for immunogens) and/or enhancement of immune responses (in case of adjuvants);

II. have been already used for in vitro and/or in vivo (i.e. they are not only result of in silico research);

III. for combination adjuvants, data and/or references showing that the combination has been tested in vitro and/or in vivo and can lead to an enhancement of immune responses compared to each component individually (i.e. separately).

3. Provide the rationale for the selection of the immunogens, adjuvants and the formulations that will to be studied, based on the contractor’s experience with the products, previous results, route(s) of administration and/or other pertinent criteria.

4. Describe plans to propose incorporation of additional immunogens and/or adjuvants throughout the contract period, including the number of immunogens and/or adjuvants that the contractor has the ability and capacity to assess for immune characterization, challenge studies, and data analysis for the performance period.

5. Describe immune characterization methods that will be used to define the innate and adaptive immune responses in the periphery and relevant tissue sites triggered by the formulations in vitro and/or in vivo using a relevant animal model(s) system.

6. Describe methods used to evaluate the durability of adaptive immune responses (memory response) in the periphery and relevant tissue sites.

7. Provide an explanation/justification of the in vitro and/or animal model(s) chosen for analysis; and

8. Discuss in vitro stimulation and assessment methods, using animal and human primary cells, to determine the immune profiles of the innate and adaptive immune response induced by the immunogen-adjuvant formulation for the evaluation of innate immune response patterns.

C. Data Analysis

1. Discuss plans and approaches to integrate the data from the biochemical and immunological characterizations to generate a profile of each immunogen-adjuvant formulation investigated.

2. Discuss plans and approaches to develop down-selection work flow and go-no-go criteria for the evaluation and screening of HIV immunogen-adjuvant formulations, employing, for example biochemical criteria, in vitro (cell culture, organoids, tissue-chips, etc.), and/or in vivo (relevant animal models) experiments to assess the innate, adaptive immune response in the periphery and at tissue-specific sites (e.g. mucosal sites), including but not limited to the assessment of immunogenicity (e.g. broad neutralizing antibodies, cytotoxicity etc.) and immune response longevity (i.e. immunological memory), protection, and taking in consideration gender and age differences, and geographic viral diversity.

SECTION 5: SCIENTIFIC AND TECHNICAL PERSONNEL

Provide information relevant to document individual training, experience, qualifications and expertise necessary for the successful completion of the proposed Statement of Work. Limit CVs to 2-3 pages and provide selected references for publications relevant to the scope of the contract.

1. Principal Investigator (PI): Describe the experience, training, expertise, qualifications, and level of effort of the proposed Principal Investigator to lead and direct the activities to be carried out under the proposed Statement of Work. In particular, address the scientific and technical expertise in: (a) HIV immunogen development, (b) adjuvant development (c) HIV vaccine testing in vertebrate animals; (d) immunologic assessments, such as neutralizing antibodies, B cell and antibody profiling, T cell functional assays (e.g., cytotoxicity, cytokine production, epitope specificity), and (d) cell-based in vitro assays. Include experience with projects of similar scope, size and complexity carried out by the offeror and any proposed subcontractors over the past 5 years.

2. Other Key Scientific and Technical Personnel: Describe the experience, training, expertise and qualifications, as well as the level of effort, for all proposed key scientific and technical personnel. Address scientific and technical expertise of the staff, as needed, to support the activities proposed in the Technical Plan, including biochemical and immunological characterization of immunogen-adjuvant formulations, project management, as well as data analysis.

SECTION 6: PROJECT MANAGEMENT

1. Provide a Project Management Plan for the overall organization that addresses the planning, initiation, implementation, conduct, monitoring and completion of tasks identified in the proposed Statement of Work. If consultants and/or subcontractors are proposed, include a plan to manage, coordinate, and oversee the work performed by consultants and/or subcontractor(s).

2. Provide a Staffing Plan that describes roles, responsibilities, and level of effort for all managerial, scientific and technical personnel, including all proposed subcontractors and consultants. Provide an administrative and technical framework indicating clear lines of authority and responsibility for all proposed personnel. Include a chart of the proposed organizational/management structure for the project.

3. Describe the project management systems that will be used to track activities and to keep multiple activities on time and budget. The plan must include a description of the quality control methods that will be used to ensure the effective and efficient initiation, implementation, management, and oversight of contract requirements.

4. Outline how the offeror will communicate with the Contracting Officer’s

Representative and Contracting Officer and how will they communicate, monitor, and manage the project both internally and externally (at subcontractor facilities).

5. Provide a Gantt chart with milestones and timelines for work proposed in the Technical Plan. Indicate the relationship between activities and the base year and 4 option periods. Activities may be undertaken simultaneously or sequentially as required for optimal work performance.

Milestones must be quantitative, reflect key criteria of success (go-no-go criteria) and tangible outcomes of each activity and sub-activity for each proposed area of study. Milestones and timelines may be revised during negotiations with NIAID if a proposal is deemed meritorious by the technical evaluation panel.

6. Provide a plan for soliciting, evaluating, negotiating, awarding, and managing subcontracts in accordance with FAR Clause 52.244-2:

https://www.acquisition.gov/far/52.244-2 (if applicable).

7. Describe the procedures that will be used to address intellectual property issues regarding access to necessary reagents including immunogens and adjuvants.

SECTION 7: FACILITIES, EQUIPMENT, AND OTHER RESOURCES

The Technical Proposal should document availability and adequacy of facilities, equipment, space and other resources necessary to carry out the proposed Statement of Work, including:

1. Location and features of facilities including a floor plan and a list of equipment and resources dedicated to the project for the prime contractor and any proposed subcontractors (lease or ownership information should be provided), including:

a. Plans for the housing of laboratory animals, including:

i. availability of appropriate facilities and capacity for NHP studies, if proposed; and provisions for complying with NIH guidelines for the housing and human care and use of laboratory animals as delineated by the Office of Laboratory Animal Welfare.

b. Provisions for ensuring safe facilities and resources and for conducting work in accordance with the Biosafety in Microbiological and Biomedical Laboratories guidelines, Centers for Disease Control and Prevention and the National Institutes of Health, 6th edition, and interim guidelines for influenza, as well as Department of Health and Human Services (DHHS) regulations regarding the use, possession, or transfer of select agents (42 CFR Part 73). Safety and Health HHSAR 352.223-70 clauses shall apply.

c. Provisions for ensuring safe facilities for the conduct of work in accordance with Recommendations for the Safe Handling of Cytotoxic Drugs, NIH Publication No. 92-2621 and the NIH Guidelines for the Laboratory use of Chemical Carcinogens, NIH Publication No. 81-2385.

2. Identification and description of ALL support resources (including

Information Technology systems) that will be required to effectively complete the proposed Statement of Work.

3. Document the availability of HIV immunogens and adjuvant(s), including, intellectual property or ownership rights information for reagents currently in the offeror’s possession, or to be provided by subcontractors or through other agreements. Note: Plans for acquisition of NIAID proposed immunogens and/or adjuvant(s) will need to be developed and provided to the COR within 60 days after an option for additional immunogens and/or adjuvant sets has been awarded.

4. Describe the proposed data management and quality control systems, procedures to assure data security and controlled access, and procedures that will be used for:

a. data entry and validation;

b. documentation of data corrections;

c. routine maintenance and backup;

d. transmission of data;

e. data reporting and exporting system;

f. data retrieval and disaster recovery.

SECTION 8: OTHER CONSIDERATIONS

Other than those detailed in the Government Furnished Property clause or otherwise publicly available, the offeror shall not propose government furnished resources, to include government employees, facilities, intellectual property or biological materials. If you propose government furnished resources your proposal will not be considered further for award.

Provide documentation that the Offeror has intellectual property (IP) protection and/or proprietary freedom to use for all immunogens and adjuvants proposed. Include letters from the IP-holder stating they will provide the agent(s), any limitations on use of that agent(s), agreement about public disclosure of results (including negative results), and whether there are legally binding agreements already in place between the Offeror and IP-holder for the products.