Amendment_8_-_QA_and_Uniform_Cost_Assumption_Revision_-_Research_Area_003.pdf

Amendment #8

Solicitation HHS-NIH-NIAID-BAA2018

AMENDMENT EIGHT (8)

OFFICE OF ACQUISITONS

National Institute of Allergy and Infectious Diseases (NIAID)

5601 Fishers Lane, Room 3D32, MSC 9821 Rockville, MD 20852

Solicitation Number: HHS-NIH-NIAID-BAA2018

Date of Solicitation Issuance: 06/01/2018

Date of Amendment No.1 Issuance: 07/03/2018

Date of Amendment No.2 Issuance: 07/03/2018

Date of Amendment No.3 Issuance: 07/20/2018

Date of Amendment No.4 Issuance: 07/24/2018

Date of Amendment No.5 Issuance: 08/02/2018

Date of Amendment No.6 Issuance: 08/31/2018

Date of Amendment No.7 Issuance: 08/31/2018

Date of Amendment No.8 Issuance: 10/24/2018

Number of Pages: 21

Issued By:

George W. Kennedy, Contracting Officer

Email: kennedyg@mail.nih.gov

Phone: 240-669-5170

The hour and date specified for receipt of Offers remains unchanged.

Offerors must acknowledge receipt of the amendment by Amendment number(s) and date of the amendment. Include a statement of acknowledgement in your proposal submission. Failure of acknowledgement may result in rejection of your offer.

Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

PURPOSE OF SOLICITATION AMENDMENT

This amendment is applicable to RESEARCH AREA 003, “Collaborative Influenza Vaccine

Innovation Centers (CIVICs)”.

mailto:kennedyg@mail.nih.gov

The purpose of this amendment is to revise Section 3.2.3.4. of solicitation HHS-NIH-NIAID-

BAA2018 as described below; and respond to questions received in response to Research Area

003: Collaborative Influenza Vaccine Innovation Centers (CIVICs).

Section 3.2.3.4. – UNIFORM COST ASSUMPTIONS, paragraphs a., b. and c., are amended as follows:

a. Vaccine Manufacturing, Formulation and Delivery Core: Assume manufacturing, formulation and delivery of two (2) cGMP-grade influenza vaccine candidates in the first year and repeated for each year thereafter.

b. GLP Toxicology Core: Assume IND-enabling safety and toxicity testing of four

(4) influenza vaccine candidates in the first year and repeated for each year thereafter.

c. Clinical Core: Assume establishment of clinical sample repository in the first year and maintenance of repository in subsequent years. Assume design and planning activities for future clinical trials and human challenge studies in the first year. Assume conduct of two (2) Phase I clinical trials in the second year and each year after. Assume conduct of one (1) Phase II clinical trial in the second, fourth and sixth year. Assume conduct of one (1) human challenge study in the second, fourth and sixth year. For the purposes of these cost assumptions, the Phase I clinical trials should include no more than 100 subjects, the Phase II clinical trials should include no more than 200 subjects and the human challenge studies should include no more than 200 subjects.

QUESTIONS AND RESPONSES:

The Government’s responses to questions received regarding RESEARCH AREA 003, “Collaborative Influenza Vaccine Innovation Centers (CIVICs)” are as follows:

1. Question: Is question submission rolling or is there a specific deadline?

Answer: Deadline is 10/31/2018

2. Question: The RFA states that you must have 3 strong vaccine candidates in order to be considered for this BAA. Currently, we have one for Influenza A class 1 strains, one for Influenza A class 2 strains, and a third for Influenza B strains. Is this considered responsive?

Answer: Offeror(s) must have at least three unique vaccine candidate/platforms in hand at the time of submission. This may include different antigens, antigen/adjuvant combinations, or platforms.

3. Question: Component B of the CIVICs BAA work plan states that the project will be responsible for toxicology studies. Are these just the clinical toxicology studies? The reason I ask is because Component A charged with performing the preclinical work on the vaccine candidates. Complete preclinical studies also include toxicology studies, which is recommended by WHO as well as the CDC. Should we plan on doing the preclinical toxicology studies?

Answer: The Vaccine Manufacturing and Toxicology Core (Component B) is responsible for the design and performance of IND-enabling GLP compliant safety and toxicity testing of candidate influenza vaccines. This includes pre-clinical safety and toxicity studies as detailed in Section 3.1.2.1.3.2, Part 2, “GLP

Toxicology.”

4. Question: While Component A of the CIVICs BAA work plan is directed to primarily focus on seasonal influenza, after the vaccine candidates are selected would it be of permissible to also examine the vaccines efficacy on the more pathogenic Pandemic and “Bird flu” strains?

Answer: The Vaccine Center (Component A) is not restricted to seasonal influenza vaccine development. The objective of the CIVICs program is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity (“universal influenza vaccines”) – see Section 3.2.2.1.2. As detailed in

Section 3.2.2.1.3.1, Part 2, “Vaccine Design and Development,” the Vaccine

Center should propose studies to rationally design robust, durable, broadly protective influenza vaccines as well as explore improvements to seasonal influenza vaccines. Thus, pre-clinical experiments to examine protection against pandemic and/or avian influenza strains would fall within the scope of the

Vaccine Center. Please note that these studies should be conducted under the appropriate level of biocontainment and within all applicable and current Federal, state, and local laws, codes, ordinances and regulations – see Section

3.2.2.1.3.1.1.

5. Question: Are offerors expected to have BSL-4 facilities available for Component C proposals?

Answer: Offerors should propose to conduct tasks under the appropriate level of biocontainment. It is not anticipated that Component C would require BSL-4 facilities to conduct the activities outlined in Section 3.2.2.1.3.3 – Research Area

003 Component C: Clinical Core.

6. Question: Is there guidance regarding the total budget limit for the base and any options for Component C?

Answer: NIAID estimates a total first year base cost of roughly $1 million for the

Clinical Core (Component C), however this may vary depending upon the scope of the project and the technical objectives of the award. The budget associated with base costs and proposed options should be commensurate with the technical approach.

As noted in Amendment #6, Section 3.2.3.4. – Uniform Cost Assumptions, paragraph c. Clinical Core, is revised to read as follows:

Clinical Core: Assume establishment of clinical sample repository in the first year and maintenance of repository in subsequent years. Assume design and planning activities for future clinical trials and human challenge studies in the first year. Assume conduct of two (2) Phase I clinical trials in the second year and each year after. Assume conduct of one (1) Phase II clinical trial in the second, fourth and sixth year. Assume conduct of one (1) human challenge study in the second, fourth and sixth year. For the purposes of these cost assumptions, the Phase II clinical trials should include no more than 200 subjects and the human challenge studies should include no more than 200 subjects.

7. Question: Please advise if offerors should include the following forms in their business proposals or technical proposals:

Summary of Related Activities (Attachment 3)

Answer: Technical

Offeror’s Points of Contact (Attachment 10)

Answer: Business

Certificate of Current Cost or Pricing Data (Attachment 11)

Disclosure of Lobbying Activities (Attachment 12)

Is the HHS Section 508 Product Assessment Template (Attachment 13) required?

Answer: Not required for this BAA Topic

8. Question: Section 3.2.3.4 Uniform Cost Assumptions (a and b) states that two GMP grade Influenza vaccines should be made and four toxicology studies should be conducted in the first year. Section 3.2.2 Budget and Award Information states that total first year base cost is roughly $500,000.

a. Question: Are the two GMP runs and four toxicology studies to be budgeted as options in addition to the base of ~$500,000 total costs for Component B?

Answer: Yes, the uniform cost assumptions for the Vaccine

Manufacturing and Toxicology Core (Component B) provided in Section

3.2.3.4, bullets a and b, should be budgeted as options.

b. Question: Would a model vaccine (influenza or other infectious disease) be appropriate to use for developing a budget?

Answer: Yes, a model vaccine (influenza or other infectious disease) would be appropriate to use for developing a budget provided that the proposed budget covers the scope of activities described in Section

3.1.2.1.3.2 – Research Area 003 Component B: Vaccine Manufacturing and Toxicology Core.

c. Question: Can non‐GMP material be used for toxicology studies?

Answer: GMP material is preferred for use in GLP toxicology studies but is not required.

9. Question: If bidding on Components A and B, do the proposed vaccine platform approaches in A have to be used for the technical and business proposals in Component

B? Or, can the Component B proposals be fully independent and use a model vaccine (i.e.

prior performance) for manufacturing/toxicology technical plan and budget/cost estimates?

Answer: Offerors must submit complete and separate proposals for each component that they are applying to. Offerors may submit proposals for multiple components, but each component must be submitted as a separate proposal (see

Section 3.2.3 – RESEARCH AREA 003 – Additional Technical Proposal

Instructions). Therefore, Component B proposals must be independent of

Component A proposals. Using a suitable model vaccine to estimate costs for

Component B is acceptable.

10. Question: Based on Section 3.2.3.4 Uniform Cost Assumptions for Vaccine

Manufacturing, Formulation and Delivery Core/GLP Toxicology Core (a and b), should proposer assume that model budgets developed for year ONE be repeated/escalated in years 2‐7?

Answer: Yes, out‐year budgets for the Vaccine Manufacturing and Toxicology

Core (Component B) may be modeled based on the cost assumptions provided in

Section 3.2.3.4, bullets a and b.

11. Question: We have assumed that samples collected by the Clinical Core in Component C will be assayed under Objective 4 in Component A. Is this correct?

Answer: The CIVICs Vaccine Center (Component A) is responsible for conducting comprehensive immunological studies of human systemic and mucosal immune responses to influenza vaccine candidates from clinical trials and human challenge studies conducted by the Clinical Core (Component C) (see

3.2.2.1.3.1, “3. Immunologic Analyses”). The Clinical Core (Component C) may conduct some immunologic analyses related to defining immunogenicity profiles of the vaccine candidates (see 3.2.2.1.3.3, bullet 2). The Vaccine Center and

Clinical Core are expected to work collaboratively post‐award to clinically evaluate influenza vaccine candidates.

12. Question: Given that there is an unknown number of vaccine candidates, can the offeror develop an “Option” budget for the costs to take a candidate into all of the proposed novel platforms, immunogenicity testing, and pre‐clinical animal models? This option could then be executed based on need by the government.

Answer: Yes, this would be acceptable for budgeting purposes.

13. Question: Given that the assays to be moved to Objective 4 are not currently known, can the offeror develop a series of Options budgets for a number of different assay platforms that could be executed based on the correlate of protection?

Answer: Yes, this would be acceptable for budget purposes.

14. Question: Is the use of mAbs (in vitro or expressed and injected or in vivo expressed via

DNA/RNA) as prophylactic treatment something that falls into the scope of the CIVIC

BAA?

Answer: The objective of the CIVICs Program is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity

(“universal influenza vaccines”). Passive immunization with monoclonal antibodies may be considered within the scope of the CIVICs BAA, provided it is part of an overall strategy to develop improved seasonal influenza vaccines or universal influenza vaccines with the desired attributes described in Section

3.2.2.1.2. – Technical Objectives. Passive immunizations alone, when not an integral component of a vaccination strategy designed to elicit durable and/or broadly protective immune responses, is outside the scope of this BAA.

15. Question: Can we participate in more than one application for the same component (i.e.

Prime for Component C and as a subcontractor in someone else's Component C application)?

Answer: Yes, you can participate in as many independent proposals as you would like.

16. Question: It’s stated in the instructions that hyperlinks are not to be included in our application. Does this also pertain to the hyperlink to an investigator’s complete list of publications in PubMed as is typically provided on a biosketch?

Answer: Yes. Please Note under SECTION 5: Scientific and Technical

Personnel on page 66, it is stated to “Limit CVs to 2-3 pages and provide selected references for publications relevant to the scope of the contract

17. Question: NIAID recently published a solicitation for Collaborative Influenza Vaccine

Innovation Centers (CIVICS) that called for a clinical core that will focus on very early phase trials, including challenge studies, testing candidate influenza vaccines. Doesn’t this overlap with VTEU activities? How does DMID see these groups interacting?

Answer: The CIVICs Clinical Core (Component C) will be very tightly linked to the activities and testing of candidate influenza vaccines developed in the CIVICs

Vaccine Centers (Component A). They will conduct Phase I/II clinical trials to evaluate vaccine safety and immunogenicity, and human challenge studies to address questions related to pathogenesis, immunity and correlates of protection, and down-select vaccine candidates for further development. The Clinical Core will work closely with the Vaccine Centers to clinically evaluate and define immunogenicity profiles of candidate influenza vaccines. They will also be responsible for establishing and maintaining a clinical sample repository for samples collected from Clinical Core-led clinical trials and human challenge studies. Promising CIVICs-generated vaccine products may progress into multi-site clinical trials conducted through the VTEUs, so NIAID envisions developing collaborations among these groups once the CIVICs contract awards are made. The

CIVICs BAA solicitation is open to all qualified offerors.

18. Question: We anticipate that NIAID would prefer we break the proposed work into a Base and multiple options. Can you provide any further guidance regarding how NIAID would like the budgets structured?

Answer: No cost assumptions are provided for Component A. Budget estimates should address all areas outlined in Section 3.2.2.1.3.1 – Research Area 003

Component A: Vaccine Center, and should be commensurate with the technical approach.

19. Question: In the Technical Requirements, Component A. Vaccine Center, Question: # 1. is “Leadership and Project Management.” Section B is also “Project

Management.” Can you clarify what should be included in Section B?

Answer: The Sample Statement of Work provided on page 18 is an example only. The headers and sub-headers may be adjusted to match the requirements as proposed in each Offeror’s individual technical proposal.

In addition to the information provided in Amendment 1, Research Area

003, “Collaborative Influenza Vaccine Innovation Centers (CIVICs),”

Offerors should review Sections 4-7 of the 2018 Omnibus Broad Agency

Announcement for additional proposal information and instructions.

Question: In that same summary table, it lists “C. Communication and Contract

Review Meetings” and “D. Reports and Deliverables.” Can NIAID provide instructions or an outline for these sections?

Answer: The Sample Statement of Work provided on page 18 is an example only. The headers and sub-headers may be adjusted to match the requirements as proposed in each Offeror’s individual technical proposal.

In addition to the information provided in Amendment 1, Research Area

003, “Collaborative Influenza Vaccine Innovation Centers (CIVICs),”

Offerors should review Sections 4-7 of the 2018 Omnibus Broad Agency

Announcement for additional proposal information and instructions.

20. Question: How many subjects should we assume for the Phase I clinical trials for

Component C?

Answer: For the purposes of cost assumptions, the Phase I clinical trials should include no more than 100 subjects.

21. Question: Since the exact study design and initiation date for the clinical trials are still pending, would it be acceptable to create a single Option budget for each trial type (Phase

I, Phase II, and Challenge) and use these same budget amounts throughout the period of performance?

Answer: Yes, this would be acceptable.

22. Question: Would DMID prefer the proposed laboratory assays be a separate option from the clinical trial option budget?

Answer: This is at the discretion of the Offeror.

23. Question: Should the sample repository budget be its own option?

Answer: This is at the discretion of the Offeror.

24. Question: Is NIAID able to provide or facilitate the provision of the influenza challenge virus for human studies under Component C?

Answer: NIAID is currently in the process of acquiring two human challenge strains (H1N1, H3N2) for use in human challenge studies. These strains will be made available to the research community including the CIVICs investigators. In addition, proposals may include the use of other well characterized human challenge strains that Offerors have access to.

25. Question: Are we to prepare Clinical Trial worksheets for each study type (Phase I, Phase II, Challenge)?

Answer: Yes, Offerors should prepare a PHS Human Subjects and Clinical Trials

Information form for each study type proposed (see Section 4.3.2.3 – HUMAN

SUBJECTS of the NIAID 2018 Omnibus Solicitation HHS-NIH-NIAID-

BAA2018). Additional Instructions on how to complete this form can be found at the following NIH website:

https://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/PHS%20Human%20Subjects%20and%20Clinical%20Trials%20Informatio n%20Form%20Instructions.pdf

26. Question: The Clinical Trial worksheets have numerous questions\data fields, but many of these form fields are not flagged as required. The actual protocols to be performed and their study design have yet to be determined. How much detail should we be including on these forms?

Answer: Offerors should complete all required components of the PHS Human

Subjects and Clinical Trials Information form based on the proposed standard clinical trial study designs. NIAID acknowledges that this information is subject to change post-award during the protocol development stage. The PHS Human

Subjects and Clinical Trials Information form, together with the rest of your proposal, should include sufficient information for the evaluation of the project, independent of any other documents. Offerors should be specific, describe each study clearly, and avoid redundancies.

27. Question: Please clarify if vaccine formulation and delivery system optimization for each of the 3 unique vaccine candidate/platforms in Component A should be included as part of Component A (Vaccine Center) or Component B (Vaccine Manufacturing and

Toxicology Core)?

Answer: The CIVICs Vaccine Manufacturing and Toxicology Core (Component

B) will collaborate with the Vaccine Centers (Component A) throughout the iterative vaccine design process and is tasked with optimizing, formulating, and manufacturing vaccines and vaccine components in accordance with relevant

FDA cGMP regulations and guidelines through approved release of product for https://www.fbo.gov/utils/view?id=4b771d8e08cda7a6f313c1f05c22ee73 https://www.fbo.gov/utils/view?id=4b771d8e08cda7a6f313c1f05c22ee73 https://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/PHS%20Human%20Subjects%20and%20Clinical%20Trials%20Information%20Form%20Instructions.pdf https://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/PHS%20Human%20Subjects%20and%20Clinical%20Trials%20Information%20Form%20Instructions.pdf https://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/PHS%20Human%20Subjects%20and%20Clinical%20Trials%20Information%20Form%20Instructions.pdf use in clinical trials and human challenge studies. The Vaccine Centers will be responsible for pre-clinical refinement and optimization of vaccine approaches earlier in the product development pipeline as well as refining and optimizing vaccine approaches based on data from pre-clinical studies, clinical trials, and human challenge studies.

28. Question: Will the necessary manufacturing, GLP toxicology and clinical services for candidate vaccines be subcontracted from Component A to Components B and C (ie – cost should be included in the budget for Component A) or will the total cost of these services be included in the annual budgets for each Component separately?

component that they are applying to. Offerors may submit proposals for multiple components, but each component must be submitted as a separate proposal (see

Section 3.2.3 – RESEARCH AREA 003 – Additional Technical Proposal

Instructions). Therefore, costs for activities conducted by Components B or C should not be included in the budget for Component A.

29. Question: Please clarify the page limits for components A, B & C as we noted discrepant numbers for these in the documents.

Answer: Page 38 of BAA lists the correct technical proposal page limits as follows:

Offerors may submit proposals for one or more of the above components;

however, each component must be submitted as a sperate proposal. Do not combine separate components into one proposal. Pages extending beyond the technical proposal page limit for each Component listed below will be removed from proposals.

Component A: Vaccine Center 250 pages

Component B: Vaccine Manufacturing and Toxicology Core 150 pages

Component C: Clinical Core 150 pages

30. Question: Page 37 of the BAA states, “The Contractor shall collaborate with industry and clinical research support services contractors with respect to study design; statistical analysis; preparation of and reporting study data for IND applications; data management and quality control; and clinical site monitoring.” Should the offeror include these services in its proposal or will the SDMCC and/or other contractors perform these services?

Answer: The SDMCC contractor will work with and provide statistical design and analyses assistance to the Clinical Core contractor. In addition, the SDMCC, in collaboration with all CIVICs contractors, will develop and maintain a data management system to support clinical data management and quality control; the

SDMCC also will provide program coordination services that are designed to assist the Clinical Core contractor in the development of IND applications and clinical site monitoring. Please see Attachment 3: Statement of Work in RFP

NIAID-DAIT-NIHAI201800018:

https://www.fbo.gov/index?s=opportunity&mode=form&id=d0eabc537333a18e4

1ef3835a89c0551&tab=core&_cview=1 ).

31. Question: Will the offeror be responsible for central laboratory safety sample analyses?

Answer: Yes, Offerors submitting proposals for the CIVICs Clinical Core

(Component C) should include activities associated with clinical trial safety oversight including safety sample analyses.

32. Question: Will the offeror be responsible for bioanalytical / immunologic sample analyses?

Answer: The CIVICs Vaccine Center (Component A) is responsible for conducting comprehensive immunological studies of human systemic and mucosal immune responses to influenza vaccine candidates from clinical trials and human challenge studies conducted by the Clinical Core (Component C) (see

Section 3.2.2.1.3.1, “3. Immunologic Analyses”). The Clinical Core (Component

C) may conduct some immunologic analyses related to defining immunogenicity profiles of the vaccine candidates (see Section 3.2.2.1.3.3, bullet 2). The Vaccine

Center and Clinical Core are expected to work collaboratively post-award to clinically evaluate influenza vaccine candidates.

33. Question: What lab services will the offeror be responsible for under the Years 2-7 phase

I, II and challenge trials versus lab services provided by Component A (Vaccine Center) or Component B (Vaccine Manufacturing and Toxicology Core)?

Answer: As noted in HHS-NIH-NIAID-BAA2018 Amendment #6, Section

3.2.3.4 –UNIFORM COST ASSUMPTIONS, paragraph c. Clinical Core, has been revised to read as follows:

Clinical Core: Assume establishment of clinical sample repository in the first year and maintenance of repository in subsequent years. Assume design and planning activities for future clinical trials and human challenge studies in the first year. Assume conduct of two (2) Phase I clinical trials in the second year and each year after. Assume conduct of one (1) Phase II clinical trial in the second, fourth and sixth year. Assume conduct of one (1) human challenge study in the second, fourth and sixth year. For the purposes of these cost assumptions, the Phase II clinical trials https://www.fbo.gov/index?s=opportunity&mode=form&id=d0eabc537333a18e41ef3835a89c0551&tab=core&_cview=1 https://www.fbo.gov/index?s=opportunity&mode=form&id=d0eabc537333a18e41ef3835a89c0551&tab=core&_cview=1

34. Question: Should all clinical trials be conducted within the USA?

Answer: Clinical trials may be conducted at foreign sites. Offerors proposing foreign sites under the Clinical Core (Component C) must still address plans for conducting studies in accordance with U.S. FDA regulatory requirements and standards (see Section 3.2.2.1.3.3 – RESEARCH AREA 003 Component C:

Clinical Core and Section 3.2.3.3 – Clinical Core) and collection of human samples must be conducted in accordance with both NIH policies and policies of the country in which the human specimens will be collected.

35. Question: Is it NIAID’s intention to utilize their previously established VTEUs or other supporting resources?

Answer: The CIVICs Clinical Core (Component C) will perform clinical testing of candidate influenza vaccines developed in the CIVICs Vaccine Centers

(Component A) including Phase I/II clinical trials to evaluate vaccine safety and immunogenicity, and human challenge studies to address questions related to pathogenesis, immunity and correlates of protection, and down-select vaccine candidates for further development. Promising CIVICs-generated vaccine products may progress into multi-site clinical trials conducted through the

VTEUs, so NIAID envisions developing collaborations among these groups once the CIVICs contract awards are made. The CIVICs BAA solicitation is open to all qualified offerors.

36. Question: Based on Section 3.2.3.4 Uniform Cost Assumptions for Clinical Core (c), should proposers assume that the Phase II and human challenges studies are to include no more than 200 subjects per trial or all three trials combined per type?

Answer: The Phase II clinical trials and human challenge studies should include no more than 200 subjects per trial. Please note that as per HHS-NIH-NIAID-

BAA2018 Amendment #6, Section 3.2.3.4 – UNIFORM COST ASSUMPTIONS, paragraph c. Clinical Core, was revised to read as follows:

Clinical Core: Assume establishment of clinical sample repository in the first year and maintenance of repository in subsequent years. Assume design and planning activities for future clinical trials and human challenge studies in the first year. Assume conduct of two (2) Phase I clinical trials in the second year and each year after. Assume conduct of one (1) Phase II clinical trial in the second, fourth and sixth year. Assume conduct of one (1) human challenge study in the second, fourth and sixth year. For the purposes of these cost assumptions, the Phase II clinical trials

37. Question: The BAA mentions the implementation of QA/QC processes to satisfy GLP, cGMP and GCP FDA regulations/guidance documents. However, none of the above listed standards covers the QA/QC requirements to oversee laboratories performing non-diagnostic, immune-monitoring assays on human clinical trial specimens. QA/QC requirements for such laboratory assays are instead carefully covered by other GxP guidance documents. Are such GxP guidance documents, designed and implemented by the NIH, acceptable standards to be listed in the writing of this CIVICS proposal?

Answer: In addition to implementing QA/QC processes to satisfy GLP, cGMP and GCP FDA regulations and guidelines as relevant, Offerors should also comply with all NIH policies and guidance, including those for human subjects research as described in HHS-NIH-NIAID-BAA2018 Omnibus Solicitation, Section 4.3.2.3 – HUMAN SUBJECTS

38. Question: Does each vaccine center need to include strategies for both universal influenza vaccine and improving seasonal vaccine or would doing one of the other suffice?

Answer: As noted in Section 3.2.2.1.2 – Technical Objectives, the objective of the CIVICs Program is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity (“universal influenza vaccines”).

Offeror(s) submitting proposals for the Vaccine Center (Component A) are responsible for both (1) rationally designing innovative influenza vaccines that provide robust, durable, broadly protectively mucosal and systemic immunity;

and (2) exploring improvements to seasonal influenza vaccines to improve immunogenicity and durability for all age groups (see Section 3.2.2.1.3.1 –

Research Area 003 Component A: Vaccine Center, paragraph 2. Vaccine Design and Development).

39. Question: What is meant by a vaccine already being “On-hand”? Preliminary data already showing evidence are capable of achieving the desired endpoints?

Answer: Offerors should provide a description of the candidate vaccine approaches to be evaluated, including data supporting induction of broadly protective, durable immunity (see Section 3.2.3.1 – VACCINE CENTER, paragraph b. Vaccine Design and Development).

40. Question: Does one vaccine platform with a minimum of 3 strategies (i.e. adjuvant, delivery, incorporation of modifications to the immunogen) to optimize the vaccine count as 3 vaccines on-hand?

Answer: Offeror(s) must have at least three unique vaccine candidate/platforms in hand at the time of submission. This may include different antigens, antigen/adjuvant combinations, or platforms.

41. Question: For the 3 unique vaccines, what is considered unique?

Question: 3 distinct immunogens formulated as one vaccine platform (i.e. DNA or protein)?

Answer: If these immunogens are combined into one candidate vaccine, this would not meet the requirement for three unique vaccine candidates/platforms.

Question: The same immunogen administered with 3 different adjuvants or 3 different vaccination regimens or delivery methods?

Answer: Yes, three different antigen/adjuvant combinations would meet the requirement for three unique vaccine candidates/platforms.

Question: Two distinct vaccines and for the 3rd, use a combination of the two?

Answer: Co-administration of two of the unique vaccine candidates proposed without changing the antigen(s), adjuvant, or platform would not meet the requirement for three unique vaccine candidates/platforms.

Question: Would formulating an existing vaccine with a novel adjuvant that broadens and increases durability of protection qualify as a distinct vaccine?

Answer: Yes, this would qualify as a unique vaccine candidate.

42. Question: Are multiple PIs (MPI) allowed?

Answer: The NIH provides offerors the opportunity to propose a multiple

Principal Investigator (PI) model on research and development contracts. The multiple PI model is intended to supplement, and not replace, the traditional single PI model. The NIH chose this BAA as a candidate for the multiple PI model. Ultimately, the decision to submit a proposal using the multiple PI versus single PI is the decision of the investigators and their institutions. The decision should be consistent with and justified by the scientific goals of the project.

It is essential that organizations consider all aspects of this approach before submitting a proposal. While there are some projects that clearly are appropriate for the multiple PI model, the "fit" of other projects may not be so clear. Offerors should base the selection of either the single PI or multiple PI option on the research proposed, to ensure optimal facilitation of the science. Projects suitable for the multiple PI model could include as few as two PIs who are jointly responsible for the scientific and technical direction of the project. The multiple

PI option is based on the proposed project, not on the number of performance sites or the number of participating institutions.

Multiple PIs under research contracts shall use the Subcontract Model. In this approach, offerors submit a single proposal, and a single award is made to the prime contractor. The prime contractor, when appropriate, will award subcontracts to fund the components of the project at the other institutions.

The relationship between the contractor and subcontractors must be designed to support all components of the project.

To facilitate communication with the NIH, the offeror must designate a Contact

PI at the time of proposal submission. The Contact PI must be employed at the prime contractor's organization. The designation of the Contact PI may rotate on an annual basis. However, this rotation is restricted to PIs located at the prime contractor's organization. The Contact PI is responsible for: relaying communications between all of the PIs and the NIH, and coordinating progress reports for the project. Being named Contact PI does not confer any special authority for the project.

Leadership Plan Offerors proposing multiple PIs will need to submit a

Leadership Plan as part of the Technical Proposal. The Leadership Plan shall describe the governance and organizational structure of the research project including communication plans, process for making decisions on scientific direction, allocation of resources, publications, intellectual property issues, and procedures for resolving conflicts.

The Leadership Plan shall follow the Table of Contents provided below:

I. Rationale Include a discussion of how the project will be enhanced by the multiple PI approach.

II. Identification of all proposed PIs Identify the proposed PIs, their point of contact information and affiliated organizations, and the percentages of time proposed for this project. Identify the Contact PI and plans for rotation of that role, if any.

III. Roles and Responsibilities Identify both the scientific and administrative roles and responsibilities of all named PIs.

IV. Approach to Fiscal and Management Coordination Describe how the project will be performed and monitored from a fiscal and management perspective.

Discuss organizational administrative coordination and support.

V. Project Direction and Resource Allocation Address how decisions will be made regarding scientific direction, and, how resources will be allocated and redistributed if needed during performance. Address plans for shared resources such as IT or other shared data considerations. If joint standard operating procedures will be developed, describe this process.

VI. Communication and Lines of Authority Address communication and lines of authority within and among PIs and within and among organizations.

VII. Data sharing, Intellectual Property, Publication, and other Proprietary

Considerations Data sharing plans, intellectual property considerations, publication agreements, and any other proprietary or confidential information sharing should be addressed in this section.

VIII. Conflict Resolution Address how conflicts will be avoided, identified, and resolved.

IX. Other Address any other information relative to the leadership approach to

Multiple PI projects.

Offerors submitting single PI proposals do not need to submit a Leadership Plan.

Offerors that include multiple PIs with their proposal must include a Leadership

Plan as described above. This leadership plan will not be counted against the technical proposal page limitation.

43. Question: Is only one assay and reagent core allowed or can we propose multiple sub-cores based on specific types of analyses pertinent to the vaccine approaches we are developing?

Answer: Offeror(s) may propose subcontractors. Only one prime contractor is allowed for each proposal.

44. Question: Does each CIVIC have to demonstrate capability for all the assays listed in the

BAA or is it expected that the 2 funded CIVICs would provide some overlapping and some distinct range in assay capability?

Answer: Offeror(s) submitting proposals for the Vaccine Center (Component A) should address all technical approach items described in Section 3.2.2.1.3.1 –

Research Area 003 Component A: Vaccine Center. All components of the

CIVICs program will be expected to collaborate post-award. This includes establishing collaborative relationships between Vaccine Centers to centralize protocols, reagents and assays; share expertise or key services/technologies; and eliminate duplication of effort.

45. Question: Does the assay and reagent core require a separate assay development and transfer plan to support future clinical testing of lead candidates?

are responsible for preparing and providing technology transfer plans, as appropriate, for vaccines and other technologies used or developed by the Vaccine

Center (see Section 3.2.2.1.3.1 – Research Area 003 Component A: Vaccine

Center, paragraph 1. Leadership and Project Management).

46. Question: How do you envision interactions between the Vaccine Center and clinical and manufacturing cores? Should there be specific information within the Vaccine Center on how coordination/communication is accomplished?

should include a plan for coordination of activities across the entire CIVICs program (see Section 3.2.2.1.3.1 – Research Area 003 Component A: Vaccine

Center, paragraph 1. Leadership and Project Management). Collaboration across

CIVICs program components is discussed throughout HHS-NIH-NIAID-

BAA2018 Amendment 1. NIAID suggests that all Offerors review Sections 3.2.2

– RESEARCH AREAS and 3.2.3 – RESEARCH AREA 003 – Additional

Technical Proposal Instructions in their entirety.

47. Question: Is there an advantage for a group putting in all 3 components – i.e. in showing an existing working relationship and needed capabilities. For example, submitting a vaccine center and manufacturing core that has the types of vaccine compositions or formulations a given Vaccine Center is focused on developing? And/or submitting a clinical core that has a track record of supporting a given Vaccine Center’s specific vaccine approach.

component that they are applying to (see Section 3.2.3 – RESEARCH AREA 003

– Additional Technical Proposal Instructions) and each component will be reviewed independently.

48. Question: How much detail on requirements for future manufacturing, toxicity, IND submissions and clinical testing of our lead candidates should we include in the vaccine center proposal?

Answer: This is at the discretion of the Offeror. Offeror(s) submitting proposals for the Vaccine Center (Component A) should provide sufficient details and information to address all technical objectives for that component. The CIVICs

Vaccine Manufacturing and Toxicology Core (Component B) will collaborate with the CIVICs Vaccine Center (Component A) throughout the iterative vaccine design process and is tasked with optimizing, formulating, and manufacturing vaccines and vaccine components in accordance with relevant FDA cGMP regulations and guidelines through approved release of product for use in clinical trials and human challenge studies. The Vaccine Center will be responsible for pre-clinical refinement and optimization of vaccine approaches earlier in the product development pipeline as well as refining and optimizing vaccine approaches based on data from pre-clinical studies, clinical trials, and human challenge studies. All components of the CIVICs program will be expected to collaborate post-award to achieve CIVICs program objectives.

49. Question: Does clinical core require a trial with influenza challenge?

i. If so, who determines what challenge virus?

ii. What is the source of the challenge virus stocks?

Answer: The CIVICs Clinical Core (Component C) will conduct early Phase I/II clinical trials to evaluate vaccine safety and immunogenicity, and human challenge studies to address questions related to pathogenesis, immunity and correlates of protection, and down-select vaccine candidates for further development (see Section 3.2.2.1.3.3 – Research Area 003 Component C: Clinical

Core), and thus must have the capabilities of conducting influenza human challenge studies. NIAID is currently in the process of acquiring two influenza human challenge strains (H1N1, H3N2) for use in human challenge studies. These strains will be made available to the research community including the CIVICs investigators. In addition, proposals may include the use of other well characterized human challenge strains that Offerors have access to.

50. Question: Does the clinical core require capability to do pediatric trials?

Answer: The CIVICs Clinical Core (Component C) is responsible for designing, executing, and managing Phase I/II clinical trials in targeted age groups and at-risk populations as directed by NIAID (see Section 3.2.2.1.3.3 – Research Area

003 Component C: Clinical Core). The exact age groups and at-risk populations proposed are at the discretion of the Offeror.

51. Question: Section 4.3.3.1.3 A. states that we must include an index, appropriately referenced, of all the certified cost or pricing data and information accompanying or identified in the proposal. Is it sufficient to create a table of contents as the first page of the supporting documentation section that identifies what pages within the pdf of the

Business Proposal each major cost category is location on (i.e. salaries pages x-x;

supplies pages x-x, travel quotes pages x-x, etc)? If not, is there any additional information you can provide regarding expected format?

Answer: Yes

52. Question: The Business Proposal instructions on page 92 indicate that the business proposals must provide three different budget formats as follows:

a. A detailed, task-linked budget that consists of a breakdown of total costs (direct costs, indirect costs and fees) to the Base and each Option proposed, accompanied by a detailed Gantt chart. We interpret this to be the ‘Summary of Proposed Costs’ excel budget workbook.

b. Should also include an annual breakdown where annual budgets will be based on the total amount of activities starting in that fiscal year. We interpret this to mean a summary presentation of our proposed budget broken out by government fiscal years in a format similar to the Breakdown of Proposed Estimated Costs but with dates reflective of each government fiscal year (10/1/xx to 9/30/xx).

c. Summary budget reflecting total costs over the period of performance of the proposed contract. We interpret this to be the one-two page ‘Breakdown of Proposed Estimated

Costs’ excel summary sheet.

Please provide additional guidance or instructions concerning the differences and/or confirm that these interpretations are correct?

Answer: Yes, to all of your interpretations.

53. Question: Regarding the business proposal, is there a preferred method of assembling the budget for the reviewers?

Answer: Please utilize Attachment 9 from the BAA - Breakdown of Proposed

Estimated Costs (plus fee) w/Excel Spreadsheet:

https://oamp.od.nih.gov/content/breakdown-proposed-estimated-cost-plus-fee-and-labor-hours https://oamp.od.nih.gov/sites/default/files/DFASDocs/buscntrctprpslsprdsht08-

2014_508.xlsx

54. Question: More specifically, is it preferred that the budgets are combined by the component breakdown below, institution involved or each subcontractor separately?

Answer: Please see the referenced spreadsheet as found in the hyperlink above contained in Attachment 9 of the BAA. All of the activities of Component A can be wrapped into your overall budget but broken down by the tabs in the excel spreadsheet. If you prefer to break them down further by the main subcomponents, that is up to you. Per the instructions on the spreadsheet, all costs should wrap into the overall SUMMARY tab proposed by Offeror

(including all costs (i.e. subcontractors). Each subcontract should in addition have its own breakdown similar to the prime proposal.

55. Question: Length of the technical proposal on pg 37 of the BAA states 250 pages for the

Vaccine Center, on page 63 it states 150 pages. For presentation of the research, is there a formatting template?

Answer: The page limitation for the Vaccine Center is 250 pages https://oamp.od.nih.gov/content/breakdown-proposed-estimated-cost-plus-fee-and-labor-hours https://oamp.od.nih.gov/content/breakdown-proposed-estimated-cost-plus-fee-and-labor-hours https://oamp.od.nih.gov/sites/default/files/DFASDocs/buscntrctprpslsprdsht08-2014_508.xlsx https://oamp.od.nih.gov/sites/default/files/DFASDocs/buscntrctprpslsprdsht08-2014_508.xlsx

56. Question: Are all subcontractors also expected to include a small business subcontracting plan if their total estimated budget exceeds $700,000?

Answer: all subcontractors (except small business concerns) that receive subcontracts in excess of $700,000 with further subcontracting possibilities should adopt a subcontracting plan that complies with the requirements of FAR

52.219-9.

57. Question: Budget spreadsheet includes Labor- by percent of effort and Labor- Hourly, but we should use only the Labor - Hourly tab?

Answer: Yes

58. Question: Could you please clarify if there is a cost-limit for quotes/pricing backup that should be provided with the budget for materials?

Answer: Please see 4.3.3.1.3 and 4.3.3.1.4 of the BAA

59. Question: Do foreign subcontracts need a Small Business Subcontracting Plan?

Answer: No

60. Question: We are providing a Certificate of Current Cost or Pricing Data. What additional pricing support/cost documentation is required with our initial submission? Does our

Business Proposal need to include:

a. Vendor quotes or some other form of price support for every element of the budget?

b. Or perhaps cost documentation is only needed for costs over a certain cost threshold ($1,000)?

c. Or do we simply need to be able to provide documentation upon request?

Answer: Please see 4.3.3.1.3 and 4.3.3.1.4 of the BAA

61. Question: Can NIH provide uniform cost assumptions for Component A?

Answer: No cost assumptions are provided for Component A. Budget estimates should address all areas outlined in Section 3.2.2.1.3.1 – Research Area 003 Component

A: Vaccine Center and should be commensurate with the technical approach.

62. Question: Is a Letter of Intent required for this solicitation? If yes, what is the due date.

Answer: No, a Letter of Intent is not required for this solicitation.

63. Question: Attachment 3 (Summary of Related Activities) – Should we place this document in the Technical or Business Proposal?

Answer: Technical.

64. Question: Regarding Attachment 15 (Cumulative Inclusion Enrollment Report) – do we need to include this report since studies have not begun yet?

Answer: Offerors should complete all required components of the PHS Human

Subjects and Clinical Trials Information form based on the proposed standard clinical trial study designs (see Section 4.3.2.3 – HUMAN SUBJECTS of the

NIAID 2018 Omnibus Solicitation HHS-NIH-NIAID-BAA2018). An inclusion enrollment report is required for all human subjects studies unless they fall under

Exemption 4. Cumulative enrollment tables should be submitted if the proposed studies will use an existing dataset or resource. If the proposed studies will not use an existing dataset or resource, planned enrollment tables should be submitted. Additional instructions on how to complete the PHS Human Subjects and Clinical Trials information form can be found at the following NIH website:

https://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/PHS%20Human%20Subjects%20and%20Clinical%20Trials%20Informati on%20Form%20Instructions.pdf

65. Question: How far must the 3 vaccine candidates be carried? Can we down-select to one candidate in the first year, or must each candidate be carried further through multiple years or even into clinical development?

Answer: NIAID will work with the CIVICs Program Contractors to down-select vaccine candidates and advance the most promising candidates into Phase I/II clinical trials. Offeror(s) for Component A (Vaccine Center) should include plans for establishing research priorities, identifying vaccine candidates for advancement to cGMP manufacturing and clinical studies, and discontinuing support of unproductive or unneeded research activities (see Section 3.2.3.1 –

Vaccine Center, Part a “Leadership and Project Management”).

66. Question: Do the universal influenza vaccine and the improved seasonal vaccine have to be separate entities or if you have 2 universal candidates and one seasonal candidate add up to the three required candidates?

Answer: This is acceptable provided that: (1) the three vaccine candidates are unique with respect to antigens, antigen/adjuvant combinations, or platforms; and

(2) the proposed studies will address the development of both robust, durable, broadly protective influenza vaccines and improvements to seasonal influenza vaccines (see…