RFP 75N93019R00023 Amendment 1.pdf

AMENDMENT #1, RFP No. 75N93019R00023 1

Amendment No. 1 RFP No. 75N93019R00023

“Preclinical and Translational Vaccine Development Support for HIV and Other Candidate Agents”

Solicitation Number: 75N93019R00023

Amendment Number: One (1)

Amendment Issue Date: June 15, 2020

Proposal Due Date/Time: August 14, 2020 at 3:00 PM, Eastern Standard Time (Changed)

Issued By: Kishan Patel

Contracting Officer

OA/DEA/NIAID/NIH/DHHS

5601 Fishers Lane, Room 3D10, MSC 9821 Bethesda, Maryland 20892-9821

Points of Contact: PRIMARY Kishan Patel, Contracting Officer Email: patelki@niaid.nih.gov Phone: 240.669.5157

SECONDARY

Michelle Scala, Contracting Officer Email: mscala@niaid.nih.gov Phone: 240.669.5156

Please note that we have extended the due date for submission of proposals as a result of this amendment. The date specified for receipt of proposals is indicated above.

Offerors must acknowledge receipt of this Amendment by identifying the amendment number and the date of the amendment on each copy of the submitted proposal. Failure to receive your acknowledgement may result in the rejection of your proposal. Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

The purpose of this Amendment is to:

(1) Provide responses to questions from potential offerors, regarding the solicitation;

(2) Revise Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Attachment 7, Statement of Work and Deliverables for Sample Task Order D-1, Attachment 8, Statement of Work and Deliverables for Sample Task Order E-1, and mailto:patelki@niaid.nih.gov mailto:mscala@niaid.nih.gov

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Attachment 9, Statement of Work and Deliverables for Sample Task Order F-1, in response to questions raised by offerors;

(3) Amend Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal, and Table of Contents, to provide clarity about what to include in Technical Proposals;

(4) Modify Section J – List of Attachments, to move the submission of the Section 508 Product Assessment Template from the Technical Proposal to the Business Proposal;

(5) Revise Section L - Instructions, Conditions, and Notices to Offerors, to include information that was inadvertently omitted; and

(6) Amend Section M – Evaluation Factors for Award, to provide clarity regarding how technical proposals will be evaluated.

RESPONSES TO QUESTIONS FROM POTENTIAL OFFERORS:

QUESTION 1: The RFP states “The total page count of the Technical Proposal for each Task Area shall not exceed 150 pages” may we interpret that as the 150 excluding appendices? As a few examples: CVs, Technical Cost Summary, Summary of Related Activities, etc.

RESPONSE: The only exclusions to the page limitation are those stated in Attachment 1, Packaging and Delivery of Proposals, Paragraph II, Formatting and Page Limitations, subparagraph B, Page Limitations, subparagraph 2 which states:

2. Total page count does not include:

a. Title and Back Page; Table of Contents; Section Dividers that do not contain information other than title of Section; and

b. The Human Subject and Clinical Trial Information Form, if required by the solicitation.

QUESTION 2: How many IDIQ contracts does DAIDS intend to award?

RESPONSE: As indicated in the solicitation, Part IV, Representations and Instructions, SECTION L, Instructions, Conditions and Notices to Offerors, Paragraph a., General Information, subparagraph d, Contract Type and Number of Awards, it is anticipated that base contract awards will be made to multiple contractors for Task Areas A, B, C, D, E, F, and G.

QUESTION 3: Upon award of a base contract, would an Offeror be required to submit a bid for each task order that is issued?

RESPONSE: Please refer to the solicitation, Part I, The Schedule, Section G, Contract Administration Data, Article G.3., Task Order Procedures, paragraph b, Requesting Task Order Proposals, 4th paragraph, which states:

“Contractors are not required to propose on all TORFPs. Those eligible Contractors that decide not to submit a proposal shall advise the Contracting Officer, in writing, of their intention not to submit a proposal on or before the closing date and time established in the TORFP. An election not to propose on a given TORFP will not negatively affect or prohibit a

AMENDMENT #1, RFP No. 75N93019R00023 3

Contractor from competing on future TORFPs. However, it may affect the Contractor's eligibility for continuations or extensions of the resultant Task Order.”

QUESTION 4: Can the government clarify if Offeror’s should provide a standalone, independent technical response to Sample Task Areas, or should they provide an integrated response? For example: Include a standalone response to the Sample Task Area(s) in Section 7 (Task Order / Sample Task Order Options) or integrate the Sample Task Order response into the Base Technical Response in Section 3 as a sub-section?

RESPONSE: Offerors do not have to submit proposals for ALL Task Areas. Both the Additional Technical Proposal Instructions (solicitation Attachment 11) and the Additional Business Proposal Instructions (solicitation Attachment 12) state the following:

Offerors may submit proposals in response to one or more Task Area(s) of their choosing, and are not expected to respond to all Task Areas. Offerors responding to multiple Task Areas must provide separate Technical and Business Proposals for each Task Area. Proposals for each Task Area will be reviewed independently.

If an Offeror intends to submit a proposal for a particular Task Area, a separate Technical Proposal must be submitted for each Task Area. Included in the Technical Proposal, in response to Technical Plan/Approach, the Offeror should address capabilities related to the Task Order/Sample Task Order Statement of Work for that Task Area. When responding to the Scientific and Technical Personnel, Facilities, Equipment and Resources, and Project Management, the Offeror should address capabilities related to the Statement of Work for the particular Task Area.

Business Proposals should be submitted for each Task Area and should address the Task Order/Sample Task Order for each Task Area to which the Offeror is responding.

Please refer to the information provided below and Attachment 11, Additional Technical Proposal Instructions, Format of Technical Proposal and Table of Contents, which has been revised to clarify how Technical Proposals are to be configured.

Attachment 11, Section 3, Technical Plan/Approach, originally stated that the Technical Proposal for each Task Area address ALL of the elements in the Task Area Statement of Work included in the Base Contract Statement of Work (Attachment 3) including the general requirements, and provide a detailed technical plan to address each of the activities within the Scope of the Task Area. The original Attachment 11, Section 3, Technical Plan/Approach, also requested Offerors respond to the requirements for the Sample Task Order for each Task Area.

For the purposes of clarification and intent, NIAID is NOT requiring the Offeror to address ALL of the elements in the Task Area SOW as part of their Technical Plan/Approach. The elements included in the Task Area SOW of the Base Contract were intended to inform the Offerors of the scope and breadth of the work expected on that specific Task Area. It is expected that, when applicable, the Offeror will include and address those elements only as related to carrying out activities in the Statements of Work for Task Order/Sample Task Orders A – G (Attachments 5

AMENDMENT #1, RFP No. 75N93019R00023 4 through 10). The Offeror is still expected to respond to the General Task Order Requirements listed in the Base Statement of Work (Attachment 3, Paragraph C). Attachment 11, Section 3, Technical Plan/Approach, has been revised to reflect NAID’s intent as described herein.

Attachment 11, Section 4, Scientific and Technical Personnel, is being revised to make it clear that the Offeror should provide information relevant to document individual training, experience, qualifications and expertise necessary for the successful completion of all Task Area requirements included in Attachment 3, Base Contract Statement of Work, Paragraph D, Description for Individual Task Areas which includes Statements of Work for Task Areas A through G.

Attachment 11, Section 5, Facilities, Equipment and Other Resources, is being revised to make it clear that the Offeror should document availability and adequacy of facilities, equipment, space and other resources necessary to carry out the Task Area requirements included in Attachment 3, Base Contract Statement of Work, Paragraph D, Description for Individual Task Areas which includes Statements of Work for Task Areas A through G.

Attachment 11, Section 6, Project Management, is being revised to make it clear that the Offeror should document Project Management capabilities related to Task Area requirements included in Attachment 3, Base Contract Statement of Work, Paragraph D, Description for Individual Task Areas which includes Statements of Work for Task Areas A through G.

QUESTION 5: Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents: The RFP states “The plan for the Task Order should stand alone and not reference other sections of the proposal.” In an effort to conserve page count and not to be redundant in our Sample Task Order response we plan to reference specific sections of the of larger Task Area Facilities, Quality, Personnel, Etc. Is this acceptable or does the Government expect to be provided as a full write up in both the Task Area and Sample Task Order sections?

RESPONSE: The statement you cited “The plan for the Task Order should stand alone and not reference other sections of the proposal” has been removed. Please refer to the response to Question 4 above and the revised Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Content

QUESTION 6: If an Offeror intends to submit a proposal in response to Tasks Areas A-F, can you confirm that the expectation is that we will submit 6 separate proposals – 1 for each Task Area?

RESPONSE: Yes, an offeror would be expected to submit 1 proposal for each Task Area.

Please also refer to our response to Question 4 above.

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QUESTIONS AND RESPONSES RELATED TO TASK AREA A and TASK ORDER A-1

QUESTION 7: Task Order A-1 is structured as a cost-reimbursement, level of effort/term type Task Order. Please clarify how level of effort should be presented for prime contractor and subcontractor personnel in order to meet the level of effort requirements of the Task Order.

RESPONSE: The total level of effort for Task Order A-1 is 1.45 Full Time Equivalents (FTEs) for the base period and each Term Option. The solicitation indicates that the number of FTEs is inclusive of subcontractor effort. Therefore, your proposal should show the total level of effort for your staff and the total level of effort for the subcontractor staff separately. However, please note that the combination of prime contractor and subcontractor level of effort may not exceed

1.45 FTEs. Please see ATTACHMENT 12, Additional Business Proposal Instructions and Uniform Cost Assumptions, for information related to Task Order A-1. Specifically, Section 4, Uniform Cost Assumptions, paragraph A.1., Technical Cost Assumptions for Task Order A-1, Research and Development Product Storage and Shipping, subparagraph a., for more information.

QUESTION 8: Task Area A: In the Attachment 3 Section D, Description for Individual Task Areas, the requirements for Task Area A indicate that “the Contractor shall manage and perform the receipt, storage, retrieval, packaging and shipping of research and development products in compliance with CGMP regulations for clinical material”. Is it your expectation that a small business submitting a proposal to this solicitation for Task Area A would be CGMP compliant and would be requested to demonstrate CGMP compliance?

RESPONSE: We would expect an offeror to be CGMP compliant for storage and to follow the appropriate and relevant regulations and guidance documents. Please refer to Attachment 4, Statement of Work and Reporting Requirements for Task Order A-1 and Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents.

QUESTION 9: Should the Quality Assurance Unit (QAU) work outside the small business and not be involved at all with any of the small business regular operations to comply with the request to “provide a QAU independent of other operations of the contractor…”

RESPONSE: Quality Assurance Unit reporting must remain independent within the organizational structure managing this Task Order. If an Offeror believes the Quality Assurance Unit should be subcontracted out, that is the Offeror’s prerogative.

QUESTIONS AND RESPONSES RELATED TO TASK AREA B and SAMPLE TASK

ORDER B-1

QUESTION 10: Sample Task Order B-1: Please specify the type of the vaccine and disease indication.

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RESPONSE: Attachment 5, Statement of Work and Deliverables for Sample Task Order B-1, Safety and Immunogenicity Studies for an HIV-Env Protein Vaccine Candidate, has been revised to reflect that the Contractor is to assume single dose administration of HIV-1 gp120 vaccine candidate at 300mcg dose with an alum adjuvant to health volunteers. Please refer to Attachment 5:

Statement of Work and Deliverables for Sample Task Order B-1, Safety and Immunogenicity Studies for an HIV-Env Protein Vaccine Candidate, Section C, Article C.1., Statement of Work, Paragraph C, Technical Requirements, subparagraph 1.

QUESTION 11: Sample Task Order B-1: Please clarify what extent of details are required for proposed toxicity studies.

RESPONSE: Please refer to Attachment 5: Statement of Work and Deliverables for Sample Task Order B-1, Safety and Immunogenicity Studies for an HIV-Env Protein Vaccine Candidate, Section C, Article C.1., Statement of Work, Paragraph C, Technical Requirements, subparagraph 5.a.4. which states: “Immunogenicity testing. At periodic intervals to be determined by the COR, blood samples shall be collected and stored for immunological analysis, including comparison controls as defined in the Study Plan.”

QUESTIONS AND RESPONSES RELATED TO TASK AREA C and SAMPLE TASK

ORDER C-1

QUESTION 12: Task Area C: What happens to a program if the product under consideration is deemed not feasible after R&D evaluation with existing capabilities?

RESPONSE: Task Area C is for Feasibility Studies and Early Manufacturability Assessments.

Sample Task Order C-1 is to perform Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 Gp120 Envelope (Env) in a Mammalian Cell Line. The Contractor will perform a feasibility study and recommend to the Government whether manufacturing is feasible.

QUESTION 13: Sample Task Order C-1: Is there a target or minimum harvest size for the batch?

RESPONSE: The target is for a 50L bioreactor run as stated in the amended Sample Task Order (see solicitation Attachment 6).

QUESTON 14: Sample Task Order C-1: Is there a time limit for completing the feasibility studies? Is there a minimum number of feasibility runs required for upstream and downstream?

RESPONSE: It is up to an Offeror to propose the timeframe for completing the feasibility study.

It is up to an Offeror to propose the number of feasibility runs required for upstream and downstream.

QUESTION 15: Sample Task Order C-1: Is production of an interim reference standard part of the feasibility study?

AMENDMENT #1, RFP No. 75N93019R00023 7

RESPONSE: The Offeror should make a determination whether an interim reference standard is required for the feasibility study.

QUESTION 16: Sample Task Order C-1: Page 1 of 7 of Attachment 6: Scope indicates: The purpose of this Task Order is to determine feasibility of early manufacturability of producing HIV-1 gp120 ENV in mammalian cell line of human origin from research material for use in clinical trial. Does DAIDS have recommendations for any specific human cell line for undertaking this work?

RESPONSE: A stable CHO producer cell line should be used to undertake this work.

Attachment 6: Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work, Paragraph B., Scope, has been revised to reflect this information.

QUESTION 17: Sample Task Order C-1: Steps 8 & 9 references performing a complete full scale 50L CGMP compliant run to obtain relevant crude harvest and a 50L bulk harvest. Please provide clarity on whether the expectation is to produce 2 separate 50L batches; one to crude harvest and one through to bulk drug substance harvest.

RESPONSE: The Contractor is not required to produce 2 separate 50L batches. The Statement of Work for Sample Task Order C-1, Section C, Article C.1., Statement of Work, Paragraph C, Technical Requirements, has been changed to revise paragraph 8 and to delete paragraphs 9-14.

Paragraph 8 is revised to read as follows:

8. Perform 2-4L manufacturing runs to demonstrate manufacturability and provide a final Tech Transfer Report appropriate to support CGMP manufacturing at a CMO.

QUESTION 18: Attachment 6: Task Area C, page 3: Under the technical requirements line 10 states – “Perform all required in-process and bulk harvest release testing using qualified assays.”

Does this include the product specific assays including potency or does this refer to just the safety testing?

RESPONSE: Sample Task Order C-1, has been revised as indicated above (see responses to questions 17 and 18). Please refer to Attachment 6: Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

QUESTION 19: For Sample Task Order C-1 the Statement of Work, Scope describes feasibility and early manufacturability whereas the Technical Requirements include performing a complete full scale 50L CGMP manufacturing run through stability and storage. Should we propose and budget for execution of a 50L run in the CGMP facility under CGMPs with quality release and CGMP storage of material?

AMENDMENT #1, RFP No. 75N93019R00023 8

RESPONSE: No, you should not propose and budget for a 50L run in the CGMP facility under CGMPs with quality release and CGMP storage of material. Sample Task Order C-1 has been revised to require the Contractor to perform appropriate small scale, non CGMP manufacturing run. Please refer to Attachment 6: Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

QUESTION 20: Attachment 6: Sample Task Order C-1, page 3: Line 8 states “Perform a complete full-scale 50L CGMP compliant run with all CGMP documentation in order to obtain relevant crude harvest.” Line 9 states “Perform one complete full-scale 50L CGMP compliant run with all CGMP documentation in order to obtain HIV-1 gp120 Env bulk harvest.” What is the difference between these requirements?

RESPONSE: As stated above in response to questions above, the Statement of Work for Sample Task Order C-1 has been revised. Please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Section C, Article C.1., Statement of Work, Paragraph C, Technical Requirements.

QUESTION 21: Attachment 6: Sample Task Order C-1, pg. 2, Line 7: states “Perform upstream production of HIV-1 gp120 Env protein under CGMP conditions for clinical trial use to determine feasibility and early manufacturability”. Is there a target amount of HIV-1 Env gp120 required in the bulk harvest?

RESPONSE: As stated above in response to questions above, the Statement of Work for Sample Task Order C-1 has been revised. Please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Section C, Article C.1., Statement of Work, Paragraph C, Technical Requirements.

QUESTION 22: Sample Task Order C-1: Does DAIDS intend that manufacture of ‘feasibility lots’ be conducted using existing processes and methods from the Product Innovator, or is it expected that process/analytical/formulation development and optimization work will be performed by the Offeror in order to produce such material?

RESPONSE: DAIDS intends that the Product Innovator will provide existing methods and processes. Attachment 6: Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work, Paragraph B., Scope, has been revised to add this information.

QUESTION 23: Sample Task Order C-1: Please clarify if CGMP production or other laboratory work by the Offeror is required under this Sample Task Order. The Sample Task Order requests feasibility assessment and CGMP production at the 50L scale but does not request early laboratory process testing, technical transfer process/analytical/formulation development and optimization prior to CGMP manufacturing.

AMENDMENT #1, RFP No. 75N93019R00023 9

RESPONSE: An upstream and downstream process needs to be developed, run at an appropriate scale and a Tech Transfer Report needs to be provided. The Statement of Work for Sample Task Order C-1 has been revised to reflect this. The Offeror needs to make their own determination as to whether CGMP is required and the extent of the laboratory worked required. Please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

QUESTION 24: Attachment 6: Sample Task Order C-1, page 2: Does the sample task order include the downstream purification of HIV-1 Env gp120 to BDS?

RESPONSE: Yes, please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

QUESTION 25: In general, does Task Area C contemplate task orders that will include downstream purification feasibility/pilot runs under GMP? Or is the expectation that all task orders will focus on upstream feasibility?

RESPONSE: Both upstream feasibility and downstream purification feasibility/pilot runs under CGMP are contemplated.

QUESTION 26: In general, does Task Area C contemplate any task orders that may include feasibility studies of BDS formulation with adjuvants or other excipients to improve product shelf life?

RESPONSE: In general, yes task orders may include feasibility studies of BDS formulation with adjuvants or other excipients to improve produce shelf life.

QUESTION 27: Sample Task Order C-1: Does DAIDS intend that CGMP production at the 50L scale will be conducted using existing methods and processes from the Product Innovator (after technical transfer) with no development or optimization by the Offeror? Or, does DAIDS intend that the Offeror should perform process/analytical/formulation development work prior to the 50L CGMP manufacturing run? Does DAIDS intend that assay qualification will be performed by the Offeror, or that assay qualification will have been performed by the Product Innovator?

RESPONSE: No, the Product Inventor will provide existing methods and processes. The Statement of Work for Sample Task Order C-1 has been revised to reflect this. Please refer to Attachment 6: Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Paragraph B., Scope.

QUESTION 28: Task Area C - Attachment 3, page 10 of 18: In the Base SOW for Task Area C, it says “Manufacture feasibility lots of each formulation in quantities appropriate to confirm the third-party formulation methods. The feasibility lots shall be prepared at a scale appropriate for

AMENDMENT #1, RFP No. 75N93019R00023 10 scale-up to the target batch size.” Is there an expectation that these Feasibility/Pilot Lots detailed in the BASE be performed under CGMP as is stated in the Sample Task Order?

RESPONSE: The final processes have to be compatible for CGMP manufacturing.

QUESTION 29: Sample Task Order C-1: Production and release of a 50L CGMP lot of gp120 is requested along with stability testing and shipping. But the 50L CGMP lot (or production of any gp120 material) is not stated as a deliverable. Only reports and recommendations are listed as deliverables. Please confirm that production and delivery of CGMP gp120 is expected under this Sample Task Order.

RESPONSE: The only deliverable is a final Tech Transfer Report appropriate to support CGMP manufacturing at a CMO. The Statement of Work for Sample Task Order C-1 has been revised to delete paragraphs 9 through 14. Please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

QUESTION 30: Sample Task Order C-1, page 3 of 7, bullet 12: Develop and perform a stability hold study on a representative harvest sample from the CGMP as directed by the COR. Please clarify, “stability hold study”. Please clarify whether this study needs be undertaken on the, “harvest of purified drug substance”?

RESPONSE: No, a stability hold study does not need to be undertaken. The Statement of Work for Sample Task Order C-1 has been amended to revise Paragraph C, Technical Requirements, subparagraphs 7 and 8 to read as follows and to delete subparagraphs 9 through 14.

7. Develop upstream and downstream processes suitable for scale up for a 50L scale manufacturing campaign.

8. Perform 2-4L manufacturing run(s) to demonstrate manufacturability and provide a final Tech Transfer Report appropriate to support CGMP manufacturing at a Contract Manufacturing Organization (CMO).

QUESTION 31: Sample Task Order C-1 requests a hold study on a representative harvest sample. Can the desired study parameters be provided? Is this study expected to be performed per ICH with Quality Oversight?

RESPONSE: Sample Task Order C-1 has been revised to remove the requirement for a 50L hold from a CGMP run. Please refer to Attachment 6, Statement of Work and Deliverables for Sample Task Order C-1, Feasibility Studies and Early Manufacturability Assessment of Production of HIV-1 GP120 Envelope (Env) in a Mammalian Cell Line, Section C, Article C.1., Statement of Work.

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QUESTION 32: Sample Task Order C-1, page 3 of 7, bullet 13: Provide a COC and a COA for the bulk harvest to the COR at the time of bulk harvest release. Please clarify whether this study needs be undertaken on the, “harvest of purified drug substance”?

RESPONSE: No, this study does not need to be undertaken. The Statement of Work for Sample Task Order C-1 has been amended to revise Paragraph C, Technical Requirements, subparagraphs 7 and 8 and to delete subparagraphs 9 through 14.

QUESTION 33: Sample Task Order C-1 requests a Project Management Plan (PMP) within 30 days of project award, but this Task Order will not be executed. Should the Sample Task Order Proposal include a Project Management Plan?

RESPONSE: A Project Management Plan is not required to be submitted with your Technical Proposal.

QUESTIONS AND RESPONSES RELATED TO TASK AREA D and SAMPLE TASK

ORDER D-1

QUESTION 34: Sample Task Order D-1, Attachment 7: Title reads, “Preclinical and Translational Vaccine Development Support for HIV and Other Candidate Agents”, please clarify whether the focus should be on recombinant Env glycoproteins (i.e., gp120, gp140) only, or a comprehensive technical plan should be included for each agent/ product (monoclonal antibody, viral vectors, nanoparticles, and nucleic acids).

RESPONSE: The title you have referred to is the title of the solicitation. The title of Attachment 7 is “Statement of Work and Deliverables for Sample Task Order D-1, Analytical Characterization and Method Development to Determine the Glycosylation of an HIV Env Vaccine Candidate.” Please only respond to the activities that are included in the Sample Task Order D-1 Statement of Work. Also, please refer to Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order D-1.

QUESTION 35: Task Area D - Currently, more than ten adjuvants are being explored (or have been studied) in the field of HIV and other vaccines. Should the 'antigen with adjuvant' analytical strategy be described using Alum only?

RESPONSE: Please only respond to the activities that are included in the Sample Task Order D- 1, Statement of Work. Also, please refer to Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order D-1.

QUESTION 36: Task Area D - For the in vivo assays, cell potency, or immune potency assays for the Phase II or Phase III programs, the exact design of the mouse immune potency study is not provided. Thus, for this proposal, technical and budgeting justifications, should we assume

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15 female mice (CRL-C57BL/6 and or Envigo-Balb/C), immunized twice on D1 and D15, with terminal bleed 4 weeks after second immunization and ELISA assay performed to measure the titer.

RESPONSE: Please only respond to the activities that are included in the Sample Task Order D- 1, Statement of Work. Also, please refer to Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order D-1.

QUESTION 37: Task Area D - Task Area D states that the contractor may develop or produce necessary reagents required for analytical development. Should a separate technical section and budget be included for the reagents needed to perform analytical testing? For technical proposal and budgeting, should two antibodies per Env antigens be assumed?

RESPONSE: It is up to the offeror to propose a technical approach to accomplish the work in the Sample Task Order. Please only respond to the activities that are included in the Sample Task Order D-1, Statement of Work. Also, please refer to Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order D-1.

QUESTION 38: Sample Task Order D-1: Attachment 7, Page 1 of 7: The Scope indicates, “Develop, characterize and standardize methods, to determine the glycosylation profiles of HIV ENV vaccine candidate(s) provided by the COR with methods such as MS Spectroscopy and others, Using standardized methods, analyze and characterize HIV ENV candidates provided by the COR, for their glycosylation profiles. indicates focus should be on analysis of HIV ENV proteins for glycosylation. Please clarify whether the focus should be on glycosylation characterization or comprehensive characterization using all analytical tools available in the field?

RESPONSE: The focus should be on glycosylation characterization. Please refer to the revised Attachment 7: Statement of Work and Deliverables for Sample Task Order D-1, Analytical Characterization and Method Development to Determine the Glycosylation of an HIV Env Vaccine Candidate, Section C, Article C.1., Statement of Work, Paragraph B, Scope, which has been revised to read as follows:

Develop, characterize and standardize methods, to determine the glycosylation profiles of a soluble gp140 HIV Envelope trimer protein derived from a CHO DG44 cell line with methods such as MS Spectroscopy and others. Using standardized methods, analyze and characterize HIV Env candidates, provided by the COR, for their glycosylation profiles.

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QUESTIONS AND RESPONSES RELATED TO TASK AREA E and SAMPLE TASK

ORDER E-1

QUESTION 39: Task Area E: Does DAIDS expect that the Offeror will create Research Cell Banks (RCBs) de novo (vector cloning → transfection →single cell cloning, etc.)? Or, will Master Cell Banks be produced from existing RCBs provided by DAIDS?

RESPONSE: Please refer to Attachment 8, Sample Task Order E-1 which states that the BDS shall be produced from a stably derived CHO DG44 clone cell line.

QUESTION 40: Sample Task Order E-1, can we assume that DAIDS will be providing a research cell line expressing gp120 that has been derived in a manner that is appropriate for use in cGMP processes?

RESPONSE: The Contractor will be provided a stable cell line. The Statement of Work for Sample Task Order E-1 has been revised to reflect this. Please refer to the revised Attachment 8:

Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV- 1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

QUESTION 41: Technical Plan, Task Area E (Attachment 8, pp1-2): The directions state in Para. A, Scope, that it encompasses all activities required for the manufacture & release of DP for Phase-1 clinical trial. Then Paras. B.1 states the technical requirement includes “Manufacture BDS and DP in compliance with GMP.” Later in Paras. B.1.a and B.1.b the instructions are again repeated that it is expected an Offeror to “produce” the specified materials “from” a stably derived CHO DG44 clone cell line. We interpret these statements to mean the Offeror is expected to make the BDS from the cell line. Cost Proposal, Task Area E (Attachment 12, p7). Para 5.c of this set of instructions states the HIV-Env protein “shall be supplied by the Government and provided to the Contractor upon Task Order award.”

RESPONSE: Please see response to Question 40 above.

QUESTION 42: Task Area E: Does DAIDS expect that vaccine candidates produced under the contract will be primarily recombinant protein formulations, or will viral vector and nucleic acid-based candidates also be produced?

RESPONSE: When responding to Task Area E, Offerors will be evaluated based on how they respond to Sample Task Order E-1. Therefore, please only respond to the activities that are included in the Sample Task Order E-1, Statement of Work.

Sample Task Order E-1 is for an Envelope protein. For clarity, Attachment 8, Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work, Paragraph B, Scope, has been revised to read as follows:

Activities under this Task Order encompass all activities required to complete a 50L CGMP manufacture of a soluble HIV gp120 Envelope protein and final release of BDS and DP for a

AMENDMENT #1, RFP No. 75N93019R00023 14

Phase I clinical trial. All activities related to the manufacture and release for clinical use shall be conducted in accordance with relevant regulatory guidelines and in compliance with GLP and CGMP regulations. Both pilot lot development and engineering lots are within the scope of this Task Order. The Contractor will be provided a Tech Transfer Report that describes 2L-scale bioreactor upstream/downstream purification processes; limited analytics and formulation studies will also be provided to the Contractor.

QUESTION 43: Task Area E: Please clarify why “Design and develop protocols for all in vitro, ex vivo or in vivo studies and provide to the COR” is requested under Process Development? Is the scope of such work different from the scope in Task Area B? Is DAIDS referring to analytical or other CMC support for such studies?

RESPONSE: The statement you are referring to is included in the Statement of Work for Task Area E. When responding to Task Area E, Offerors will be evaluated based on how they respond to Sample Task Order E-1. Therefore, please only respond to the activities that are included in the Sample Task Order E-1, Statement of Work.

QUESTION 44: Task Area E: Please confirm if the scope of fill finish operations under Task Area E is limited to BDS in the manufacturing. Attachment 3: Page:92/180 cGMP manufacturing describes Vialing, packaging and labeling.

RESPONSE: The information you are referring to is included in the Statement of Work for Task Area E. When responding to Task Area E, Offerors will be evaluated based on how they respond to Sample Task Order E-1. Please address only what is required in the Statement of Work for Sample Task Order E-1.

QUESTION 45: Sample Task Order E-1: Please confirm the Drug Product Stability program should be included along with BDS under this Task Area. DP stability design will also be provided.

RESPONSE: Drug Product stability is required. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work, Paragraph B, Technical Requirements, specifically paragraph 2., Perform vaccine lot characterization tests, subparagraph d.

QUESTION 46: Sample Task Order E-1: Attachment 8 Page 3 of 9 – bullet 3 Test for purity:

Makes a reference to, “Evaluate residual moisture”, please clarify?

RESPONSE: The requirement to evaluate residual moisture has been deleted. The Statement of Work for Sample Task Order E-1 has been revised to reflect this deletion. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work, Paragraph B, Technical Requirements, specifically paragraph 2.a.3).

AMENDMENT #1, RFP No. 75N93019R00023 15

QUESTION 47: Sample Task Order E-1: Attachment 8 of 9: For Items 7 and 8 should the Delivery schedule read, “Due at the end of completion of the fill-finish campaign”?

RESPONSE: Delivery of the Certificate of Analysis and Certificate of Compliance should be due 30 days after final release of product. The Deliveries Schedule has been revised to reflect this change. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section F, Deliveries or Performance, Article F.1., Deliveries, specifically paragraph a., items 7 and 8.

QUESTION 48: Sample Task Order E-1: Should the Offeror assume that all process development has been completed and the scope of the Sample Task Order begins with a pilot production (confirmation) lot?

RESPONSE: The Contractor will be provided a technical transfer package and will need to complete process development. The Statement of Work has been revised to reflect this information. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work, Paragraph A, Scope.

QUESTION 49: Sample Task Order E-1: Is the cell source for Bulk Drug Substance provided from the NIH AIDS Reagent program, HIV NL4-3 gp120 secreting CHO cells (NIH Catalog No.

4125)?

RESPONSE: The Government will provide the stable cell line. The Statement of Work for Sample Task Order E-1 has been revised to reflect this information. Please refer to Attachment 8:

Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV- 1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

QUESTION 50: Sample Task Order E-1: What is the level of expression of Bulk Drug Substance (mg/mL) by this source, and in what cell culture medium?

RESPONSE: Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work, paragraph 1.f., that reads as follows:

f. Deliver to the NIAID no less than 2000 final container doses per lot of CGMP vaccine product at a final concentration of 0.7mg/ml and 0.5ml per vial diluent along with all necessary supporting documentation such as letters of cross-reference to allow the NIAID to perform subsequent clinical trials or any other Government purpose.

QUESTION 51: Sample Task Order E-1: There is no direct specification in the Sample Task Order E-1 about how Drug Product is to be returned to the Government, whether as frozen liquid or dry powder. Under Test for Purity (2.a.3) there is a statement that residual moisture should be determined, and this presumes dry powder. Is the Drug Product to be provided as a dry powder?

AMENDMENT #1, RFP No. 75N93019R00023 16

RESPONSE: The final fill finished vialled drug product should be returned back to the government at -70C. The requirement to evaluate residual moisture has been deleted. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

QUESTION 52: Sample Task Order E-1: Part 2.g calls for detailed evaluative written report of closeout activities including outstanding deviations, OOS, CAPA, etc. There can be none of these excursions in a theoretical example. Are we expected to create them and resolve them to demonstrate methodology, or is it sufficient to state these will be done if they had occurred?

RESPONSE: The activities are necessary for completion of production and therefore you must address how you would accomplish them in your proposal.

QUESTION 53: Sample Task Order E-1: Similarly, to the points made above, Section 4, Technical Reports and Deliverables describes the format for reports. Are Offerors expected to submit theoretical reports or is it responsive to again state the expected contents of these various reports as stated in the text of E-1 Section 4?

RESPONSE: No, Offerors are not expected to submit theoretical reports. Please refer to Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order E-1.

QUESTION 54: Sample Task Order E-1: Attachment 8, B.1.b states “The BDS shall be produced from a stably derived CHO DG44 clone cell line”, but nowhere else in the Task Order text except the title is the BDS identified. The literature describes different subtypes of HIV-1 gp-120 (Wen et. al., https://doi.org/10.1371/journal.pone.0194266). It seems unreasonable to expect an Offeror to on its own identify a subtype that will then be taken forward by NIH to Phase-1 human clinical trials. Can the NIH provide better definition here about what the BDS sough actually is?

RESPONSE: The Government will provide an HIV Env producer cell line. The Statement of Work for Sample Task Order E-1 has been revises to reflect this. Please refer to Attachment 8:

Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV- 1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

QUESTION 55: NIH provides CHO cell lines expressing GP-120 through its AIDS Reagent program. Specifically, HIV NL4-3 gp120 secreting CHO cells (NIH Catalog No. 4125) is an example. We are unable to determine whether this cell line is equivalent to CHO DG44 and therefore acceptable. Does this cell line meet the requirements?

RESPONSE: The Government will provide an HIV Env producer cell line. The Statement of Work for Sample Task Order E-1 has been revised. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

AMENDMENT #1, RFP No. 75N93019R00023 17

QUESTION 56: Sample Task Order E-1: CHO DG44 established cell line cultures already certified for making human use products and having master files suitable for FDA IND filings are available for purchase from some large lab suppliers like ThermoFisher. Use of these lines is restricted for research purposes unless licenses are negotiated. As it now looks, any Offeror responding to this Task Area E sample task order and not having a certified CHO DG44 cell line must include the purchase and negotiated license to these cells for use in human trials by NIH from the supplier. We find it disingenuous to enter a fake negotiation with a supplier for a Task Order that has no expectation of being issued and occupy their time for something that will not happen.

RESPONSE: The Government will provide an HIV Env producer cell line. The Statement of Work for Sample Task Order E-1 has been revised. Please refer to Attachment 8: Statement of Work and Deliverables for Sample Task Order E-1, CGMP Manufacturing of HIV-1 GP120 Envelope (ENV), Section C, Article C.1., Statement of Work.

QUESTION 57: Sample Task Order E-1: These cell lines must be transfected with the desired gene(s) to make the HIV-1 gp-120 glycoprotein. Attachment 3, Task Area E of the RFP in Para.

1, Scope, states “…These services will range from initial product discovery to production and activities required to support clinical trials and/or product licensure.”. Does this mean that an Offeror should be able to carry out or provide basic R&D (i.e., product discovery) in addition to process development, manufacturing and the other tasks listed? If so, then must the response to the Sample Task Order also include R&D to determine the gene for cell line transfection since the HIV-1 gp120 is not really identified?

RESPONSE: The statement you are referring to “These services will range from initial product discovery to production and activities required to support clinical trials and/or product licensure” is included in the Statement of Work for Task Area E. When responding to Task Area E, Offerors will be evaluated based on how they respond to Sample Task Order E-1. Please address only what is required in the Statement of Work for Sample Task Order E-1.

QUESTIONS AND RESPONSES RELATED TO TASK AREA F and SAMPLE TASK

ORDER F-1

QUESTION 58: Task Area F – Our assumption is the stand alone fill product specific testing will be done by whoever developed the BDS. Does the Government accept this assumption?

RESPONSE: This assumption is incorrect. This is a stand alone Task Order.

QUESTION 59: Sample Task Order F-1: Attachment 9 Page 1 of 8” Title reads, “Preclinical and Translational vaccine development support for HIV and other candidate agents”. Please clarify whether the focus should be on HIV Env gp120 as indicated in the Background and Introduction. Please clarify, “Other Candidate Agents”. Are separate sections expected for other agents/ products (monoclonal antibody, viral vectors, etc.,)?

RESPONSE: The focus should be on HIV Env gp120 as indicated in Attachment 9: Statement of Work and Deliverables for Sample Task Order F-1, Fill-Finish, Release, and Stability Testing

AMENDMENT #1, RFP No. 75N93019R00023 18 of HIV-1 GP120 Proteins. The title you have referred to is the title of the solicitation. The reference to “other candidate agents” is not included in the Statement of Work for Sample Task Order F-1. When responding to Task Area F, Offerors will be evaluated based on how they respond to Sample Task Order F-1. Please address only what is required in the Statement of Work for Sample Task Order F-1. Also, please refer to Attachment 11, Additional Technical Proposal Instructions, Format for Technical Proposal and Table of Contents, for the information that should be included in your Technical Proposal regarding the technical plan/approach for Sample Task Order F-1.

QUESTION 60: Sample Task Order F-1: Part C.2 states that at least 50-75% of the Fill-Finished Bulk Drug Substance must be returned to the Government, but we cannot locate anywhere in the Sample Task order the amount of material required to be supplied for Fill-Finish Please stipulate.

RESPONSE: The Contractor will be required to provide 2,000 vials of 0.7mg/ml at 0.5ml volume. Attachment 9, Statement of Work and Deliverables for Sample Task Order F-1 has been revised to reflect this information. Please refer to Attachment 9: Statement of Work and Deliverables for Sample Task Order F-1, Fill-Finish, Release, and Stability Testing of HIV-1 Gp120 Proteins, Section C, Article C.1., Statement of Work.

QUESTION 61: Sample Task Order F-1: We cannot locate anywhere in Sample Task Order F-1 the volume or amount/volume of Drug Product to be vialed in filling/finishing the Drug Product.

RESPONSE: The Contractor will be required to provide 2,000 vials of 0.7mg/ml at 0.5ml volume. Attachment 9, Statement of Work and Deliverables for Sample Task Order F-1 has been revised to reflect this information.

QUESTION 62: We cannot locate anywhere in F-1 whether the finished Drug Product is to be provided as frozen solution or dry powder. Please stipulate.

RESPONSE: The final product is to be frozen at -70C. The Contractor will be provided 1gm of material. Attachment 9, Statement of Work and Deliverables for Sample Task Order F-1 has been revised to reflect this information.