Amendment 2(Final).pdf

AMENDMENT #2:

RFP 75N95023R00020

The purpose of this Amendment is to:

(1) Update Section M (6)-Technical Evaluation Factors as follows:

6. Response to Sample Task Order (20 points)

Considering the preceding criteria, the extent to which the response to the Sample Task Order shows:

A. The appropriateness of the proposed summary of labor and direct costs to successfully fulfill the requirements described in the Sample Task Order.

B. The offeror's ability to appropriately address potential future task orders of similar size, scope, and complexity, and the feasibility for future task orders to be fulfilled successfully.

(2) Clarify that Attachment 2-Proposal_Intent_Reponse_Form should be returned to the Contract Specialist at samson.shifaraw@nih.gov by 3 pm EST on June 9, 2023.

(3) Replace Attachment 3-SOW with Attachment 3-REVISED_SOW (6.1.23)

(4) Replace Attachment 15 Breakdown_of_Proposed_Estimated_Costs(plusfee) with Attachment 15_REVISED_Breakdown_of_Proposed_Estimated_Costs(plusfee) (5.19.23).

(5) Within the RFP, Update Section 2b TECHNICAL PROPOSAL INSTRUCTIONS as follows:

b. A detailed work plan must be submitted indicating how each aspect of the statement of work is to be accomplished. Your technical approach should be in as much detail as you consider necessary to fully explain your proposed technical approach or method. The technical proposal should reflect a clear understanding of the nature of the work being undertaken. The technical proposal must include information on how the project is to be organized, staffed, and managed.

Information should be provided which will demonstrate your understanding and management of important events or tasks.

Note to Offerors: Beginning May 25, 2008, the offeror shall include the applicable PubMed Central (PMC) or NIH Manuscript Submission reference number when citing publications that arise from its NIH funded research.

See Attachment 7 in SECTION J – LIST OF ATTACHMENTS for Additional Technical Proposal Instructions.

1. Technical Evaluation mailto:samson.shifaraw@nih.gov

Proposals will be technically evaluated in accordance with SECTION M - Evaluation Factors for Award of this solicitation.

(6) Answer the following questions that were received during the period of May 16-26, 2023:

Q: We are interested in Technical Area 1, but we typically only focus on small molecules that are classified as amino acid derivatives. Does this small molecule represent an amino acid or is this unclear now?

A: The small molecule compound referred to in Sample Task Order 1 is not an amino acid or amino acid derivative. Although there is no specific structure or detailed step-by-step synthetic scheme provided in Sample Task Order 1, additional clarifying details have been provided.

Sample Task Order 1 was revised via AMENDMENT 1. See “Attachment 4-Revised SampleTO_Area1(5.18.23)”. Task orders related to amino acid derivatives are expected to be issued under Technical Area 2 (Process Development, Manufacture and Analysis of Synthetic Peptides, Oligonucleotides and Related Drug Substances). It is less likely that task orders issued under Technical Area 1 (Process Development, Manufacture and Analysis of Small Molecule Drug Substances) would be related to amino acid derivatives.

Q: Is this RFP open to viral vector production?

A: Yes. Viral vector production is encompassed by Technical Area 3 (Process Development, Manufacture and Analysis of Biopharmaceutical Drug Substances).

Q: Can you please confirm the following? This RFP is open to viral vector production?

A: Yes. Viral vector production is encompassed by Technical Area 3 (Process Development, Manufacture and Analysis of Biopharmaceutical Drug Substances).

Q: If we submit a bid for vector production, what batch size should we assume? Is there a target genome copy (gc) total? Or, should we submit a bid based on a typical batch size (for example, one 200L GMP run)?

A: With respect to viral vector production under Technical Area 3 (Biologic Drug Substance), we have revised the relevant portions of the Statement of Work to reflect the expected deliverable units / sizes of various modalities (e.g., proteins, cells, gene vectors). [See Attachment 3- REVISED_SOW (6.1.23).] The Technical Evaluation Factors (Section M) provides more details about how the overall response will be evaluated. In brief, the response will be used to assess the offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: Is it a requirement to be able to supply services for every aspect of the RFP or is a “No Bid” section permitted?

A: It is not necessary to bid on all three technical areas. It is entirely acceptable to propose on only one technical area, and that does not put an offeror at a disadvantage. Our expectation is that many vendors specialize in only one or two areas at the most. Each technical area proposed upon is scored on its own merits. We expect to make multiple awards within each technical area so that the Government has a roster of qualified vendors to serve the needs of each technical area. See Attachment 7-Additional Technical Proposal Instructions_5.9.23, and Attachment 12-Additional_Business_Proposal_Instructions_Template_5.11.23 for additional guidance.

Q: Wondering if you have a detailed RFP, meaning the chemistry part of the deliverables for this request. All I saw was the general information in the documents. I am looking for specific product or chemical structures, quantities, qualities, timelines, etc.

A: The more specific technical details are to be found in the Sample Task Orders. One Sample Task Order is provided for each Technical Area, and they are to be found in Attachments 4, 5, and 6. Please note that Sample Task Order 1 was revised via AMENDMENT 1 to the RFP. See “Attachment 4-Revised SampleTO_Area1(5.18.23)”.

Q: Will you be able to share the current process and chemical structure of the molecule?

A: There is no specific compound structure or detailed, step-by-step synthetic scheme, but additional clarifying details are now provided. Please note that Sample Task Order 1 was revised via AMENDMENT 1 to the RFP. See “Attachment 4-Revised SampleTO_Area1(5.18.23)”. The Technical Evaluation Factors (Section M) provide more details about how the overall response will be evaluated. In brief, the response will be used to assess the offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach. The additional clarifying details should help offerors frame their response and provide a basis for estimating key cost elements (e.g., labor, potential process improvements).

Q: What date should the proposal response form be sent in by? There is not a date identified in the document itself.

A: Please provide your intent to submit a proposal via email to the contract specialist at Samson.shifaraw@nih.gov by 3 pm EST on June 9, 2023.

Q: Can we get more specific information about technical area 3? Is it service about biologics (proteins, antibodies) or viral vectors for gene therapy?

A: As noted in the overall Scope and Objectives, product formats under this IDIQ “may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats may be needed. Formats could also include Devices or Combination Products.” With respect to Technical Area 3, this encompasses a range of potential biopharmaceutical drug substances, inclusive of proteins, antibodies, cell-based therapies and viral vectors for gene therapy.

Q: If the RFP is for biologics (antibodies, proteins), can we provide partial services, from stable cell line generation to cell banking?

A: The intent of this RFP is to receive proposals from Offerors that fulfill the comprehensive range of requirements detailed within each Technical Area proposed upon. In cases where an Offeror may not be able to fulfill all requirements using purely internal resources, it is acceptable to propose partnering / subcontracting arrangements that would enable the Offeror to mailto:Samson.shifaraw@nih.gov complement their own internal expertise and capabilities to provide that comprehensive support.

Per the Additional Technical Proposal Instructions (See Attachment 7-Additional Technical Proposal Instructions_5.9.23), “Offerors proposing Subcontracts to perform portions of the Statement of Work should clearly identify the specific tasks for which they plan to utilize subcontractors, as well as the method and level of integration/coordination between the prime Contractor and all proposed Subcontractors, and the expected advantages of such an approach.”

Q: Can the peptide sequence be disclosed? Does the peptide sequence contain any unusual amino acids? Does the peptide require any type of modification, such as cyclization?

A: There is no specific amino acid sequence for the therapeutic candidate noted in Sample Task Order 2, under Technical Area 2 (Synthetic Peptides, Oligonucleotides and Related Drug Substances). The sequence can be assumed to contain no unusual amino acids or required modifications (e.g., cyclization). Generally, Offerors should consider the presence of D-amino acids, common homo-amino acids (addition of a methylene group to the alpha-carbon of an amino acid), and the presence of several hydrophobic amino acids in sequence.

The Sample Task Order within a given Technical Area is meant to serve as an example of the type of requirements that the Government might have in future, specific task orders under the wider umbrella. The Technical Evaluation Factors (Section M) will provide more details about how the overall response will be evaluated. In brief, the response will be used to assess the Offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: Would [an offeror] be allowed to subcontract a DS activity to external vendors rather than execute the activity internally within [offer’s company] when internal capabilities are limited?

A: The intent of this RFP is to receive proposals from Offerors that fulfill the comprehensive range of requirements detailed within each Technical Area proposed upon. In cases where an Offeror may not be able to fulfill all requirements using purely internal resources, it is acceptable to propose partnering / subcontracting arrangements that would enable the Offeror to complement their own internal expertise and capabilities to provide that comprehensive support.

Per the Additional Technical Proposal Instructions (See Attachment 7-Additional Technical Proposal Instructions_5.9.23), “Offerors proposing Subcontracts to perform portions of the Statement of Work should clearly identify the specific tasks for which they plan to utilize subcontractors, as well as the method and level of integration/coordination between the prime Contractor and all proposed Subcontractors, and the expected advantages of such an approach.”

Q: Re: Technical Area 3- The request is somewhat vague in terms of the requirements of the program. Is there currently a specific program request, or is this more of a generalized, high-level bid?

A: As noted in the overall Scope and Objectives, product formats under this IDIQ “may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats may be needed. Formats could also include Devices or Combination Products.” This speaks to the overall breadth of the development portfolio to be supported by this contract.

With respect to Technical Area 3, this encompasses a range of potential biopharmaceutical drug substances of interest, inclusive of proteins, antibodies, cell-based therapies and viral vectors for gene therapy. The Sample Task Order within a given Technical Area is meant to serve as an example of the type of requirements that the Government might have in future, specific task orders under the wider umbrella. Neither the overall response to a given Technical Area nor the response to the related Sample Task Order is meant to contain a highly precise cost estimate directed to a defined molecule / therapeutic candidate per se (e.g., costs of specific raw materials) or to include a fully realized proposed cGMP process.

The Technical Evaluation Factors (Section M) provide details about how the overall response will be evaluated. In brief, the response will be used to assess the Offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: We have the capabilities to support both mammalian and microbial development and manufacturing programs, but the requirements of the two expression systems differ. Should we focus our bid on one or the other? If both, I think we’d be looking at two separate proposals. Is that acceptable?

A: As indicated in Technical Area 3 (Biopharmaceutical Drug Substances), the Government anticipates activities in any of the named areas, including, but not limited to, development of mammalian cells lines and microbial strains. As such, Offerors should provide information for any relevant types of systems with which they have expertise within the single Technical Area response.

The Additional Technical Proposal Instructions (See Attachment 7-Additional Technical Proposal Instructions_5.9.23) provide details as to how an Offeror’s proposal should be structured. In brief, an Offeror should seek to convey the breadth and depth of their capability to support the range of activities noted in the Statement of Work for any Technical Areas proposed upon, in as efficient and succinct a manner as possible within the single response. The Technical Evaluation Factors (Section M) provide details about how the overall response will be evaluated. In brief, the response will be used to assess the Offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: If microbial expression is preferred, should we focus our bid on E. coli, Pichia, or some other microbial expression system?

A: The Government is interested in a range of potential expression systems, as future task orders may be served better by some expression technologies over others. An Offeror should seek to convey the breadth and depth of their capability to support the range of activities noted in the Statement of Work, highlighting the key tools and technologies to which they have access that enable successful performance of said activities.

Q: Should we focus our bid on a mAb? Fc-fusion? Complex recombinant? Molecule type will have a large impact on what the overall bid will look like.

A: Technical Area 3 encompasses a range of potential biopharmaceutical drug substances of interest, inclusive of proteins, antibodies, cell-based therapies and viral vectors for gene therapy. For the purposes of developing the overall Technical Proposal, Offerors should provide information for the breadth of modalities with which they have expertise within the single Technical Area response. The Sample Task Order provides an example of the type of requirements that the Government might have in future, specific task orders under the wider umbrella.

The Technical Evaluation Factors (Section M) provide more details about how the overall response will be evaluated. In brief, the response will be used to assess the Offeror’s understanding of the types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: Article B.2.b includes the following text: The minimum guarantee will be satisfied by the issuance of a task order to each IDIQ awardee. The task order will be issued concurrently with the IDIQ contract and will require a kick-off meeting. Subsequent task orders will be issued in accordance with Article G.3. TASK ORDER PROCEDURE. Question: The RFP does not include a task order for the kick off or other management activities. Is this something the government would like offerors to propose?

A: The Government will issue a Task Order to each awardee in the amount of the minimum guarantee for the kick-off meeting.

Q: “Specifically, the offeror shall describe in its technical proposal the information described below:”

Please confirm that “information described below” is (as applicable) 1) Scientific Premise; 2) Scientific Rigor; 3) Consideration of Relevant Biological Variables, including Sex; and 4) Authentication of Key Biological and/or Chemical Resources.

A: Adherence to ARTICLE H.5. NIH POLICY ON ENHANCING REPRODUCIBILITY THROUGH RIGOR AND TRANSPARENCY is required by all contractors. Please see updated RFP Section 2b TECHNICAL PROPOSAL INSTRUCTIONS, and Attachment 7-Additional Technical Proposal Instructions_5.9.23, for further guidance.

Q: "Subsections 3.A., 3.B., and 3.C. (of Attachment 7) must be complete on their own and include all requested information for that subsection. Subsections may not refer to other subsections for information." Please confirm that the subsections should be complete, but remain within the same Volume document, and not standalone documents.

A: Each Technical Area should be completely addressed within its own section but not as a standalone document.

Q: SOW-Technical Area 2 On Page 6- Oligonucleotides and Related Drug Substances: The Contractor shall perform activities related to the process development, manufacture and analysis of synthetic peptides, oligonucleotides, and related substances >>> Could you please expand or provide clarity on the RELATED SUBSTANCES? What do these include?

A: As noted in the overall Scope and Objectives, product formats under this IDIQ “may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats may be needed. Formats could also include Devices or Combination Products.” In this overall context, “related substances” can be considered to refer broadly to materials such as preliminary formulation components (e.g., nanoparticles, liposomes) or targeting-ligand conjugates other than the discrete oligo / peptide drug substance itself, as well as process impurities, potential genotoxic impurities and starting materials.

Q: SOW: Technical Area 3 on Page 6: Process Development, Manufacture and Analysis of Biopharmaceutical Drug Substances: The Contractor shall perform activities related to the process development, manufacturing and analysis of biopharmaceuticals. >>>> o DRUG SUBSTANCES: This Technical area is limited to (stops at) DRUG SUSTANCES ONLY? Or does this go beyond Drug Substance into the stages of Drug Product-Development, Fill and Finish etc.?

A: The objective of this request for proposals (RFP), “Chemistry, Manufacturing and Controls and Related Services for Development of Drug Substances,” is to obtain support services to ensure receipt of Drug Substances (DS) of sufficient quality and quantity to support preclinical and IND-enabling studies across a range of product formats. The focus of Technical Area 3 is on production activities, including upstream (cell culture expansion, production and harvest) and downstream work. The requirements detailed in each Technical Area define the expected scope of activities necessary to deliver the subject DS.

With respect to drug product development activities, we will be issuing a separate RFP in the coming weeks. That RFP, “Chemistry, Manufacturing and Controls and Related Services for Development of Drug Products,” will encompass later-stage drug product development activities, including fill and finish services, to ensure receipt of formulated Drug Products (DP) of sufficient quality and quantity to support preclinical, IND-enabling and clinical studies. A Pre- Solicitation Notice for this additional RFP is available online at https://sam.gov/opp/52fff54c7b1346a0836bdfb3da6e7f30/view.

Q: BIOPHARMACEUTICCALS-Do these include CELL BASEDTECHNOLOGIES /

THERAPIES?

A: As noted in the overall Scope and Objectives, product formats under this IDIQ “may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats may be needed. Formats could also include Devices or Combination Products.” With respect to Technical Area 3, this encompasses a range of potential biopharmaceutical drug substances, inclusive of proteins, antibodies, viral vectors for gene therapy and cell-based technologies / therapies.

ALL OTHER TERMS AND CONDITIONS REMAIN UNCHANGED.

https://sam.gov/opp/52fff54c7b1346a0836bdfb3da6e7f30/view