Amendment 1.pdf

Amendment No. 1 RFP 75N95024R00094

The purpose of this Amendment is to :

1. Update Article H.14 as follows:

ARTICLE H.14. STORAGE FACILITY REQUIREMENTS AND CERTIFICATION

The Contractor shall ensure that all materials generated under this contract for which commercial records storage is required, shall be stored in a facility that meets National Archives and Records Administration (NARA) requirements for safe, secure and certified storage as required by 36 CFR 1228, subpart K.

The Contractor shall provide the Contracting Officer with the name(s) and location(s) of the commercial records storage facility used to store materials under this contract. In addition, the Contractor shall provide a copy of the “Records Storage Certification Statement," found at:

https://www.archives.gov/records-mgmt/storage-standards-toolkit/certification-statement.html self-certifying that the facility being used to store federal records meets established NARA standards. NARA Standards are available at: https://www.govinfo.gov/content/pkg/CFR-2013-title36-vol3/pdf/CFR-2013-title36-vol3-part1234.pdf

Sixty (60) days prior to contract end date, the Contractor shall submit to the Contracting Officer's Representative(COR) and Contracting Officer, an inventory of all materials stored. The disposition of these materials shall be determined no later than the expiration date of the contract.

Additional information about Records Storage Facility Standards can be found at:

http://www.archives.gov/records-mgmt/storage-standards-toolkit/

2. Answer the following questions that were received during the questions period:

Q: The SOW mentions a number of modalities including viral vectors for gene therapy, but none of the STO technical areas mention vectors (only small molecules, peptides, and fusion proteins). Is this RFP open to viral vectors, and is it necessary to bid on all three Technical Areas?

A: It is not necessary to bid on all three Technical Areas. Offerors may propose on one, two, or all three Technical Areas, depending upon their area(s) of expertise.

Viral vector production is encompassed by Technical Area 3 (Process Development, Manufacture and Analysis of Biopharmaceutical Drug Substances). The Sample Task Orders (STOs) are just examples of work / needs that might arise within a given Technical Area, but they are not meant to be comprehensive of all work / needs that might arise.

For the purposes of developing the overall Technical Proposal, Offerors should provide information for the breadth of modalities with which they have expertise within a given Technical Area response.

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 https://www.archives.gov/records-mgmt/storage-standards-toolkit/certification-statement.html http://www.archives.gov/records-mgmt/storage-standards-toolkit/ types of requirements that the Government might have in future task orders, and the overall soundness, feasibility and completeness of the proposed approach.

Q: Attachment 7, Additional Technical Proposal Instructions, Section 2. The numbered listing under this Section goes from 3 to 5. Can you advise if this is just an error in the numbering or if something is missing from the listing?

A: There is an error in the numbering. No additional content is missing.

Q: The SOW section on scope mentions vectors for gene therapy. Can it be clarified which vector type(s) are of interest, and what is the total amount of vector that would be required?

A: Vector types of interest include adeno-associated virus (AAV), lentivirus, and any other emerging viral vectors. As noted in the SOW for Technical Area 3, the Government expects an estimated 1E15 genome copies in a non-GMP lot of drug substance, and 1E16 genome copies in a GMP lot.

Q: The solicitation #75N95023R00020, titled 'Chemistry Manufacturing and Controls and Related Services for Development of Drug Substances,' was awarded in May 2024. What is the purpose of issuing the solicitation now?

A: The purpose of issuing a new solicitation is to exercise “Ramp-On Procedures” which permit the Government to reopen and resolicit for additional vendors if in the Government’s best interest.

Q: If an organization is part of an awardee’s team under RFP #75N95023R00020(as a subcontractor), is the organization ineligible to bid on solicitation #75N95024R00094?

A: An organization awarded as a subcontractor under an award under RFP 75N95023R00020 is eligible to receive an award under RFP 75N95024R00094.

Q: Should the contractor be completing and submitting the NIH forms and questionnaires, or will NIDA look after these?

A: Offerors are required to prepare and submit all documents requested in the RFP in order to ensure that their proposal package is complete and properly responsive. Instructions for submitting the full proposal package are detailed in (See Attachments 1, 7, and 11 for guidance additional information on submission of proposals).

Q: Can a contractor propose to execute work in India or is the RFP limited to USA contractors?

A: The RFP is not limited to organizations in the USA. Note that foreign vendors may be subject to additional Government approvals.

Q: What is the expression system?

A: As indicated in Technical Area 3 (Biopharmaceutical Drug Substances) of the overall Statement of Work (SOW), 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-Ramp-On-TRND 1-Additional Technical Proposal Instructions 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 SOW 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.

In addition, please note that an Offeror’s response to the Sample Task Order in a given Technical Area is not meant to contain a highly precise cost estimate directed to a defined molecule / therapeutic candidate or expression system per se (e.g., costs of specific raw materials) or to include a fully realized proposed cGMP process. Rather, the details of the Sample Task Order should help Offerors frame their response and provide a basis for estimating general cost elements (e.g., labor, overall materials and supplies) and timelines.

Q: Is the PoI mAb fusion protein or Antigen fusion protein or bioactive fusion protein?

A: In the Sample Task Order for Technical Area 3 (Biopharmaceutical Drug Substances), BIOL001 can be assumed to be a bioactive fusion protein (not a mAb or antigen fusion protein).

Q: is the proposal to be made for tech transfer or from cell line development?

A: Depending upon the details of a future, specific Task Order to be issued under this IDIQ, the Offeror may need to develop cell lines de novo or there may be existing materials (e.g., plasmids, cell lines) to be further developed after initial technology transfer activities from a third party (e.g., from the Government or a Government collaborator). As such, Offerors should provide relevant description of their experience under either scheme within the single overall Technical Area response. The Sample Task Order within Technical Area 3 indicates the need to perform initial technology transfer for relevant starting materials and then fully develop a cell line with a suitably scaled process.

Q: Is there a list of specific analytical methods that we must include in the response to the Sample Task Order for Technical Area 3?

A: The Sample Task Order in Technical Area 3 requests that the Offeror “generate SOPs for analytical methods to determine critical quality attributes (CQA) and qualify the methods for release of cGMP DS.” As a list of specific tests is not provided in the Sample Task Order, the Offeror should propose standard compendial (e.g., USP) assays and any molecule-specific, non-compendial assays appropriate for analysis of the exemplar bioactive human fusion protein, BIOL001.

Q: Scale of GMP batch is required as per the expression calculation it can be 200 or 500 L as both costs are very different.

A: The general scale of expected cGMP batches under Technical Area 3 are indicated, depending upon the subject drug substance. Protein products are generally expected to be on the 10 g to 300 g scale; cell therapies are expected at 200 L scale; and gene therapies are expected to deliver 1E16 genome copies at a single 1000 L batch scale or through multiple 200 L batches. The Sample Task Order for Technical Area 3 specifies delivery of 1 kg of cGMP-grade BIOL001 DS.

Q: What are typical process times, upstream and downstream including number of steps?

A: Process times will vary depending upon the complexity of the individual, specific Task Order and subject drug substance. In their response, an Offeror should seek to convey the breadth and depth of their capability to support the range of activities noted in the SOW 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. Within the response to the Sample Task Order, if no specific process times / steps are indicated, it would be appropriate for an Offeror to propose an estimated process time or number of key steps in fulfilling the stated requirements.

Q: What is the clinical phase of the development?

A: These are drug substances typically to be used in preclinical safety studies and phase I clinical trials.

Q: Is the small molecule chiral, if so, how many chiral centers?

A: There is no chiral center for the small molecule indicated in the Sample Task Order.

Q: For the Small Molecule Sample Task Order, how many steps can be considered as the GMP pockets (n through n-3, etc.)?

A: 3 steps in GMP is reasonable.

Q: Are there specified vendors for the small molecule starting material?

A: The Contractor is expected to select vendors to obtain the necessary starting materials.

Q: Is there an existing experimental procedure for the synthesis of SMDC free base?

A: All formal task orders issued under this IDIQ for small molecule development will come with existing procedures. For the Sample Task Order, there is no specific compound structure or detailed, step-by-step synthetic scheme. Please note that an Offeror’s response to the Sample Task Order in a given Technical Area is not 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 more details about how the responses to the Sample Task Orders 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 details of the Sample Task Order should help Offerors frame their response and provide a basis for estimating general cost elements (e.g., labor, overall materials and supplies) and timelines.

Q: Are any impurities known for the small molecule?

A: Only process intermediates are available, and no impurity profile is available.

Q: For stability indicating, is forced degradation of the small molecule required?

A: Yes, forced degradation is required, but impurity identification is not required for the early development.

Q: Is there an expectation to qualify PSD method?

A: No

Q: Will the CTD preferred format be provided?

A: The Contractor is expected to follow ICH guidelines.

Q: Does the “residue solid state properties” mean running the solid-state characterization on the residue after solubility testing?

A: Yes

Q: Please confirm if the duration on the demo batch for SMDC (due in 3 months after TO award) refers to the process development and cGMP manufacturing of just the salt and polymorph step?

A: This refers to the process development and non-GMP demo batch.

Q: Is USP <62> required?

A: No

Q: Will the SMDC reference standard be provided and be accompanied with a CoA?

A: The Contractor shall generate and qualify a reference standard.

Q: For the Peptides Sample Task Order, can we have markers for chirality? Will the markers for related substances be provided?

A: We only can provide API, and the chirality of the API will be demonstrated by chiral amino acid analysis.

Q: For the Peptides Sample Task Order, how many steps can be considered as the GMP pockets (n through n-3, etc.)?

A: If SPPS is used, all steps will be performed under GMP.

Q: Are any impurities known for the peptide drug substance?

A: No impurity profile is available.

Q: For stability indicating, is forced degradation of the peptide required?

A: Yes, forced degradation is required.

Q: For the Peptides Sample Task Order, how is the reference standard expected to be qualified? Will the markers for reference standards and intermediates be provided? Will the reference standard be accompanied with a CoA?

A: Only small quantity of API can be provided (~10-15 mg) as a marker. The reference standard shall be qualified based on appearance, identification, purity, impurity, counter ion, optical purity, etc. A COA shall be provided.

Q: Will the Government grant an extension due to the week prior to submission being a typical 4-day holiday weekend?

A: At this time, we are not prepared to offer any extension. Should that change, we will post an amendment to the RFP.

Q: Attachment 7, page 1 states margins must be no less than ½ inch; however, Attachment 1, II.A.6 states margins must be at least one inch on all sides. What size margin is required?

A: Margins must be no less than ½ inch around, exclusive of headers and footers.

Q: When the Offeror performs an audit for Sample Task Area Two, will the Government be attending the audit?

A: The Government will likely not be present at any audit; however, reserves the right to be present if in the best interests of the Government.

Q: Will the Government please confirm that no stability testing is required or to be proposed for Task Area Three?

A: Stability testing is generally required for biologics being developed under Technical Area 3, but will depend on the specific requirements of any future issued task order. For the purposes of responding to the Sample Task Order for Technical Area 3, stability studies are not required.

Q: Enhancing reproducibility through rigor and transparency (Solicitation page 74) seems to be missing “the information described below:” Will the Government please provide the missing information?

A: Please reference Article H.5, and reference NOT-OD-15-103 located here.

https://grants.nih.gov/grants/guide/notice-files/not-od-15-103.html

Q: Does the Government anticipate the use of select agents during any task orders?

A: The Government does not anticipate the use of select agents during any task orders.

Q: FAR 52.222-41 Service Contract Labor Standards and associated clauses are included in the Solicitation (page 57-58); however, there is no Wage Determination attachment. Will the Government provide the Wage Determination for this opportunity?

A: If service employees are used, a Wage Determination will be incorporated into the contract.

Q: Will the Government provide working links to the www.archives.gov and www.govinfo.gov sites mentioned in Section H.15 Storage Facility Requirements and Certification on page 22 of the Solicitation?

A: Article H.14 is updated to include accurate links. See Section 1 above.

Q: STO-5 Peptides, some tests are missing the method in the specification table. Please provide the missing methods.

A: An HPLC method for purity and impurity shall be developed by the Offeror. Other methods not otherwise specified can be the Offeror’s in-house method or a corresponding compendial (USP) method.

Q: STO-6 Biologics, Section E, Base Task 2, page 4: Produce research cell banks (20 each for the top 3 clones) and identify the best high-producing cell line. For clarity is this a minimum of 20 vials each for each of the 3 clones? (60 vials total?)

A: That is correct.

Q: Will prime contractors be permitted to add new subcontractors at the Task Order level without prior approval?

A: Not without prior approval. While new subcontractors are permitted at the task order level, all subcontractors shall be approved by the Government before they can be issued any task-related work.

Q: Technical Area 1 Small Molecules: Can more detail be provided about the following items for costing and scope:

Synthetic scheme Stoichiometry(s) Yields Volumes Days per stage Safety data Occupational exposure level Dosage Reagent list

A: This is a Sample Task Order, and no specific scheme is available. Since the DS is a new chemical entity, occupational exposure level is unknown, but generally OEB-3 is applicable to all early-stage compounds. An SDS will be provided when the task order is in place. For the Sample Task Order, there is no specific compound structure or detailed, step-by-step synthetic scheme. Please note that an Offeror’s response to the Sample Task Order in a given Technical Area is not 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 more details about how the responses to the Sample Task Orders 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 details of the Sample Task Order should help Offerors frame their response and provide a basis for estimating general cost elements (e.g., labor, overall materials and supplies) and timelines.

Q: Technical Area 3 Biologics: In order to understand the technical challenges typically seen when manufacturing fusion proteins, please provide a description/design of the molecule to aid in assessing the cell line upstream and downstream development plan.

A: Process times will vary depending upon the complexity of the individual, specific Task Order and subject drug substance. In their response, an Offeror should seek to convey the breadth and depth of their capability to support the range of activities noted in the SOW 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. Within the response to the Sample Task Order (Developing BIOL001), if no specific process times / steps are indicated, it would be appropriate for an Offeror to propose an estimated process time or number of key steps in fulfilling the stated requirements.

Q: Technical Area 3 Biologics: To assess titers in transient expression, is there an expected cell line or platform to be used (e.g. cell culture, bacterial, yeast)?

A: As indicated in Technical Area 3 (Biopharmaceutical Drug Substances) of the overall Statement of Work (SOW), 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.

Q: Technical Area 3 Biologics: Can more detail be provided about expected downstream processing for costing and scope (e.g. use of an affinity chromatography step ProA capture)?

A: If Clarification is a part of upstream development, the downstream process shall include, but not be limited to, the following activities: capture chromatography (affinity ligands, cation exchange, etc.), purification chromatography (ion exchange, SEC, RP-HPLC, etc.), virus removal filtration, concentration diafiltration, etc.

Q: Technical Area 3 Biologics: Will thermostability and/or other studies for the molecule in the desired buffer need to be performed?

A: I Formulation buffer design should take into account and assay for amidation, oxidation, sulfation, thermostability, truncation, and any other quality attribute that would have an effect on the functional activity of the molecule.