Amendment Two 3_22_2022.pdf

RFP-NIAID-75N93022R00004

“PRECLINICAL SERVICES FOR BIOPHARMACEUTICAL PRODUCT DEVELOPMENT”

AMENDMENT No. 2

Amendment Number: Two (2)

Amendment Issue Date: March 22, 2022

Proposal Due Date: April 18, 2022, 3:00PM EST (UNCHANGED)

Issued By:

Tasha Lee Contract Specialist Office of Acquisitions, DEA National Institute of Allergy and Infectious Diseases National Institutes of Health 5601 Fishers Lane

MSC 9821

Rockville, Maryland 20852-9821

Point of Contact:

Tasha Lee, Contract Specialist Email: tasha.lee@nih.gov.

Offerors must acknowledge receipt of the final posting of Amendment #2, on each copy of the proposal submitted. Failure to receive your acknowledgment of this Amendment may result in the rejection of your proposal.

The hour and date specified for receipt of proposals HAS NOT been extended.

PURPOSE OF SOLICITATION AMENDMENT:

The purpose of this amendment is to address questions regarding RFP 75N93022R00004.

Questions Related to Task Area A:

Question 1: Can you please define and elaborate on the activities and goals for ‘Concept Development Plans’?

Answer 1: The Offeror will identify, collect, and analyze relevant information for the COR designated product, necessary to move onto a full project or design with specifications. The plan would enable the COR to determine technical and economic merits and feasibilities, and appropriate activities for development of the product.

Questions Related to Sample Task Order A-01:

Question 2: Sample Task Order A-1 requests the Offeror to assess the current development status, pre-clinical and clinical studies, and assess manufacturing feasibility and regulatory strategy. Will NIAID provide any technical information on which to base these assessments?

mailto:tasha.lee@nih.gov.

Answer 2: Information obtained so far about product components and bench-scale production process mentioned in this sample is provided as the introduction. The Offeror is to identify relevant information for the product specified in the SOW and provide its assessment and make proposals and recommendations to accomplish tasks in the SOW.

Question 3: The Sample Task Order states to assume that information for the composition of each component and the be bench-scale production process is available and will be provided. Will the information be provided for the Sample Task Order in order to assess feasibility?

Answer 3: Information obtained so far about product components and bench-scale production process mentioned in this sample is provided as the introduction. The Offeror is to identify, collect, and analyze relevant information to accomplish tasks in the SOW.

Question 4: The Sample Task Order asks to include ‘proposed efficacy studies’ in the Product Development Plan. Is the request for efficacy studies in animal models or human clinical trials?

Answer 4: Please refer to the Technical Requirement #3 that states “Develop and/or update Pre-clinical and/or Product Development Plans for candidate products. Plans shall include regulatory, pre-clinical, clinical, non-clinical, and manufacturing activities to be undertaken for a product. Both pre-clinical and clinical efficacy models will be considered, analyzed, and proposed.

Questions Related to Sample Task Order B-01:

Question 5: Are the 3 mAbs co-formulated?

Answer 5: This information is an outcome of the solicitated Task Order studies. The Offeror is to make technical assessments and recommendations based on the study results.

Question 6: Can each of the three monoclonal antibodies against α-BoNTA, which binds to botulism neurotoxin A be provided individually for assay validation?

Answer 6: Yes, if available.

Question 7: What is the concentration of the combination product and individually formulated mAbs?

Answer 7: This information is an outcome of the solicitated Task Order studies. The Offeror is

Question 8: How is the product(s) formulated – Liquid vs Lyo?

Answer 8: This information is an outcome of the solicitated Task Order studies. The Offeror is

Question 9: What is the formulation buffer/components? Will the buffer be provided?

Answer 9: This information is an outcome of the solicitated Task Order studies. The Offeror is

Question 10: Are there any specific storage and handling requirements – Freeze thaw, Shaking, etc.? Will stability data be provided on these antibodies?

Answer 10: This information is an outcome of the solicitated Task Order studies. The Offeror is

Question 11: Can botulism neurotoxin A standard be procured commercially or can be procured from NIAID for assay validation? Will stability data be provided on this reagent?

Answer 11: Yes, if available. What mAb to be used will depend on the SOW.

Question 12: Can NIAID provide a list of preferred laboratories specializing and approved for developing this assay?

Answer 12: The Offeror is to identify those laboratories.

Question 13: Will NIAID support payment of fees for licensing the cell line for assay development?

Answer 13: The Offeror will NOT need to pay the licensing fee.

Question 14: Does NIAID expect several batches of the therapeutic candidate be tested on an annual basis? Will this assay be used for conducting long term stability testing?

Answer 14: The assay and service will be completed within the contract term specified in the SOW and the signed contract.

Question 15: Is NIAID’s expectation that the selected laboratory perform future testing after the assay is developed or will expect this laboratory to transfer this assay to NIAID?

Answer 15: The assay and service will be done within the contract term specified in the SOW and the signed contract.

Questions Related to Sample Task Order C-01:

Question 16: In Sample Task Order C-1, what is the isotype of mAb m709.2 – IgG1, IgG2a, etc.?

Answer 16: These are examples. Details of the real products will be specified in the SOW and the provided information package.

Question 17: How much purified mAb m709.2 should be produced for NIAID?

Answer 17: These are examples. Details of the real products will be specified in SOW and the provided information package.

Questions Related to Sample Task Order D-01:

Question 18: In reference to Nuovomycin B or STREPTOMYCES SP K01-0607. Additional guidance from NIAID will help to better understand the manufacturing process and find an appropriate CDMO suitable to perform this work.

Answer 18: This is a hypothetic product. The Offer will propose studies for a real product (with published information or information provided by the Government).

Question 19: (Page 149) NIAID has indicated that the downstream process is performed with six total steps. Is it reasonable to assume the order of downstream processing steps is CEX followed by AEX, concentration of AEX pool followed by HIC and concentration of HIC fractions and finally lyophilization? Can NIAID share more specific information regarding these steps to enable work with the CMOs to get a proposal and corresponding budget?

Answer 19: This is a hypothetic product. The Offer is to propose steps and activities to accomplish tasks in the SOW. Sufficient information of the interested product will be provided (if available) to Offerors to assist proposal generation. Offeror’s proposed steps and activities, particularly for new products with little information or novel procedures will represent its experience and knowledge.

Question 20: (Page 148) In the assumptions it is stated that a previously cGMP lot of products was manufactured at a lower scale. Will NIAID share development reports with the technology transfer package to better understand the process and its scalability?

Answer 20: Sufficient information of the interested product will be provided (if available) to Offerors to assist proposal generation. Offeror’s proposed steps and activities will represent its experience and knowledge.

Question 21: Are there any established CROs for any of the analytical tests or will all assays be transferred and established at the new CMO/CRO(s)?

Answer 21: The Offeror is to identify and/or propose appropriate CRO or actions.

Question 22: (Page 151) A certificate of the Reference Standard with all the testing is shared in Exhibit 1. Can an in-process and drug substance testing plan from the previous cGMP run be shared prior to the award as well?

Answer 22: Sufficient information of the interested product will be provided to Offerors to assist proposal generation.

Questions Related to Task Area E:

Question 23: Technical requirements 1 and 2 refer to a Manufacturing Report as an example of required documentation to be prepared by the contractor. Could NIAID please clarify the specific type of Manufacturing Report or Reports they are referring to and distinguish between a Manufacturing Report and CMC documents prepared according to ICH CTD requirements? Manufacturing Reports (process development reports, batch records, validation studies) are generally used as source documents to prepare the Module 2 and 3 CTD modules.

Answer 23: In the assumption, there is a list of documents/reports that the Government will provide. The Offeror is to identify and/or propose what it needs to accomplish tasks in the SOW.

Offeror’s proposed steps, activities, and reports will represent its experience and knowledge.

Question 24: Technical requirement 7 calls for the submission of all data and information required to support a BLA submission. Please clarify if this requirement covers all BLA modules (1-5). Please clarify if this requirement includes any authoring activities, or if all documents will be provided to the contractor in a format suitable for assembly, publishing, and submission of a BLA?

Answer 24: The Offeror is to identify and/or propose documents, data, and their format data suitable for tasks in the SOW. Offeror’s proposed documents, format, criteria, and discussion on bottlenecks and solutions will represent its experience and knowledge.

Questions Related to Sample Task Order E-01:

Question 25: The title for Sample Task Order refers to a pre-IND submission while the statement of work refers to an IND submission, please clarify what type of submission is the deliverable?

Answer 25: This example mentioned the briefing book for a pre-IND meeting with a regulatory agency that will include materials for IND submission. This example is not for an IND submission.

Question 26: If the Task Order is an IND submission, please confirm that the pre-IND meeting package and meeting minutes will be provided?

Answer 26: See answer above. If it is for an IND submission, in the assumption, there is a list of documents and reports the Government will provide. The Offeror is to propose what documents and their format it needs/requests to accomplish tasks in the SOW. Offeror’s proposed steps, activities, and reports, etc. will represent its experience and knowledge.

Question 27: A general understanding of the overall product development program and the status of planned and completed activities in other areas (preclinical, clinical) is needed to prepare certain CMC sections. For example, the history and manufacturing of batches used in critical preclinical studies should be included in Batch Analysis. Please confirm that adequate documentation across the clinical and preclinical development programs will be provided or made available upon request as needed while preparing the regulatory submission?

Answer 27: In the assumption, there is a list of documents and reports the Government will provide. The Offeror is to propose what documents and their format it needs/requests to accomplish tasks in SOW. Offeror’s proposed steps, activities, and reports, etc. will represent its experience and knowledge.

Question 28: The drug product is planned as a combination of 3 monoclonal antibodies.

Please confirm that the CMC documentation will require preparation of 3 separate Drug Substance sections, one for each monoclonal antibody. Please confirm that the batch records for the drug product include labeling and secondary packaging?

Answer 28: Yes, in the assumption, there is a list of documents and reports the Government will provide for each component unless there are product specific analytical methods that allow analysis of individual product in the mixture. The Offeror is to propose what documents it needs/requests. Offeror’s proposed steps, activities, documents etc. to accomplish tasks in the SOW will represent its experience and knowledge.

Question 29: Additional source documents that may be required to complete a CMC section include analytical testing method and qualification reports, a viral safety assessment report (if applicable), engineering run production and testing records (including stability), batch history, and additional characterization studies. Please confirm that these reports will be provided to the contractor.

Answer 29: The Offeror is to propose what documents it needs/requests to accomplish tasks in the SOW. Offeror’s proposed steps, activities, and documents will represent its experience and knowledge.

Question 30: If the Task Order is for an IND submission, please confirm if both a Module 2 QOS and a Module 3 section should be included as deliverables?

Answer 30: The Offeror is to propose what documents it needs/requests to accomplish tasks in the SOW. Offeror’s proposed steps, activities, and documents will represent its experience and knowledge.

Question 31: Please clarify if the IND preparation should include building, publishing, and validating all documents to be submission-ready via an FDA gateway or if the deliverable consists of hyperlinked and indexed PDF files.

Answer 31: The Offeror is to propose steps, activities and documents to accomplish tasks in the SOW and those will represent its experience and knowledge.

General Questions:

Question 32: Are foreign companies eligible to submit a response to this RFP?

Answer 32: Yes, US and international companies are eligible.

Questions 33: For technical Proposal Overview it is indicated that there would be max 3-pages, but there is no indication for other sections. Are there any limitations/suggestions about length of each Section?

Answer 33: The page limit of the technical proposal for all Task Areas is 125 pages. Refer to Attachment 1, Packaging and Delivery of Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website in the solicitation.

Question 34: If applying for more “Task Areas” there is still only one document (e.g.:

only one Section 1, only one section 2…), but in “Section 3” there are all Tasks Areas described. Is our understanding correct?

Answer 34: Section 3 describes the TECHNICAL PLAN/APPROACH FOR EACH TASK AREA.

Offerors shall provide responses to each task area they wish to bid on and the responses must be broken down by task area. Each individual response to a task area shall be clearly separated in the technical proposal but included in the overall 125-page count maximum.

Question 35: We may have to utilize subcontractors for some of the work within the task areas. Are we still eligible to apply for this task area?

Answer 35: Yes, subcontracting in all task areas is allowed.

Question 36: Technical Plan/Approach for each Task Area. Do we write just our capabilities, or do we also include prices? Or are prices included only in Sample Task Orders?

Answer 36: Please refer to the Business Proposal Instructions (page 91) and Attachment 7

“ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST

ASSUMPTIONS”.

Question 37: Sample Task Order – If we understand correctly this is example of actual RFP. We are in general applying only for working with phages, yet if we understand Task Order A is for phages, but it is for developing a Product Development Plan. Other Task areas are for other biomolecules. Is it possible to prepare “Sample Task Order” for phages also for: Analytical Assay Development and Product Characterization, Process Development and Related Activities, CGMP Manufacture and Related Activities and Regulatory Activities and Documentation?

Answer 37: Samples of task order are hypothetical. Depending on the task areas and products that your company is interested in responding with proposals, please see appropriate technical instructions. Taking phages as an example, describe what your company would do to accomplish task orders in the Task Area A, B, C, D or E for a phage product(s).

Question 38: Attachment 5 Page 37 states "Offerors may propose on any or all tasks and must provide separate technical proposals for each proposed task" however per the table of content the offeror are required to follow (Page 38) Section 3 indicates that Technical Proposal document should consists of all the Task areas that the offeror is submitting for within 1 tech proposal document not multiple tech proposals (i.e one for each Task Area). eCPS portal allows only 1 Tech Proposal document. Can you clarify.

Answer 38: The technical proposal shall contain your responses to all task areas within one document. Each offeror will submit one technical proposal

Question 39: Attachment 7 Page 44 states "Offerors may propose on any or all tasks and must provide separate business proposals for each proposed task". Please confirm for offerors responding to multiple Task Areas/Task orders if they should have a separate Business Proposal for each Task Area/Task Order or otherwise considering eCPS portal permits only 1 attachment for the Business Proposal.

Answer 39: The offeror shall submit one business proposal document which includes business proposal(s) for the task area(s) they wish to bid on. Please clearly separate the task area proposals within the business proposal document.