RFP_Amendment_No_01_(N01TR-17-2001).pdf

“CRO Support for Drug Substance Development and Manufacture”

Amendment of Solicitation No.: RFP N01TR-17-2001

Amendment No.: 01

Amendment date: May 12, 2016

Due Date for Proposals: Tuesday, July 12, 2016 at 3:00 PM EDT (CHANGED)

Issued By:

National Center for Advancing Translational Sciences NINDS R&D Contracts Management Branch NIDA Office of Acquisition National Institutes of Health Neuroscience Center 6001 Executive Boulevard Suite 3287, MSC 9531 Bethesda, Maryland 20892-9531

* For FedEx/UPS/Courier/Hand-Delivery, use Rockville, MD 20852

Primary Point of Contact: Secondary Point of Contact:

Jeffrey Schmidt, Contracting Officer Lisa Bielen, Contracting Officer Phone: (301) 402-1488 Phone: (301) 451-7167 E-Mail: schmidtjr@mail.nih.gov E-Mail: lisa.bielen@nih.gov

NAME AND ADDRESS OF CONTRACTOR: To All Offerors

The above numbered solicitation is amended as set forth below. Offerors must acknowledge receipt of this amendment on each copy of the offer submitted. FAILURE OF YOUR

ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE

RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN

REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by letter, provided each letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

PURPOSE: (1) to change the due date for proposals; and (2) to respond to formal questions submitted in response to the solicitation.

All other terms and conditions of the RFP remain unchanged.

RFP No. N01TR-17-2001 RFP Amendment No. 01

PROPOSAL DUE DATE (CHANGED)

The proposal due date is changed to: Tuesday, July 12, 2016 at 3:00 PM EDT.

RESPONSES TO QUESTIONS

QUESTION 1: In Attachment 4: Sample Task Order Request for Proposals No. 4 – Technical Area 4, it is not clear whether Offerors should assume that a stable cell line for STO4 would be provided or if development of a stable cell line and production of cell banks (development, master, working) should be included in the proposal. What should Offerors assume is the starting material for this Task Order? Please advise.

ANSWER 1: Currently, academic transiently transfected cell line is used. The Offeror shall develop a stable cell line and produce cell banks (development, master, working).

QUESTION 2: Can you confirm that accession cell bank, development cell bank and/or GMP master cell bank production is required under STO 4.

ANSWER 2: Confirmed.

QUESTION 3: Please confirm that plasmid production is required under STO 4.

ANSWER 3: Currently, academic transiently transfected cell line is used. The Offeror shall develop a stable cell line and produce cell banks (development, master, working). Plasmid production may be required at the initial stages of development. However, a stable cell line needs to be generated.

QUESTION 4: Can you please provide the reasons for "Lot A" and "Lot B" to be produced separately and pooled for TFF?

ANSWER 4: Cell culture production was done in two lots due to available reactor capacity.

Purification was done in two streams to minimize resin use through column cycling.

QUESTION 5: Please provide clarification on "propose all CMC activities that should be completed for IND filing." Is the contractor required to provide CMC?

ANSWER 5: The contractor should provide a detailed plan for CMC support that will be completed at contractor’s facilities, including manufacture of BDS and DP to support the project up to Phase I clinical studies. Main requirements are listed in the Sample Task Order.

QUESTION 6: STO 4 specifies the current lab scale manufacturing process of the CHO-S cell line produces 0.5 g per 1 L. Is this the production rate in culture media or does it account for loss after downstream processing?

ANSWER 6: This accounts for loss after downstream processing.

QUESTION 7: In Attachment 4: Sample Task Order Request for Proposals No. 4 – Technical Area 4, for proposal purposes, should Offerors include storage costs for each lot of material to be produced (i.e., non-GMP and GMP drug substance, GMP drug product and reference standard)? If so, for how long?

ANSWER 7: Yes, please include a separate cost of storage of each material for 1 year.

QUESTION 8: In Attachment 4: Sample Task Order Request for Proposals No. 4 – Technical Area 4, for proposal purposes, can the Government provide guidance on the assumptions that Offerors should make regarding duration of the planned stability studies for non-GMP and GMP drug substance, GMP drug product and reference standard?

ANSWER 8: Please provide cost of stability study per each time point. Assume 3 storage conditions for each study. Duration of the study - non-GMP BDS: 24 m; GMP BDS, RS and DP:

48 m.

QUESTION 9: Please clarify the costing format requested for STO 1-4. Attachment 4 specifies NCATS intends to award STO 1 as a fixed price task order. However, details requested in the Contractor’s Response to the TORP and upon completion of the task order, including breakouts of indirect and direct costs, are not in alignment with a fixed price contract. The Cost Template provided in Attachment 11 covers only Cost Reimbursement plus Fixed Fee contract. Similarly, STO 2-4 reference fixed price but request details in alignment with Cost Reimbursement plus Fixed Fee contract.

ANSWER 9: STO 1 is meant to be a fixed price task order. Responses to STO 1 must provide sufficient information to allow the Government to conduct a cost and price analysis and to determine whether proposed costs are fair and reasonable.

STO 2-4 may be either fixed-price or cost-reimbursement; offerors may elect to respond with either a fixed-price proposal or a cost-reimbursement proposal. A cost and price analysis will be conducted on all fixed-price proposals. A cost realism and price analysis will be conducted on all cost-reimbursement proposals. In either instance, Offerors must provide sufficient information to allow the Government to determine whether proposed costs are fair and reasonable.

With respect to STOs 2-4, the Government is attempting to give Offerors the flexibility to choose the cost structure that, in the opinion of the Offeror, best suits the services being requested/provided.

QUESTION 10: Due to the complexity of the RFP, would NIDA consider extending the proposal deadline?

ANSWER 10: Yes, the new deadline for proposals is Tuesday, July 12, 2016 at 3:00 PM EDT.

QUESTION 11: In Attachment 1: Packaging and Delivery of the Proposal, it is not clear if Offerors should deliver 1 original and 10 copies (Technical Proposal) and 1 original and 5 copies (Business Proposal) to NIDA in paper format and CD-ROM or if the Offeror can deliver in either paper or CD-ROM format. Please advise.

ANSWER 11: Offerors must submit one original hardcopy and ten additional hardcopies of the Technical Proposal; and one original hardcopy and five additional hardcopies of the Business Proposal. In addition to the required hardcopies, Offerors have the option to submit electronic copies of their Technical Proposal and Business Proposal via CD-ROM. Though not required, electronic copies of the Technical Proposal and Business Proposal expedite the review.

QUESTION 12: In Sample Task Order Request for Proposals No. 2, the objectives all reference final compound STO2, but the compound structure is labeled as STO1. Should it instead be labeled as STO2?

ANSWER 12: Yes, it should read STO2 and not STO1 on page 108 of the RFP.

QUESTION 13: For STO#2, can you please specify the size of the demo batch you want run?

There is reference to having 25g of material set up as a reference standard and we are assuming that this will come from demo run but will you also need material for tox studies or other purposes?

ANSWER 13: The intent of the demo batch is to demonstrate readiness of the process for further scale up to manufacture the 5 kg GMP lot; generate 25-g qualified reference standard;

generate material for polymorph screen. Demonstration batch will not be used for toxicology. It is the intent to use a single GMP lot of the API for both toxicology and Phase I clinical studies.

The offeror shall propose the size of the demo lot suitable to meet the above objective, based on their best practices.

QUESTION 14: It appears that it is acceptable to do one direct and one total costing table for each sample task order as opposed to costing by activity. This would be a very efficient way to capture everything (a lot less paperwork and modifications) and I just want to confirm that our understanding is indeed correct.

ANSWER 14: Ultimately, how cost information is presented in your proposal is your business decision. The budget submitted needs to provide enough information to allow the Government to determine whether proposed costs are fair and reasonable.

QUESTION 15: Typically a flat monthly fee is used for storage costs. How should we capture this as part of what otherwise appears to be a cost plus model?

ANSWER 15: See Q&A Nos. 14. Note, future task orders can be either fixed price or cost reimbursement. Whether TOs are awarded on a fixed price or cost reimbursement basis will depend on the study.

QUESTION 16: Since STO2 and STO3 do not require DP formulation, might there be a separate solicitation for this work that we could respond to?

ANSWER 16: Yes, my office is planning a Formulation RFP. It will likely be released in late FY16 and result in an FY17 award.

QUESTION 17: For Sample Task Order RFP No. 1—Technical Area 1, should Offerors include costs for a contract initiation/kick-off meeting?

ANSWER 17: No.

QUESTION 18: Is an Offeror required to propose for all three items (STO 2, 3, 4) to be eligible to quote?

ANSWER 18: No. Offerors must propose on Technical Area 1 (STO 1) and must propose on at least one other Technical Area (i.e. Technical Area 2, Technical Area 3, and/or Technical Area

4) and submit respond to the corresponding sample task order (i.e. STO 2, STO 3, and/or STO4).