Amendment__2_FINAL.pdf

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing items 8 and 15, and returning or (c) By separate letter or electronic communication which includes a reference to the solicitation and amendment numbers. 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 or electronic communication, provided each letter or electronic communication makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

E. IMPORTANT: Contractor is not is required to sign this document and return copies to the issuing office.

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The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers is extended. is not extended.

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IT MODIFIES THE CONTRACT/ORDER NUMBER AS DESCRIBED IN ITEM 14.

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Previous edition unusable

Mandie White

The purpose of this amendment is to provide responses to questions received from potential offerors regarding RFP N01CN87006-18. There is no extension to the closing date or time as a result of this amendment.

National Institutes of Health National Cancer Institute Frederick, MD 21701

TO ALL POTENTIAL OFFERORS

N01CN87006-18

1 3

12/19/2018

11/13/2018

Mandie S. White -S Digitally signed by Mandie S.

White -S Date: 2018.12.19 09:44:04 -05'00'

Amendment #2, RFP N01CN87006-18

RFP N01CN87006-18

The following questions were received regarding this RFP and the Government’s response is provided in bold font below each question.

Technical Proposal Questions

1. The initial Task Order “Manufacture of a Vaccine Targeting Frame-Shift Mutations Characteristic of Tumors with Microsatellite Instability” requests 1,500 vials of three co-formulated peptides to cover toxicology, clinical and stability studies. Does it mean that the designs of pre-clinical tox, stability studies and clinical study are known?

No.

Can the NCI share the assumptions underlying the calculation for the requested number of vials? Calculations have not been made. It is assumed that there will be very limited toxicology requirements for a peptide vaccine.

2. The initial Task Order “Manufacture of a Vaccine Targeting Frame-Shift Mutations Characteristic of Tumors with Microsatellite Instability” requests final product to be delivered as sterile solution rather than in lyophilized form.

Most peptides have poor stability when stored in solution, but it is understood that these three peptides have already been used in earlier Phase 1 clinical study. Can NCI share the formulation used in that Phase 1 study? Not available.

If the request for liquid co-formulated peptides is not based on acceptable stability information would it be suitable to propose formulation development, including possibly lyophilized presentation of the final product in our proposal? Yes.

3. Since the candidate has been evaluated in a Phase I clinical study, can NCI share analytical strategy for Drug Substance (DS) and Drug Product (DP) release and stability testing? Not available.

Can the “specifications” for the DS and DP testing be shared? Not available.

In addition, can the analytical test methods be made available to the TO awardee to avoid any redundant method development for DS and DP? Not available.

4. Can NCI provide details on the salt form of the peptide that is expected? Any pharmaceutically acceptable salt can be proposed.

5. Can NCI provide estimates of amount of peptide requirement for next clinical study? No. This will depend on the results of the first study. Different or additional frame-shift peptides may be included in a next generation vaccine.

6. Can NCI provide expected purity requirements of the peptide for DS/DP and for the reference standard, in case those expectations have been established? Purity requirements have not been established. Offerors should propose what they view as attainable and acceptable.

7. Can NCI share stability expectations for the vaccine DP? Will stable DP at storage condition for 24-36months be acceptable? Thirty-six month stability will be acceptable.

8. In general, since this candidate has undergone clinical development, what process development and manufacturing assumptions can NCI provide to align with existing clinical development strategy that may have been already development in the past? None. These details are not available to NCI.

9. Requested stability testing frequency for co-formulated peptides (quarterly over three years) exceed the typical schedule recommended by ICH guidelines. Would reduced frequency of testing of the drug product over the second year (bi-annual) and annual testing afterwards be acceptable for the Initial Task Order? Yes, if adequately justified.

Amendment #2, RFP N01CN87006-18

10. Is it correct to assume that “validated” test methods for stability assessment of formulated product mean “qualified” methods? We noted that the published work related to these peptide products utilizes an adjuvant. Is there an expectation that this adjuvant will be required/procured as a part of the sample task order? If so, is the expectation that the adjuvant will be formulated with the peptides to create the drug product? Well developed, documented and characterized test methods are required. Adjuvant for the peptide antigens will be procured separately and the final vaccine for injection will be prepared at the hospital pharmacy by combining peptides in solution with adjuvant in solution.

11. Peptides are often provided as lyophilized products. Is there an expectation that the drug product be lyophilized?

A lyophilized product is acceptable, but not required (frozen solution can be proposed).

12. The fill requirements for the drug product are 400 ug/ml in 0.7 ml volume. Is this requirement for each peptide in a single vial i.e. total fill volume to be 2.1 ml? Or is this requirement for all three peptides in a single 0.7 ml formulation? All three peptides in a single 0.7 ml formulation.

13. In the initial task order statement of work, has a toxicology study been conducted for the peptide? Is one needed?

Toxicology testing will be handled by NCI in a separate Task Order.

14. Should cost be calculated for all three peptides or just one? All three.

Business Proposal Questions

1. Budgets: The Business Proposal instructions on Page 84 of the RFP (Section L) indicate that subcontractor must submit a complete cost proposal in the same format as the offeror’s cost proposal. Several subcontractors that we have been in communication with will be providing fixed price proposals. Does NCI require a detailed excel budget in the format provided in the RFP (Attachment 12) from subcontractors offering a fixed price proposal budgeted based on commercial market pricing? If fixed-price subcontracts are proposed for commercial items (meeting the definition found in FAR 2.101), information shall be provided to support the proposed price (e.g., data on prices and quantities at which the offeror has previously sold the same or similar items).

If fixed-price subcontracts are proposed for non-commercial items, detailed supporting cost/price information shall be submitted. Additional information on the supporting documentation for proposed cost/price is provided in Section L of the RFP.

2. Task Order #1- Contract Orientation and Kick-Off Meeting (See SECTION J-Attachment 5). Please confirm that you only require a budget in response to this Task Order. The submission for this Task Order should include a Business Proposal cover sheet as well as a detailed budget proposal as described on page 2 of Attachment 5, “Task Order Request for Proposal- TORFP #1”. There is no separate Technical Proposal required for this task order.

Also, please confirm that the budget should include FTE allocations for the two (2) individuals traveling to attend the kick off meeting plus travel related expenses. The budget may include labor/effort for the individuals attending the kick-off meeting and travel related expenses, assuming none of these costs are more appropriately reflected as an indirect cost to the organization.