DHHS-NIH-NIAID-AO-2009029 - RFP Amendment 2.pdf

AMENDMENT OF SOLICITATION / MODIFICATION OF

CONTRACT

1. CONTRACT ID CODE

PAGE OF PAGES

1 1

2. AMENDMENT/MODIFICATION NO.

3. EFFECTIVE DATE

April 27, 2010

4. REQUISITION/PURCHASE REQ. NO

5. PROJECT NO.

(If applicable)

6. ISSUED BY

National Institutes of Health, NIAID, AMOB

CODE

7. ADMINISTERED BY

10401 Fernwood Road, MSC 4813 Bethesda, MD 20817

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP code)

Any Prospective Offeror

9A. AMENDMENT OF SOLICITATION NO.

DHHS-NIH-NIAID-AO-2009029

9B. DATED (SEE ITEM 11)

April 15, 2010

10A. MODIFICATION OF CONTRACT/ORDER NO.

10B. DATED (SEE ITEM 13)

FACILITY CODE

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

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.

Offerors 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 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT 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 telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO. IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation data, etc.) SET

FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, is required to sign this document and return 1 copy to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible)

The purpose for this amendment is to respond to questions posed by Offeror(s). See Page 2 of this amendment

The due date for any offers/proposals submitted in response to this RFP is not extended

All OTHER TERMS AND CONDITIONS OF THE SOLICIATION REMAIN UNCHANGED

The Offeror should review the Federal Business Opportunities website (www.fedbizopps.gov) periodically for any updates to this solicitation

15A. NAME AND TITLE OF SIGNER (Type or print)

16A NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

Terrie Nestor, Contracting Officer

15B. CONTRACTOR/OFFEROR

(Signature of person authorized to sign)

15C. DATE SIGNED

16B. UNITED STATES OF AMERICA

(Signature of person authorized to sign)

16C. DATE SIGNED

NSN 7540-01-152-8070

PREVIOUS EDITION UNUSABLE

30-105

STANDARD FORM 30 (Rev. 10-83) Prescribed by GSA

FAR (48 CFR) 53.243

http://www.fedbizopps.gov/�

DHHS-NIH-NIAID-AO-2009029

Responses to Questions

Q1. Would it be possible to complete the Influenza A production in a stable cell line such as Vero or

MC+DCK cells. Would it also be acceptable to obtain CEF’s from a third party in which to produce the Influenza A.

A1. We anticipate that the majority of influenza A lots will be produced in our qualified Vero cell line. However, there may be strains that do not replicate well in Vero cells and these will need to be produced in eggs. We do not have access to qualified MDCK or CEF cells

Q2. Box 10 of the SF1449 is blank. Please confirm this is an unrestricted RFP.

A2. This requirement is unrestricted Q3. Are there any restrictions which would require the Prime contractor to perform at least 50% or more of the work under this contract?

A3. No

Q4. Would it be possible to harvest materials on one day, and ship the bulk viral material overnight to a foreign subcontractor for filling?

A4. This may be feasible depending on the method. If the contractor chooses to proceed in this manner, they need to be aware of several factors: 1) many of the viruses that we anticipate producing are not highly stable and could lose potency prior to final freezing or during freeze/thaw. The final vialed virus lots would still need to meet the minimum potency requirements as listed in the Statement of Work. 2) R & D expenses to validate/support this method would not be paid by the contract. 3) The contractor would still be expected to meet the time restrictions set forth in the Statement of Work. 4) The contractor would be responsible for obtaining all necessary shipping permits. All associated shipping costs to and from the fill subcontractor would be the responsibility of the contractor.

Q5. Would the process development work be required to be carried out within the 6 month time frame?

A5. There would be some time flexibility for mutually agreed upon development activities. All significant process development activities to be paid by the contract must be pre-approved by the contract officer. It is anticipated that the contractor will conduct their own incidental development activities as part of their normal operating procedures to ensure that the lots they produce will be acceptable as described in the Statement of Work.

Q6. On page 3 of the RFP under Paragraph 1 regarding the Price, the instructions indicate that Contractors must provide a Price for all the line items listed in Attachment 2. The instructions then indicate “[A]ny documentation (information other than cost or pricing data) required to support the Contractor’s prices shall be included within the Contractor’s business proposal submission only.” Does the Government require any supporting documentation?

A6. The Offeror is not required to provide specific supporting documentation with their business proposal, but may be directed by the Contracting Office to provide such documentation at some later point, if needed in order to adequately evaluate the Offeror’s proposed pricing. In this instance, the instructions are primarily to be used as a guide for assembling the Offeror’s proposal.

Q7. On page 4 of the RFP in Paragraph II.A, the RFP states that during a contract year, “the

Government shall request a minimum of two (2) and a maximum of six (6) virus suspensions ….”

During a contract year, if the Government, for whatever reason, requests zero (0) virus suspensions, will Contractors be able to invoice the Government up to the minimum two (2) virus suspensions?

A7. Your assumption is correct.

Q8. Will the Government or sponsor provide indemnification for the contractor with regard to injuries related to the trials which use the material manufactured under this contract to the extent that any injuries are not caused by problems with the manufacturing process and where all Government specifications have been followed?

A8. No

Q9. If the Government requests a fill of 2,500 vials, would it be permissible for the contractor make two fill runs totaling 2,500 vials or do all vials have to be manufactured as part of a single fill lot?

A9. All vials need to be manufactured as a single fill lot.

Q10. Please confirm that the Representations and Certifications can be included in the Business Proposal volume?

A10. The Representations and Certifications are to be included in the Offeror’s Business Proposal

Q11. There are several methods of cryopreservation. Will the Government consider alternate methods rather than what is indicated in the SOW? For example, can the contractor propose lyophilization as an alternate to flash freezing or freeze drying?

A11. Yes, the government will consider alternative methods, but only has experience with flash freezing and storage at -80C. Minimum potency specifications will still need to be achieved.

Q12. For preparing killed viral suspensions, does the Government intend to specify the method or is it up to the Contractor to propose a suitable method? If the Government intends to specify the method, can it be provided now for inclusion in our cost analysis? Please clarify

A12. The government has not requested preparation of killed virus suspensions.

Q13. Is it possible the contractor will be required to manufacture multiple batches of the same virus or multiple batches of the different viruses at the same time? For example: Two batches of Dengue and one batch of Influenza at the same time?

A13. It is very unlikely that the government will request the manufacture of multiple batches of the same virus. It is possible that requests for the manufacture of different viruses will occur at the same time; therefore the Offeror must have the requisite facilities and resources to handle the increased lots. The government would provide prioritization of the projects.

Q14. Does the Government have an anticipated percentage effort for the Program Manager and Project Director?

A14. No

Q15. With reference to Section II.B – page 5: Does the Government want USP sterility testing of seed virus, and will they also supply enough virus vials to perform USP sterility test?

A15. Yes, the government requests sterility testing of the seed virus and will provide enough vials for bacterial sterility and mycoplasma testing.

Q16. With reference to Section III.A.1 - page 6, third paragraph: The instructions indicate the

Government wants the vials to have screw caps and to be flash frozen. Will the Government consider an alternate methodology?

A16. Yes, the government will consider alternative methods, but only has experience with flash freezing and storage at -80C. Minimum potency specifications will still need to be achieved. The government has used gasketed, screw-cap cryovials successfully in the past and acknowledges the contractor’s concerns. The government does not intend to pay the development cost for this or any alternative methodology.

Q17. With reference to Section III.A.1 – page 6, third paragraph and other sections: What is the

Government’s definition of “flash frozen”? There are varying approaches to this. Can the Government provide further details on this requirement?

A17. In general, flash freezing should be completed in 2 – 3 minutes and should be uniform across all vials. In the past, flash freezing was accomplished by placing racks of vials in a pan of liquid nitrogen (preferred) or dry ice/ethanol. Regardless of the method proposed, the Contractor is required to maintain potency of the product during the freezing process.

Q18. With reference to Section III.A.1 – page 6, third paragraph: What is “approximately 2500 vials”?

A18. The government shall consider accepting between 2000 to 2500 vials. No less than 2000 vials containing 0.75 mL would be considered an acceptable delivery.

Q19. a) With reference to Section III.A.1 – page 6, fifth paragraph: Will the Government give the

Contractor a set process to implement (a batch record process)?

b) Has the Government identified a serum free medium good enough to get the yields required under this solicitation? We have usually used serum from acceptable origins to start growth, then removed serum traces later. Would this methodology be acceptable?

A19. a) The government expects that all manufacture and fill will be accomplished through a batch record process. The contractor is responsible for creating the batch record. The batch record will need to be approved by a government representative prior to it implementation.

b) The government maintains its requirement for serum-free manufacture. The Government has successfully used Invitrogen OptiPro SFM (Cat no. 12309019) in the past. The government’s

Vero working cell bank can be cultured directly in this medium without adaptation and virus yields have been excellent.

Q20. With reference to the last paragraph on page 7 of the RFP, the instructions indicate that

“Benzonase should not be detectable in the vaccine preparation administered to humans.” May the contractor use a different nuclease, such as Cyanase or Protamine to remove Vero cell DNA?

A20. The government only has experience in the use of Benzonase, which has been reduced to undetectable levels by microfiltration and diafiltration steps. However, the government would consider alternative nucleases capable of reducing the size and concentration of Vero cell DNA.

Q21. With reference to Section III.C.1 – Page 11: The SOW indicates that qualified cell lines may include the production of Master Cell Banks (200 vials, >107 viable cells/mL), Working Cell Banks (200 vials, >107 viable cells/mL), and End of Production Cell Banks (usually 10 passages beyond Working Cell Bank passage level). Would the Government allow the EPC to be done in research lab instead of a GMP clean room?

A21. Yes, the EPC does not need to be created in a GMP clean room since it is created only for further testing purposes.

Q22. With reference to Section III.D on pages 11-12, the SOW indicates the Contractor may be asked to assist with the “development of improved manufacturing methods designed to: (a) increase vaccine potency (titer); (b) determine optimal day of virus harvest, (c) improve vaccine stability;

and (d) increase vaccine purity by the reduction of undesirable contaminants such as cellular DNA, serum, and animal derived proteins.” Since these are process developments or process improvements, would the Government allow this work to be done in a research lab instead of a GMP clean room?

A22. Yes, these activities can be performed in non-GMP areas.

Q23. The solicitation requires delivery of virus suspensions within six months of the date that a suitable seed virus is made available to the Contractor. How will the Government handle situations if a deadline is not met?

A23. The government expects a good faith effort in meeting the six month deadline. Justifiable delays will be handled on a case-by-case basis. Failed lots and non-acceptance of delayed lots do not serve the government’s purposes; therefore the government is committed to working with the contractor to achieve its goals within a mutually acceptable timeframe.

Q24. Will the Government extend the submission date for the RFP to May 13?

A24. Not at this time

Q25. What is the total page limitation on the Business Proposal section, body and attachments

A25. There is no page limitation on Business Proposals

AMENDMENT OF SOLICITATION / MODIFICATION OF CONTRACT