RFP 11100SOL00020amendment0002.pdf

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 2

LIST OF CHANGES TO THE RFP

SECTION B

1. B.2 CONTRACT LINE ITEM NUMBERS (CLINs)

2. B.3 CONTRACT TYPE

SECTION C

3. C.1 Background

4. C.1 Summary of CLINs

5. C.2 Detailed Description of CLINs (CLIN 0002, 0004, 0005, 0012, 0013, 0014B, 0016, 0017)

6. C.3 Additional Requirements

SECTION F

7. F.2 PLACE AND METHOD OF DELIVERY OF ITEMS UNDER THIS CONTRACT

8. F.5 F.O.B. – DESTINATION, WITHIN CONSIGNEE’S PREMISES APR 1984

SECTION H

9. H.2 SALARY RATE LIMITATION, HHSAR 352.231-70 (January 2010) – DELETED

10. H.14 MANUFACTURING STANDARDS (NOTE: MANUFACTURING STANDARDS IS NOW H.13)

SECTION I

11. I.1.a 52.227-14 (Alternate II added)

12. I.3.g Option to Extend the Term of the Contract (MAR 2000)

SECTION J

13. ATTACHMENT 4 – PAST PERFORMANCE QUESTIONNAIRE

SECTION L

14. L.2.a. PRE-PROPOSAL CONFERENCE

15. L.4.a TECHNICAL PROPOSAL INSTRUCTIONS

SECTION M

16. M.3 TECHNICAL EVALUATION CRITERIA

a. 1. Technical Merit, Methodology and Approach

17. M.6 EVALUATION OF PAST PERFORMANCE

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 3

SECTION B--SUPPLIES OR SERVICES AND PRICES/COSTS

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

The goal of this solicitation is the development and acquisition of Medical Countermeasures (MCMs) for Pandemic Influenza Preparedness and Response. The following specific objectives highlight a comprehensive strategy and commitment by HHS to provide MCMs against pandemic influenza and influenza strains with pandemic potential: Master and working virus seed for production of influenza pre-pandemic and pandemic vaccine product; influenza pre-pandemic and pandemic vaccine production at pilot, clinical and commercial scale; adjuvant production at commercial scale; vaccine and adjuvant storage and stability programs;

formulation, fill, finish of pre-pandemic, pandemic influenza vaccine and adjuvant; international and domestic shipping of vaccine, disposal of vaccine bulk and final container, non-clinical and clinical studies using pre-pandemic and pandemic influenza vaccine;

storage services and stability program for vaccine and adjuvants, (bulk and final containers) from current contracts, when applicable.

B.2. CONTRACT LINE ITEM NUMBERS (CLINs)

The Contractor shall be reimbursed by the Government in an amount not less than a total of $ (minimum) nor more than a total of $ (maximum) if all optional CLINs are exercised.

The prices set forth in this ARTICLE B.2. will cover the contract period from _____________ through _____________.

Upon delivery and acceptance of the item(s) described in SECTION C of this contract and identified in the schedule of charges below, the Government shall pay to the Contractor the unit price(s) set forth below. Contractors shall provide the following items for the manufacturing, testing, packaging, delivery, storage and disposal of influenza MCM products. Items shall be provided according to US licensed influenza vaccine or non-licensed products as applicable:

BASE PERIOD: (Contract Award through thirty six (36) Months)

ITEM ITEM NAME UNIT

MAXIMUM

QUANTITY

UNIT PRICE

TOTAL EXTENDED

PRICE

cGMP Influenza Vaccine Master and Working Seed Lot

LOT 15

Non-GMP Influenza Vaccine: Pilot Lot(s)

LOT 15

cGMP Influenza Vaccine:

Clinical Lot (s)

LOT 15

cGMP Influenza Vaccine:

Bulk Lot(s)

LOT 750

cGMP Adjuvant: Bulk Lot(s)

LOT 25

Storage of Bulk Lot(s) of Vaccine and/or Adjuvant

LOT 50

0007A Storage of Bulk Lots of Vaccine from Prior Contracts

LOT 285

0007B Storage of Bulk Lots of Adjuvant from Prior Contracts

LOT 390

Formulation of Vaccine - Fill single dose vials

SDV 200,000

0009A Formulation of vaccine - Fill syringes or sprayers

PFS/S 1 – 250,000

0009B Formulation of vaccine - Fill syringes or sprayers

PFS/S

250,001 - 100,000,000

0010A Formulation of vaccine - Fill multi-dose vials

MDV 1 – 25,000

0010B Formulation of vaccine - Fill multi-dose vials

MDV

25,001 – 1,000,000

0010C Formulation of vaccine - MDV 1,000,001 -

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 4

Fill multi-dose vials 10,000,000

0011A Formulation of vaccine and adjuvant - Fill syringes

PFS/S 1 – 250,000

0011B Formulation of vaccine and adjuvant - Fill syringes

PFS/S

251,000 -

0012A Formulation of vaccine and adjuvant - Fill multi-dose vials

MDV 1 - 25,000

0012B Formulation of vaccine and adjuvant - Fill multi-dose vials

MDV

0012C and adjuvant - Fill multi-dose vials

MDV

1,000,001 - 10,000,000

Storage and Stability in Final Containers of CLINS 0008-0012

SDV or MDV or

PFS/S

5,000,000

0014A Domestic Shipping of

CLINS 0008-0012

PALLETS 100

0014B International Shipping of

CLINS 0008-0012

PALLETS 100

Disposal of CLINS 0001 – 0005, 0007A, 0007B& 0008 - 0012

PALLETS 25

Influenza Vaccine and/or Adjuvant Animal Test

STUDY 25

Influenza Vaccine and/or Adjuvant Clinical Immunogenicity Test

STUDY

5 studies with 300 people each

Additional Reporting and Inventory Requirements

Report Not separately priced

GRAND TOTAL (BASE PERIOD): $________________________________________

OPTION PERIOD I: (August xx, 2015 through August xx, 2016)

QUANTITY

UNIT

PRICE

TOTAL EXTENDED

PRICE

cGMP Influenza Vaccine Master and Working Seed Lot

LOT 5

Non-GMP Influenza Vaccine: Pilot Lot(s)

LOT 5

cGMP Influenza Vaccine: Clinical Lot (s)

LOT 5

cGMP Influenza Vaccine: Bulk Lot(s)

LOT 150

cGMP Adjuvant: Bulk Lot(s)

LOT 10

Storage of Bulk Lot(s) of Vaccine and/or Adjuvant

LOT 20

0007A Storage of Bulk Lots of Vaccine from Prior Contracts

LOT 285

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 5

0007B Storage of Bulk Lots of Adjuvant from Prior Contracts

LOT 390

Formulation of Vaccine

- Fill single dose vials

SDV 200,000

0009A Formulation of vaccine

- Fill syringes or sprayers

PFS/S 1 – 250,000

0009B Formulation of vaccine

- Fill syringes or sprayers

PFS/S

- Fill multi-dose vials

MDV 1 – 25,000

0010B Formulation of vaccine

- Fill multi-dose vials

MDV 25,001 – 1,000,000

0010C Formulation of vaccine

- Fill multi-dose vials

MDV

0011A and adjuvant - Fill syringes

PFS/S 1 – 250,000

0011B Formulation of vaccine and adjuvant - Fill syringes

PFS/S

and adjuvant - Fill multi-dose vials

MDV 1 - 25,000

0012B Formulation of vaccine and adjuvant - Fill multi-dose vials

MDV

25,001 – 1,000,000

0012C Formulation of vaccine and adjuvant - Fill multi-dose vials

MDV

Final Containers of

CLINS 0008-0012

SDV or MDV or

PFS/S

5,000,000

0014A Domestic Shipping of

CLINS 0008-0012

PALLETS 100

0014B International Shipping of CLINS 0008-0012

PALLETS 100

Disposal of CLINS 0001 – 0005, 0007A, 0007B& 0008 - 0012

PALLETS 25

Influenza Vaccine and/or Adjuvant Animal Test

STUDY 5

Influenza Vaccine and/or Adjuvant Clinical Immunogenicity Test

STUDY

2 studies with 300 people each

Additional Reporting and Inventory Requirements

Report Not separately priced

GRAND TOTAL (OPTION PERIOD I): $________________________________________

OPTION PERIOD II: (August xx, 2016 through August xx, 2017)

QUANTITY

UNIT PRICE

TOTAL EXTENDED

PRICE

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 6 cGMP Influenza Vaccine Master and Working Seed Lot

LOT 5

Non-GMP Influenza Vaccine: Pilot Lot(s)

LOT 5

cGMP Influenza Vaccine:

Clinical Lot (s)

LOT 5

cGMP Influenza Vaccine:

Bulk Lot(s)

LOT 150

cGMP Adjuvant: Bulk Lot(s)

LOT 10

Storage of Bulk Lot(s) of Vaccine and/or Adjuvant

LOT 20

0007A Storage of Bulk Lots of Vaccine from Prior Contracts

LOT 285

0007B Storage of Bulk Lots of Adjuvant from Prior Contracts

LOT 390

Formulation of Vaccine - Fill single dose vials

SDV 200,000

0009A Formulation of vaccine - Fill syringes or sprayers

PFS/S 1 – 250,000

0009B Formulation of vaccine - Fill syringes or sprayers

PFS/S

Fill multi-dose vials

MDV 1 – 25,000

0010B Formulation of vaccine - Fill multi-dose vials

MDV

0010C

Fill multi-dose vials

MDV

0011A and adjuvant - Fill syringes

PFS/S 1 – 250,000

0011B Formulation of vaccine and adjuvant - Fill syringes

PFS/S

and adjuvant - Fill multi-dose vials

MDV 1 - 25,000

0012B Formulation of vaccine and adjuvant - Fill multi-dose vials

MDV

0012C and adjuvant - Fill multi-dose vials

MDV

Final Containers of CLINS 0008-0012

SDV or MDV or

PFS/S

5,000,000

0014A Domestic Shipping of

CLINS 0008-0012

PALLETS 100

0014B International Shipping of

CLINS 0008-0012

PALLETS 100

Disposal of CLINS 0001 – 0005, 0007A, 0007B& 0008 - 0012

PALLETS 25

Influenza Vaccine and/or Adjuvant Animal Test

STUDY 25

0017 Influenza Vaccine and/or STUDY 2 studies with

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 7

Adjuvant Clinical Immunogenicity Test

300 people each

Additional Reporting and Inventory Requirements

Report Not separately priced

GRAND TOTAL (OPTION PERIOD II): $____________________________________

TOTAL CONTRACT VALUE (BASE AND ALL OPTION PERIODS): $____________________________________

B.3. CONTRACT TYPE

This is an indefinite-delivery, indefinite-quantity (IDIQ) contract for the acquisition of MCMs for pandemic Influenza preparedness and response. During the ordering period of the contract, authorized officials assigned to the contract may order, and the Offeror shall provide, supplies and services at the unit prices listed above.

1. Delivery Order and Task Order Type

Delivery orders and task orders issued under this contract will be firm-fixed price. Ordering instructions can be found in Section H.18.

2. Minimum and Maximum Quantity

The minimum ordering limitation and Government guarantee under this contract is one (1) lot of CLIN 0001 at a total value of $____________.

The estimated maximum ordering limitation under this contract is __________ at a total value of

B.4. ADVANCE UNDERSTANDINGS:

Invoicing for these CLINS shall be done at a minimum on a quarterly basis and no greater than on a monthly basis.

The offeror will be responsible for maintaining Government Property (GP) in accordance with FAR 52.245-1. The products purchased, shipped and stored under this contract are considered GP and should be appropriately stored, labeled and inventoried. As defined in FAR 45.101 and 52.245.-1 ,“Contractor-acquired property” means property acquired, fabricated, or otherwise provided by the contractor for performing a contract and to which the Government has title.

“Government property” means all property owned or leased by the Government. Government property includes both Government-furnished property and contractor-acquired property. Government property includes material, equipment, special tooling, special test equipment, and real property. Government property does not include intellectual property and software.

B.5. MULTIPLE AWARD ORDERING:

Under Indefinite Quantity clause, orders will be issued to all contractors awarded a contract under this solicitation. All contractors may receive orders for CLINs 0001 up to the minimum guaranteed amount. Additional quantities may be ordered upon the Government’s need and contractor’s ability to produce the requirement. The Government reserves the right to make multiple awards.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 8

SECTION C – STATEMENT OF WORK

C.1. STATEMENT OF WORK

Background

Human influenza pandemics continue to be a public health concern. Four human influenza pandemics have occurred in the past century. We have recently completed the preparation and response to the 2009 H1N1 pandemic influenza virus which fortunately produced only mild illness and had low transmissibility. The mortality of a future severe influenza pandemic has been estimated at over 60 million deaths worldwide. At this time it is uncertain which influenza virus variant will cause the next pandemic.

Pillar One of the National Strategy for Pandemic Influenza (2005) describes the activities to be undertaken before a pandemic to ensure preparedness. The strategy seeks to “establish domestic production capacity and stockpile of countermeasures to ensure sufficient vaccine to vaccinate front-line personnel and at-risk populations”. In the Implementation Plan for the National Strategy for Pandemic Influenza (2006) two primary goals are set“(1) establishment and maintenance of stockpiles of pre-pandemic vaccine adequate to immunize 20 million persons against influenza strains that present a pandemic threat; and (2) expansion of domestic influenza manufacturing surge capacity for the production of pandemic vaccines for the entire domestic population within 6 months of a pandemic declaration”. To accomplish these goals, the Federal Government expanded stockpiles of influenza countermeasures, as well as domestic vaccine manufacturing capacity. In addition substantial new investments were made in the advanced development of cell-culture-based influenza vaccine candidates, with a goal of establishing the domestic surge vaccine production capacity to meet the pre-pandemic stockpile and post-pandemic vaccine production goals.

On December 2009 Secretary Sibelius called for the Public Health Medical Countermeasure Enterprise Review which was issued in August 2010 and stated “The ultimate goal of this review is a modernized countermeasure production process where we have more promising discoveries, more advanced development, more robust manufacturing, better stockpiling, and more advanced distribution practices. In other words, we want to create a system that can respond to any threat at any time.”

The 2009 H1N1 influenza pandemic demonstrated the criticality of having active contracts with manufacturers to respond to an influenza pandemic event; in 2009 the Federal Government rapidly modified the existing stockpile contracts and issued task orders to manufacturers for producing millions of doses of H1N1 influenza vaccine.

The competition will be open to companies that currently produce inactivated, recombinant and LAIV, seasonal, pre-pandemic and pandemic influenza vaccine at commercial scale. The Offeror needs to demonstrate a successful experience in the manufacturing of influenza vaccines at commercial scale, have completed (final Clinical Study Report) Phase 3 clinical studies for influenza vaccines and have a documented BLA in preparation for an influenza vaccine.

The Contractor shall provide the following items and/or services:

Master and working virus seed for production of influenza pre-pandemic and pandemic vaccine product; production at small scale, clinical and commercial scale influenza pre-pandemic and pandemic vaccine; adjuvant production at commercial scale; vaccine and adjuvant storage and stability studies; formulation, fill, finish of pre-pandemic, pandemic influenza vaccine and adjuvant; international and domestic shipping of vaccine, disposal of vaccine bulk and final container; non-clinical and clinical studies using pre-pandemic and pandemic influenza vaccine; storage services and stability program for vaccine and adjuvants, (bulk and final containers) from current expiring contracts. Contractors without adjuvant programs will not be required to provide.CLIN 0005, 0007B, 0011 and 0012.

Scope of Work:

Independently and not as an agent of the US Government (USG), the Contractor shall furnish all the necessary services, qualified personnel, materials, supplies, equipment and facilities not otherwise provided by the USG as needed to perform the work described below.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 9

The Contractor shall provide Medical Countermeasures (MCMs) for Pandemic Influenza Preparedness and Response or as required in response to a HHS designated Public Health Emergency. The contractor shall produce vaccines against influenza and influenza strains with pandemic potential; shall demonstrate a successful experience in the manufacturing of influenza vaccine by:

Holding a US influenza vaccine license OR Have developed an influenza vaccine as evidenced by a final clinical study report from a Phase 3 clinical study conducted under a FDA Investigational New Drug application sponsored by the Offeror..

Summary of CLINs It is mandatory for offerors to respond to all CLINs except for the following:

Offerorors without adjuvant programs will not be required to provide CLIN 0005, 0007B, 0011 and 0012.

Offerors without prior contracts for stockpiling vaccine and adjuvants will not be required to provide CLINs 0007A and 0007B.

Offerors with products that are not suitable for a specific filling presentation and who do not respond to a filling

CLIN should provide supporting information to justify the lack of response to the CLIN.

As directed by HHS, the Contractor shall provide inactivated, live attenuated or recombinant technology produced vaccine bulk product for influenza viruses as follows:

Master and working virus seeds for production of influenza vaccine product;

CLIN 0001: cGMP Influenza Vaccine Master and Working Seed Lot

Small scale pilot, clinical and commercial lots of vaccines and/or adjuvants;

CLIN 0002: Non-GMP Influenza Vaccine: Pilot Lot(s) CLIN 0003: cGMP Influenza Vaccine: Clinical Lot (s) CLIN 0004: cGMP Influenza Vaccine: Bulk Lot(s) CLIN 0005: cGMP Adjuvant: Bulk Lot(s)

Storage and Stability of Bulk Product from these CLINs and prior contracts.

CLIN 0006: Storage of Bulk Lot(s) of Vaccine and/or Adjuvant CLIN 0007A and 0007B: Storage of Bulk Lots of Vaccine and/or Adjuvant from Prior Contracts

Formulation, filling and packaging in a variety of final containers (nasal-sprayers, multi-dose vials, syringes, non-adjuvanted and adjuvanted formulations).

CLINs 0008-0012: Formulation and Filling of Influenza Vaccine and/or Adjuvant in a Variety of

Final Containers.

Storage and stability of product in the final container.

CLIN 0013: Storage and Stability in Final Containers of CLINS 0008-0012 International shipping of bulk vaccine and adjuvant and final container.

CLIN 0014A and CLIN 0014B: International and Domestic Shipping of CLINS 0008-0012 Disposal of bulk vaccine, adjuvant and final container

CLIN 0015: Disposal Pre-clinical and clinical evaluation of products.

CLIN 0016: Influenza Vaccine Animal Test CLIN 0017: Influenza Vaccine Clinical Test

Reporting and inventory CLIN 0018: Reporting and Inventory Requirements

C.2. Detailed Description of CLINs:

CLIN 0001: cGMP Influenza Vaccine Optimized Master and Working Seed Lot Under Item 0001, the Contractor shall provide optimized master and working seed lots for inactivated, live attenuated or recombinant influenza vaccine product suitable for efficient commercial scale manufacturing of vaccine. The seeds lots for influenza vaccine product shall be manufactured using the same facilities, systems, equipment, processes and testing as those used for the FDA-licensed influenza vaccine or as described in the BLA in preparation. The influenza vaccine seed lot shall be produced using a qualified virus reference strain as designated by HHS.

The Contractor shall, as specified in the note above:

Manufacture the seed lot from the influenza virus vaccine candidate specified by HHS. Manufacture the seed lot at commercial scale in commercial manufacturing facilities described and referenced for this activity in the FDA license or in-process BLA according to current Good Manufacturing Practices (cGMP) under 21 CFR parts 210, 211, and 600, as applicable, and store at appropriate conditions.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 10

Use a validated, commercial-scale production process for influenza vaccine to manufacture the seed lots.

Where applicable use processes detailed in the licensed vaccine manufacture. For un-licensed vaccine products, use processes described in the in-process BLA.

Provide lot release product testing of the influenza seed lot (using lot release specifications similar to those of the FDA-licensed influenza product, or the in-process BLA filing). Submit seed samples to the FDA for testing and approval for use in vaccine production.

Store seed lots according to FDA cGMP guidelines.

CLIN 0002: Non-GMP Influenza Vaccine: Pilot Lot(s) Under Item 0002, the Contractor shall provide an influenza vaccine non GMP pilot lot.

The Contractor shall:

The size of the pilot lot will be defined by the Contractor as specified in their proposal.

Provide all data derived from process yield improvement efforts.

Make available batch records for review by HHS Provide Certificates of Analysis for the manufactured lot.

Execute a stability program for thirty six (36) months. Stability testing shall be performed applying FDA cGMP guidelines. Provide the study plan, interim results and final report to HHS.

Prepare purified influenza immunogen for antisera reagent preparation. Prepare materials for antigen reference standard(s). This activity will be requested by HHS if needed and coordinated with CBER.

CLIN 0003: cGMP Influenza Vaccine: Clinical Lot (s) Under Item 0003, the Contractor shall provide influenza vaccine clinical lot.

The Contractor shall:

The size of the clinical lot will be defined by the Contractor as specified in their proposal.

Manufacture the clinical vaccine lot in manufacturing facilities according to current Good Manufacturing

Practices (cGMP) under 21 CFR parts 210, 211, and 600.

Use a validated and licensed, or BLA document in preparation, production methods for influenza vaccine manufacture.

Perform lot release product testing of the influenza vaccine including potency using lot release specifications similar to those of the FDA-licensed influenza vaccine product or described in the BLA document in preparation. Provide results to HHS.

Make batch records available for review by HHS.

Provide Certificates of Analysis for the manufactured clinical lots to HHS.

Provide a master stability program for thirtysix (36) months to HHS. Stability testing shall be performed applying FDA cGMP guidelines and in accordance with the stability requirements that apply to FDA-licensed trivalent influenza vaccine product, if applicable.

Execute a master stability program for thirtysix (36) months and provide interim and final results to HHS.

Prepare Prepare purified influenza immunogen for antisera reagent preparation. Prepare materials for antigen reference standard(s). This activity will be requested by HHS if needed and coordinated with CBER.

CLIN 0004: cGMP Influenza Vaccine: Bulk Lot(s) Under Item 0004, the Contractor shall provide influenza vaccine bulk product from viruses with pre-pandemic and pandemic potential suitable for formulation and filling.

The unit for this item will be bulk lot(s) of influenza vaccine product.

The size of a lot will be defined by the manufacturers (number of eggs, bioreactor size in liters, etcetera) as described in their proposal.

The bulk lot of influenza vaccine shall be manufactured, if applicable, using the same facilities, systems, equipment, processes and testing as those used for the FDA-licensed influenza vaccine or the in-process BLA. The influenza vaccine shall be produced using a qualified virus reference strain designated by HHS.

The Contractor shall:

Manufacture the bulk vaccine product at commercial scale in (FDA-licensed or in-process BLA documented) manufacturing facilities, when such production does not interfere with inter-pandemic influenza vaccine manufacturing, or when required by HHS.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 11

Manufacture the bulk vaccine product according to current Good Manufacturing Practices (cGMP) under 21 CFR parts 210, 211, and 600, as applicable, and store at appropriate conditions during lot release testing and prior to formulation.

Use a validated and licensed (or in-process BLA documented) commercial-scale production process for influenza vaccine to manufacture monovalent influenza bulk vaccine.

Conduct lot release product testing of the influenza bulk vaccine. Provide results to HHS.

Make batch records available for review by HHS.

Provide Certificates of Analysis for the manufactured lots to HHS.

Provide a master stability program for thirtysix (36) months to HHS. Ensure that sufficient samples are included to extend the stability program up to sixty(60) months.

Execute stability testing of vaccine complying with FDA cGMP guidelines and in accordance with the stability requirements that apply to FDA-licensed influenza vaccine product, if applicable. Report interim data and results to HHS.

Prepare purified influenza immunogen for antisera reagent preparation. Prepare materials for antigen reference standard(s). This activity will be requested by HHS if needed and coordinated with CBER.

CLIN 0005: cGMP Adjuvant: Bulk Lot(s) Under Item 0005, the Contractor shall provide an adjuvant bulk product suitable for formulation and filling. The unit for this item will be bulk lot(s) of adjuvant product.

The size of a lot will be defined by the manufacturers (lot size in e.g. liters) as described in their proposal and accepted by the HHS.

The Contractor shall:

Manufacture the bulk adjuvant product at commercial scale according to current Good Manufacturing Practices (cGMP) under 21 CFR parts 210, 211, and 600, as applicable, and store at appropriate conditions during lot release testing.

Execute lot release product testing of bulk adjuvant. Provide final report to HHS.

Make available batch records for review by HHS.

Provide Certificates of Analysis for the manufactured lots to HHS.

Provide a master stability program for thirtysix (36) months to HHS. Ensure that sufficient samples are included to extend the stability program up to sixty(60) months.

Execute stability testing of adjuvant compliant FDA cGMP guidelines. Report interim data and results to HHS.

CLIN 0006: Storage of Bulk Lot(s) of Vaccine and/or Adjuvant Under Item 0006, the Contractor shall provide cGMP controlled storage for all manufactured lots for sixty (60) months at the Contractor site or at a designated facility approved by HHS.

The Contractor shall perform storage using cGMP facilities.

The unit for this item will be storage of bulk lot(s) of vaccine or adjuvant product / month.

The Contractor shall:

Store vaccine and adjuvant lots in (FDA-licensed) storage facilities. Storage shall be physically segregated from other products and product will be identified as USG property.

Store vaccine and adjuvant at the Contractor site or at a designated facility approved by HHS applying FDA cGMP guidelines and in accordance with the storage requirements that apply to FDA-licensed influenza vaccine product, if applicable.

The government reserves the right to review the security system in place and request updates as needed.

The Contractor is responsible for all costs (including replacement of lost materials) associated with their discretionary movement of the materials storage site.

The Contractor shall request USG approval of discretionary movement of materials and storage sites.

CLIN 0007A and 0007B: Storage of Bulk Lots of Vaccine and/or Adjuvant from Prior Contracts Under Item 0007A and 0007B, The Contractor shall provide cGMP controlled storage for sixty (60) months at the Contractor site or at a designated facility approved by HHS.

Contractors who receive awards and may be currently storing vaccine or adjuvant. The unit for this item will be storage of lot(s) of vaccine or adjuvant product / month.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 12

The government reserves the right to review the security system in place and request updates as needed.

The Contractor shall:

Transfer storage of pre-pandemic influenza bulk vaccine and bulk adjuvant produced under previous contracts to the present Item (CLIN 0007A or 0007B) at the expiration of previous contracts.

Perform storage using cGMP facilities with equivalent systems, equipment, and processes, as those used for the FDA-licensed product or as documented in the in-process BLA.

Obtain HHS concurrence on selection of the storage facility.

Store vaccine and/or adjuvant lots in FDA-licensed storage facilities.

Storage shall be physically segregated from other products.

Continue stability testing of stored bulk for sixty (60) months.

CLINs 0008-0012: Formulation and Filling of Influenza Vaccine and/or Adjuvant in a Variety of Final Containers.

When executing CLINS 0008-0012, the contractor shall:

Perform formulation and filling activities in compliance with FDA cGMP guidelines and license (or in-process BLA documentation).

Affix labels onto filled final containers with FDA-approved text for a similar product such as licensed influenza vaccine. The label for filled vials shall adhere to BARDA specifications and may include barcodes or radio frequency identification tags on primary containers and/or secondary packages for product identification, serialization, lot number and expiration dating in accordance with FDA and GS1 / ISO standards.

Package filled and labeled final containers into FDA approvable containers.

Execute lot release product testing of the influenza vaccine final container using lot release specifications similar to those of the FDA-license influenza vaccine product. Provide a final report to HHS.

CLIN 0008: Formulate vaccine at the approved concentration designated by the HHS. Fill single dose vials with formulated vaccine product at the volume designated by the HHS. Note the additional requirements of CLINs 0008-0012 above.

CLIN 0009: Formulate vaccine at the approved concentration designated by the HHS. Fill syringes or sprayers with formulated vaccine product at the volume designated by the HHS. Note the additional requirements of CLINs 0008-0012 above.

CLIN 0010: Formulate vaccine at the approved concentration designated by the HHS. Fill multi-dose vials with formulated vaccine product at a volume to be designated by HHS. Note the additional requirements of CLINs 0008-0012 above.

CLIN 0011: Formulate vaccine and adjuvant at the approved concentration designated by HHS. Fill syringes with formulated adjuvanted vaccine product with a volume to be designated by HHS. Note the additional requirements of CLINs 0008-0012 above.

CLIN 0012: Formulate vaccine and adjuvant at the approved concentration designated by HHS. Fill multi-dose vials with formulated adjuvanted vaccine product at a volume designated by HHS. If vaccine and adjuvant are filled separately in multi dose-vials use CLIN 0010 for purpose of providing costs. Note the additional requirements of CLINs 0008-0012 above.

CLIN 0013: Storage and Stability in Final Containers of CLINS 0008-0012.

Under Item 0013, the Contractor shall provide cGMP controlled storage and stability program for final containers (CLINs 0008, 0009, 0010, 0011 and 0012) for up to thirty six (36) months at the Contractor site or at a designated facility approved by HHS.

The unit for this item will be storage of final container(s) of vaccine or adjuvant product / month.

The Contractor shall perform storage using the cGMP facilities, systems, equipment, and processes, as those used for the product release for FDA-licensed influenza vaccine.

The Contractor shall:

Store the final containers in an FDA approved storage facilities. Storage shall be physically segregated from other products.

RFP No. 11-100-SOL-00020 - Acquisition of MCMs for Pandemic Influenza Preparedness and Response 13

Store final containers up to thirty six (36) months at the Contractor site or at a designated facility approved by HHS applying FDA cGMP guidelines and in accordance with the storage requirements that apply to FDA-licensed influenza vaccine product.

The government reserves the right to review the security system in place and request updates as needed.

The contractor shall define storage density for each product and provide details to HHS for concurrence.

Execute stability testing of final containers under this program. Stability testing shall be performed applying

FDA cGMP guidelines and in accordance with the stability requirements that apply to ICH guidelines / FDA-licensed influenza vaccine product.

CLIN 0014A: Domestic Shipping of CLINS 0008-0012 Under CLIN 0014, the Contractor will transport final containers under CLINs 0008-0012 to countries designated by HHS.

As noted in Section C.3., CLIN 0014 does not apply to material produced internationally and imported into a US storage facility.

The unit for this item will be pallet(s).

The Contractor shall:

Package, store, handle and ship CLINs 0008-0012 from their site or temporary storage site to a final destination.

Include all cost and expenses for transit, delivery and insurance of product.

Be responsible for delivering material in a condition fit for its intended use (e.g. cold chain handling).

Address all applicable permitting and regulations.

Propose costs for shipment of 10 pallets to Chicago Propose costs for shipment of 10 pallets to Seattle Propose costs for shipment of 10 pallets to Pittsburgh

CLIN 0014B: International Shipping of CLINS 0008-0012 Under CLIN 0014, the Contractor will transport final containers under CLINs 0008-0012 to countries designated by HHS.

As noted in Section C.3., CLIN 0014 does not apply to material produced internationally and imported into a US storage facility.

The unit for this item will be pallet(s).

The Contractor shall:

Package, store, handle and ship CLINs 0008-0012 from their site or temporary storage site to a final destination.

Include all cost and expenses for transit, delivery and insurance of product.

Be responsible for delivering material in a condition fit for its intended use (e.g. cold chain handling).

Address all applicable import/export permitting and regulations.

Propose costs for shipment of 10 pallets to Bangladesh-Dhaka Propose costs for shipment of 10 pallets to El Salvador-San Salvador Propose costs for shipment of 10 pallets to Nigeria- Lagos

CLIN 0015: Disposal Under CLIN 15, the Contractor will dispose of all products from CLINs 0001-0005, 0007 (A & B), and CLINs 0008-0012 as directed by the USG.

The Contractor shall:

Dispose of product following any federal, state regulation for the appropriate waste category; hazardous waste (e.g. thimerosal-containing vaccines), regulated medical waste (e.g. LAIV), solid waste (e.g. non thimerosal-containing vaccine, non LAIV).

Provide documentation and reports on the performed and completed disposal activity

CLIN 0016: Influenza Vaccine and/or Adjuvant Animal Testing Under Item 0016, the Contractor shall perform animal studies using the vaccine and/or adjuvant:

Animal studies of influenza vaccine and/or adjuvant may be requested to monitor safety,stability and immunogenicity.

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The protocol will be provided by HHS. For example: An immunogenicity study to be conducted using 80 mice, divided in 4 groups. Each group will receive two IM vaccinations with vaccine and/or adjuvant at different dosages, with three blood collections (Day 0, 21 and 35) Serology testing will include hemagglutination inhibition assay (HAI) and microneutralization assay Alternative animal models will be considered on a case-by-case, scientific merit basis.

CLIN 0017: Influenza Vaccine and/or Adjuvant Clinical Testing Under Item 0017, the Contractor shall perform clinical studies to assess immunogenicity, safety and/or dose-range of manufactured vaccines and/or adjuvant.

The protocol will be provided by HHS prior to execution of the Delivery Order. For example: A US- based dose ranging study to evaluate the immunogenicity and safety of the influenza vaccine product in adults, elderly or children. Five 60 subject arms, receiving two doses of vaccine and/or adjuvant at concentrations to be determined by HHS, and a placebo/active comparator arm; three bleedings (one pre and two post-vaccinations), six-month follow up. Serology testing will include hemagglutination inhibition assay (HAI) and microneutralization assay (MN).

CLIN 0018: Additional Reporting and Inventory Requirements Under Item 0018, the Contractor shall submit inventory reports, monthly progress reports, executive summaries, ad hoc reports of urgent developments related to this program and a final report as described in detail in the Reporting requirements and Deliverables. Release protocols and reports shall be also provided to HHS after each manufacturing campaign.

C.3. Additional Requirements

The complete Phase 3 clinical study report for a study conducted under a US IND sponsored by the Offeror must be ready for submission to the FDA with no modifications.

It is the preference of HHS that the Contractor manufacture bulk vaccines and bulk adjuvant in the US. Bulk manufacturing facilities shall be in compliance with biosafety level biocontainment procedures. All lots will be evaluated for acceptance by HHS.

When a Contractor manufacturers outside the US, the bulk vaccine, adjuvant and filled containers shall be shipped to the US as soon as the lots are released. Shipment of the vaccine or adjuvant to the US shall be coordinated with HHS and other offices/agencies involved in importation of vaccines. Importation of bulk vaccine and adjuvant into the US requires testing which should be performed according to applicable federal guidelines (FDA, USDA, CDC and etcetera). The Contractor shall bear all costs for shipping and testing required for import into the US. The Unit process under CLINs 0001-0018 shall not include any costs related to shipping and testing required for import into the US resulting from manufacture outside of the US.

The contractor, using a FDA approved cGMP compliant storage site, shall receive approval by HHS for the location and terms of the storage contract prior to execution of the contract.

Formulation, fill-finish activities of vaccine and adjuvant shall be carried out at facilities in compliance with FDA-cGMP guidelines. Activities described under CLINs 0008 – 0012 shall follow all the requirements of the FDA licensed influenza vaccine product.

Contractors holding a US license for an influenza vaccine shall perform all activities described in the CLINS according to those of their FDA-licensed influenza vaccine product processes, including but not limited to using the same facilities, systems, equipment, processes and testing as for the licensed product. In lieu of a licensed process, Contractors with unlicensed influenza vaccine products that have completed the final clinical study report for their Phase 3 trial and are preparing the BLA shall perform all activities described in the following CLINS using the same facilities, systems, equipment, processes, and testing as those described in the BLA document in preparation. Only Contractors without a licensed influenza vaccine may use unlicensed processes to perform CLINS 0001-0013. Contractors that receive licensure during the course of this contract are required to use the licensed processes for the duration of the contract.

The Contractor shall allow HHS-designated personnel including BARDA staff to perform on-site auditing, inspection and review of release documents, test results, equipments and facilities when requested by HHS.

In case of a pandemic event, HHS staff and/or designees will be on the Contractor’s site to monitor daily activity and progress under the terms of the contract and facilitate discussion between the Contractor and HHS.

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In case of a pandemic event the contractor must submit a detailed production and delivery schedule for bulk vaccine, bulk adjuvant, final containers within 24 hrs after delivery order is received.

In case of a pandemic event the contractor shall submit a detailed daily report to HHS on all activities on–going under contract and as specifically requested by HHS.

Within one year after award, contractors must submit information requested by HHS to allow HHS to prepare a pre-EUA document for subsequent submission to FDA.

Employ approved biosafety measures compliant with WHO biosafety guidelines for influenza vaccine including protective garments, equipment, sufficient monitoring to assure safe handling of potentially hazardous materials for the safety and protection of workers. Conduct work under the contract in accordance with all applicable and current Federal, state, and local laws, codes, ordinances and regulations, as well as all PHS Safety and Health provisions.

C.4. Reporting Requirements and Deliverables

The Contractor(s) shall submit to the Contracting Officer (CO) and the Contracting Officer’s Representative (COR) technical progress reports, executive summaries and stability data covering the work accomplished during each monthly reporting period. On or before the completion date of the contract a Draft Final Report due will be submitted. A final report will be submitted within 30 days after Government comments. Reports shall be submitted electronically via e-mail to the COR, CO and any others they designate. Two hard copies shall be submitted to the CO. Any attachments to the e-mail report shall be submitted in Microsoft Word, Microsoft Excel, Microsoft Project or Microsoft Powerpoint or other file types compatible with the Microsoft Office suite of products. Specialized files can be submitted with prior discussion.

Monthly Technical Progress Reports:

On the fifteenth (15th) of each month the Contractor shall submit a report for the previous calendar month to the COR and the CO. The format and type of Technical Progress Report and Executive Summary will be provided by the COR.

Technical Progress Reports will include baseline and updated project timelines, milestones and summaries of product manufacturing, testing, and clinical evaluation. A Technical Progress Report will not be required for the period when the Final Report is due. The Contractor shall submit one copy of the Technical Progress Report electronically via e-mail to the COR, CO and any others they designate. Such reports shall include the following specific information:

Title page- containing Technical Progress Report, the contract number and title, the period of performance or milestone being reported, the contractor's name, address, and other contact information, the author(s), and the date of submission.

Introduction/Background - An introduction covering the purpose and scope of the contract effort Progress - The report shall detail, document, and summarize the results of work performed, test results, and milestones achieved during the period covered. Also to be included is a summary of work planned for the next reporting period.

Issues - Issues resolved, new issues and outstanding issues are enumerated with options and recommendations for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if project activity is delinquent, then what corrective steps are planned. Revised timelines are provided Invoices – Summary of any invoices submitted during the reporting period Action Items – Summary table of activities or tasks to be accomplished by a certain date and by whom.

Distribution List – A list of persons receiving the Technical Progress report Attachments – Results on the project are provided as attachments

Executive Summary The executive summary shall accompany each Technical Progress Report, will be formatted in Microsoft Power Point presentations and include the following:

Title page containing Executive Title, the contract number and title, the period of performance or milestone being reported, the contractor's name and the date of submission. Project Progress presented as milestone events, test results, tasks, and other activities achieved during the reporting period as talking point bullets. Project Issues presented headings and each item as a talking point bullet.

Final Reports By the expiration date of the contract, the Contractor shall submit a comprehensive Final Report that shall detail, document, and summarize the results of the entire contract work. The report shall explain comprehensively the results achieved. A draft Final Report will be submitted to the COR for review and revision, then the original, four copies, and an electronic file containing the Final Report with revisions shall be submitted to the COR for distribution to the CO and the Program.

SECTION D – PACKAGING, MARKING AND SHIPPING

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D.1. SHIPPING

1. Method of Delivery

Unless otherwise specified by the CO, delivery of items – reports, documents, invoices, etc. not stored by the contractor under this contract, to be furnished to the government under this contract (including invoices), shall be made by United States Postal Service mail delivery, overnight mail delivery or courier service.

2. Addressees – For all contract deliverables

Contracting Officer’s Representative (COR) Contracting officer (CO)

HHS/OS/ASPR/BARDA HHS/OS/ASPR/AMCG

330 Independence Avenue, SW 330 Independence Avenue, SW Room G640 Room G640 Washington, D.C. 20201 Washington, D.C. 20201

D.2. PREPARATION OF VACCINES FOR TRANSPORT

All materials shall be labeled and packaged in accordance with GCP (Good Clinical Practices) and/or GMP (Good Manufacturing Practices) as appropriate. Products shall be packed to ensure compliance with known product stability requirements that maintain satisfactory product temperatures during transit and arrival at destination. Products shall be packed to ensure maintenance of FDA recommended temperature during transit and safe arrival at destination. Freeze Watch Indicators (FWI) or equivalent temperature indicating devices shall be packed in each container containing influenza vaccine. The Contractor is required to maintain records that document the date of delivery receipt, and that the vaccine was properly maintained within the recommended cold chain temperatures during transit and receipt.

Concurrence on planned shipment protocols shall be obtained from HHS prior to transport.

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SECTION E – INSPECTION AND ACCEPTANCE

E.1. INSPECTION AND ACCEPTANCE

The CO or the duly authorized representative (who for purposes of this contract will be the COR) will perform inspection and acceptance of materials and services to be delivered under the contract.

COR Upon receipt and inspection of final lot release data and material, the CO will notify the Contractor of acceptance or rejection. If applicable, a task order for the storage of product shall be issued. Any product produced or stored under this contract shall be subject to inspection by the CO and the COR.

Inspections of material created under this contract may be made by a duly authorized US Government representative, and with reasonable notice (i.e. not less than 24 hours). HHS reserves the right to conduct an audit, either by HHS and/or HHS designee(s), of the facilities used under this contract and all records related to the manufacture, testing and storage of the product.

E.2 FAR 52.252-2 CONTRACT CLAUSES INCORPORATED BY REFERENCE (Feb 1998)

This contract incorporates one or more solicitation clauses by reference, with the same force and effect as if they were given in full text. Upon request, the CO will make their full text available. Also, the full text of a clause may be accessed electronically at https://www.acquisition.gov/far/

FAR REFERENCE TITLE DATE

FAR 52.246-1 Contractor Inspection Requirements Apr 1984 FAR 52.246-2 Inspection of Supplies – Fixed Price Aug 1996 FAR 52.246-16 Responsibility for Supplies Apr 1984

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SECTION F – DELIVERIES OR PERFORMANCE

F.1. ORDERING PERIOD AND PERIOD OF PERFORMANCE

a. The ordering period for this contract will be thirty six (36) months from date of award.

b. The period of contract performance of this contract is anticipated for thirtysix (36) months from date of award.

c. If the Government exercises its option(s) pursuant to the OPTION PROVISION Article in Section H of this contract, the period of performance will be increased as listed below:

Option Option Period

Option 1

Twelve (12) Months (Year 4)

Option 2

Twelve (12) Months (Year 5)

F.2. PLACE AND METHOD OF DELIVERY OF ITEMS UNDER THIS CONTRACT

a. The delivery of the items under this contract and related supplies shall be F.O.B. Destination.

b. The place and time of delivery shall be negotiated within individual Task Orders.

F.3. REPORTING REQUIREMENTS

a. Reporting Requirements

Reports shall be submitted in accordance with Section C.

b. Point of Contact

The contractor shall provide primary and secondary points of contact that will be available 24 hours per day, 7 days per week, to be notified in case a public health emergency.

c. Sample Inspection

At the discretion of the Government and independent of testing conducted by the contractor, the Government reserves the right to conduct site visits and collect samples of products held and stored by the contractor.

d. Disposition of the Inventory

Upon expiration or termination (including partial termination) of this contract, the Government may affect final distribution of any product created with this contract, and remaining in storage at the Contractor’s facility by any one or combination of the following methods:

(i) The Government may elect to direct the contractor to ship to a consignee(s) designated by the Government, all products remaining in storage at the Contractor’s facility.

(ii) The Government may request disposal of unshipped products stored at the Contractor’s facility

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F.4. CONTRACT DELIVERABLES & DISTRIBUTION

Delivery will be required F.O.B. Destination as set forth in FAR 52.247-35, F.O.B. DESTINATION, WITHIN CONSIGNEE’S PREMISES (APR 1984), and in accordance with and by the dates specified below and any shipping specification detailed in SECTION D. All reports and deliverables will be printed double sided in accordance with FAR 52.204-4.

Technical Reports:

Item Deliverable Quantity Due Date

1. Technical Progress Report Original – C.O.

1 Copies – COR.

1 Electronic Copy –

COR

1st Report due on/before…