RFP_15-100-SOL-00003.pdf

Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response

Acquisition Management Contracts and Grants

Request for Proposal

15-100-SOL-00003

Solicitation Package

Medical Countermeasures for Pandemic Influenza Preparedness and Response

Period of Performance: September 1, 2015 through August 31, 2018

+ Two 12-month option periods

Issue Date: January 12, 2015 Proposals Due: February, 20, 2015, 5:00 PM EST To be timely offers must be received by the date and time indicated above.

Medical Countermeasures for Pandemic Influenza Preparedness and Response

Provision/Clause Title Page Number(s)

Section C - Statement of Work

SOW for Medical Countermeasures for Pandemic Influenza Preparedness and Response

4-15

Section D - Packaging and Marking

Method of Delivery 16

Section E - Inspection and Acceptance

Inspection and Acceptance 16

FAR Inspection Clauses Incorporated by Reference 16

Section F - Deliveries and Performance

Ordering Period and Period of Performance 17

Place and Method of Delivery 17

Reporting Requirements and Deliverables 17-28

FAR Clauses Incorporated by Reference 29

Section G - Contract Administration Data

Contracting Officer (CO) 29

Contracting Officer Representative (COR) 29

Key Personnel - HHSAR 352.270-5 29-30

Payment by Electronic Funds Transfer 30

Invoice Submissions 30-31

Payment Conditions 31

Government Property 31

Post Award Evaluation of Past Performance 31

Contract Communications/Correspondence 31

Section H - Special Contract Requirements

Prohibition on the Use of Appropriated Funds for Lobbying Activities 32

Salary Rate Limitation - HHSAR 352.231-70 32

Needle Distribution 33

Subcontracting Provisions 33

Reporting Matters Involving Fraud, Waste, and Abuse 34

Publication and Publicity - HHSAR 352.227-70 34

Acknowledgement of Federal Funding 34

Final Distribution 35

Human Subjects 35

Protection of Human Subjects HHSAR 352.270-4(b) 35

Human Materials 36

Notice to Offerors of Requirements for Compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals

Manufacturing Standards 36

Dissemination of False or Deliberately Misleading Scientific Information 36

Restriction on Employment of Unauthorized Alien Workers 36

Option Provision 36

Method of Ordering 37

Multiple Award Ordering 37

Exceptions to the Fair Opportunity 37

Task Order Procedures 37-39

BARDA Security Requirements 39-43

Section I – Contract Clauses 44-46

52.252-2, Clauses Incorporated by Reference (February 1998) 47

HHS Acquisition Regulation Clauses Incorporated by Reference 47

FAR Clauses in Full Text 47-60

Order Limitations 61

Section J – List of Attachments

Attachment Chart 61

Section L – Instructions, Conditions, and Notices to Offerors

Packaging and Delivery of Proposal 62-63

FAR Provisions in Full Text 63-67

HHS Provisions 68

General Info 68

Instructions to Offerors 69-79

Section M – Evaluation Factors for Award

Mandatory Eligibility Criteria 80

Evaluation Ratings 80

Evaluation Criteria 81-83

Relative Importance of Price and Other Evaluation Factors 83

Evaluation to the Extent of Small Disadvantaged Business Participation 83-84

Evaluation of Options 84

Section C-Statement of Work

STATEMENT OF WORK

Medical Countermeasures for Pandemic Influenza Vaccine Preparedness and Response

C.1 BACKGROUND:

The potential for a human influenza pandemic continues to be a public health concern. Four influenza pandemics occurred over the last century. In 2009, we completed responded to the most recent pandemic caused by a H1N1 virus. Sporadic infections of humans with avian influenza viruses with high mortality

(H5N1, H7N9) suggest the public is at risk for a severe influenza pandemic. An outbreak of severe pandemic influenza could cause over 60 million deaths worldwide by some estimates.

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 were 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 established 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 Sebelius 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”

Vaccination remains the primary countermeasure against pandemic influenza. Supporting the need for ongoing acquisition of novel subtypes of influenza, currently licensed vaccines for influenza are virus subtype specific. It remains uncertain which influenza subtype will cause the next pandemic. As a result, the ability of vaccines in the National Pre-pandemic Influenza Vaccine Stockpile to protect against emerging strains of influenza is unknown.

The current contracts for “Acquisition of MCMs for Pandemic Influenza Preparedness and Response” awarded in 2012 to five manufacturers expire in September 2015. It is critical, therefore to award contracts to manufacturers for this program in order to guarantee continuity of the pandemic influenza preparedness and response capabilities and to maintain current stockpiled vaccines and adjuvants.

The 2009 H1N1 influenza pandemic demonstrated how crucial it is to have active contracts with manufacturers to respond to an influenza pandemic event; in 2009 the Federal Government rapidly modified existing stockpile contracts and issued task orders to manufacturers to produce millions of doses of H1N1 influenza vaccine.

This program will serve as a continuation and expansion of the US Pandemic Preparedness Plan which currently includes contracts with five influenza vaccine experienced companies. The competition will be open to companies that are currently licensed for inactivated, recombinant and live attenuated influenza vaccine

(LAIV), both seasonal and pandemic. In addition, competition is open to Offerors that demonstrate a successful experience in the manufacturing of influenza vaccines at commercial scale, have completed

Phase 3 clinical studies (including a final Clinical Study Report) for influenza vaccines with a documented US

BLA in preparation for an influenza vaccine.

C.2.1. 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.

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:

o A pivotal Phase 3 final clinical study report AND o Official Minutes from an US FDA Pre-BLA meeting

C.2.2. Detailed Description of Contract Line Item Numbers (CLINs):

Note: Numbers referenced for CLINs below reflect numbers identified for base period of performance for any resultant contract. CLINs will differ for option periods with item name unchanged.

CLIN 0001: cGMP Influenza Vaccine Master and Working Seed Lot

The Contractor shall provide yield optimized master and working seed lots for inactivated, live attenuated or recombinant influenza vaccine product.

The Contractor shall:

Manufacture Master and Working seeds lots for influenza vaccine using the same facilities, systems, equipment, processes and testing as those described and referenced in the FDA-licensed influenza vaccine or as described in the BLA in preparation, according to current Good Manufacturing Practices (cGMP) as applicable and store at appropriate conditions during lot release testing.

Manufacture the seed lot using the qualified influenza candidate vaccine virus (CVV) reference strain as specified by HHS.

Provide seed lot testing results in accordance to specifications as requested by FDA as part of the FDA-licensed influenza product, or the in-process BLA filing.

Provide seed lot samples to the FDA for identity verification, and other testing as specified by

HHS.

Store seed lots according to FDA cGMP guidelines.

Conduct stability and other testing as appropriate or specified by HHS.

Add manufactured seed lots to ongoing inventory reports and controlled storage.

Submit standard data report ‘MN001’ according to instructions in ‘Reporting Requirements’ ‘Attachment 2’

Provide a final report including, at minimum, the information identified in the Final Report Requirements Table 1.

CLIN 0002: Influenza Vaccine Research Lot(s)

The Contractor shall provide an influenza vaccine small scale, research lot.

The Contractor shall:

Prepare a research lot as directed by HHS and specified in the RTOR.

Provide data derived from the manufacturing process.

Provide a final report including, at minimum, the information in the Final Report Requirement

Table 1.

CLIN 0003: cGMP Influenza Vaccine: Investigational Lot(s)

The Contractor shall provide influenza vaccine investigational lot(s).

The Contractor shall:

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 production method for influenza vaccine manufacture that is described and referenced in the FDA license or BLA under preparation.

Perform lot release product testing of the influenza vaccine using lot release specifications 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.

Set aside samples for stability testing up to 120 months.

Storage methods including containers, stoppers, and other relevant storage supplies need to be approved by HHS.

Upon Request, submit standard data reports according to instructions in ‘Reporting Requirements’ ‘Attachment 2”

CLIN 0004: cGMP Influenza Vaccine: Commercial Scale Bulk Lot(s)

The Contractor shall provide influenza vaccine bulk product.

The Contractor shall:

Manufacture the commercial scale bulk vaccine lot in manufacturing facilities according to current Good Manufacturing Practices (cGMP) under 21 CFR parts 210, 211, and 600. Use a validated production method for influenza vaccine manufacture that is described and referenced in the FDA license or BLA under preparation.

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

Set aside samples for stability study testing for up to 120 months. Selection of lots for stability testing will be determined after manufacture is complete and should be approved by HHS.

Conduct lot release product testing of the influenza bulk vaccine according to the licensed (or in-process BLA documented) product. Provide results to HHS. Make batch records available for review by HHS.

Storage methods including containers, stoppers, and other relevant storage supplies need to be approved by HHS

Submit standard data report ‘MN004’ according to instructions in ‘Reporting Requirements’ and ‘Attachment 2’.

CLIN 0005: cGMP Adjuvant: Clinical or Commercial Scale Bulk Lot(s)

The contractor shall provide adjuvant bulk product suitable for formulation and filling. Proposed adjuvant shall have completed Phase 2 development in combination with a pandemic or pre-pandemic antigen.

Clinical evidence of antigen sparing and/or adjuvant benefit for the pandemic or pre-pandemic antigen is required.

The Contractor shall:

Manufacture the bulk adjuvant product at clinical or 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.

Make available batch records for review by HHS.

Set aside samples for stability study testing for up to 120 months Selection of lots for stability testing will be determined after manufacture is complete and should be approved by HHS.

Execute lot release product testing of bulk adjuvant.

Storage methods including containers, stoppers, and other relevant storage supplies need to be approved by HHS.

Upon request, submit standard data reports according to instructions in ‘Reporting Requirements’ and ‘Attachment 2’

CLIN 0006: Formulation and Filling

The unit for this item is each (vial, syringe and sprayer)

The contractor shall:

Formulate and fill influenza antigen and/or adjuvant in final containers specified in CLIN 0006 A-H.

Formulation, fill-finish activities of vaccine and/or adjuvant shall be carried out at facilities in compliance with FDA-cGMP guidelines and if applicable, in accordance with the formulation and filling requirements that apply to FDA-licensed influenza vaccine product unless otherwise requested, specified and approved by HHS.

Formulate material at the concentration or dosage determined by HHS.

Fill each unit to a volume determined by HHS.

Assure compliance of formulation and filling activities with the license or in-process BLA documentation as required by HHS.

Assure compliance of filling activities with relevant FDA cGMP guidelines.

Execute lot release product testing of the final container using lot release specifications of the FDA-licensed influenza vaccine product or in-process BLA.

Affix labels onto filled final containers with HHS approved text. HHS will require coding on primary containers and 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 as required/specified by HHS.

Set aside final containers for stability study testing for up to 120 months. Selection of lots for stability testing will be determined after manufacture is complete and should be approved by

HHS.

Submit standard data report ‘MN007’ according to instructions in ‘Reporting Requirements’ and ‘Attachment 2’.

Provide a final report including, at minimum, the information identified in the Final Report Requirements Table 1.

CLIN 0006A: Antigen: Single dose vials

CLIN 0006B: Antigen: Syringes or sprayers

CLIN 0006C: Antigen: Multi-dose vials

CLIN 0006D: Adjuvant: Single dose vials

CLIN 0006E: Adjuvant: Multi-dose vials

CLIN 0006F: Co-formulated antigen and adjuvant: Single dose vials

CLIN 0006G: Co-formulated antigen and adjuvant: Syringes

CLIN 0006H: Co-formulated antigen and adjuvant: Multi-dose vials

CLIN 0007: Storage and Stability

Provide temperature controlled storage at the Contractor site approved by HHS, according to cGMP and the Contractor’s product specifications.

Store bulk lots and final containers physically segregated from other products

Ensure proper labeling of stored materials as USG property.

Execute stability testing of stored material in a manner consistent with the stability testing plan approved by HHS. Report interim data and results to HHS on a monthly basis.

Ensure sufficient representative samples are available at the time of ‘Storage and Stability’ task order award for stability testing for 120 months from the date of manufacture.

Ensure stored materials are compliant with the Contractor’s internal quality control system and are ready for use in further cGMP governed manufacturing of clinical material or licensed doses as directed by HHS.

Provide the government access to review the security system in place and request updates as needed.

Include in monthly report inventory (lot number, number of lots, number of vials), including inventory quantity changes, current quantity, storage facility/location, manufacturing date, latest stability result for potency, date of next expected stability result and the current expiration date (if applicable).

Ensure that material being relocated for the contractors’ convenience is adequately insured at no cost to the government and with CO approval.

Conduct testing necessary to ensure continued use of the stored material for pre-pandemic preparation, pandemic response and, where appropriate, manufacture of licensed doses.

Make appropriate updates to the regulatory documentation supporting the continued use of the stored material for pre-pandemic preparation, pandemic response and, where appropriate, manufacture of licensed doses.

If using a subcontracted storage site, provide the quality agreement, specify the location and terms of the storage contract and receive approval by HHS.

Submit standard data reports ‘MN014’ and ‘MN017’ according to instructions in ‘Reporting Requirements’ and ‘Attachment 2’.

Provide a final report including, at minimum, the information identified in the Final Report Requirements Table 1.

CLIN 0007A: Storage of investigational lots of antigen

The unit for this item is a lot, which equals storage and stability for one (1) lot/month.

CLIN 0007B: Storage of commercial scale bulk lots of antigen

The unit for this item is a lot, which equals storage and stability for one (1) lot/month.

CLIN 0007C: Storage of antigen in final container

The unit for this item is a final container which equals storage and stability for a single (1) final container/month.

CLIN 0007D: Storage of clinical/commercial scale lots of adjuvant

The unit for this item is a lot which equals a single (1) month of storage and stability for a single (1) lot/month.

CLIN 0007E: Storage of adjuvant in final container

The unit for this item is a final container which equals storage and stability for a single (1) final container/month.

CLIN 0007F: Storage of licensed product in final package

The unit for this item is a package, which equals storage and stability for a single (1) package/month.

CLIN 0008: Shipping

The unit for this item is each (lot, package and pallet)

Package, handle and ship material to the destination specified in the RTOR.

Arrange for transit, delivery and insurance of material shipped. Send EDI 856 Advanced Shipping Notices upon request.

Be responsible for delivering material shipped in a condition fit for its intended use.

Provide program and contracting offices with (transportation document (e.g. bill of lading and associated documents) upon request.

Submit standard data report ‘DM002’ according to instructions in ‘Reporting Requirements’ (see Attachment 2).

Provide a final report including, at minimum, the information identified in the Final Report

Complete Attachment 6: BARDA Request For Shipment to Clinical Study Sites

CLIN 0009: Candidate Vaccine Virus (CVV)

Prepare non-GLP and/or GLP influenza candidate vaccine viruses using high yield donor viruses or genes as directed by HHS and specified in the RTOR.

Perform characterization and provide results of in vitro and in vivo bio-safety level testing as necessary and specified in the RTOR.

CLIN 0010: Potency reagent and standards manufacture and testing

The Contractor shall provide influenza vaccine reagents and standards.

The Contractor shall:

As directed by HHS, execute activities related to reagent and standards manufacture and testing including purified HA for antibody production, primary liquid standard antigen reference, secondary antigen reference and antibody production.

As directed by HHS and specified in the RTOR, develop and produce influenza vaccine reagents and standards for other reagent process (HPLC, Mass Spec and others)

CLIN 0011: Analytical Laboratory Testing/Assay

The contractor shall:

Conduct laboratory testing/assay as required by HHS and specified in the RTOR

Provide costs for testing as described in the Technical/Business Proposal Instruction for

CLIN0011.

CLIN 0012: Non-Clinical Studies

Conduct non-clinical studies as required by HHS and specified in the RTOR.

Upon request, submit standard data reports according to instructions in ‘Reporting Requirements’

CLIN 0013: Clinical Studies

Conduct Clinical studies as required by HHS and specified in the RTOR.

Upon request, submit standard data reports according to instructions in ‘Reporting Requirements’ and ‘Attachments.”

Provide a final report including, at minimum, the information identified in the Final Report Requirements Table 1.

Post-Use Monitoring Data to be collected on the use of the product from other MCM access mechanisms (expanded access or EUA) as required by HHS and specified in the RTOR.

Upon request, provide serum/tissue aliquots to HHS as directed by HHS for immunological evaluation

CLIN 0014: Disposal of product

The unit for this item is each (lot, vial and package)

The Contractor will dispose of all products related to this contract, as required by the USG.

The Contractor shall:

Dispose of product following all federal and state regulations for the appropriate waste category; hazardous waste (thimerosal-containing vaccines), regulated medical waste (LAIV), solid waste (non thimerosal-containing vaccine, non LAIV).

Provide documentation and reports on the performed and completed disposal activity.

Upon request, submit standard data reports according to instructions in ‘Reporting Requirements’ and ‘Attachments.”

Provide a final report including, at minimum, the information identified in the final report requirements table.

CLIN 0015: BARDA Tracking Tool-Development and Testing of New Standard Data Reporting Formats

Plan and create new data sets for submission to the BARDA Tracking Tool (BTT) as described by contract and/or RTOR. These are additive to the data sets identified in Section F ‘Reporting Requirements and Deliverables’ For planning purposes, BARDA is considering the following data sets for evaluation and testing with the BARDA Tracking Tool and may add other data sets in the future.

Data Set Description Aligns with CLIN #

MN005 Production of Bulk Adjuvant Lots CLIN #0005

MN008 Formulation, Fill and Finish of Adjuvant Lots

CLIN #0006D and 0006E

MN009 Storage of Bulk Drug Substance CLIN #0007B

MN010 Storage of Bulk Adjuvant Lots CLIN #0007D

MN012 Storage of Clinical Lots CLIN #0007A

MN013 Storage of Final Drug Product CLIN #0007E and 0007E

MN018 Storage of Master Seed CLIN #0001

DS002 Disposal of Bulk Drug Substance CLIN #0015

DS006 Disposal of Final Drug Product CLIN #0015

Conduct testing and validation of new data sets submitted to the BARDA Tracking Tool (BTT) Program as described by contract and/or RTOR. Guidance and instructions regarding new data sets (types of data, what to submit, when to submit, how to submit, frequency of submission) will be provided in the RTOR.

Upon validation, submit new data set on a recurring basis to the BTT for all materials that are currently under contract and/or incorporated from previous contracts. New data sets, upon validation, become part of Standard Data Report baseline.

For additional information on the current baseline requirements please review Section F ‘Reporting requirements and Deliverables’ and ‘Attachment “A”.

CLIN 0016: Additional Reporting

Submit inventory reports, monthly progress reports, executive summaries, Government Property reports, ad hoc reports of urgent developments related to this program and a final report as described in detail in the Reporting Requirements and Deliverables. Provide a final report including, at minimum, the information identified in the final report requirements table.

In Q1 of each calendar year, submit an updated table describing facility availability to complete all CLIN activities throughout the year. A template will be provided by the CO for completion.

Respond to information requests from HHS pertaining to the ongoing activities.

Inform the CO and COR of all issues involving any of the material managed under this contract within three (3) business days of the incident. An impact assessment and remediation plan shall be provided within twenty (20) business days of the incident.

Provide copies of reports from regulatory inspections of facilities proposed under this contract for the completion of CLIN work to the CO and COR within five (5) business days of the inspection or receipt of the report. Provide warning letters to the CO and COR within five (5) business days of receipt.

Make appropriate updates to the regulatory documentation supporting the continued use of the stored material for pre-pandemic preparation, pandemic response and, where appropriate, manufacture of licensed doses. Submit documentation of regulatory update(s) with the monthly report.

Provide regulatory documentation as required by HHS.

C.2.3. Additional Requirements

Alternative potency assays may be used when CBER reagents are not available and must be approved by the CO. When reagents become available, potency determination should be bridged to

SRID testing. Parallel testing with both assays shall continue for the duration of the stability program to document comparability. Where appropriate and requested by HHS, such comparability documentation may be submitted to FDA to evaluate feasibility of alternate potency testing for lot release under 21 CFR 610.9 Equivalent Methods and Processes.

When a Contractor manufacturers outside the US, manufactured material shall be shipped to the

US within 60 days of lot release. An exception to this requirement may be requested from HHS.

Shipment of the vaccine and/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 may require testing which shall be performed according to applicable federal guidelines (e.g., FDA, USDA, and/or CDC). The Contractor shall bear all costs for shipping and testing required for import into the US. This requirement can be unilaterally modified by HHS during a public health emergency to allow for international formulation and filling prior to shipment to the US. If the contractor has domestic/international facilities for primary and secondary manufacturing or storage, products must be shipped from/to different facilities at no cost to the US government.

Bulk manufacturing facilities shall be in compliance with appropriate biosafety level bio-containment procedures.

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 the same facilities, systems, equipment processes and testing as for the licensed product. In lieu of a licensed processes, 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 work described in the

CLINs. Contractors that receive licensure during the course of this contract are required to use the licensed processes for the duration of the contract and to ensure that materials previously purchased by Gov’t from vendor prior to license are compliant with the licensed process, to the extent practical or reasonable with HHS approval.

Products manufactured and stored under this contract are ‘Government Furnished Property’. These materials should be maintained in the contractor’s quality and inventory systems, ready for use in the continued manufacture of bulk material or final container doses intended for clinical use or use under the license.

When appropriate, Contractors shall use the same validated facilities, systems, equipment, and manufactured processes for cGMP manufacturing of licensed influenza vaccine and adjuvant product or influenza vaccine and adjuvant product with an in-process BLA.

When appropriate, Contractors shall use the same validated and approved assays and equipment for lot release of influenza vaccine product and final container influenza vaccine products and stability studies.

When appropriate, Contractors shall use the same validated facilities, systems, and equipment suitable for cGMP storage of influenza vaccine and adjuvant products.

When appropriate, contractors shall use the approved facilities, equipment, and policies to receive, store, utilize, and dispose of bio-hazardous materials in appropriate conditions (e.g. Biosafety Level 2+ as appropriate).

As appropriate, Contractors shall 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. Contractors shall 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.

Notification shall be given to US Government prior to any disposal of material, records, documentation, and/or reports for consultation and disposition.

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

Upon request from HHS, 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.

Contractors must submit documents as requested by HHS to support the preparation of a pre-EUA document for their vaccine or adjuvant.

Section D-Packaging, Marking, Shipping

METHOD OF DELIVERY

Unless otherwise specified by the Contracting Officer, delivery of items, e.g., 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.

Deliveries via the United States Postal Deliveries via Courier, e.g., UPS, FedEx Service (USPS):

[Contracting Officer’s Name] [Contracting Officer’s Name ASPR – AMCG ASPR-AMCG-Phone Number. SW 330 Independence Avenue SW, Room G644 200 C St Washington, D.C. 20201 Washington, D.C. 20024

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 http://farsite.hill.af.mil/.

FAR Inspection Clauses Incorporated by Reference

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 http://farsite.hill.af.mil/

Section F-Deliveries and Performance

F.1. ORDERING PERIOD AND PERIOD OF PERFORMANCE

a. The base ordering period for this contract will be from date of award through August 31, 2018.

b. The period of contract performance of this contract is a base period of thirty-six (36) months:

September 1, 2015 through August 31, 2018.

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 Duration/Performance Period

Option 1 12-month – Year Four

Option 2 12-month – Year Five

F.2. PLACE and METHOD of DELIVERY

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 AND DELIVERABLES

The Contractor(s) shall submit to the Contracting Officer (CO) and the Contracting Officer’s Representative

(COR) 1) executive summaries, 2) technical progress reports, and 3) Standard Data Submission covering the work accomplished during each monthly reporting period. By the expiration date of any issued task order(s), the Contractor shall submit a comprehensive draft and revised Final Report.

Reports shall be submitted electronically via e-mail to the COR, CO and any others they designate. One original hard copy 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.

1) Monthly Executive Summary:

On the fifteenth (15th) of each month for the previous calendar month the Contractor shall submit a Monthly

Executive Summary to the COR and the CO. A copy of the summary will also be sent to the following email address: BardaTrackingToolInfo@hhs.gov. The executive summary will be formatted as a Microsoft Power

Point presentation and will 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 mailto:BardaTrackingToolInfo@hhs.gov project progress presented as milestone events, test results, tasks, and other activities achieved during the reporting period as talking point bullets and project issues presented headings and each item as a talking point bullet.

2) Monthly Technical Progress Reports:

On the fifteenth (15th) of each month the Contractor shall submit a report to the COR and the CO describing work accomplished in the previous calendar month. 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 the following email address: BardaTrackingToolInfo@hhs.gov. 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.

Task Orders - Discuss each open Task Order; describe the technical progress and issues.

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 are to be furnished. Revised timelines are provided.

Contractual Issues- Include an updated table of contractual issues with columns for Issue Number, Task

Order, Issue Description, Date of Initial Request, Impact, Status/Comment.

Invoices – Summary of any invoices submitted during the reporting period. Include an updated table with columns for Invoice number, Date Submitted, Amount, Activity/Comments and Date paid. The summary invoice table should include all invoices to date of the report.

Action Items – Summary table of activities or tasks to be accomplished by a certain date and by whom.

Summary - Include an updated table with columns for Task Order, Description, Period of Performance and

Current Status. The summary table should contain all task orders since award

Distribution List – A list of persons receiving the Technical Progress report.

Attachments – Results on the project are provided as attachments.

mailto:BardaTrackingToolInfo@hhs.gov

3) Standard Data Submissions:

Standard Data Submissions is the electronic transfer of manufacturing and supply chain data sets from the contractor’s automated information management systems or other data sources and files directly to a secure data capture system known as the BARDA Tracking Tool.

The Contractor(s) shall submit the following data sets to the BARDA Tracking Tool within three months of award.

Data Set Number

Description Aligns with CLIN #

MN001 Seed Development, Selection and Production CLIN #0001

MN004 Production of cGMP Bulk Drug Substance CLIN #0004

MN007 Formulation, Fill and Finish of Final Drug Product CLIN #0006

MN014 Stability Information / Studies of Bulk Drug Substance CLIN #0007

MN017 Stability Information / Studies of Final Drug Product CLIN #0007

DM002 Domestic Shipment of Final Drug Product CLIN#0008

Instructions for connecting with the BTT will be provided at Contract Award.

Instructions for preparing data sets are defined under BARDA Tracking Tool (Attachment 2)

New data sets will be communicated in future ‘Requests for Task Order Response’ under CLIN 15.

4) Monthly Teleconference – A monthly teleconference to review the content of the written monthly report. The Contractor shall provide minutes for the monthly teleconference with the next monthly report.

5) Task Order Final Report and Contract Final Report– By the expiration date of each individual Task Order and contract, the Contractor shall submit a comprehensive Final Report that shall detail, document, and summarize the results of the entire Task Order and contract work. The report shall explain comprehensively the results achieved. A draft Final Report will be submitted to the CO for the COR to review and provide comments. Next, the original, and an electronic file containing the Final Report with revisions shall be submitted to the CO for distribution to the COR.

Provide the information identified in Table 1: Task Order Final Report Requirements.

Final Report Requirements Table 1:

C L

IN

M

V S

/W V

S

IN

R e s e a rc h

L o t( s

C L

IN

I n v e s ti g a ti o n a l L o ts

IN

A n ti g e n

C o m m e rc ia l S c a le

B u lk l o t( s

C L

IN

A d ju v a n t C lin ic a l/ C o m m e rc ia l S c a le l o t( s

C L

IN

F o rm u la ti o n a n d f ill in g

IN

S to ra g e a n d

S ta b ili ty

IN

S h ip p

IN

n d id te c c e ir u s

IN

P o te n c y R e a g a n d S ta n d M n fc g a n d T e s ti n

IN

A n a ly ti c a l L a b o ra to ry

T e s ti

IN

N o n -c lin ic a l T e s ti

IN

C lin ic a l T e ts

IN

D is p o s a l o f p ro d u c t

C L

IN

S ta n d a rd

D a ta

S u b m is s io

IN

A d d it io n a l R e p o rt

Manufacturing location (building, room, city/country) x x x x x x x x x

Dates of major manufacturing steps x x x x x x Major process inputs (# eggs, bioreactor size/working volume, cell bank#, CVV, MVS/WVS, lot number) x x x x x x x x x

Volume (volume produced, lot size, quantity/number) x x x x x x x

Antigen yields (e.g. µg/ml, ffu/ml)) x x x x x

Manufacturing deviations x x x x x x x

Certificates of Analysis (in English) x x x x x

CBER Identity certification letter x Storage location and inventory (building, room, refrigerator, shelf) x x x x x x x

Pictures of produced material clearly marked with an appropriate US Government Property label x x x x x x

Final Pre-Clinical Study Report x

Final Clinical Study Report x

Clinical Study Database x

CBER Lot release letter for licensed products x

Stability or other testing results x x x x x x x x x

Final report at the end of the POP x x x x x x x x x x x x x

BARDA TRACKING TOOL: Instructions for Preparing and Submitting Standard Data Sets

Standard Data Submissions refers to the electronic transfer of manufacturing and supply chain data sets from the contractor’s automated information management systems or other data sources directly to another automated information management system. BARDA’s information management system is automated.

Submission of data to BARDA’s system will be done through secure file transfer protocol (sFTP). Data submission can be done manually or automatically, depending on the contractor’s preference and capability.

Similarly, in most cases data will be able to be automatically generated from a contractor’s system. The

BARDA Tracking Tool will go through a testing phase to ensure appropriate handover of data from contractors. BARDA’s secure data capture system is known as the BARDA Tracking Tool or BTT.

The BTT capitalizes on the lessons learned from the 2009 H1N1 Pandemic Influenza campaign during which extensive manual effort and precious time was expended to communicate and manage a response. By defining and standardizing data sets that represent key elements of manufacturing and supply chain activities, BARDA aims to significantly reduce the management burden and enhance the efficiencies in communications by taking advantage of current technologies and applications.

Contractors will be expected to submit data sets as defined in the formats detailed below. These data sets form the baseline for automated reporting. New data sets that are generated through CLIN #0015 requirements become part of baseline once they are tested and validated.

Baseline Datasets

Data Set Number

Description

MN001 Seed Development, Selection and Production

MN004 Production of cGMP Bulk Drug Substance

MN007 Formulation, Fill and Finish of Final Drug Product

MN014 Stability Information / Studies of Bulk Drug Substance

MN017 Stability Information / Studies of Final Drug Product

DM002 Domestic Shipment of Final Drug Product

Submission Instructions:

In general, data set files will be transmitted to the BTT whenever there is a change or update in the data.

New files will overwrite existing files such that the latest file submitted represents the most current information. The only exception to the overwrite rule are submissions for MN014 and MN017. Only new data will be reported for MN014 and MN017.

All files that are submitted to the BTT will go through an error check step prior to processing. A comprehensive list of error checking/validation processes will be provided at contract award.

All data sets have primary key fields that must never be NULL. Some fields have a two-step primary key system. In these cases if certain data objects are non-null, then additional primary key fields become necessary. These details are provided for each data set.

Details on how to submit data / connect with the BTT will be provided at contract award.

Baseline Data set descriptions are identified in the following pages.

MN001 Seed Development, Selection and Production

Column Name Display Name Description Datatype Size Precision Key? FK To NULL? Default Value Example Values

Activity_Type Activity Type Activity Type Code for data received from manufacturer varchar 5 PK no MN001 MN001

Report_Date Data Reported as of Date/Time activity data w as received from manufacturer datetime PK no Today 2013.01.01 12:00:00.000

Contract_Num Contract # Contract number for data received from manufacturer varchar 50 PK no N/A HHSO100200800000I

CLIN_Num CLIN Contract Line Item number for data received from manufacturer varchar 5 no N/A 0002

Strain Strain Vaccine strain varchar 7 no N/A H1N1

Subtype_Wildtype Strain Subtype Wild Type Strain / Subtype: Wild Type Virus Name varchar 100 no N/A A/California/08/2009 (H1N1)

Subtype_Candidate Strain Subtype Candidate Strain / Subtype: Candidate Vaccine Virus Name varchar 150 no N/A A/California/08/2009 (H1N1)

Candidate_Recv_Date Candidate Seed Recv Date Date Seed Candidate Received datetime no N/A 2013.01.01 12:00:00.000

Recv_From Received From Received From varchar 255 no N/A

Seed_Prod_Date Seed Produced Date Date Seed Produced datetime yes null 2013.01.01 12:00:00.000

Seed_Sent_Date Working Seed Send Date Date Working Seed Sent to FDA datetime yes null 2013.01.01 12:00:00.000

Seed_Cert_Date Working Seed Certif ication Date Date of FDA Certif ication of Working Seed datetime yes null 2013.01.01 12:00:00.000

Seed_Concur_Date Working Seed Concurrence DateDate of CDC Concurrence of Working Seed datetime yes null 2013.01.01 12:00:00.000

Seed_SKU Seed SKU Seed Stock Keeping Unit varchar 30 yes null

Seed_SKU_Descr Seed SKU Description Seed Stock Keeping Unit Description varchar 255 yes null 2013.01.01 12:00:00.000

Seed_Lot_Num Seed Lot # Seed Lot # varchar 30 PK yes null HH100738 01A

Site_Loc Site Location Site Location varchar 300 no null Washington, DC

Task_Order_Num Task Order # Task Order number associated w ith the contract varchar 50 no N/A HHSO10033001T

Remarks Remarks Remarks varchar MAX yes null

If dates are reported for seed production, send to FDA, certif ication, or concurrence then Seed Lot # becomes part of the primary key. It should be f illed in w ith a non-null <blank> string until data is available.

MN004 Production of cGMP Bulk Drug Substance

Column Name Display Name Description Datatype Size Precision Key? FK To NULL? Default Value Example Values

Activity_Type Activity Type Activity Type Code for data received from manufacturer varchar 5 PK no MN004 MN004

Report_Date Data Reported as of Date/Time activity data w as received from manufacturer datetime PK no Today 2013.01.01

12:00:00.000

Contract_Num Contract # Contract number for data received from manufacturer varchar 50 PK no N/A HHSO100200800000I

CLIN_Num CLIN Contract Line Item number for data received from manufacturer varchar 5 no -1 0002

Strain Strain Vaccine strain varchar 7 no N/A H1N1

Subtype Subtype Strain / Subtype: Wild Type Virus Name varchar 100 no N/A A/California/08/2009

(H1N1)

Seed_Lot_Num Seed Lot # Vaccine Seed Manufacturer Lot # varchar 30 no N/A HH10001

HA_Submit_Date Purif ied HA Submit Date Date Purif ied HA (Bromelainted Bulk) submitted to

FDA

datetime yes null 2013.01.01

12:00:00.000

HA_Ack_Date Purif ied HA Acknow ledgement DateDate Purif ied HA (Bromelainted Bulk) acknow ledged by FDA datetime yes null 2013.01.01

12:00:00.000

HA_Target_Antisera_Date Purif ied HA Target Antisera DateTarget Date of Purif ied HA (Bromelainted Bulk)

Completion - Sheep Antisera datetime yes null 2013.01.01

12:00:00.000

HA_Actual_Antisera_Date Purif ied HA Actual Antisera DateActual Date of Purif ied HA (Bromelainted Bulk)

Completion - Sheep Antisera datetime yes null 2013.01.01

12:00:00.000

SRID_Receive_Date SRID Reagent Received Date Date Standardized (SRID) calibarated reagent received from FDA datetime yes null 2013.01.01

12:00:00.000

LYO_Receive_Date LYO Antigen Receive Date Date Calibrated (lyo) reference antigen received from FDA datetime yes null 2013.01.01

12:00:00.000

BDS_Submit_date Bulk Drug Substance Submit DateDate Comparator Bulk Drug Substance (BDS) Lots submitted to FDA datetime yes null 2013.01.01

12:00:00.000

BDS_SKU BDS_SKU Stock Keeping Unit varchar 30 PK no N/A HHVN200001

SKU_Descr SKU Description Stock Keeping Unit Description varchar 255 no N/A Influenza A (H1N1)

2009 Monovalent

Vaccine Bulk Drug

SubstanceBDS_Lot_Num BDS Lot # Bulk Drug Substance Manufacturer Lot # varchar 30 PK no N/A HH100738 01A

Vol_On_Hand Volume On Hand Volume on hand (in Liters) decimal 6 2 yes 0 123456.12

Exp_Date Expiration Date Expiration Date date yes null 2013.01.01

BDS_Mfg_Loc BDS Manufacturing Location Bulk Drug Substance Manufacturing Location varchar 300 PK yes null Washington, DC

Mfg_Start_Date Mfg Start Date Manufacturing Start Date datetime yes null 2013.01.01

12:00:00.000

Dose_Yield_Alt Dose Yield Alternative Assay Dose Yield (Alternative assay mcg/ml - LAIV

Alternative Assay) decimal 6 2 yes null 1234.18

Dose_Yield_Final Dose Yield Final Assay Dose Yield Final Assay (mcg/ml) - LAIV Final

Assay (FFU) decimal 12 2 yes null

Scrap_Factor Scrap / Loss Factor Scrap / Line Loss Factor decimal 4 2 yes null 0000.12

Int_Lot_Release_Date Internal Lot Release Date Internal Lot Release Date datetime yes null 2013.01.01

12:00:00.000 Task_Order_Num Task Order # Task Order number associated w ith the contract varchar 50 no N/A HHSO10033001T

If Internal Lot Release Date contains data (is non-null) then Vol on Hand and either Dose_Yield_Final…