2017-Stockpile_SOW.pdf

Stockpile 2017

Acquisition of MCMs for Pandemic Influenza Preparedness and Response

STATEMENT OF WORK

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 the preparation and response to the most recent pandemic caused by the 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 with options exercised will expire on August 31, 2017.

Therefore, it is critical to award contracts to manufacturers for this program in order to guarantee continuity of the influenza pandemic 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).

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.

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:

1) Provide Medical Countermeasures (MCMs) for Pandemic Influenza Preparedness and Response or as required in response to a HHS designated Public Health Emergency.

2) Produce vaccines against influenza and influenza strains with pandemic potential

3) Vendor must:

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

Detailed Description of CLINs:

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 unit for this item will be a seed lot.

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’.

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 unit for tis item will be a development lot.

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

Provide data derived from the manufacturing process.

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

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

The unit for this item will be an investigational lot.

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.’

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

The Contractor shall provide influenza vaccine bulk product.

The unit for this item will be a bulk lot (with a minimum final volume)

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.

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

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 unit for this item will be a bulk lot (with a minimum final volume)

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.

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.

Upon request, submit standard data reports according to instructions in

CLIN 0006: Formulation and Filling

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

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

Formulation, fill-finish activities of vaccine and 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

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

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

Provide temperature controlled storage for up to sixty (60) months 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 – vial size and fill volume), 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 Contractor’s 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

CLIN 0007A: Storage/Stability 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/Stability of commercial scale bulk lots of antigen

CLIN 0007C: Storage/Stability 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/Stability of commercial scale bulk 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/Stability 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/Stability 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 (any unit of issue identified in SOW)

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

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

Complete Attachment 2: BARDA Request for Shipment to various sites for clinical studies, storage and testing.

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.

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).

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

CLIN 0011: Laboratory Testing/Assay

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 CLIN 0011.

CLIN 0012: Non-Clinical Studies

The unit for this item is one study.

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

CLIN 0013: Clinical Studies

The unit for this item is study.

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

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, final container and package)

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

USG.

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.

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 new development 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.’

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 for 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 works to the CO and COR within five (5) business days of the inspection receipt of the report. Provide warning letters to the CO and COR within five (5) business days of receipt.

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.

CLIN 0017: Storage and Stability of materials from prior contracts

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

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 – vial size and fill volume), 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.

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

CLIN 0017A: Storage/Stability of bulk lots of antigen

CLIN 0017B: Storage/Stability 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 0017C: Storage/Stability of bulk 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 0017D: Storage/Stability 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.

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, Contractors should conduct SRID testing potency as soon as possible. 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 manufactures 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 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 (FDA, USDA, and 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. 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.

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

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.

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.

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