75A5012R00003_AVAT_mAb_RFI_Att1_draftSOO.SAM.Final.docx

RFI 75A5012R00003 Attachment #1 Document: draft Statement of Objectives (SOO)

DRAFT

Statement of Objectives (SOO) Project Title: Manufacturing Optimization for Filovirus Human Monoclonal Antibodies Background The Biomedical Advanced Research and Development Authority (BARDA) works with its industry partners to develop vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies such as chemical, biological, radiological, and nuclear (CBRN) accidents, incidents and attacks; pandemic influenza (PI), and emerging infectious diseases (EID). As a part of this mission, BARDA seeks to support cost-effective countermeasures that can fill the gaps in our national preparedness.

In 2006, the Department of Homeland Security (DHS) determined that Ebola virus and Marburg virus are material threats to national health security. The threat of filovirus agents being used as biological/bioterror weapons led the DHS to issue a Material Threat Determination (MTD) based on its Material Threat Assessment (MTA) for Ebola virus and Marburg virus. Medical countermeasures (MCM) that can be deployed in the event of a filovirus outbreak are a crucial component to the United States Government’s (USG’s) outbreak response plan. BARDA is seeking to augment the USG’s response capabilities with therapeutics targeting filovirus disease caused by Ebola virus (EBOV), Marburg virus (MARV), or Sudan virus (SUDV). There are currently two US Food and Drug Administration (FDA) approved therapeutics for treatment of Ebola Virus Disease (EVD), Inmazeb and Ebanga, both of which are monoclonal antibodies or antibody cocktails. There are no therapeutics approved for the treatment of patients infected with SUDV or MARV.

Scope As a part of BARDA’s commitment to develop therapeutic countermeasures against filovirus disease, BARDA is interested in advancing manufacturing development for a monoclonal antibody (mAbs) cocktail composed of two mAbs, which was developed by an academic institute that currently holds the intellectual property (IP) for the product. These mAbs target the glycoprotein (GP) trimer to potently neutralize diverse ebolaviruses. BARDA investment in the manufacturing is aimed at identifying a high yield manufacturing process that will subsequently enable development of a cost-effective therapeutic product.

BARDA is seeking submissions from contract development and manufacturing organizations (CDMOs) to perform cell line development (Chinese Hamster Ovary (CHO) cell lines preferred; other cell lines will be considered with justification) and initial manufacturing process development of the mAb cocktail at a scale greater than or equal to 5 Liters (L). The comparability material will be provided by the academic partner and used as a benchmark for performance to measure against the mAbs from CDMOs at the end of the period of performance.

Objectives If selected, the CDMO will be awarded a Base period to execute cell line generation and initial process development as detailed below (Section 4.2). Multiple project award agreements are anticipated to be made for the Base period. Offerors may propose development of an internal potency assay and may be provided with a protocol for the potency assay currently used by the academic institute as a template. Base period activities should focus on producing high yield cell lines that support a scalable manufacturing process without negatively impacting product potency.

3.1 Base Period: Generation of Stable mAb – Expressing Cell Lines BARDA anticipates awarding agreements to multiple CDMOs to complete Base Period activities with a period of performance of 16 months. At BARDA’s instruction, upon completion of the Base period and deliverables, cell line vials and product manufactured in the Base Period will be shipped to an external partner and undergo external potency testing. Upon request, the results will be shared with the CDMO.

3.2 Option Period: Expression and Manufacturing Optimization at Pilot Scale At the Government’s discretion, an option period may be exercised, based on performance within the Base Period. No more than two candidates will be chosen for Option activation, and award of the Option will be based on quality and process attributes such as potency and titer. During the Option period, the CDMO will perform expression optimization to improve manufacturing yield and efficiencies at a pilot scale manufacturing level.

3.3 No commercialization plan is required.

It is expected that cell lines and manufacturing processes could be tech transferred later to another CDMO, or the CDMO could reach an agreement with the IP holder for later stage development efforts.

3.4 Joint Material Transfer Agreement – Parties: BARDA, academic IP holder, Awardee CDMOs will be required to execute a Joint Material Transfer agreement (MTA) with BARDA and the Intellectual Property (IP) holder in order to obtain the mAb sequences and comparability material. This condition is non-negotiable. Offeror will submit a Letter of Intent with their proposal verifying their intent to successfully negotiate and execute the Joint MTA after award. Successful awardees will have opportunity to negotiate MTA terms within a reasonable period of time after project award. Under no circumstances will negotiations of the MTA be allowed to delay contract performance. Offeror agrees to negotiate in good faith and make best efforts to execute the MTA in a timely manner.

3.5 Applicable Documents (to be included in final SOO release)

1.1.1. Description of Potency assay

1.1.2. Manufacturing report on current process

1.1.3. DRAFT Joint Material Transfer Agreement_version 1

Tasks Awards made under this Other Transaction Authority (OTA) will support all efforts required to perform cell line development and initial manufacturing process development of the mAb cocktail.

1.1. Specific Tasks

4.1.1 Base Period: Cell Line Generation and Initial Process Development

· Establishment of an MTA with BARDA and IP holder: Successful execution of Joint MTA with BARDA and the IP holder to obtain the mAb sequences and access to comparability material is required for the performance of the anticipated award. Failure to execute an MTA within 120 days after award will result in termination of the effort.

· Establishment of a clonal cell line (CHO preferred; other lines will be considered with justification. Selected cell line should be appropriate for tech transfer to other CMOs, if required, and offeror should provide in the Base period report all relevant information in terms of fees and access rights for utilizing the cell line for follow on work)

· Establishment of a Cell Culture process in a scalable bioreactor (greater than or equal to 5L)

· Optional tasks: Development of a potency assay, for internal assessment of material

· Optional tasks: Optimization of the mAb sequence, if determined to be of value to enhance manufacturability

4.1.2 Option Period 1: Expression and Manufacturing Optimization

This Option Period may be awarded at the Government’s discretion based on offeror performance in the Base Period and demonstration of superior cell line yield with potency maintained.

· Optimization of upstream and downstream processes for drug substance (DS) production, prioritizing cost of goods and manufacturing and supporting proof of concept for manufacturability

· Formulation development to identify a DS formulation and support DS stability

· Pilot scale manufacture (200-2000L)

4.1.3 Option Period 2: Technology transfer (TT)

This Option Period may be awarded at the Government’s discretion and will support all activities necessary to enable the technology transfer of the process developed in the Base period and/or Option Period 1.

1.2. PROGRAM MANAGEMENT

Offeror is expected to provide program management which allows timely completion of all Deliverables listed in Appendix 1, including, but not limited to:

· Delivery of a signed Joint MTA with BARDA and the IP holder.

· Identification and management of distinct stages of the product development pathway that are gates for Go/No-Go decisions for advancing to the next stage of the Integrated Product Development Plan;

· Establishment and tracking of milestones and timelines for the initiation, conduct, and completion of product development activities for each stage, with a budget (in direct costs) linked to each stage;

· Maintaining and managing staff (in-house and contracted) to assure the necessary expertise and dedicated effort to perform the work;

· Conducting performance measurement that shall include:

· establishing an initial plan;

· defining measurable parameters;

· defining how these parameters relate to cost and schedule impacts;

· approach in providing a detailed schedule that generates a critical path for the project; and

· description of the cost-accounting system used or intended to be used based on budget estimates to monitor all costs related to the contract award for both prime- and sub- contractors on a real time basis;

· Directing and overseeing subcontractors and consultants to assure successful performance of planned activities within the cost and schedule constraints of the contract; and

· Development of a risk evaluation and mitigation strategy for the overall project.

DELIVERABLES

See Appendix 1.

PHYSICAL PROPERTY

Title or interest in equipment acquired by Recipient under this Agreement will vest with the Recipient.

SPECIAL TERMS

Terms related to awardee’s consideration for USA Investment are SUBJECT TO NEGOTIATION.

PERIOD OF PERFORMANCE

RISK MANAGEMENT

The Offeror must identify all anticipated project risks and track them via a Risk Register. The Offeror must manage all project risks, and report to BARDA changes to all identified risks as they occur/arise. BARDA must be permitted to participate in the risk management and mitigation processes associated with this project.

INTELLECTUAL PROPERTY

Neither BARDA nor the Offeror will obtain IP rights to the monoclonal antibodies developed under this agreement. The Offeror will be required to enter into an MTA with the IP holder to obtain the data package required to complete the objectives detailed in this SOO. A proposed draft MTA is included as APPENDIX 2 for consideration; this may be amended upon mutual agreement of the parties.

APPENDIX 1. Project Agreement Deliverables

Reporting Frequency[endnoteRef:3][endnoteRef:4] [3: Unless otherwise specified, ALL deliverables shall be emailed to the Other Transaction Agreements Officer (OTAO) and Other Transaction Technical Representative (OTTR) listed in the Agreement AND uploaded to USG-specified database/folder.] [4: All Final Deliverable Submissions are subject to USG review and comment which may result in additional Deliverable submissions by the RECIPIENT.]

Provide meeting minutes.

Kickoff meeting conducted within 5 days of award.

Minutes to be submitted within 3 business days of meeting.

Minutes to be submitted within 3 business days of meeting.

Recipient to send brief 3 working days in advance of meeting.

Base Period:

· Cell Line Development Report, including all restrictions and requirements relevant for licensing the cell line by other CDMOs or development partners

· Cell Line Stability Report

· All antibody material generated under this effort

· Cell line vials generated under this effort Option Period 1:

· Process Development Report

· Upstream Process Description

· Downstream Process Description

· Stable Formulation Development Report

· Final Manufacturing Report for DS at Pilot Scale

· Any available potency data generated by CDMO

· Tech transfer package from final manufacturing process to include cell line, manufacturing process, and any developed assays Option Period 2:

· Tech Transfer report When specifically requested via e-mail by USG Project Manager (or designee), post latest version of requested documents to shared documents site

Submitted if/as required with monthly technical progress report.

Report format: Microsoft Word and PDF

The Security Plan must include but is not limited to;

· Internal management security measures that meet the ASPR, IT, and OPSEC security requirements

· Plan to ensure Project Agreement security compliance, to include roles and responsibilities

· Plan to manage Consortium member physical, IT, and OPSEC security compliance as a contingency of Consortium membership Initial submission 30 Days after Award, updated as necessary

See BARDA Security Plan checklist

Initial submission 30 Days after Award, updated as necessary Report format: Microsoft Word and PDF

a. Plan should describe in detail the proposed plan to the objective outlined above.

b. Plan should include all analytical assumptions that will be employed in preparing and executing the sustainment effort.

c. Plan should include a range of assumptions/variables that can be used to assess various market conditions.

d. Plan should include metrics, variables, and milestones for gauging domestic and global market progress of required technologies and infrastructure that will be needed to sustain capacities beyond the period of US Government investment.

e. Plan should include all metrics, variables and milestones that define the various gates and decision points (distinct from the bullet above).

f. Plan should include a detailed description of the proposed sustainment effort. Details should include the basic steps for each phase of implementation, and which includes all dependencies between phases.

g. Plan should include identification of risks associated with execution of the plan.

Initial submission 30 Days after Award, updated as necessary Report format: Microsoft Word and PDF

Report format: Microsoft Word and PDF

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