MCM CSO AoI W911QY-20-S-C001-A003 COVID-19 SARS-CoV-2 MCM Therapeutics.pdf

U.S. Army Contracting Command – Aberdeen Proving Ground, Natick Division (ACC-APG-Natick) Joint Program Executive Office - Chemical Biological Radiological Nuclear Defense (JPEO-CBRND)

Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA)

Medical Countermeasures (MCM) Commercial Solutions Opening (CSO) Solicitation Number: W911QY-20-S-C001

Area of Interest (AOI) Number A003:

SARS-CoV-2 Medical Counter Measures (MCM) Therapeutics

1. AoI Background:

In December 2019, a novel (new) coronavirus known as SARS-CoV-2 (“the virus”) was first detected in Wuhan, Hubei Province, People’s Republic of China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. The Secretary of Health and Human Services (HHS) declared a public health emergency on January 31, 2020, under section 319 of the Public Health Service Act (42 U.S.C. 247d), in response to COVID-19. On March 1, 2020, the President of the United States, pursuant to sections 01 and 301 of the National Emergencies Act (50 U.S.C. 1601 et seq.) and consistent with section 1135 of the Social Security Act (SSA), as amended (42 U.S.C. 1320b-5), proclaimed that the COVID-19 outbreak in the United States constitutes a national emergency.

Under the President’s Operation Warp Speed Mission, HHS is leading a whole of nation effort with the primary goal to execute on a well-defined portfolio of COVID-19 medical countermeasure candidates to maximize probability of having safe and effective diagnostics, therapeutics and vaccines as fast as possible for mass distribution. As such, BARDA has an Area of Interest (AoI) for therapeutics manufacturing and fill-finish of advanced SARS-CoV-2 MCMs.

Therapeutics manufacturing is expected to meet the necessary US Food and Drug Administration (FDA) requirements for beginning a Phase 3 clinical trial, and the product be granted licensure by the FDA.

2. AoI Objective:

Manufacturing shall occur using cGMP validated manufacturing processes for bulk drug substance and fill and finished drug product. The specific objective is the acquisition of a minimum of 100,000 treatment courses for a targeted US population by March 31, 2021, to treat the US population indicated in the Offeror’s target population. The intent is “Large Scale production capability in a short period of time with little to no advance notice under the conditions for which the MCM is required.”

Candidate MCM therapeutics shall have at minimum, capability of obtaining Emergency Use Authorization (EUA) and/or a reasonable chance of moving to Phase 3 clinical trials by 4Q 2020 including all development plans and efforts, manufacturing, all done in support of the goal of achieving FDA approval/licensure in 2021. Offerors must have started, or have completed, a Phase 1 clinical study no later than August 31, 2020.

3. AoI Tasks:

Task 1: Establish a quality agreement between the US Government and Offeror on requirements for the US Government to accept packaged drug product as a completed deliverable. Quality agreement must be negotiated within the first 30 days of award and prior to Government acceptance of drug product.

Task 2: Provide within 30 days of award Product Development Source Material and Manufacturing Plan to fulfill the US Government order. The manufacturing plan should include all materials required for drug substance/active pharmaceutical ingredient manufacturing and finished drug product, an acquisition plan for acquiring necessary materials, all key subcontractors and manufacturing sites, and a detailed schedule for providing the final product to the US Government.

Task 3: Manufacture of the therapeutic product shall occur using an established manufacturing process for bulk drug substance and fill and finished drug product, with a ramp-up capacity plan that provides enough doses to meet the desired number of treatment courses.

Task 4 – Storage

Offeror shall store the packaged drug product under cGMP conditions until Emergency Use Authorization and/or FDA approval/licensure is achieved. Following, EUA or FDA approval/licensure, product will be stored until the US Government has directed the allocation of the product.

Task 5 – Distribution

Offeror shall distribute the product as directed by the US Government through the offeror’s commercial distribution network. Distribution will not occur until an EUA or FDA approval/licensure is achieved.

Task 6 – Program Management Activities:

The offeror must establish the capacity in compliance with Food and Drug Administration (FDA) current good manufacturing practices (cGMP) regulations, and Biosafety Level standards if applicable. The offeror must be responsible for management of all activities, subcontractors, etc.

to meet the goals of the contract, including holding routine meetings with USG, and completion of meeting minutes. On a monthly basis, the offeror(s) must provide a monthly report that includes capacity availability and utilization, as well as any issues that affect the operational availability of the reserved capacity.

4. AoI Deliverables:

CDRL# Deliverable Deliverable Description Reporting Procedures and Due Dates

01 Meetings

01.1 Post Award

Teleconference

The contractor shall complete an initial teleconference after contract award

1. Outline activities for the next 30 days

2. Discuss agenda items for the post-award Kickoff Meeting (01.2)

• Within one week of contract award

• Contractor shall provide agenda and establish a teleconference number at least 3 business days in advance of the teleconference unless notified that BARDA will supply one

• COR edits/approves and instructs contractor to distribute agenda prior to meeting by at least 2 business days

• Contractor provides meeting minutes to COR within 3 business days after the meeting

• COR reviews, comments and approves minutes within 10 business days

01.2 Kickoff Meeting The Contractor shall complete a Kickoff

meeting after contract award

• Within a month of contract award, pending concurrence by the contracting officer

• Contractor shall provide itinerary and agenda at least 5 business days in advance of site visit or virtual meeting

• COR edits/approves and instructs contractor to distribute agenda prior to meeting by at least 3 business days

• Contractor provides meeting minutes to COR within 3 business days after the meeting

• COR reviews, comments, and approves minutes within 10 business days

01.3 Every 2 weeks

Teleconference

The Contractor shall participate in teleconferences every 2 weeks, with BARDA to discuss the performance on the contract. Meeting frequency can be increased as needed during the course of the project

• Contractor provides agenda to COR no later than 2 business days in advance of meeting

• COR edits/approves and instructs contractor to distribute agenda prior to meeting

• Contractor distributes agenda and presentation materials at least 24 hours in advance

• Contractor provides meeting minutes to COR within 3 business days of the meeting

• COR reviews, comments, and approves minutes within 6 business days

01.4 Quarterly Meetings

At the discretion of the government the Contractor shall hold recurring teleconference or face-to-face Project

Review Meetings up to four per year either in Washington D.C or at work sites of the Contractor or sub-contractors.

Face-to-face meetings shall alternate between Washington DC and Contractor, sub-contractor sites. The meetings will be

• Contractor shall provide itinerary and agenda at least 5 business days, and presentation materials at least 3 business days in advance of site visit

• COR edits/approves and instructs contractor to distribute agenda prior to meeting by at least 3 business days

• Contractor provides meeting minutes to COR within 3 business days after the meeting

• COR reviews, comments, and approves minutes within 10 business days used to discuss contract progress in relation to the Program Management deliverables described below as well as study designs, technical, regulatory, and ethical aspects of the program.

01.5 FDA Meetings

The Contractor shall forward the dates and times of any meeting with the FDA to BARDA and make arrangements for appropriate BARDA staff to attend the FDA meetings. BARDA staff shall include up to a maximum of four people (typically COR and up to 3 subject matter experts)

• Contractor shall notify BARDA of upcoming FDA meeting within 24 hours of scheduling Type A, B or C meetings OR within 24 hours of meeting occurrence for ad hoc meetings

• The Contractor shall forward initial Contractor and

FDA-issued draft minutes and final minutes of any meeting with the FDA to BARDA within 2 business days of receipt

01.6 Daily check in with

project staff for COVID-19 Contract

Upon request of the Government, the Contractor shall participate in a daily check-in update with the project staff (via teleconference or email).

The updates will address key cost, schedule and technical updates. Daily updates may be shared with senior Government leaders during the COVID- 19 response and should be provided on a non-confidential basis, unless the update includes confidential information in which case Contractor shall provide the update in both confidential and non-confidential formats.

Daily check-ins may occur on weekdays, excluding federal holidays. Upon request of the Government, check-ins may also occur on weekends and on federal holidays, provided at least 24 hours’ notice.

• No agenda will be required for the meeting

• No meeting minutes are required

• Contractor will provide bulleted email updates following any call or in lieu of a call by 2PM for that day

02 Technical Reporting

02.1 (Monthly)

02.2 (Annual)

Monthly & Annual Technical Progress

Reports/Annual Meeting

The Monthly and Annual Technical Progress reports shall address each of the below items and be cross-referenced to the Work Breakdown Structure (WBS), Statement of Work (SOW), Integrated Master Schedule (IMS), and Contract Performance Report (CPR) – or as applicable

1. An Executive Summary highlighting the progress, issues and relevant manufacturing, non-clinical, clinical and

• Monthly Reports shall be submitted on the 20th day of the month covering the preceding month;

Annual Reports submitted on the 30th calendar day of the month after each contract anniversary.

Monthly progress reports are not required for the months when the Annual Report(s) are due, and Monthly/Annual Report(s) are not due during a month when the Final Report (final version, not draft) is due (see deliverable 02.4). The COR and CO will review regulatory activities. The Executive Summary should highlight only critical issues for that reporting period and resolution approach; limited to 2 pages

2. BARDA Contractor Clinical Trials Information Sheet – covering ongoing BARDA-sponsored clinical studies. This form shall provide data on relevant activities during the period covered, by study site, including: cumulative enrollment; new enrollments; screen failures; patients dropped from study;

AE and SAEs; activation or inactivation of study sites; investigator appointments or changes; and status of IRB/IEC review/approval/renewal

3. Progress in meeting contract milestones organized by WBS, overall project assessment, problems encountered and recommended solutions. The reports shall detail the planned and actual progress during the period covered, explaining any differences between the two and the corrective steps

4. A three-month rolling forecast of the key planned activities, referencing the

WBS/IMS

5. A tracking log of progress on regulatory submissions with the FDA number, description of submission, date of submission, status of submission and next steps

6. Estimated and Actual Expenses

a. This report shall also contain a narrative or table detailing whether there is a significant discrepancy (>10%) at this time between the % of work completed and the cumulative costs incurred to date. Monthly and actual expenses should be broken down to the appropriate WBS level. This section of the report should also contain estimates for the Subcontractors’ expenses from the previous month if the Subcontractor did not submit a bill in the previous month. If the subcontractor(s) was not working or did not incur any costs in the previous month, then a statement to this effect should be included in this report for those respective subcontractors If the COR and CO are satisfied that the contractor’s reporting is sufficient to convey this information, this section may be waived.

the monthly reports with the Contractor and provide feedback

• Contractor shall provide FINAL versions of reports within 10 business days after receiving BARDA comments/edits

02.3 (Draft)

02.4 (Final)

Draft and Final Technical Progress

Report

A draft Final Technical Progress Report containing a summation of the work performed and the results obtained over the entire contract. This report shall be in sufficient detail to fully describe the

• The Draft Technical Progress Report shall be submitted 75 calendar days before the end of the PoP and the Final Technical Progress Report on or before the completion date of the PoP progress achieved under all milestones.

Report should contain a timeline of originally planned and baselined activities and milestones overlaid with actual progress attained during the contract.

Descriptions and rationale for activities and milestones that were not completed as planned should be provided. The draft report shall be duly marked as ’Draft’

The Final Technical Progress Report incorporating feedback received from BARDA and containing a summation of the work performed and the results obtained for the entire contract PoP. The final report shall document the results of the entire contract. The final report shall be duly marked as ’Final’. A cover letter with the report will contain a summary (not to exceed 200 words) of salient results achieved during the performance of the contract

• COR will provide feedback on draft report within 15 calendar days of receipt, which the Contractor shall consider incorporating into the Final Report

02.5 FDA Manufacturing

Reports

At BARDA’s request, Contractor shall provide Manufacturing Reports to BARDA for review and comment prior to submission to FDA

The COR and CO reserve the right to request within the PoP a non-proprietary Manufacturing Report for distribution within the USG

• Contractor will submit Manufacturing Reports at least 15 business days prior to FDA submission

• The Government will provide written comments to the manufacturing report within 15 business days after the submission

• If corrective action is recommended, Contractor must address all concerns raised by BARDA in writing

• Contractor shall consider revising reports to address BARDA’s concerns and/or recommendations prior to FDA submission

02.6

Product Development Source Material and

Manufacturing Reports and Projections

The Contractor shall submit a detailed spreadsheet regarding critical project materials that are sourced from a location other than the United States, sources, and manufacturing sites, including but not limited to: physical locations of sources of raw and processed material by type of material; location and nature of work performed at manufacturing sites; and location and nature of non-clinical and clinical study sites.

The Contractor will provide manufacturing reports and manufacturing dose tracking projections/actuals utilizing the “COVID-19 Dose Tracking Templates” or similar, on any contract/agreement that is manufacturing product, including product for clinical trial use.

• Contractor will submit Product Development Source Material Report o Within month of contract award o Within 30 days of substantive changes are made to sources and/or materials o Or on the 6th month contract anniversary.

• Contractor will update the Dose Tracking

Template weekly during manufacturing campaigns and daily during response operations (where a Public Health Emergency has been declared) and COVID-19 response, with the first deliverable submission within 15 days of award/modification. Updates to be provided weekly in advance of commercial-scale manufacturing and daily once material for use in response operations begins manufacture.

• The Government will provide written comments to the Product Development Source Material and Manufacturing Report within 15 business days after the submission

• If corrective action is recommended, Contractor must address all concerns raised by BARDA in writing

• Product Development and Source Material report to be submitted via spreadsheet; Dose Tracking can be completed via spreadsheet or other format (e.g. XML or JSON) as agreed to by USG and company.

02.7 Contractor Locations

The contractor shall submit detailed data regarding locations where work will be performed under this contract, including addresses, points of contact, and work performed per location, to include sub-contractors.

ntractor will submit Work Locations Report:

• Within 5 business days of contract award

• Within 30 business days after a substantive location or capabilities change

• Within 2 business days of a substantive change if the work performed supports medical countermeasure development that addresses a threat that has been declared a Public Health Emergency by the HHS Secretary or a Public Health Emergency of International Concern (PHEIC) by the WHO

2.8 Pandemic

Management Plan

A pandemic facility and/or operational management plan including change procedures from normal to pandemic operations Contractor will prepare an operational plan to continue operations in the event of a declared pandemic emergency.

Contractor will submit Pandemic Management Plan:

• Draft within 15 days of award

• Final within 30 days of award

02.9 Final Data

Submission Package

Contractor must submit a data package consisting of all raw data produced under this contract. Data may be used by BARDA for analysis, evaluation, shared with other agencies, or shared outside of the government consistent with FAR 52.227-

14. This submission package must be delivered in a non-proprietary format.

If clinical trial data is included, that data must be provided consistent with applicable privacy laws to protect personally identifiable information (PII).

ntractor will submit at least 15 days prior to contract end date. Partial data-sets may also be requested for delivery prior to submission of the Final Data Submission Package.

02.10 Supplemental

Technical

Upon request and also as part of deliverables the Contractor shall provide ntractor shall provide the Technical Documents upon request from the CO or COR

Documents, Raw Data, Tabulation Data

(e.g., CDISC-compliant SDTM SAS

XPT datasets), or Data Analysis (e.g., CDISC-compliant ADaM SAS XPT datasets) raw data, Tabulation Data (e.g., CDISC-compliant SDTM SAS XPT datasets), or Data Analysis (e.g., CDISC-compliant ADaM SAS XPT datasets), or data report to BARDA.

02.11 Supply Chain and

Distribution Tracking

Distribution Concept of Operations.

BARDA, CDC, and MCM Manufacturers play an important role in the distribution of therapeutics to the American people under a nationwide response. BARDA will work with the manufacturer to monitor what is in the manufacturing pipeline using the enclosed dose tracking templates (see above). BARDA will relay final drug product information as it is being released to the CDC for allocation and ordering by state public health departments. This information will be returned to BARDA as CDC replenishment orders (CDC PO) on a daily basis with shipping instructions on where to send final drug product.

Manufacturers will use that information to ship vaccines or therapeutics in bulk to designated distribution centers for final distribution to end users and end user networks. BARDA will provide the contractor with a list of distribution centers and contact information prior to the start of a dispensing campaign.

Provide the following information in order to coordinate the movement and delivery of vaccine product from manufacturing locations to USG distribution centers:

• Provide Points of Contact information (name, title, phone, email) for manufacturing / supply chain personnel for each manufacturing, CMO, storage and distribution locations:

• Head of Manufacturing

• Production Planning

• Logistics

• Distribution

• Labeling

• Provide therapeutic labeling, packaging and distribution information as soon as it becomes available. At a minimum, include the following:

• Primary Container Information

• Number of doses per primary container

• Unit of Sale (carton, box, package, other)

• Quantity per Unit of Sale

• National Drug Code (NDC) or

NDC-like code under EUA

• Unit of Sale dimensions (H,W, L)

• Unit of Sale weight

• Intermediate Package

• Intermediate Package dimensions

• Intermediate Package weight

• Quantity Unit of Sale per pallet

• Storage Requirements

• Stability Information

• Obtain concurrence on planned shipment protocols prior to transport

• If therapeutic will require ultra-cold storage temperatures at the designated distribution centers, products should be packaged in 100-dose units to facilitate pick/pack process and reduce exposure of workers to ultra-cold temperatures.

• Include the following DSCSA data elements, TI, TH and TS in packing lists.

• Include the contract number and CDC’s PO number (which BARDA will provide at the time the bulk order is submitted) on the packing list for all shipments

• Include a copy of the MSDS (with QR code) in the packing list envelope with each shipment.

• Send EDI 856 Advanced Shipment Notice for all products shipped to a USG directed location. CDC will provide EDI mapping specifications that include the CDC generated PO number.

• Send electronic/scanned copies of all bulk shipment related documents to the COR for three-way matching on the day shipment occurs.

02.12 Manufacturing

Development Plan

This plan shall describe("describe the manufacturing process for the drug/biologic product to ensure conformity with §501(a)(2)(B) of the Food, Drug, and Cosmetics Act (FD&C Act, Title 21 United States Code (USC) §351 (a)(2)(B)), regarding good manufacturing practices (GMP)), but is not limited to planned or completed drug substance studies; list of excipients and information to support the safety of excipients that, when appropriate, shall be cross-referenced; drug product and formulation development summary from initial concept through final design;

physicochemical and biological properties;

manufacturing process development and validation program documents; container closure system documents [description, choice, rationale]; microbiological attributes documents and plans; compatibility documents (e.g., precipitation); assay development and validation, stability plan;

and any associated risks.")

• Plan will be delivered electronically within 30 days of contract award to the CO and COR

02.13 Quality Management

Plan

Plan may include, but is not limited to the quality policy and objectives, management review, competencies and training, process document control, feedback, evaluation, corrective action and preventive action, process improvement, measurement, and data analysis processes. The framework is normally divided into infrastructure, senior management responsibility, resource management, lifecycle management, and quality management system evaluation

• Plan will be delivered electronically within 30 days of contract award to the CO and COR

02.14 Quality Agreement Agreement will determine the conditions of acceptance by the USG of the purchased

• Agreement will be signed by the USG and the manufacturer within 30 days of contract award

• Agreement will be delivered electronically to product. No product will be accepted by the USG until a quality agreement is in place.

the CO and COR

03 Audits

03.1 BARDA Audit

Contractor shall accommodate periodic or ad hoc site visits by BARDA. If BARDA, the Contractor, or other parties identifies any issues during an audit, the Contractor shall capture the issues, identify potential solutions, and provide a report to BARDA

• If issues are identified during the audit, Contractor shall submit a report to BARDA detailing the finding and corrective action(s) within 10 business days of the audit

• COR and CO will review the report and provide a response to the Contractor with 10 business days

• Once corrective action is completed, the

Contractor will provide a final report to BARDA

03.2 FDA Audits

In the event of an FDA inspection that occurs in relation to this contract and for the product, or for any other FDA inspection that has the reasonable potential to impact the performance of this contract, the Contractor shall provide the USG with an exact copy (non-redacted) of the FDA Form 483 and the Establishment Inspection Report (EIR). The Contractor shall provide the COR and CO with copies of the plan for addressing areas of non-conformance to FDA regulations for GLP, GMP, or GCP guidelines as identified in the audit report, status updates during the plans execution and a copy of all final responses to the FDA. The Contractor shall also provide redacted copies of any FDA audits received from subcontractors that occur as a result of this contract or for this product. The Contractor shall make arrangements for BARDA representative(s) to be present during the final debrief by the regulatory inspector

• Contractor shall notify CO and COR within 10 business days of a scheduled FDA audit or within 24 hours of an ad hoc site visit/audit if the FDA does not provide advanced notice

• Contractor shall provide copies of any FDA audit report received from subcontractors that occur as a result of this contract or for this product within 1 business day of receiving correspondence from the FDA or third party

• Within 10 business days of audit report, Contractor shall provide CO with a plan for addressing areas of nonconformance, if any are identified

03.3 QA Audits

BARDA reserves the right to participate in QA audits performed by the contractor.

Upon completion of the audit/site visit the Contractor shall provide a report capturing the findings, results and next steps in proceeding with the subcontractor. If action is requested of the subcontractor, detailed concerns for addressing areas of non-conformance to FDA regulations for GLP, GMP, or GCP guidelines, as identified in the audit report, must be provided to BARDA. The Contractor shall provide responses from the subcontractors to address these concerns and plans for corrective action

• Contractor shall notify CO and COR a minimum of 10 business days in advance of upcoming, audits/site visits of subcontractors

• Contractor shall notify the COR and CO within 5 business days of report completion.

• COR and CO will review the report and provide a response to the Contractor with 10 business days

03.4 Risk Management

Plan (RMP)

The Contractor shall provide an RMP that outlines the impacts of each risk in relation to the cost, schedule, and performance objectives. The plan shall include risk mitigation strategies. Each risk mitigation strategy will capture how the corrective action will reduce impacts on cost, schedule and performance

• A Draft is due 90 business days within contract award; updates to the RMP are due concurrent with Monthly Technical Progress Reports. The contractor may choose to notify the government up to two times every three months if there are no changes from the prior submission, and not submit an update

• BARDA will provide Contractor with a list of concerns in response plan submitted

• Contractor must address, in writing, all concerns raised by BARDA within 20 business days of Contractor’s receipt of BARDA’s concerns

03.5 Integrated Master

Schedule (IMS)

The contractor shall provide an IMS that illustrates project tasks, dependencies, durations throughout the period of performance, and milestones (GO/NO- GO). The IMS must map to the WBS, and provide baseline, and actual or forecast dates for completion of tasks

• The IMS is to be submitted in both PDF and Microsoft Project Form to the COR

• The first Draft of the IMS is due 30 business within contract award

• The Government will request revisions within 10 business days, at which point the schedule baseline for the period of performance will be set

• Thereafter an updated IMS is due concurrent with

Monthly Technical Progress Reports

• During a declared Public Health Emergency, the

IMS is to be delivered within 10 days of contract award, updates are due weekly, and any significant change (I.e. a change which would impact the schedule by greater than one week) must be reported immediately to the COR and/or designee.

03.6 Deviation Notification

and Mitigation Strategy

Process for changing IMS activities associated with cost and schedule as baselined. Contractor shall notify BARDA of significant proposed changes the IMS defined as increases in cost above 5% or schedule slippage of more than 30 days, which would require a PoP extension.

Contractor shall provide a high level management strategy for risk mitigation

• Due at least 10 business days prior to the Contractor anticipating the need to implement changes

03.7 Incident Report

Contractor shall communicate to BARDA and document all critical programmatic concerns, issues, or probable risks that have or are likely to significantly impact project schedule and/or cost and/or performance. “Significant” is frequently defined as a 10% or greater cost or schedule variance within a control account, but should be confirmed in consultation with the COR. Incidents that present liability to the project even without cost/schedule impact, such as breach of GCP during a clinical study, must also be reported

• Due within 48 hours of activity or incident or within 24 hours for a security activity or incident

• Email or telephone with written follow-up to COR and CO

• Additional updates due to COR and CO within 48 hours of additional developments

• Contractor shall submit within 5 business days a

Corrective Action Plan (if deemed necessary by either party) to address any potential issues

• If corrective action is deemed necessary, Contractor must address in writing, its consideration of concerns raised by BARDA within 5 business days of receiving such concerns

09 Advanced R&D Products

09.1 Technical Documents

Upon request, Contractor shall provide CO and COR with deliverables from the following contract funded activities: quality agreements between contractors and sub-contractors, process Development Reports, Assay Qualification Plan/Report, Assay Validation Plan/Report, Assay Technology Transfer Report, Batch Records, SOPs, Master Production Records, Certificate of Analysis, Clinical Studies Data or Reports. The CO and COR reserve the right to request within the PoP a non-proprietary technical document for distribution within the Government

• Contractor shall provide technical document within 10 business days of CO or COR request.

Contractor can request additional time on an as needed basis

• If corrective action is recommended, the

Contractor must address, in writing, concerns raised by BARDA in writing

09.2 Animal Model or

Other Technology Transfer Package

Contractor shall provide Animal Model or Other Technology Transfer Package containing relevant methodology and data sufficient to enable other practitioners in the field to successfully replicate experimental conditions developed and tested with BARDA support

• Contractor shall provide a draft package within 20 business days of COR or CO request

• Contractor shall revise the package to address

BARDA’s concerns, recommendations and/or requests for additional detail

09.3

Raw Data, Tabulation Data (e.g., CDISC-compliant SDTM SAS XPT datasets), or

Data Analysis (e.g., CDISC-compliant ADaM SAS XPT datasets)

Contractor shall provide raw data, Tabulation Data (e.g., CDISC-compliant SDTM SAS XPT datasets), or Data Analysis (e.g., CDISC-compliant ADaM SAS XPT datasets), to BARDA upon request

• Contractor shall provide raw data, Tabulation Data (e.g., CDISC-compliant SDTM SAS XPT datasets), or Data Analysis (e.g., CDISC-compliant ADaM SAS XPT datasets) to CO and COR within 20 business days of request

09.4 Publications

Any manuscript or scientific meeting abstract containing data generated under this contract must be submitted to BARDA for review prior to submission.

Acknowledgment of BARDA funding must be included as noted in contract articles H.9 and H.24

• Contractor must submit all manuscript or scientific meeting abstract to PO and CO prior to submission/presentation by 30 business days for manuscripts and 15 business days for abstracts or posters

• Contractor must address in writing all concerns raised by BARDA in writing

• Final submissions shall be submitted to BARDA concurrently or no later than one (1) calendar day of its submission

10 Regulatory Documents

10.1 FDA Correspondence

The Contractor shall memorialize any correspondence between Contractor and FDA and submit to BARDA

• Contractor shall provide copies of any FDA correspondence within 2 business days of correspondence

10.2 FDA Submissions

The Contractor shall provide BARDA the opportunity to review and comment upon all draft submissions before submission to the FDA. Contractor shall provide BARDA with an electronic copy of the final FDA

• Contractor shall submit draft FDA submissions to BARDA at least 15 business days prior to FDA submission

• BARDA will provide feedback to Contractor within

10 business days of receipt submission. All documents shall be duly marked as either “Draft” or “Final”

• The Contractor must address, in writing, its consideration of all concerns raised by BARDA prior to FDA submission

• Final FDA submissions shall be submitted to

BARDA concurrently or no later than 1 calendar day of submission

11 Press Releases Contractor agrees to accurately and factually represent the work conducted under this contract in all press releases

• Contractor shall ensure that the CO has received and approved an advanced copy of any press release to this contract not less than 5 business days prior to the issuance of the press release

• If corrective action is required, the Contractor agrees to accurately and factually represent the work conducted under this contract in all press releases

• Any final press releases shall be submitted to BARDA no later than one (1) calendar day prior to its release

2. Detailed Description of Select Contract Deliverables

A. Monthly and Annual Progress Reports In addition to those reports required by the other terms of this contract, the Contractor shall prepare and submit the following reports in the manner stated below and in accordance with this Article F of this contract, and in the Statement of Work, attached to this contract as Attachment 1 (SECTION J-List of Attachments).

i. Monthly Progress Report This report shall include a description of the activities during the reporting period, and the activities planned for the ensuing reporting period. The first reporting period consists of the first full month of performance plus any fractional part of the initial month. Thereafter, the reporting period shall consist of each calendar month.

The Contractor shall submit a Monthly Progress Report according to the dates set forth in the summary table (“Summary of Contract Deliverables”) under this article. The progress report shall conform to the requirements set forth in the DELIVERIES Article in SECTION F of this contract.

The format should include:

• A cover page that includes the contract number and title; the type of report and period that it covers; the Contractor’s name, address, telephone number, fax number, and e-mail address; and the date of submission;

• SECTION I – EXECUTIVE SUMMARY

• SECTION II – PROGRESS

• SECTION II Part A: OVERALL PROGRESS - A description of overall progress.

• SECTION II Part B: MANAGEMENT AND ADMINISTRATIVE UPDATE -

A description of all meetings, conference calls, etc. that have taken place during the reporting period. Include progress on administration and management issues (e.g., evaluating, and managing subcontractor performance, and personnel changes).

• SECTION II Part C: TECHNICAL PROGRESS - For each activity related to Gantt chart, document the results of work completed and cost incurred during the period covered in relation to proposed progress, effort and budget. The report shall be in sufficient detail to explain comprehensively the results achieved. The description shall include pertinent data and/or graphs in sufficient detail to explain any significant results achieved and preliminary conclusions resulting from analysis and scientific evaluation of data accumulated to date under the contract. The report shall include a description of problems encountered and proposed corrective action; differences between planned and actual progress, why the differences have occurred and what corrective actions are planned; preliminary conclusions resulting from analysis and scientific evaluation of data accumulated to date under the project.

• SECTION II Part D: PROPOSED WORK - A summary of work proposed related to Gantt chart for the next reporting period and preprints/reprints of papers and abstracts.

• SECTION III: Estimated and Actual Expenses.

a. This section of the report shall contain a narrative or table detailing whether there is a significant discrepancy (>10%) at this time between the % of work completed and the cumulative costs incurred to date. Monthly and actual expenses should be broken down to the appropriate WBS level.

b. This section of the report should also contain estimates for the Subcontractors’ expenses from the previous month if the Subcontractor did not submit a bill in the previous month. If the subcontractor(s) was not working or did not incur any costs in the previous month, then a statement to this effect should be included in this report for those respective subcontractors.

A Monthly Progress Report will not be required in the same month that the Annual Progress Report is submitted.

ii. Annual Progress Report

This report shall include a summation of the results of the entire contract work for the period covered. Monthly Progress Reports shall not be submitted in the same month when an Annual Progress Report is due. Furthermore, an Annual Progress Report will not be required for the period when the Final Report is due.

The first Annual Progress Report shall be submitted in accordance with the date set forth in the table (“Summary of Contract Deliverables”) under ARTICLE F.2. of this contract. The progress report shall conform to the requirements set forth in the DELIVERIES Article in SECTION F of this contract.

Each Annual Progress Report shall include:

• A Cover page that includes the contract number and title; the type of report and period that it covers; the Contractor's name, address, telephone number, fax number, and email address; and the date of submission;

• SECTION I: EXECUTIVE SUMMARY - A brief overview of the work completed, and the major accomplishments achieved during the reporting period.

• SECTION II: PROGRESS

• SECTION II Part A: OVERALL PROGRESS - A description of overall progress.

• SECTION II Part B: MANAGEMENT AND ADMINISTRATIVE UPDATE - A high level summary of critical meetings, etc. that have taken place during the reporting period. Include progress on administration and management to critical factors of the project (e.g. regulatory compliance audits and key personnel changes).

• SECTION II Part C: TECHNICAL PROGRESS - A detailed description of the work performed structured to follow the activities and decision gates outlined at the Integrated Baseline Review and as described in the Integrated Master Plan.

The Report should include a description of any problems (technical or financial) that occurred or were identified during the reporting period, and how these problems were resolved.

• SECTION II Part D: PROPOSED WORK - A summary of work proposed for the next year period to include an updated Gantt Chart.

• SECTION III: Estimated and Actual Expenses.

a. This section of the report shall contain a narrative or table detailing whether there were discrepancies between estimated and actual expenses over the past year.

Actual expenses should be broken down to the appropriate WBS level. This section of the report should also contain estimates for outstanding costs for the previous year which may have been incurred, but not yet billed.

Contractor also should include the following in the Annual Progress Report:

1. Copies of manuscripts (published and unpublished), abstracts, and any protocols or methods developed specifically under the contract during the reporting period; and

2. A summary of any Subject Inventions per the requirements under FAR Clause 52.227-11.

iii. Draft Final Report and Final Report

These reports are to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Draft Final Report and Final Report shall be submitted in accordance with the DELIVERIES Article in SECTION F of the contract. An Annual Progress Report will not be required for the period when the Final Report is due. The Draft Final Report and the Final Report shall be submitted in accordance with the dates set forth in the table (“Summary of Contract Deliverables”) under ARTICLE F.2. of this contract.

The report shall conform to the following format:

1. Cover page to include the contract number, contract title, performance period covered, Contractor's name and address, telephone number, fax number, email address and submission date.

2. SECTION I: EXECUTIVE SUMMARY - Summarize the purpose and scope of the contract effort including a summary of the major accomplishments relative to the specific activities set forth in the Statement of Work.

3. SECTION II: RESULTS - A detailed description of the work performed related to WBS and Gantt chart, the results obtained, and the impact of the results on the scientific and/or public health community including a listing of all manuscripts (published and in preparation) and abstracts presented during the entire period of performance and a summary of all inventions.

Draft Final Report: The Contractor is required to submit the Draft Final Report to the Contracting Officer’s Representative and Contracting Officer. The Contracting Officer’s Representative and Contracting Officer will review the Draft Final Report and provide the Contractor with comments in accordance with the dates set forth in ARTICLE F.2. of this contract.

Final Report: The Contractor will deliver the final version of the Final Report on or before the completion date of the contract. The final version shall include or address the COR’s and CO’s written comments on the draft report. Final Report shall be submitted on or before the completion date of the contract.

iv. Summary of Salient Results

The Contractor shall submit, with the Final Report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract.

v. Audit Reports

Within thirty (30) calendar days of an audit related to conformance to FDA regulations and guidance, including adherence to GLP, GMP, GCP guidelines, the Contractor shall provide copies of the audit report (so long as received from the FDA) and a plan for addressing areas of nonconformance to FDA regulations and guidelines for GLP, GMP, or GCP guidelines as identified in the final audit report.

vi. Other Technical Reports

1. Supplemental Technical Documents

Upon request, Contractor shall provide CO and COR with the following contract funded documents as specified below but not limited to: Process Development Reports; Assay Qualification Plan/Report, Assay Validation Plan/Report, Assay Technology Transfer Report, Batch Records, Contractor/Subcontractor Standard Operating Procedures (SOP’s), Master Production Records, Certificate of Analysis, Clinical Studies Data or Reports. The CO and COR reserve the right to request within the Period of Performance a non-proprietary technical document for distribution within the USG. Contractor shall provide technical document within 10 business days of CO or COR request. Contractor can request additional time on an as needed basis. If edits are recommended, the Contractor must address, in writing, concerns raised by BARDA.

B. Deliverables Arising from FDA Correspondence

i. FDA Meetings

The Contractor shall forward the dates and times of any meeting with the FDA to BARDA and make arrangements for appropriate BARDA staff to attend the FDA meetings. BARDA staff shall include up to a maximum of four people.

• Contractor shall notify BARDA of upcoming FDA meeting within 24 hours of scheduling Type A, B or C meetings OR within 24 hours of meeting occurrence for ad hoc meetings.

• The Contractor shall forward initial Contractor and FDA-issued draft minutes and final minutes of any meeting with the FDA to BARDA within 5 business days of receipt. All documents shall be duly marked as either “Draft” or “Final.”

ii. FDA Submissions

The Contractor shall provide BARDA all documents submitted to the FDA.

Contractor shall provide BARDA with an electronic copy of the final FDA submission. All documents shall be duly marked as either “Draft” or “Final.”

• When draft documents are submitted for BARDA review, BARDA will provide feedback to Contractor within 10 business days of receipt.

• When BARDA reviews draft documents, the Contractor shall revise their documents to address BARDA’s written concerns and/or recommendations prior to FDA submission.

• Final FDA submissions shall be submitted to BARDA concurrently or no later than 1 calendar day of their submission to FDA.

iii. FDA Audits

In the event of an FDA inspection which occurs as a result of this contract and for the product, or for any other FDA inspection that has the reasonable potential to impact the performance of this contract, the Contractor shall provide the USG with an exact copy (non-redacted) of the FDA Form 483 and the Establishment Inspection Report (EIR) within five (5) business days after the Contractors receipt of those documents. The Contractor shall provide the COR and CO with copies of the plan for addressing areas of non-conformance to FDA regulations for GLP, GMP, or GCP guidelines as identified in the audit report, status updates during the plans execution and a copy of all final responses to the FDA. The Contractor shall also provide redacted copies of any FDA audits received from subcontractors that occur as a result of this contract or for this product. The Contractor shall make arrangements for BARDA representative(s) to be present during the final debrief by the regulatory inspector.

• Contractor shall notify CO and COR within 10 business days of a scheduled FDA audit or within 24 hours of an ad hoc site visit/audit if the FDA does not provide advanced notice.

• Contractor shall provide copies of any FDA audit report received from subcontractors that occur as a result of this contract or for this product within 5 business days of receiving correspondence from the FDA, Subcontractor, or third party.

• Within 10 business days of audit report, Contractor shall provide CO with a plan for addressing areas of nonconformance, if any are identified.

iv. Manufacturing Campaign Reports

Contractor shall provide Manufacturing Campaign Reports to BARDA for review and comment prior to submission to FDA.

The COR and CO reserve the right to request within the Period of Performance (PoP) a non-proprietary Manufacturing Campaign Report for distribution within the USG.

• Contractor will submit Manufacturing Campaign Reports at least 15 business days prior to FDA submission.

• If corrective action is recommended, Contractor must address, in writing, all concerns raised by BARDA.

• Contractor shall revise the reports to address BARDA’s concerns and/or recommendations prior to FDA submission.

• Final FDA submission shall be submitted to BARDA concurrently or no later than 1 business day after submission to the FDA.

v. Other FDA Correspondence

The Contractor shall memorialize any correspondence between Contractor and FDA and submit to BARDA. All documents shall be duly marked as either “Draft” or “Final.”

Contractor shall provide written summary of any FDA correspondence within 5 business days of correspondence.

i. Risk Management Plan

The Contractor shall provide a Risk Management Plan that outlines the impacts of each risk in relation to the cost, schedule, and performance objectives. The plan shall include risk mitigation strategies. Each risk mitigation strategy will capture how the corrective action will reduce impacts on cost, schedule and performance.

• Due within 90 days of contract award

• Contractor provides updated Risk Management Plan in Monthly Progress Report

• BARDA shall provide Contractor with a written list of concerns in response plan submitted

• Contractor must address, in writing, all concerns raised by BARDA within 20 business days of Contractor’s receipt of BARDA’s concerns.

5. AoI Constraints:

a. Offeror (s) selected to receive an award will be required to be registered in the System for Award Maintenance (sam.gov). It is critical offerors are registered in the System for Award Management (SAM), https://www.sam.gov/. Companies will be ineligible for an award if not registered in SAM. Additionally, verify that you are registered to receive contracts (not just grants) and that your address matches your proposal and

SAM.

b. When registering in SAM.gov, be sure to select ‘YES’ to the question ‘Do you wish to bid on contracts?’ in order to be able to compete for CSO. If you are only registered to compete for grants, you may be ineligible for award.

c. The government is working to move expeditiously to execute contract(s), therefore it is extremely important that all companies double check your CAGE codes and DUNS numbers to ensure they are accurate. If they are not accurate at the time of submission, you may be ineligible for award.

d. If applicable under Food and Drug Administration (FDA or USFDA) guidance addressing the current public health emergency, offerors will be required to comply with the Drug Supply Chain Security Act (DSCSA).

e. The…