Draft PWS - Human Monoclonal Antibody (mAb) Development.docx

DRAFT PERFORMANCE WORK STATEMENT (PWS)

Human Monoclonal Antibody (mAb) Development for Walter Reed Army Institute of Research (WRAIR), Armed Forces Research Institute of Medical Sciences (WRAIR-AFRIMS)

26 March 2024

PART 1

GENERAL INFORMATION

1. General: This is a non-personal service(s) contract under which the personnel rendering the service(s) are not subject, either by the contract’s terms or by the manner of its administration, to the supervision and control usually prevailing in relationships between the Government and its employees.

1.1 Description of Services/Introduction: This is a non-personal service(s) contract to provide human Monoclonal Antibody (mAb) development.

1.2 Background: Since 1893, the Walter Reed Army Institute of Research (WRAIR) has been a leader in solving the most significant threats to Soldier readiness and lethality such as disease and battle injury. WRAIR’s broad research capabilities afford Soldiers the best medical protection and support possible before, during, and after deployment by addressing both longstanding and emerging threats. Though WRAIR’s research is focused on Soldier health, its products have important civilian applications, saving countless lives around the world. Though WRAIR’s research is focused on Soldier health, its products have important civilian applications responsible for saving countless lives around the world.

The WRAIR, Armed Forces Research Institute of Medical Sciences (WRAIR-AFRIMS) is a directorate of the WRAIR under the United States Army Medical Research and Development Command (USAMRDC). The mission of WRAIR-AFRIMS is to optimize Soldier lethality and mission effectiveness by developing solutions to infectious disease capability gaps through product development and surveillance research in Asia. With research focus areas including arboviruses, multidrug-resistant organisms, respiratory viruses, sexually transmitted infections, and vector-borne illness, WRAIR-AFRIMS has a rich and successful history developing drugs and vaccines against diseases such as drug resistant malaria, diarrhea and dysentery, dengue, Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS), influenza, Japanese encephalitis, leptospirosis, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), scrub typhus, and other emerging infectious diseases.

1.3 Scope/Period of Performance (PoP):

1.3.1 Scope: The contractor shall provide non-personal service(s). This shall include providing all necessary personnel, equipment, supplies, facilities, transportation, tools, materials, supervision, and other items necessary to perform services as described in the Performance Work Statement (PWS) and associated contract documents, except for those items specified in Part 3, Government Property and Services. The contractor shall perform to the standards and Acceptable Quality Levels (AQLs) identified in this PWS and associated contract documents.

1.3.2 Period of Performance (PoP): The Period of Performance (PoP) for this requirement shall be as follows:

1.4 Objectives: The objective of this contract is to perform feasibility studies for the development and production of a panel of fully human mAbs for AFRIMS-supplied target antigens or using AFRIMS-supplied cultured B cells for use in developing immunotherapeutics against bacterial pathogens associated with wound infection and sepsis. This shall include immunization in transgenic animal model expressing fully human Immunoglobulin G (IgG) antibodies, high-throughput single-cell screening for antigen-specific Antibody-Secreting Cells (ASCs), and cloning and expression of recombinant mAbs.

1.5 General Information:

1.5.1 Quality Control Plan (QCP): Because this acquisition is for commercial services, the Government shall rely on the contractor’s existing Quality Assurance (QA) system In Accordance With (IAW) Federal Acquisition Regulation (FAR) 12.208. The contractor shall inform the Contracting Officer’s Representative (COR) of issues or potential issues that might affect performance within 24 hours of identifying those issues. Verbal reports shall be followed up by written reports to be submitted to the COR within two days of identification of issue (A.001).

1.5.2 Quality Assurance (QA): The Government will evaluate the contractor’s performance under this contract IAW the Quality Assurance Surveillance Plan (QASP). This plan is primarily focused on what the Government must do to ensure that the contractor has performed IAW the performance standards. It defines how the performance standards will be applied, the frequency of surveillance, and the AQLs (performance thresholds).

1.5.3 Recognized Holidays: The following provides information on recognized holidays for the purpose of this PWS. If deadlines for submittal of any documentation (e.g., deliverables, submittals, etc.) fall on a holiday, the closest work day prior to the holiday will apply as the deadline for submittal.

1.5.3.1 United States (U.S.) Holidays: Work shall not be performed on United States (U.S.) federally recognized holidays occurring during the normal workweek unless otherwise directed by the Contracting Officer (KO). When a U.S. holiday occurs on a Saturday or a Sunday, the holiday is observed on the preceding Friday or following Monday, respectively.

New Year’s Day, January 1st Martin Luther King Jr. Day, 3rd Monday in January Presidents’ Day, 3rd Monday in February Memorial Day, last Monday in May Juneteenth, June 19th Independence Day, July 4th Labor Day, 1st Monday in September Indigenous Peoples Day, 2nd Monday in Oct.

Veteran’s Day, November 11th Thanksgiving Day, 4th Thursday in November Christmas Day, December 25th

1.5.3.2 Host Nation Holidays: RESERVED.

1.5.4 Operating Hours: The Government facility office hours, Government facility operating hours, and the contractor support hour requirements may differ. The contractor is not expected to provide support during the same hours as the supported Government organization (WRAIR-AFRIMS) which is located in Bangkok, Thailand. The contractor shall maintain an adequate workforce at all times to execute uninterrupted performance of all tasks defined within this PWS.

1.5.4.1 Contractor Work Plan: The contractor shall prepare and maintain a work plan. The plan, as a minimum, shall identify regularly scheduled work to include location, work to be completed, timeline, etc. The contractor’s proposed work plan shall be submitted to the KO via the COR for review within 10 days after contract award. The Government will review and either accept or return their comments to the contractor within 10 days. The contractor shall then have three days to submit a final work plan. Any proposed change to the accepted final work plan is required to be resubmitted to the COR for review and acceptance by the KO at least 30 days prior to implementation. The timeline noted above shall apply for review and acceptance of proposed changes (A.002).

1.5.5 Training Holidays: RESERVED.

1.6 Place of Performance: The work to be performed under this contract shall be performed off-site at contractor facilities that may be located anywhere in the Continental United States (CONUS).

1.6.1 Contractor Facility Capabilities: The contractor’s facility shall have access to a Beacon® optofluidic high-throughput cell screening platform.

1.7 Security Requirements: The contractor will not require access to Government facilities or networks to perform work under this PWS; however, the contractor shall safeguard all Government materials (e.g., information, antigen samples, cultured cell samples) provided for contractor use.

1.7.1 Security Program: RESERVED.

1.7.2 Personnel Security Clearance Requirements: RESERVED.

1.7.3 Installation Access: RESERVED.

1.7.3.1 Installation Pass Log: RESERVED.

1.7.3.2 Individual Termination or Expiration of Employment: RESERVED.

1.7.3.3 Contract Termination or Cancellation: RESERVED.

1.7.3.4 Common Access Cards (CAC) and CAC Log: RESERVED.

1.7.4 Background Checks:

1.7.4.1 United States (U.S.) Citizen: RESERVED.

1.7.4.2 Local Nationals and Third Country Nationals: RESERVED.

1.7.5 Physical Security: RESERVED.

1.7.6 Operations Security (OPSEC) Requirements: RESERVED.

1.7.7 Key Control: RESERVED.

1.8 Post Award Conference/Periodic Progress Meetings: The contractor shall attend any post award conference convened by the contracting activity or contract administration office IAW FAR Subpart 42.5. The KO, COR, and other Government personnel, as appropriate, may meet periodically with the contractor to review the contractor's performance. At these meetings the KO will apprise the contractor of how the Government views the contractor's performance and the contractor shall apprise the Government of problems, if any, being experienced. Appropriate action shall be taken to resolve outstanding issues. These meetings shall be at no additional cost to the Government.

The contractor shall attend, participate in, and furnish input to scheduled and unscheduled meetings, conferences, and briefings that relate to the functions and services herein as required by the Government to provide effective communication and impart necessary information. The contract manager or designated representative shall attend meetings as requested by the Government. Meeting attendees shall at times include contractor managerial, supervisory, and other personnel knowledgeable of the subject matter. Meetings may start or end outside of regular duty hours (A.003).

1.9 Contracting Officer’s Representative (COR): Refer to Part 2 of this PWS for the definition of a COR. As determined by the KO, a COR will be appointed and identified by letter of designation, a copy of which will be provided to the contractor by the KO. The designation letter states the responsibilities and limitations of the COR, especially with regard to changes in cost or price, estimates, or changes in delivery dates. The COR is not authorized to change any of the terms and conditions of the resulting order. The COR monitors all technical aspects of the contract and assists in contract administration. The COR is not authorized to obligate the Government. If the work is not written in the contract, the COR is not authorized to request new work. The COR is authorized to perform the following functions: assure that the contractor performs the technical requirements of the contract; perform inspections necessary in connection with contract performance; maintain written and oral communications with the contractor concerning technical aspects of the contract; issue written interpretations of technical requirements, including Government drawings, designs, and specifications; monitor contractor's performance and notify both the KO and contractor of any deficiencies; coordinate availability of Government property (if applicable); and coordinate site entry of contractor personnel (if applicable).

1.10 Key Personnel: The contractor shall possess the necessary training, qualifications, and experience to accomplish all tasks identified in this PWS. The contractor shall provide key personnel IAW the minimum requirements listed below. The following personnel are considered key personnel by the Government:

a. Immunologist: The immunologist shall meet the following minimum qualifications:

i. Ph.D. in immunology or related field

ii. Over five years of experience with mAb screening, expression, and purification

1.10.1 Substitution or Replacement: Substitutions of proposed key personnel shall not be allowed for a period of six months after contract award, except under extreme circumstances. Any substitution or replacement key personnel shall have the necessary experience and knowledge required to perform the duties defined herein. For temporary and/or permanent replacement of key personnel, the contractor shall provide a resume or Curriculum Vitae (CV) for each individual to the COR. Resumes/CVs shall be provided at least two weeks (or as mutually agreed upon) prior to making any personnel changes. The Government reserves the right to pre-approve any replacement or substitution of key personnel. Substitution or replacement personnel shall be replaced within 30 days (A.004).

1.10.2 Evaluation Criteria: When contractor personnel are evaluated in a source selection process and used as an evaluation factor in a best value procurement, an offer can be rejected if it does not have a firm commitment from the person(s) listed in the proposal to fulfill the key personnel role(s).

1.11 Identification of Contractor Employees: All contractor personnel attending meetings, answering Government telephones, and working in other situations where their contractor status is not obvious to third parties must identify themselves, to include proper marking of signature blocks in correspondence, to avoid creating an impression in the minds of members of the public that they are Government officials. The contractor shall ensure that all documents or reports produced by contractors are suitably marked as contractor products or that contractor participation is appropriately disclosed.

1.11.1 Contractor Communication: Contractor employees shall identify themselves by name and company affiliation when answering the telephone, presenting briefings, and conducting or attending meetings and seminars. All contractor correspondence (e.g., written, facsimile, and email display) shall include their company name.

1.11.2 Contractor Identification Badges: RESERVED.

1.12 Contractor Travel: RESERVED.

1.13 Other Direct Costs (ODCs): Cost type Contract Line Item Numbers (CLINs) under this contract will be invoiced as Other Direct Costs (ODCs). Examples of ODCs anticipated under this contract include humanized transgenic mice and consumables (e.g., reagents, supplies) for cell culture, expression, and purification. The contractor shall manage and account for all costs associated with ODCs, which shall not exceed the ODC price ceiling listed in this contract. All ODCs exceeding $3,000 require the contractor conduct appropriate competition and obtain approval from the COR prior to purchase. Equipment purchases are not authorized under this contract.

1.13.1 Invoices: The contractor shall electronically submit invoices monthly to Wide Area Work Flow (WAWF) with sufficient documentation to provide certification of invoice. The contractor is responsible for properly preparing and forwarding the invoice and receiving report for payment to the appropriate Government official. The WAWF – Receipt and Acceptance application is the required method of submission (A.005).

1.13.2 Backup: The contractor shall attach backup information to receiving reports for ODCs. Backup information for ODCs shall list all elements of costs (A.005).

1.14 Data Rights: The Government has unlimited rights to all documents and materials produced under this contract. All documents and materials, to include the source codes of software, produced under this contract shall be Government owned and are the property of the Government with all rights and privileges of ownership and copyright belonging exclusively to the Government. These documents and materials may not be used or sold by the contractor without written permission from the KO. All materials supplied to the Government shall be the sole property of the Government and may not be used for any other purpose. This right does not abrogate any other Government rights.

1.15 Non-Disclosure Requirements: Performance under this contract may require the contractor to access data and information proprietary to a Government agency, another Government contractor, or of such nature that its dissemination or use other than as specified in this PWS would be adverse to the interests of the Government or others. The contractor and contractor personnel shall not divulge or release data or information developed or obtained under performance of this PWS except to authorized Government personnel or upon written approval of the KO. The contractor shall not use, disclose, or reproduce proprietary data, which bears a restrictive legend, other than as specified in this PWS. All documentation showing individual names or other personal information shall be controlled and protected under the provisions of the Privacy Act of 1974, Public Law 93-579, and 5 United States Code (U.S.C.) Section 552a.

1.15.1 Non-Disclosure Statements: All contractors shall provide a signed non-disclosure agreement to the Government prior to commencement of work under this contract. Disclosure of information by contractor personnel may result in removal of contractor personnel from performance under this contract (A.006).

1.16 Protection of Government and Contract Information: Per Public Use Notice of Limitations stated by Defense Imagery Management Operations Center (DIMOC) and contained at www.dimoc.mil/resources/limitations/, the contractor shall not cite any information (e.g., contract information, pictures, locations, etc.) obtained through this contract on any hard copy or digital marketing tools to include its company website.

1.17 Organizational Conflict of Interest (OCI): Contractor and subcontractor personnel performing work under this contract may receive, have access to, participate in the development of proprietary or source selection information (e.g., cost or pricing information, budget information or analyses, specifications, or work statements, etc.), or perform evaluation services which may create a current or subsequent Organizational Conflict of Interest (OCI) as defined in FAR Subpart 9.5. The contractor shall notify the KO immediately whenever it becomes aware that such access or participation may result in any actual or potential OCI and shall promptly submit a plan to the KO to avoid or mitigate any such OCI. The contractor’s OCI mitigation plan will be determined to be acceptable solely at the discretion of the KO. In the event the KO unilaterally determines that any such OCI cannot be satisfactorily avoided or mitigated, the KO may affect other remedies as he or she deems necessary, including prohibiting the contractor from participation in subsequent contracted requirements which may be affected by the OCI (A.007).

1.18 Phase In /Phase Out Period: RESERVED.

1.19 Safety: The following provides information pertaining to safety and accident prevention:

1.19.1 Safety Laws and Regulations: The contractor shall comply with FAR 52.236-13, Accident Prevention (November 1991), and the references contained therein (e.g., U.S. Army Corps of Engineers Safety and Health Requirements Manual (EM 385-1-1)).

The requirements under FAR 52.236-13 and specifically of the EM 385-1-1 include, but are not limited to, the following:

a. Before initiation of work at the job site, an Accident Prevention Plan, written by the contractor for the specific work and hazards of the contract and implementing in detail the pertinent requirements of EM 385-1-1, will be reviewed for acceptance by designated Government personnel. Specific requirements for development of the Accident Prevention Plan are found in Appendix A of EM 385-1-1. EM 385-1-1 is available online at www.usace.army.mil (A.008).

b. Before beginning each activity involving a type of work presenting hazards not experienced in previous project operations or where a new work crew or subcontractor is to perform work, an Activity Hazard Analysis (AHA) shall be prepared by the contractor performing the work activity (see EM 385-1-1) (A.009).

c. The contractor shall require subcontractors to submit their plan of operations showing methods they propose to use in accomplishing major phases of work.

d. The contractor shall discuss the plans in conferences convened by the KO prior to starting work on each major phase of operation. Plans shall include all pertinent information such as layout of haul roads, access roads, storage areas, electrical distribution lines, methods of providing minimum exposure to overhead loads, and methods of access to work areas. The plan for accomplishing the initial work phase shall be submitted within 15 days after contract award. Plans for subsequent major phases of work shall be submitted no later than 15 days prior to initiation of work on each major phase (A.010).

e. In all areas where construction, demolition, alteration, building, or similar related activities take place, the contractor shall have the following minimum personal protective clothing and equipment requirements in place for any person working on or visiting the site:

i. Short sleeve shirt;

ii. Long trousers;

iii. Steel-toed safety boots; and

iv. Hard hat.

1.19.2 In addition to other requirements for accident prevention specified in this contract, the contractor shall comply with all Federal and State requirements governing safety and health protection on construction sites and other applicable occupational safety codes. The contractor shall indicate its plan for compliance considering conditions of the work described by the design, technical proposal, operational activities of the Government or others in the area of the work, identification of the coordinator, and implementation of all other accident prevention provisions of this contract (A.011).

1.19.3 The contractor shall complete and provide all required safety notifications and provide documented proof to the KO via the COR within five days of such notifications being made (A.012).

1.20 Environmental Compliance: The following provides information on environmental compliance.

1.20.1 Environmental Compliance Plan and Program: RESERVED.

1.21 Required Training: All contractor personnel, including subcontractor personnel, shall complete all standard Department of Defense (DoD) and component level annual training requirements as identified and instructed by the COR. Training courses may be available on Joint Knowledge Online (JKO) (https://jkodirect.jten.mil) or instructions for completion will be provided by the COR. Most trainings are approximately one to two hours in duration and will be required prior to beginning work on the TO, with refresher training required annually. Example courses include, but are not limited to, the following:

a. Anti-Terrorism Level I

b. Controlled Unclassified Information (CUI)

c. Health Insurance Portability and Accountability Act (HIPPA)

d. DoD Cyber Awareness Challenge (Information Assurance (IA))

e. Information Security (InfoSec) Program

f. Privacy and Civil Liberties

g. Army OPSEC Level I

The contractor shall develop and include procedures for monitoring training compliance and certificates of completion shall be provided to the COR upon request (A.013).

1.22 Authorization to Perform Services in Foreign Countries: RESERVED.

1.23 Notice to Proceed: RESERVED.

1.24 Electromagnetic Compatibility Directive: RESERVED.

1.25 Government Property and Services: RESERVED.

1.26 Conventional Forces Europe (CFE) Treaty Verification Inspection: RESERVED.

PART 2

DEFINITIONS AND ACRONYMS

2. Definitions and Acronyms

2.1 Definitions: Although not inclusive of every term used within this PWS, the following provides a list of definitions used throughout this PWS and commonly used in the acquisition field.

Contracting Officer (KO) – means a person with the authority to enter into, administer, and terminate contracts and make related determinations and findings on behalf of the Government. Note: The only individual who can legally bind the Government.

Contracting Officer's Representative (COR) – As defined in Defense Federal Acquisition Regulation Supplement (DFARS) 202.101, means an individual designated and authorized in writing by the KO to perform specific technical or administrative functions. DoD Instruction (DoDI) 5000.72, Part II Definitions, states the following when defining a COR: “Defined in subpart 202.101 of Reference (f). Any individual delegated responsibilities pursuant to subpart 1.602-2 of Reference (e), regardless of local terminology, must be certified IAW this instruction. For example, local terminology can be COR, KO’s technical representative, technical point of contact, technical representative, alternate COR, administrative COR, assistant COR, line item manager, task order manager, QA personnel, QA evaluator, or COR management.” In addition, Army Regulation (AR) 70-13, Chapter 2, paragraph 2-2g, states, in part, the following when providing other surveillance support personnel to assist the COR when needed, “…These other surveillance support personnel may serve as on-site representatives of the COR in performance of actual contract surveillance if they meet all COR requirements and have been appointed by the KO as alternate CORs.”

Contractor – means a supplier or vendor awarded a contract to provide specific supplies or service to the Government. The term used in this contract refers to the prime.

Contractor Acquired Property (CAP) - means property acquired, fabricated, or otherwise provided by the contractor for performing a contract and to which the Government has title.

Day – means, unless otherwise specified, a business day (i.e., Monday through Friday).

Defective Service – means a service output that does not meet the standard of performance associated with the PWS.

Deliverable – means anything that can be physically delivered, but may include non-manufactured things such as meeting minutes or reports.

Government Furnished Property (GFP) – As reflected in FAR 52.245-1, Government Furnished Property (GFP) “means property in the possession of, or directly acquired by, the Government and subsequently furnished to the contractor for performance of a contract. GFP includes, but is not limited to, spares and property furnished for repair, maintenance, overhaul, or modification. GFP also includes Contractor Acquired Property (CAP) if the CAP is a deliverable under a cost contract when accepted by the Government for continued use under the contract.

Government Property - means all property owned or leased by the Government. Government property includes both GFP and CAP. Government property includes material, equipment, special tooling, special test equipment, and real property. Government property does not include intellectual property and software.

Property Administrator - means an authorized representative of the KO appointed IAW agency procedures, responsible for administering the contract requirements and obligations relating to Government property in the possession of a contractor.

High Level Objective (HLO) – means a key overarching result-based objective for a project necessary to achieve the project’s vision. High Level Objectives (HLOs) are similar to Level 2 in a Work Breakdown Structure (WBS). Each HLO may contain several statements to flesh out the areas necessary to meet the objective.

Physical Security – means that part of security concerned with physical measures designed to safeguard personnel; to prevent unauthorized access to equipment, installations, material, and documents; and to safeguard against espionage, sabotage, damage, and theft.

Quality Assurance (QA) - means the various functions, including inspection, performed by the Government to determine whether a contractor has fulfilled the contract obligations pertaining to quality and quantity.

Quality Assurance Surveillance Plan (QASP) – means the key Government-developed surveillance process document, and is applied to Performance-Based Service Contracting (PBSC). The QASP is used for managing contractor performance assessment by ensuring that systematic QA methods validate that contractor QC efforts are timely, effective, and are delivering the results specified in the contract. The QASP directly corresponds to the performance objectives and standards (e.g., quality, quantity, timeliness) specified in the PWS. It provides specific details on how the Government will survey, observe, test, sample, evaluate, and document contractor performance results to determine if the contractor has met the required standards for each objective in the PWS. The QASP, with very few if any exceptions, is an internal to Government document.

Quality Control (QC) – means all necessary measures taken by the contractor to assure that the quality of an end product or service shall meet contract requirements.

Statement – means the specific results-based activities required to satisfy HLOs. A statement contains a result, the context of the statement, and the required action(s). Statements focus on “what” is to be accomplished; however, they are not prescriptive in describing “how” the outcome is to be achieved. Each HLO may have several statements to flesh out the areas necessary to meet the objective. Statements are similar to Level 3 in a WBS.

Subcontractor – means one that enters into a contract with a prime contractor. The Government does not have privity of contract with the subcontractor.

Work Day - The number of hours per day the contractor provides services IAW the contract.

Work Week - Monday through Friday, unless otherwise specified.

2.2 Acronyms: Although not inclusive of every term used within this PWS, or that may be included in an acquisition, the following provides a list of acronyms commonly used in the acquisition field.

PART 3

GOVERNMENT PROPERTY AND SERVICES

3. Government Property and Services:

3.1 Services: RESERVED.

3.2 Facilities: RESERVED.

3.3 Utilities: RESERVED.

3.4 Equipment: RESERVED.

3.5 Special Tooling and Test Equipment: RESERVED.

3.6 Materials: The Government will provide antigen and cultured B cell samples for feasibility studies.

3.7 Training: The Government will provide the required training identified in PWS paragraph 1.21 above.

3.8 Common Access Cards (CACs): RESERVED.

PART 4

CONTRACTOR FURNISHED ITEMS AND SERVICES

4. Contractor Furnished Property and Services:

4.1 General: The contractor shall furnish all necessary personnel, equipment, supplies, facilities, transportation, tools, materials, supervision, and other items necessary to perform services as described in the PWS and associated contract documents, except for those items specified in Part 3, Government Property and Services.

4.2 Facility Clearance: RESERVED.

4.3 Materials: The contractor shall provide all necessary materials and supplies to perform the work described in this PWS.

4.4 Equipment: The contractor shall provide all necessary equipment to perform the work described in this PWS.

4.5 Background Checks: RESERVED.

PART 5

SPECIFIC TASKS

5.1 Basic Support: The contractor shall perform feasibility studies to facilitate the development and production of a panel of fully human mAbs for AFRIMS-supplied target antigens or using AFRIMS-supplied cultured B cells for use in developing immunotherapeutics against bacterial pathogens associated with wound infection and sepsis. This shall include immunization in transgenic animal model expressing fully human IgG antibodies, high-throughput single-cell screening for antigen-specific ASCs, and cloning and expression of recombinant mAbs.

5.2 Tasks: Tasks 5.2.1 (antigen 1), 5.2.2 (antigen 1), 5.2.3 (antigen 1), and 5.2.4 (antigen 2) are expected to be completed during the base period. Task 5.2.5 (cultured B cells) is considered optional and will be activated by contract modification. The Government does not anticipate exercising optional support for cultured B cells within the base period. Tasks consist of the following:

5.2.1 Immunization in Transgenic Animal Model Expressing Fully Human IgG Antibodies for Antigen 1

5.2.1.1 Immunize animal model with AFRIMS-provided target antigen in order to induce the production of antigen-specific ASCs that can be screened for the production of antigen-specific mAbs. Perform immunization of at least one group of transgenic animals with the target antigen. Monitor immunogenicity in immunized animals through measurement of antibody responses to target antigen up until the harvest time point to confirm immunogenicity of the target antigen. Antibody response measurements shall be collected at least weekly for each animal up until the harvest time point. At the harvest time point where immune responses are deemed sufficiently robust, sacrifice each animal to collect ASCs. ASC isolates shall be stored in a manner that maintains the viability of the cells for single-cell screening. Deliver a technical report on the immunization procedure from study design through immunization and harvest, including immunogenicity measurements collected during that time (A.014).

5.2.2 High-Throughput Single-Cell Screening for Antigen-Specific ASCs for Antigen 1

5.2.2.1 Sort and isolate ASCs for subsequent use in high-throughput single cell screening. Utilize a flow cytometry-based method to sort and isolate ASCs from the harvest cells. The method used shall maintain the viability of the ASCs for high-throughput single cell screening. Measure the ASCs frequency from each sample and obtain an estimate for the total ASC count in each sample.

5.2.2.2 Perform high-throughput single-cell screening to identify antigen-specific ASCs that produce human IgG mAbs that are specific for the target antigen. Utilize a high-throughput single-cell screening platform to isolate and screen ASCs for 1) sufficient growth kinetics, 2) production of human IgG, and 3) specificity and binding activity for the target antigen. The high-throughput single-cell screening platform shall be capable of screening over 5,000 cells in under 12 hours using a fully automated or semi-automated method. Utilize the antigen provided by AFRIMS to measure antigen-specificity of each mAb isolate. Target antigen-binding assay shall be able to distinguish between ‘no binding’ and ‘low,’ ‘medium,’ and ‘high’ affinity binding and distinguish between specific and non-specific binding. At least 1,000 ASCs shall be screened for growth, IgG production, and antigen specificity and binding to be completed within a one month period. Deliver a technical report on the results of the high-throughput single-cell screening. Report shall include the high-throughput screening workflow, the number of ASCs in each step of the process, and data on the growth kinetics, IgG production, and target antigen binding and specificity measurements. Rationale shall be provided for how the ASCs were selected for cloning (A.015).

5.2.3 Cloning and Expression of Recombinant mAbs for Antigen 1

5.2.3.1 Select antigen-specific ASCs for mAb cloning and expression based on IgG expression and antigen specificity data. The criteria for selecting ASCs for mAb cloning and expression shall include binding affinity to the target antigen, binding specificity to the target antigen, and IgG production level. Select a sufficient number of ASCs to ensure there is a diverse panel of mAbs produced by this effort. At least 100 ASCs shall be selected for cloning to be completed within a one month period.

5.2.3.2 For each ASC, perform cloning of Variable Heavy Chain (Vh) and Variable Light Chain (Vl) genes into an expression vector for sequencing and for expression. For each ASC selected for mAb expression, extract chromosomal Deoxyribonucleic Acid (DNA) and clone the Vh and Vl gene sequences encoding the mAb into a human IgG1 expression vector platform suitable for transfecting mammalian cells. Perform sequencing of the Vh and Vl genes for each mAb; carry out gene annotation of the Vh genes; and estimate somatic hypermutation positions for each mAb. Ninety percent of the sequences shall be successfully annotated. Select at least 30 mAbs for expression based on antigen-binding characteristics as well as genetic diversity and somatic hypermutation rates to be completed within a one month period. Verify that all major allelic combinations found in the sequencing data are represented among the selected mAbs to maximize diversity of the mAb panel. Deliver a technical report on mAb sequencing, diversity, and selection for expression. Antigen-binding characteristics assessed in Task 5.2.2.2 shall be combined with the gene sequencing and annotation results in the report. Rationale shall be provided for how mAbs were selected for expression (A.016).

5.2.3.3 For each mAb cloned in Task 5.2.3.2, perform expression and purification to produce recombinant mAbs to be shipped to AFRIMS for in vitro and in vivo testing. Transfect the mAb expression vectors into a CHO-based cell line. Express and purify each recombinant mAb to sufficient purity for use in in vitro testing and in vivo animal studies. A quantity of at least 300µg of recombinant mAb shall be produced for each mAb cloned in Task 5.2.3.2. Carry out assays that confirm binding activity and specificity to the target antigen. Deliver a technical report on the expression of the mAbs cloned in Task 5.2.3.2. Data shall be included on the purity, yield, and binding activity of each mAb. Compile and analyze all binding activity data, sequencing data, gene annotation, and somatic hypermutation data for the mAbs selected for expression in Task 5.2.3.2 (A.017 and A.018).

5.2.3.4 Store the recombinant mAb samples at -80C and ship them to AFRIMS for testing. Samples shall be transported at -80C and shipped with temperature monitoring to verify that samples remained at the appropriate temperature from packaging through shipping and delivery. Temperature excursions shall not exceed -70C during shipping. Frozen samples for each mAb cloned in Task 5.2.3.2 shall be delivered to AFRIMS for in vitro and in vivo testing (A.019).

5.2.4 Antigen 2

Task 5.2.4 mirrors the tasks and deliverables outlined within paragraphs 5.2.1, 5.2.2, and 5.2.3 (including sub-paragraphs) for a second antigen as follows:

5.2.4.1 Immunization in Transgenic Animal Model Expressing Fully Human IgG Antibodies for Antigen 2 (A.020).

5.2.4.2 High-Throughput Single-Cell Screening for Antigen-Specific ASCs for Antigen 2 (A.021).

5.2.4.3 Cloning and Expression of Recombinant mAbs for Antigen 2 (A.022; A.023; A.024; and A.025).

5.2.5 Optional Support - Cloning and Expression of Recombinant mAbs from Cultured B Cells

The purpose of optional support is to facilitate the timely and efficient execution of requirements necessary to meet the objectives and perform the tasks described in this PWS when there is additional funding support or when a need is identified in support of WRAIR’s current mission. The potential exists that additional support may be required, which would be executed in optional CLINs to provide continuity with minimal interruption in workflow. Optional support will be created and exercised via contract modification and could be for a month, several months, or longer based on the needs of the organization. The Government does not anticipate exercising optional CLINs within the base period.

5.2.5.1 Receive, thaw, and culture AFRIMS-provided frozen cultured B cell samples. Assess cell growth, IgG expression, and antigen-specificity data from cells. Select antigen-specific ASCs for mAb cloning and expression based on cell growth, IgG expression, and antigen specificity. Select a sufficient number of ASCs to ensure there is a diverse panel of mAbs produced by this effort. At least 100 ASCs shall be selected for cloning to be completed within a one month period.

5.2.5.2 For each ASC, perform cloning of antigen-specific mAb Vh and Vl genes into an expression vector for sequencing and for expression in mammalian cells. Additionally, perform sequencing of the Vh and Vl genes and select a subset of mAbs for expression. For each ASCs selected for mAb expression, extract chromosomal DNA and clone the Vh and Vl gene sequences encoding the mAb into a human IgG1 expression vector platform suitable for transfecting mammalian cells. Perform sequencing of the Vh and Vl genes for each mAb; carry out gene annotation of the V, D, and J segments of the Vh genes; and estimate somatic hypermutation positions for each mAb. Ninety percent of the sequences shall be successfully annotated. Select at least 30 mAbs for expression based on antigen-binding characteristics as well as genetic diversity and somatic hypermutation rates to be completed within a one month period. Verify that all major V and J allele combinations found in the sequencing data are represented among the selected mAbs to maximize diversity of the mAb panel. Deliver a technical report on mAb sequencing, diversity, and selection for expression. Antigen-binding characteristics shall be combined with the gene sequencing and annotation results in the report. Rationale shall be provided for how mAbs were selected for expression (A.026).

5.2.5.3 For each mAb cloned in Task 5.2.5.2, perform expression and purification to produce recombinant mAbs and ship them to AFRIMS for in vitro and in vivo testing. Transfect the mAb expression vectors into a CHO-based cell line. Express and purify each recombinant mAb to sufficient quantity and purity for use in in vitro testing and in vivo animal studies. A quantity of at least 300µg of recombinant mAb shall be produced for each mAb cloned in Task 5.2.5.2. Carry out assays that confirm binding activity and specificity to the target antigen. Deliver a technical report on the expression of the mAbs cloned in Task 5.2.5.2. Data shall be included on the purity, yield, and binding activity of each mAb. Compile and analyze all binding activity data, sequencing data, gene annotation, and somatic hypermutation data for the mAbs selected for expression in Task 5.2.5.1 (A.027 and A.028).

5.2.5.4 Store the recombinant mAb samples at -80C and ship them to AFRIMS for testing. Samples shall be transported at -80C and shipped with temperature monitoring to verify that samples remained at the appropriate temperature from packaging through shipping and delivery. Temperature excursions shall not exceed -70C during shipping. Frozen samples for each mAb cloned in Task 5.2.5.2 shall be delivered to AFRIMS for in vitro and in vivo testing (A.029).

Steps for Submitting a Service Contract Report (SCR):

1. Go to www.sam.gov and log in.

2. Select Entity Registrations and then select Service Contract Reporting.

3. SAM displays your entities which have service contracts and meet the reporting criteria. Select View by entity to see the service contracts for each entity.

4. Next, select Add for the service contract against which you want to create a Service Contract Report. Each service contract which meets the FAR Subpart 4.1703 reporting thresholds is displayed.

5. You will be taken to the Complete Service Contract Report page. SAM displays the contract details and allows you to report. You are required to enter the following information:

· Total Amount Invoiced: Total dollar amount invoiced for services performed during the previous Government FY under the contract (this amount should include the prime and any subcontract amount).

· Prime Contractor Hours Expended: Prime contractor direct labor hours expended on the services performed during the previous Government FY. The amount you enter is automatically divided by 2,080 hours to calculate a Full Time Employee (FTE) equivalent, displayed under the Prime Contractor Hours Expended as Prime Contractor FTEs.

6. Report any required Tier 1 subcontractor information by selecting the Add Tier 1 Subcontract Information button.

7. When you are ready to submit the report, select Submit. This saves your report and returns you to the Select Service Contract page where you can create other SCRs or edit an existing SCR.

Steps for Editing a Submitted Report:

1. Follow steps 1-4 above. Any previously submitted SCR will have a View/Edit button instead of an Add button.

2. Select View/Edit. You will be able to view the current SCR, edit available fields, and resubmit the record. You can also delete previously entered information altogether.

STD: All information provided by the Contractor shall be accurate, complete, and not exceed suspense dates noted in corresponding paragraph above.

AQL: 100% Compliant

(A.030).

PART 6

APPLICABLE PUBLICATIONS

6. Applicable Publications (Current Editions): Publications, manuals, regulations, and references mentioned in this PWS are listed below.

a. FAR 12.208, Contract QA

b. FAR Subpart 42.5, Post Award Orientation

c. Privacy Act of 1974

d. Public Law 93-759

e. 5 U.S.C. Section 552a

f. FAR Subpart 9.5, Organizational and Consultant Conflicts of Interest

g. FAR 52.236-13, Accident Prevention

h. EM 385-1-1, U.S. Army Corps of Engineers Safety and Health Requirements Manual

i. DFARS 202.101, Definitions

j. DoDI 5000.72, DoD Standard for Contracting Officer’s Representative Certification

k. AR 70-13, Management and Oversight of Service Acquisitions

l. FAR 52.245-1, Government Property

m. FAR Subpart 4.1703, Reporting Requirements

PART 7

ATTACHMENT AND TECHNICAL EXHIBIT LISTING

7. Attachment and Technical Exhibit List

7.1 Technical Exhibit A – Performance Requirements Summary (PRS)

7.2 Technical Exhibit B – Deliverables Schedule

TECHNICAL EXHIBIT A

PERFORMANCE REQUIREMENTS SUMMARY (PRS)

PRS#1 – Immunization for Antigens (paragraphs 5.2.1.1 and 5.2.4.1)

The contractor shall immunize animal model with target antigen in order to induce the production of antigen-specific ASCs that can be screened for the production of antigen-specific mAbs.

Peak antibody levels to target antigen are ≥1000x pre-immunization level Meets:

Peak antibody levels to target antigen are ≥100x pre-immunization level Does not meet:

Peak antibody levels to target antigen are <100x pre-immunization level

100% inspection

PRS#2 – Sort and Isolate ASCs for Antigens (paragraphs 5.2.2.1 and 5.2.4.2)

The contractor shall sort and isolate ASCs from the harvest material from immunized animals.

Viability is ≥90% Does not meet:

Viability is <90% 100% inspection

PRS#3 – High-Throughput Single-Cell Screening for Antigens (paragraphs 5.2.2.2 and 5.2.4.2)

The contractor shall utilize a high-throughput single-cell screening platform to isolate and screen ASCs for 1) sufficient growth kinetics, 2) production of human IgG, and 3) specificity and binding activity for the target antigen.

The high-throughput single-cell screening platform shall be capable of screening over 5,000 cells in under 12 hours using a fully automated or semi-automated method; at least 1,000 ASCs shall be screened for growth, IgG production, and antigen specificity within a one month period.

Meets:

≥1000 ASCs screened Does not meet:

<1000 ASCs screened 100% inspection

PRS#4 – Clone Antigen-Specific ASCs for Antigens (paragraphs 5.2.3.1 and 5.2.4.3)

The contractor shall select antigen-specific ASCs for mAb cloning and expression.

≥100 ASCs cloned Does not meet:

<100 ASCs cloned

100% inspection

PRS#5 – Cloning and Sequencing for Antigens (paragraphs 5.2.3.2 and 5.2.4.3)

The contractor shall perform cloning of antigen-specific mAb Vh and Vl…