Redacted Duke HHSN272201700061 JOFOC-Approved.pdf

Attachment 3 bank and an EQA reagent repository of characterized material that supports EQAPOL proficiency testing programs and are made available to NIAID-supported investigators.

The contract�s scope involves quality assurance/quality control (QA/QC) and operational activities, including the following:

QA/QC activities include: (1) providing proficiency testing programs and evaluating the performance of laboratories conducting assays measuring cellular, antibody, and cytokine responses in a variety of tissue types; (2) developing new assays; and (3) acquiring/establishing/characterizing unique clade-specific virus panels.

Operational activities include: (1) the maintenance and expansion of a specimen and reagent repository; (2) the maintenance of a database to support contract activities;

and (3) providing advice on assay validation, regulatory compliance and statistical issues.

As a result of a solicitation, which utilized full and open competitive procedures, a cost-reimbursement, term type/level of effort contract (Contract No.

HHSN272201700061C) for �External Quality Assurance Program Oversight Laboratory (EQAPOL)� was awarded to Duke University Medical Center (Duke), 2200 West Main St., Suite 820, Erwin Square Plaza, Durham, NC 27705, on August 29, 2017, for the delivery of 1,682% direct labor effort per year. The total value of the contract, including options, was $41,463,666. The Base Period of the contract was from September 30, 2017 through September 29, 2018. The contract includes options for the extension of the term (Options 1-6), for a total maximum performance period of 7 years, through September 29, 2024, and quantity options for increases in the level of effort during the term of the contract, as follows:

options for additional level of effort to support unanticipated increases in demand (Options 7-34), and options for the development and implementation of an EQA Program for HIV Incidence Assays (Options 35-41). The purpose of the contract is to provide confidence that individual laboratories generate reliable data to support vaccine immunogen advancement. EQAPOL supports these efforts by participating in the development and availability of validated assays, providing common and well-characterized reagents and Standard Operating Procedures (SOPs), and providing external quality assurance (EQA) programs to measure and monitor laboratory performance.

The COVID-19 Prevention Trials Network (CoVPN) was established by NIAID in 2020 to respond to the global COVID-19 pandemic, by investing in and coordinating the development and testing of COVID-19 vaccines and monoclonal antibodies to prevent COVID-19 disease and/or virus transmission. The CoVPN was formed by merging the capacities and expertise of four existing NIAID-funded clinical trials networks: the HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network (HPTN), the Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group (ACTG). These individual networks continue to perform clinical trials for HIV vaccine and prevention, and other infectious diseases, in addition to their new COVID-19 roles. The CoVPN employs a harmonized vaccine protocol, which enables analyses of correlates of protection across multiple clinical trials. More than 100 trial sites across the United States and internationally perform assessments of COVID-19 countermeasures under the CoVPN.

The CoVPN-affiliated laboratories have relevant expertise to perform serologic and cellular assays. Data from these assays, combined with systems immunology computational approaches, allow potential identification of correlates of protection, in efficacy trials of SARS-Cov-2 vaccines and antibodies. Performing laboratories have close integration with quality assurance programs in applying rigorous research methodology, quality control verification, and appropriate transfer of sample analyses for clinical trials. The institutions are compliant with Good Clinical Laboratory Practice (GCLP) and have expertise in rapidly onboarding new assay types through assay qualification and validation. However, it is imperative that primary laboratories are able to transfer the immunology assays to backup Contract Research Organization (CRO) laboratories, in order to ensure adequate laboratory capacity. Assay transfer requires close monitoring of laboratory performance, in order to ensure that all stakeholders have confidence in the data to support emergency use authorization and/or Biologics Licensure Applications (BLAs) for the vaccines and monoclonal antibodies. The EQAPOL contract is able to immediately support IQC and EQA programs for COVID-19 tasks.

On October 7, 2020, in response to the COVID-19 pandemic, an Addendum to HHS Class J&A for COVID-19 Acquisitions was approved by Eileen Webster-Cissel, Chief, AIDS RCB, OA, DEA, NIAID. The HHS Class J&A for COVID-19 Acquisitions was utilized to support the sole source acquisition, based on unusual and compelling urgency, of additional level of effort to address unanticipated increases in contract activity in response to COVID-19 related work [specifically, for Duke to provide SARS-CoV-2 EQA programs to monitor binding and neutralizing antibodies for this virus, and assay transfer support for the Operation Warp Speed (OWS)-funded CRO labs (which are responsible for performing the immunology assays after transfer from the CoVPN-affiliated academic laboratories)]. Since the focus of the EQAPOL contract is currently HIV/AIDS, the above required COVID-19 support services were outside of the original scope of the contract, and included the following activities:

Design, set up, manage, and coordinate EQA programs for neutralization and binding antibodies to SARS-CoV-2 to provide an unbiased assessment of data quality from participating laboratories;

Develop, maintain and expand an EQA reagent repository to support the

SARS-CoV-2 immune assays;

Provide data management, biostatistics and project management support for the EQA programs; and

Monitor and trend positive/negative control assay results to determine any shifts in data as an indication of laboratory performance.

This resulted in the creation of Options 42 (315% effort) and 43 (315% effort), which were incorporated into the contract via Modification No. 4 (executed on November 12, 2020), and are broken out as follows:

Option 42 (11/12/2020 � 9/29/2021):

Option 43 (9/30/2021 � 10/31/2021):

Total (Options 42 and 43):

As a result of Modification No. 4, the total maximum potential contract value (i.e., the total value if all options are exercised) was increased by , from to .

At this time, in order to provide intra-laboratory reliability of fit-for-purpose humoral antibody assays with new mutant SARS-Cov-2 virus strains (for example B1.1.7 and B.1.351, P.1, identified in the UK, South Africa and Brazil, respectively), the implementation of a SARS-Cov-2 Neutralizing Assay Concordance Survey (SNACS) program is urgently needed. The program will be designed to provide data on the comparability of the different live virus, pseudovirus neutralizing antibody assays, and other humoral assays performed with different SARS-CoV-2 virus strains. The data from this program will determine how the data from these assays correlate with the results from Spike-binding assays and/or assays that measure blocking antibodies that block Spike protein from binding to the angiotensin-converting enzyme 2 (ACE2) receptor, as possible surrogates of neutralization among performing laboratories. The data generated will provide critical information about the assays� accuracy, specificity, precision, and comparability among different laboratories, but, more importantly, it will provide critical information about the in vitro fitness of vaccines and antibody preparations against new mutant SARS-Cov-2 virus strains. We anticipate that about 50 laboratories, in the United States and abroad, will participate in the program.

The EQAPOL contract can immediately provide the needed support for COVID-19 [Duke is able to immediately support internal quality control (IQC) and external quality assurance (EQA) activities for COVID-19 tasks, and is uniquely able to immediately develop and implement SNACS program activities]. However, since the focus of the contract is currently HIV/AIDS, this work does not fall within the scope of the contract. As stated above, the contract�s scope involves quality assurance/quality control (QA/QC) and operational activities, including the following:

QA/QC activities include: (1) providing proficiency testing programs and evaluating the performance of laboratories conducting assays measuring cellular, antibody, and cytokine responses in a variety of tissue types; (2) developing new assays; and (3) acquiring/establishing/characterizing unique clade-specific virus panels.

Operational activities include: (1) the maintenance and expansion of a specimen and reagent repository; (2) the maintenance of a database to support contract activities;

and (3) providing advice on assay validation, regulatory compliance and statistical issues.

The purpose of the External Quality Assurance Program Oversight Laboratory (EQAPOL) contract is to provide stakeholder confidence that individual laboratories generate reliable and accurate data to support vaccine immunogen advancement and regulatory licensure. EQAPOL supports these efforts by participating in the development, standardization, and validation of immune assays, providing common and well-characterized reagents and Standard Operating Procedures (SOPs), and providing Internal Quality Control (IQC) and External Quality Assurance (EQA) programs to measure and monitor laboratory performance. The infrastructure, processes, and workflow that are needed for these COVID-19 activities are identical to the existing infrastructure, processes, and workflow currently being provided under the EQAPOL contract, for HIV/AIDS. Importantly, given the emergency created by the COVID-19 pandemic, there is no time to develop a comparable contract with other entities who have the combination of Immunology, Virology and GCLP expertise.

The purpose of this action is to increase the required level of effort to be delivered under the EQAPOL contract, to accommodate the work associated with providing a SARS-CoV-2 IQC and EQA program, and assay transfer support from the OWS-funded laboratories to identified CRO laboratories. The CRO laboratories will perform the immunology assays after transfer from the CoVPN-affiliated academic laboratories. Specifically, the Contractor shall:

Maintain, adjust, and expand an Internal Quality Control (IQC) and External

Quality Assurance (EQA) program and reagent repository (e.g., viruses, monoclonal antibodies, convalescent and vaccine clinical trial plasma/serum/cells), to support SARS-CoV-2 immune assays;

Design, set up, manage, and coordinate proficiency programs for fit-for-purpose neutralization and binding antibody assays with mutant SARS-CoV-2 virus strains [i.e., the SARS-Cov-2 Neutralizing Assay Concordance Survey (SNACS)], to provide an unbiased assessment of data quality from participating laboratories;

and

Provide data management, biostatistics, and project management support for the IQC and EQA programs.

Approximately 606% additional effort per year will need to be added to the contract to address these SARS-CoV-2 requirements. The level of effort includes the effort of any subcontractors and consultants. The period of performance of an Option for increased level of effort for this purpose will not exceed the term of the Option year in which the Option is exercised. The total estimated cost of the contract will be increased by (Options 44, 45, and 46), from (current value of the Base Period and Options 1-43) to (Base Period and Options 1- 46), dependent on negotiations, in order to cover performance from September 30, 2021 through September 29, 2024.

3. Description of the supplies or services required to meet the agency�s needs (including the estimated value).

a. Project title.

�External Quality Assurance Program Oversight Laboratory (EQAPOL)�

b. Project description.

The objective of this acquisition is to allow the Contractor to provide a SARS-CoV-2 IQC and EQA program, and assay transfer support from the OWS-funded laboratories to identified CRO laboratories. The CRO laboratories will perform the immunology assays after transfer from the CoVPN-affiliated academic laboratories. Specifically, the Contractor shall:

Maintain, adjust, and expand an Internal Quality Control (IQC) and External

Quality Assurance (EQA) program and reagent repository (e.g., viruses, monoclonal antibodies, convalescent and vaccine clinical trial plasma/serum/cells) to support SARS-CoV-2 immune assays;

Design, set up, manage, and coordinate proficiency programs for fit-for-purpose neutralization and binding antibody assays with mutant SARS-CoV-2 virus strains [i.e., the SARS-Cov-2 Neutralizing Assay Concordance Survey (SNACS)], to provide an unbiased assessment of data quality from participating laboratories;

and

Provide data management, biostatistics, and project management support for the IQC and EQA programs.

The revised Statement of Work for this action (Modification No. 5) is attached to this document as a reference (Attachment A), and the new work that is being added pursuant to this action (Options 44-46) has been highlighted in the revised Statement of Work (Attachment A) for ease of reference.

Requirement Type Research & development (R&D) R & D support services Support services (non-R&D) Supplies/equipment Information technology (IT) Construction Architect-engineer (A & E) services Design-build Other (specify): ____________________

Type of action.

New requirement Follow-on Other (specify): New Work Modification

Proposed contract/order type.

Firm-fixed-price Other fixed-price (specify, e.g., fixed-price award-fee, fixed-price incentive-fee):

Cost-plus-fixed-fee Other cost reimbursement (specify, e.g., cost-plus-award-fee, cost-plus-incentive-fee): Cost-reimbursement (no fee) Time and materials Indefinite delivery (specify whether indefinite quantity, definite quantity, or requirements): ___________ Other (specify): ___________ Completion Form Term form

Acquisition identification number: HHSN272201700061C

c. Total estimated dollar value and performance/delivery period.

The total estimated dollar value for this acquisition is [See Attachment B � Independent Government Cost Estimate (IGCE) for this JOFOC], for the period from September 30, 2021 through September 29, 2024.

The table below provides a breakdown of the additional funds needed for this contract, by related option, which align with the three remaining term options/contract years [since the work associated with this action is specifically for COVID-19 and must be tracked separately, new options must be created to accommodate/fund this work (Options 44, 45, and 46)]:

variants, which may result in potential booster shots or be in combination with the original vaccines. Reliable laboratory data are essential to the clinical evaluation of candidate SARS-Cov-2 vaccine and antibody platforms.

To provide the required support, the contractor must have expertise and experience in the following areas:

1- Virology � the expertise in the field of virology is necessary to understand the mechanism of SARS-CoV-2 viral mutation, as well as for the manipulation, maintenance, and generation of viruses and pseudoviruses as assay reagents and repository for participant CRO laboratories;

2- Immunology � the activities will require a deep understanding of the immune response to vaccines, generation, acquisition, and development of protein and preventive and/or therapeutic monoclonal and polyclonal antibody preparations, as well as development of immunological assays, for evaluation of the aforementioned products. Specifically, expertise in the development, qualification, and validation of virus neutralization and binding assays are critical;

3- Biostatistics � the evaluation of the SNACS program will heavily depend on methodologies to define critical assay parameters, such as accuracy, precision, and sensitivity. Moreover, given the large number of participant institutions, the biostatistical support needed will require the ability to manage and analyze large databases; and

4- Laboratory management � the complex structure necessary to procure, select, aliquot, and maintain the repository of assay reagents, controls, and samples employed in the surveillance programs depends on a well-structured organization.

The team will be in charge of coordinating shipments of samples for each survey and receipt of results for statistical processing.

The Contractor, Duke University, is uniquely positioned to carry out the proposed work because it already has the above required expertise and experience, infrastructure, processes, and workflow in place to immediately support such complex IQC and EQA programs for COVID-19 countermeasures activities, including the investigation of the impact of new SARS-CoV-2 mutant variants. The EQAPOL team is uniquely qualified and has more than 11 years of experience in establishing IQC and EQA programs for the evaluation of vaccines, including the development and optimization of assays and SOPs, transfer of technology to CROs, and management and bioinformatics support.

Due to the high degree of expertise and experience necessary to plan, develop, and execute the SARS-CoV-2 Neutralization Assay Concordance Survey (SNACS) program activities, this work can only be completed using the current contractor, Duke. Any change in Contractor would certainly result in a catastrophic delay in the implementation of IQC and EQA activities, due to the lead time necessary to plan and develop those efforts without having previous practical in-depth understanding and familiarity with the processes. No other source can immediately provide these expedited essential services, which require extensive knowledge and expertise in vaccine evaluation, management of immunological laboratories, assessment of assay performance, and procurement, test, and qualification of critical reagents and controls. Further, due to the complexity of the SNACS program, any attempt to integrate a different contractor to perform such activities would result in substandard assays, substandard SOPs, a substandard reagent repository, and a substandard quality control program. Failure to immediately and correctly implement and maintain the SNACS program will, most certainly, jeopardize the availability of preventive and therapeutic COVID-19 countermeasures, potentially leading to misinterpretation or false assay results. If the SNACS program and all of its components (i.e., assay and SOP development, assay performance surveillance, reagent repository, and statistical analyses) are not correctly executed, many vaccines and antibody preparations could fail to be properly assessed. In fact, the FDA will not accept results generated by laboratories that do not follow the proper procedures for qualified and validated assays, which are monitored by external quality surveillance programs like those promoted by EQAPOL. That scenario would likely result in further loss of life due to COVID-19 and would deprive the world of safe and effective preventive measures and/or therapies during this unprecedented pandemic.

6. Description of the efforts made to ensure that offers are solicited from as many potential sources as practicable. Indicate whether a FedBizOpps notice was or will be publicized as required by FAR Subpart 5.2 and, if not, which exception under FAR

5.202 applies:

A Research and Development Sources Sought Notice (Attachment C) was posted on the System for Award Management (beta.SAM.gov) website for a period of 15 days, on March 22, 2021, with responses due by April 6, 2021. This notice described the work being sought by NIAID and requested capability statements from potential sources. Further information regarding the results of this notice is provided below, under item 10.

A Pre-solicitation Notice (Attachment D) was posted on the beta.SAM.gov website for a period of 15 days on April 7, 2021 with responses due by April 22, 2021. This notice described the work being sought by NIAID, stated NIAID�s intent to negotiate with the present Contractor on a sole source basis, under the authority of FAR 6.302-1 and HHSAR 306.302-1, and provided responsible sources with the opportunity to express their interest by submitting a capability statement. Further information regarding the results of this notice is provided below, under item 10.

7. Determination by the Contracting Officer that the anticipated cost/price to the Government will be fair and reasonable.

The Independent Government Cost Estimate (IGCE) [Attachment B] was developed using knowledge of this type of work, as well as the historical costs of the current contract. In addition, the Contracting Officer will obtain certified cost and pricing data, to establish a fair and reasonable price for the services being acquired, as required by FAR 15.403-4. Finally, the Contracting Officer will conduct a cost analysis and cost realism analysis, as part of the proposal analysis. Negotiations will be conducted, if needed, to ensure that the proposed costs are fair and reasonable for performance of the proposed work. A field audit will not be performed, as it is not considered necessary, because NIAID has historical cost data to assist in the analysis of the proposed costs.

8. Description of the market research conducted (see FAR Part 10) and the results, or a statement of the reasons market research was not conducted.

The NIAID performed market research by: (a) issuing a Research and Development Sources Sought Notice (Attachment C) and a Pre-solicitation Notice (Attachment D), in beta.SAM.gov, as described in item 6., above, and item 10., below (a copy of each notice is attached to this document); (b) reviewing literature published by qualified organizations; and (c) contacting knowledgeable acquisition and program officials in Government and industry regarding market capabilities. As a result of the foregoing, it was determined that there is only one responsible source (Duke) and no other supplies or services will satisfy agency requirements. Due to the complex nature of the SNACS program and the urgent public health need for a COVID-19 preventive and/or therapeutic measures, this work can only be completed using the current contractor.

Attempting to bring in a new contractor would result in a significant disruption to critical services and could jeopardize the quality of the survey program and data generated/available for FDA emergency use authorization, including regulatory approval of new biologicals (i.e. SARS-CoV-2 vaccines and antibodies). Further, attempting to bring in a new contractor would result in a catastrophic disruption of ongoing assay quality control activities, reagent availability and statistical analyses. This scenario would likely result in further loss of life by depriving the nation of countermeasures during the unprecedented COVID-19 pandemic.

9. Any other facts supporting the use of other than full and open competition.

None.

10.Listing of sources, if any, that expressed, in writing, an interest in the acquisition.

As stated above, under item 6., a Research and Development Sources Sought Notice was posted on the System for Award Management (beta.SAM.gov) website for a period of 15 days, on March 22, 2021, with responses due by April 6, 2021 (a copy of the Research and Development Sources Sought Notice is included as Attachment C to this document). The notice requested capability statements from potential sources. We did not receive any capability statements in response to the Research and Development Sources Sought Notice. As stated above, it was determined that there is only one responsible source (Duke) and no other supplies or services will satisfy the agency�s requirements.

A Pre-solicitation Notice was published on the beta.SAM.gov website for a period of 15 days, on April 7, 2021, with responses due by April 22, 2021 (a copy of the Pre-solicitation Notice is included as Attachment D to this document). This notice described the work to be performed, stated NIAID�s intent to negotiate with the present Contractor on a sole source basis, under the authority of FAR 6.302-1 and HHSAR 306.302-1, and provided responsible sources with the opportunity to express their interest by submitting a capability statement. We did not receive any capability statements in response to the Pre-solicitation Notice. As a result of the foregoing, it was again determined that there is only one responsible source (Duke), and no other supplies or services will satisfy the agency�s requirements.

Again, due to the complex nature of the SNACS program and the urgent public health need for a COVID-19 preventive and/or therapeutic measures, this work can only be completed using the current contractor. Attempting to bring in a new contractor would result in a significant disruption to critical services and could jeopardize the quality of the survey program and data generated/available for FDA emergency use authorization, including regulatory approval of new biologicals (i.e., SARS-CoV-2 vaccines and antibodies). Further, attempting to bring in a new contractor would result in a catastrophic disruption of ongoing assay quality control activities, reagent availability, and statistical analyses. This scenario would likely result in further loss of life by depriving the nation of countermeasures during the unprecedented COVID-19 pandemic.

11. Statement of the actions, if any, the agency may take to remove or overcome any barriers to competition before any subsequent acquisition for the required supplies or services.

The contract will be re-competed prior to the expiration date of the current contract, in order to have a new contract in place by 9/30/2024.

ATTACHMENT A � STATEMENT OF WORK (revised March 14, 2021) Contract No. HHSN272201700061C Page 1 of 12

ATTACHMENT A: STATEMENT OF WORK

REVISED 3/14/2021

EXTERNAL QUALITY ASSURANCE PROGRAM

OVERSIGHT LABORATORY (EQAPOL)

Contract #HHSN272201700061C

A. BACKGROUND AND INTRODUCTION

The mission of the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), is to increase basic knowledge of the pathogenesis and transmission of the human immunodeficiency virus (HIV), support the development of therapies for HIV infection and its complications, and support the development of vaccines and other prevention strategies. Reliable laboratory data are essential to the clinical evaluation of candidate HIV vaccine platforms and immunogens.

Data from multiple laboratories performing assays in support of single or multiple vaccine candidate trials must be accurate and reproducible. The purpose of the External Quality Assurance Program Oversight Laboratory (EQAPOL) is to provide confidence that individual laboratories generate reliable data to support vaccine immunogen advancement. EQAPOL supports these efforts by participating in the development and availability of validated assays, providing common and well-characterized reagents and Standard Operating Procedures (SOPs), and providing External Quality Assurance (EQA) programs to measure and monitor laboratory performance.

The current contract, awarded in 2010 (HHSN272201000045) to Duke University, established proficiency testing programs serving over 60 laboratories in more than 40 sites worldwide and provided a panel of fully characterized viruses from early acute HIV infections to develop new assays and validate assay platforms. The contract also established a peripheral blood mononuclear cell (PBMC) bank and an EQA reagent repository of characterized material that supports EQAPOL proficiency testing programs and are made available to NIAID-supported investigators.

The new contract will support existing activities, develop new assays, and provide assistance in the standardization, validation, and development of new proficiency testing programs. The contract will continue to make materials available to NIAID-sponsored domestic and international investigators. Options will be included to extend the contract for up to six years beyond the base year, to increase level of effort for unanticipated increases in demand, and to develop/implement a new EQA program. Requirement changes from previous EQAPOL competition include an EQA Program for Multiplex/Array, EQA of Mucosal Specimens, and an option for HIV Incidence Assays.

B. SCOPE

This contract�s scope involves quality assurance/quality control (QA/QC) and operational activities, including the following:

QA/QC activities include: (1) providing proficiency testing programs and evaluating the performance of laboratories conducting assays measuring cellular, antibody, and cytokine responses in a variety of tissue types; (2) developing new assays; and (3) acquiring/establishing/characterizing unique clade-specific virus panels. Operational

Contract No. HHSN272201700061C Page 2 of 12 activities include: (1) the maintenance and expansion of a specimen and reagent repository; (2) the maintenance of a database to support contract activities; and (3) providing advice on assay validation, regulatory compliance and statistical issues.

C. TECHNICAL REQUIREMENTS

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work as stated herein.

Work shall follow the DAIDS Guidelines for Good Clinical Laboratory Practice (GCLP) Standards http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Documents/gclp .pdf .

Contractor staff shall have appropriate accreditations where applicable (e.g. College of American Pathologists (http://www.cap.org) and/or American Association for Laboratory Accreditation (http://www.a2la.org). When necessary the Contractor shall have local Institutional Review Board (IRB) approval for its activities.

Specifically, the Contractor shall:

1. MAINTAIN AND EXPAND A PERIPHERAL BLOOD MONO-NUCLEAR CELL

(PBMC) BANK AND EQA REAGENT REPOSITORY

a. Maintain a reagent repository consisting of peptides, antigens/antibodies, serum, plasma, viruses, cell lines and other materials used for EQA programs, panel development, or assay development.

b. Maintain a repository consisting of PBMCs from HIV-1 uninfected human volunteers (HIV-1 seronegative, HIV-1 and other infectious disease vaccinated volunteers) and PBMCs from HIV-1 infected/positive human volunteers.

c. Expand and/or replenish this PBMC bank with cells from additional human subjects as directed by the Contract Officer�s Representative (COR).

d. Upon request of the COR characterize PBMC samples:

1) For cytomegalovirus (CMV), Epstein Barr Virus (EBV), hepatitis B titer or other pathogens.

2) Perform molecular based HLA class I typing to 4 digit resolution for A, B and C alleles.

3) Provide immunophenotyping and characterize PBMCs to include assessment of viability and recovery and T cell function as determined by ELISpot and Intracellular cytokine staining (ICS).

4) Include human leukocyte antigen (HLA) Class II and (killer cell immunoglobulin-like receptors) KIR genotyping.

e. Receive, store, ship and inventory PBMC and EQA reagents including:

1) Provide for appropriate storage and 24-hours a day/seven days a week monitoring of refrigerator/freezer conditions by automatic temperature alarm to guarantee continuous proper storage and integrity of cryopreserved PBMC

Contract No. HHSN272201700061C Page 3 of 12 and EQA reagents to include peptides, antigens, antibodies, serum, plasma, viruses, cell lines.

2) Provide: (a) uninterruptible power to accommodate freezers and refrigerators; (b) continuously monitored central alarm system connected to refrigerators and freezers, and staff to be notified in the event of equipment malfunction; (c) emergency stand-by refrigerators and freezers to be available in case of mechanical failure of storage space; and (d) equipment maintenance services.

3) Ship infectious and non-infectious PBMC and EQA reagents to domestic and international laboratories, using shipping conditions appropriate for preserving the PBMC or EQA reagents. Use biocontainment shipping procedures that comply with International Air Transport Association (IATA) Dangerous Goods Regulations (www.iata.org) for shipment by air transportation or with Department of Transportation (DOT) regulations for shipment by ground transportation, and obtain export permits as required.

4) Establish an inventory control system for PBMC and EQA reagents so that their use and disposition can be monitored.

2. EQA PROGRAM FOR ELISpot

Within 30 calendar days of award provide the COR a plan to design, set up, manage and coordinate an interferon- for NIAID supported research laboratories to provide an unbiased assessment of data quality from participating laboratories. Implement the plan within 30 calendar days of COR approval, and update the plan, as needed or requested by the COR. The plan will include the following:

a. Manage and coordinate an ELISpot EQA Program.

b. Design consensus protocols, prepare SOPs and instructions for participating laboratories.

c. Conduct QC and QA of reagents and materials to define standard performance and ensure optimal quality, consistency, reproducibility and lot-to-lot comparability over time.

d. Acquire, aliquot, store, assemble and ship standardized reagents including PBMCs, peptides, controls, evaluation panels and other reagents.

e. Process and evaluate proficiency data received from participating laboratories and the Contractor�s facility to define assay acceptability criteria (pass/fail) for performance assessment. Monitor performance of laboratories over time and report trending analyses to participating laboratories.

f. Work with laboratories as directed by the COR to develop corrective action plans.

3. EQA PROGRAM FOR FLOW CYTOMETRY-BASED ASSAYS

and coordinate a flow cytometry ICS program. Implement the plan within 30

Contract No. HHSN272201700061C Page 4 of 12 calendar days of COR approval, and update the plan, as needed or requested by the COR. The plan shall include the following:

a. Generate a standardized set of reagents consisting of antigens and antibody cocktails that ensure convenience, stability and standardization.

b. Design specifications and perform QC tests based upon physical properties (appearance, residual moisture, etc.) of the lyophilized reagents to ensure consistency and quality. Determine the standard performance of each lot, document and track the lot-to-lot reproducibility of the reagents.

c. Create a set of instructions and gating templates for these reagents. The instructions shall provide a suggested method that has been validated to provide optimal results. The Contractor shall determine any unique changes that a particular laboratory may have made in comparison to the suggested instructions to be used in case of troubleshooting.

d. Evaluate primary data received from participating laboratories and produced in the Contractor�s facility to define assay acceptability criteria for overall performance assessment. Monitor performance of laboratories over time and report to participating laboratories trending analyses to demonstrate where each laboratory�s data fit in the overall data set. Provide information to the COR to determine the success of the program in maintaining or improving precision across laboratories.

e. Work with NIAID supported laboratories in consultation with the COR to develop a corrective action plan as needed.

f. Upon direction from the COR, design and optimize additional phenotypic and functional flow cytometry panels, design/implement new flow cytometry assays and/or variations of other flow cytometry based assays, design/implement novel T cell assays, and evaluate test results as needed.

4. EQA PROGRAM FOR MULTIPLEX/ARRAY

and coordinate a Luminex cytokine assay EQA program. Implement the plan within 30 calendar days of COR approval, and update the plan, as needed or requested by the COR. The plan shall include the following:

a. Manage and coordinate an EQA program for Luminex cytokine assays to provide participating laboratories with two scheduled evaluations per year. Design consensus protocols and prepare SOPs and instructions for participating laboratories.

b. Acquire, aliquot, store, assemble and ship all necessary reagents and controls to perform a 5-plex Luminex-bead assay to detect IL-2, IL-6, IL-10, TNF alpha and aterials to define standard performance and ensure optimal quality, consistency, reproducibility and lot-to-lot comparability over time for different rounds of testing.

c. Evaluate primary data received from participating laboratories and the Contractor�s facility to define assay acceptability (pass/fail) criteria for

Contract No. HHSN272201700061C Page 5 of 12 performance assessment. Monitor performance of laboratories over time and report trending analyses to participating laboratories to demonstrate where each laboratory�s data fit in the overall data set.

d. Work with NIAID supported laboratories, as directed by the COR, to develop corrective action plans as needed.

e. Upon request of the COR, design and implement additional EQA programs for other multiplex/array platforms, e.g. Meso Scale Discovery.

5. EQA PROGRAM TO ASSESS COLLECTION, STORAGE, AND TESTING OF

MUCOSAL SPECIMENS

Upon request of the COR, the Contractor shall participate in assay development and validation for mucosal immune factors and assist in development of an EQA program to assess collection, storage, and testing parameters of mucosal specimens for host pathogens (microbiota) or anti-vaccine immune responses.

6. SUPPORT THE DEVELOPMENT OF ANTIBODY CHARACTERIZATION ASSAYS

AND EQA PROGRAMS

Laboratory assays used to assess candidate vaccine immunogens based on the antibody responses they elicit are continuing to be developed. These include tests to measure neutralizing antibodies and ELISAs to measure binding antibodies in addition to multiplex technologies anti-HIV responses. Various vaccination strategies are likely to produce a variety of antibody isotypes with unique functional abilities, such as antibody dependent cellular cytotoxicity (ADCC), opsonization, fixation of complement, binding of Fc receptors and specific localization of immune mediators (e.g. mucosal immunoglobulin). Assays for these will require a rigorous process of optimization and validation before use in clinical trials. Key reference reagents, development of SOPs, assay validation, and proficiency test panels for newly developed antibody characterization assays are critical.

The Contractor shall:

a. Design and execute a program to provide logistical support for the optimization of new assays by receiving, storing, quality assuring, and redistributing reagents/materials, and tracking shipments to laboratories supporting assay development.

b. Prepare stocks of reagents/materials and necessary cell lines.

c. Prepare and implement a QA/QC plan (including bridging studies and trending analysis) for these reagents/materials and cell lines to ensure lot-to-lot comparability.

d. Develop and distribute SOPs to the laboratories and assist in implementation of the assay in laboratories.

e. Receive and analyze data from the laboratories. Notify laboratories of performance in collaboration with the COR.

Contract No. HHSN272201700061C Page 6 of 12

f. Provide assistance to participating laboratories as directed by the COR to troubleshoot assay results and protocol deviations, and report outcomes to the

COR.

7. ESTABLISH AND CHARACTERIZE UNIQUE CLADE-SPECIFIC HIV VIRUS

PANELS

The Contractor shall perform the following activities:

a. Receive and catalog source material (e.g. plasma) from NIAID collaborators

(domestic and international) and perform HIV virus characterization. This includes isolating, culturing, propagating, and aliquoting clarified supernatant containing virus for storage, testing, and re-distribution as requested by the COR.

b. Aliquot and store cultured virus as supernatant and/or in defibrinated plasma.

c. Perform HIV viral load assays to support the virus characterization.

d. Characterize selected HIV strains for host co-receptor usage, and perform full length sequencing, sterility testing for endotoxin and mycoplasma, p24, and

TCID50.

e. Store and distribute viruses and/or plasma. Activities shall include reviewing the storage inventory, retrieving the required vials, packaging for safe and proper shipment, and shipment to labs as approved by the COR.

8. OPERATE AND MAINTAIN A CENTRAL WEB DATABASE FOR ACTIVITIES

Operate and maintain a centralized database for the following:

a. Track EQAPOL activities including real time inventory of cells, viral samples, serum, plasma, etc. (including characterization data).

b. Provide an interface to permit participating laboratories to directly provide EQA testing data of primary and processed results.

c. Allow participating laboratories to retrieve their individual test data reports.

d. Store data analyses and statistical analyses; track protocol/assay deviations and tracking performance of laboratories over time (trending analysis).

e. Share technical and scientific documents with laboratories participating in the EQA Programs.

f. Maintain the computerized system security documentation as required by OMB Circular A-130, Appendix III and the Federal Information Security Management Act (FISMA). This shall include a comprehensive assessment of the management, operational, and technical security controls in the system to determine the extent to which the controls are implemented correctly, operating as intended, and producing the desired outcome with respect to meeting a specified set of security requirements for the system. These actions are referred to as System Assessment and Authorization (SA&A). The NIAID Information System Security Officer (ISSO) performs the Assessment to support the NIAID Chief Information Officer�s (CIO) decision to authorize operation of an information system and to

Contract No. HHSN272201700061C Page 7 of 12 explicitly accept the risk to NIAID data based on the implementation of an agreed-upon set of security controls.

g. Upon COR approval the Contractor shall place in operation and maintain the system. COR approval shall be required for updates to the system that include hardware and/or software.

h. Although the Contractor may choose to use a different web-based database from the established database, this contract will not cover costs for developing a new database.

9. COORDINATE OPTIMIZATION EFFORTS FOR NEW ASSAYS AND ADVISE ON

ASSAY VALIDATION, REGULATORY, COMPLIANCE, AND STATISTICAL

ISSUES

The Contractor shall provide high-level strategic, product and assay development consulting services to NIAID. The Contractor will perform a complete assessment of the methods, including the validation and �cross-validation� of specific analytical methods performed by NIAID supported laboratories.

The Contractor shall perform the following tasks:

a. Provide advice to NIAID and NIAID-supported laboratory staff in the development, optimization and validation of novel immunological assays needed for candidate vaccine immune monitoring. This advice shall be provided through teleconferences/videoconferences, participation in site visits, writing and reviewing reports, and writing consensus SOPs.

b. Review methods development and validation packages and provide a comprehensive evaluation of the scientific merit and regulatory compliance of these packages. This review shall be provided to the COR in a formal written report within three weeks of receipt of information.

c. Provide recommendations to the COR for additional assay development, assay transfer, or validation necessary to meet regulatory agency requirements.

d. Provide training or guidance templates on biological assay development, validation, HIV diagnostic algorithms, cross validation, and assay transfer methodologies, as requested.

e. At the request of the COR, provide training at investigator meetings and regional training events. Obtain COR pre-approval of training materials at least 3 business days prior to the date of the presentation.

f. At the request of the COR and upon approval of the Contracting Officer, share data and research results with the scientific community at investigator meetings and regional training events.

10. MEETINGS AND TELECONFERENCES

a. Contract Initiation Meeting Within 60 calendar days after the effective date of the contract, participate in a one-day Contract Initiation Meeting with the COR, the Contracting Officer and

Contract No. HHSN272201700061C Page 8 of 12 other NIAID personnel designated by the COR, to be held at the Contractor�s site.

The purpose of the Contract Initiation Meeting will be to orient the Contractor to NIAID contract procedures.

b. Monthly Meetings/Teleconferences

Plan and conduct meetings of the Contractor�s Principal Investigator and Project Manager with the COR at a minimum of monthly intervals, either in person or via teleconference, to review overall progress and/or to discuss any matters relevant to the scientific and financial administration of the contract and future activities.

The schedule for those meetings will be established by the COR after contract award. Prepare and distribute the agenda and meeting/teleconference materials to all participants at least one business day prior to the meeting.

c. Annual Site Visit

Arrange for and facilitate annual site visits for NIAID Program staff, the Contracting Officer, and External Advisory Group members (see below) to review and discuss: project progress; problems and obstacles and approaches to overcoming identified problems and obstacles; recommendations for modifications in project timelines, External Advisory Group recommendations, objectives, and research approaches/methodologies based on outcomes to date;

and future plans. These site visits shall be attended by the Principal Investigator, the Contractor�s business representative, and all key personnel. The Contractor shall:

i. Plan and submit the agenda to the COR for approval at least 10 business days before the site visit.

ii. Develop written and oral presentation materials

iii. Arrange the logistics associated with the site visits and for travel costs for non-Government site visit attendees

iv. Prepare and submit Annual Site Visit reports to the COR and Contracting

Officer within 30 calendar days of completion of each annual site visit.

d. Establish an Independent External Advisory Group Within 3 months of the effective date of the contract, establish an Independent External Advisory Group consisting of 5 members to periodically review performance and progress toward achieving defined technical and strategic goals and milestones based on negotiated objectives. The membership of the Independent External Advisory Group shall be proposed by the Contractor after award, and agreed to by the COR.

11. INITIAL AND FINAL TRANSITION

a. Initial Transition The Contractor shall be required to receive shipment(s) of characterized PBMCs, virus isolates, and plasma that will be transferred from Duke University in Durham, North Carolina no later than three (3) months from the effective date of the contract. There are approximately 100,000 cryovials (1.8 ml volume size) with attached bar-coded labels that shall require storage in vapor phase liquid nitrogen. Specifically, the Contractor shall:

i. Within 30 calendar days of the contract effective date, develop and submit, for COR review and approval, a Draft Initial Transition Plan to ensure the

Contract No. HHSN272201700061C Page 9 of 12 storage of the cryovials in the Contractor�s facility no later than three (3) months following the contract effective date. The Draft Initial Transition Plan shall delineate the activities to be undertaken and the timelines for the completion of the cryovial transfer. This plan shall include the procedures to maintain specimen integrity upon receipt of the cryovials to storage in the liquid nitrogen freezers, transfer of all paper and electronic files that contain cryovial specimen characterization data into the Contractor�s inventory database, and QC procedures. Revise the Draft Initial Transition Plan to accommodate COR comments that will be returned within two weeks of receipt, and submit the Final Initial Transition Plan no later than two (2) weeks after receipt of COR comments.

ii. Participate in teleconferences with personnel at Duke University, the COR and his/her designees to: (i) discuss the bar-coded label identifiers on the cryovials and paper/electronic file information for the cryovials; (ii) review the shipping schedule for delivery of cryovials to the Contractor�s facility; and (iii) discuss any issues required to complete the transfer.

b. Final Transition

The Contractor shall prepare and implement a Final Transition Plan to ensure the orderly, efficient and safe transition of all contract activities and materials. This shall include the following:

i. No later than six (6) months prior to the completion date of this contract, develop and submit, for COR review and approval, a Draft Final Transition Plan delineating the transition activities to be undertaken, timelines for the completion of each transition activity, Contractor staff to be assigned and their roles and responsibilities. The Draft Final Transition Plan shall include a listing of and plans for transferring contract-generated materials, e.g., samples, reagents, all paper and electronic regulatory files, databases, software and hardware, SOPs, training plan, and QA/QC plan, and methods proposed to plan and conduct thorough briefings of the new Contractor.

Revise the Draft Final Transition Plan to accommodate COR comments, and submit the Final…