Attachment 3 - NRGR_Statement of Work Sep 2024.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Contract Title: Scientific Management and Support to the National Institute of Mental Health (NIMH) Repository and Genomics Resource (NRGR)

Statement of Need and Purpose:

The NIMH Repository and Genomics Resource (NRGR) is a centralized national biorepository funded by National Institutes of Health (NIH). NRGR provides to the research community DNA, RNA, cell lines, and other biospecimens from large collections of individuals with psychiatric illness along with neurotypical controls. NRGR provides basic demographic and diagnostic data for all biospecimens and genotype, DNA sequence, and gene expression data associated with a subset of biospecimens.

The NIMH seeks a Contractor to sustain, enhance, and enrich NRGR for genetic and cellular studies of psychiatric disorders to facilitate and accelerate the scientific understanding of the genetic risk architecture and basic biology underlying mental disorders. This effort is expected to involve a functionally integrated, multi-disciplinary team that will continue to manage broad sharing of biospecimens and data resources through a single, centralized, national resource to advance basic and translational research in the genetics of mental disorders.

Background Information and Objective:

Background Information: Identification of genetic and environmental contributions to the etiology of brain disorders remain a public health challenge. While recent technological advances offer promise in understanding the genetic etiology and mechanistic basis of mental disorders, realizing this potential requires the free and open sharing of genetic material, genetic and phenotypic data, and genetic analyses among researchers. This is especially true for mental disorders and other complex diseases, for which gene effect sizes are frequently modest and the integration of samples/data into a common analytical framework is often critical to achieve sample sizes that have adequate statistical power for disease association, gene mapping, and mutation detection.

The quality and quantity of genomic and phenotypic information have presented a challenge to the broad sharing of such resources. Genetic and phenotypic information is currently distributed across many heterogeneous and autonomous information systems, each with their own interfaces, control languages, data models, and formats. The lack of data harmonization and federation amongst databases prevents optimal utilization of the data resources currently available. It is necessary to provide uniform, integrated, and semantically-consistent structured data resources to fully access the power of broad data sharing and allow investigators to address the complex biology underlying mental illness.

In 1989, NIMH launched the Human Genetics Initiative (HGI) with the goal of creating a centralized national genomic resource aimed at accelerating gene discovery through the sharing of clinical information, DNA samples, and cell lines coordinated through an electronic database. Additionally, a stem cell repository for human induced pluripotent stem cells (iPSCs) and related resources was established in 2011. Collectively, these two resources are now referred to as the “NIMH Repository and Genomics Resource (NRGR)” and serve as the largest biorepository in psychiatry, providing access to high-quality biomaterials collected from over 200,000 phenotypically well-characterized control and patient subjects representing a wide range of mental illnesses across ancestrally diverse populations. To date, NRGR has distributed over one million samples to over 450 investigators world-wide and has supported approximately 1,800 genetic research studies on mental illnesses. NRGR support has resulted in over 800 publications, including many high-profile papers in psychiatric genetics, and several hundred replicated genetic findings reported from large scale genome-wide studies.

The biospecimens stored and distributed by the NRGR include but are not limited to human-derived saliva, blood, cerebrospinal fluid (CSF), DNA, RNA, plasma, biopsied materials, fibroblast cell lines (FCLs), lymphoblastoid cell lines (LCLs), cryopreserved lymphocytes (CPLs), and induced pluripotent stem cell lines (iPSCs).

The existing NRGR collection encompasses over 3.5 million biospecimens, including:

1.4 million LCLs in 1.8 mL glass ampules or plastic cryovials; 300,000 CPLs in 1.8 mL plastic cryovials; 66,000 iPSCs in 1.8 mL plastic cryovials; 1 million aliquots of DNA and 100,000 aliquots of RNA in both tubes and 96-well plates; 750,000 samples of blood plasma; 7,000 urine samples; 40,000 whole blood samples; and 2,000 saliva samples.

On average, NRGR currently receives and processes a minimum of 25,000 biospecimens per year, including 750 saliva samples, 15,000 blood samples, 2,000 DNA samples, 25 FCLs, and 60 iPSC lines. Annually, NRGR currently distributes over 15,000 biospecimens. In 2023, NRGR received and banked 67 externally produced iPSC lines and generated 15 iPSC lines for NIMH investigators, and these numbers are expected to grow. From 1989 – 1999 NRGR was supported by a contract. From 1999 to present NRGR has been managed by a U24 mechanism. NRGR is currently supported via a U24 mechanism awarded to Rutgers University in Piscataway, New Jersey.

Objectives: The objective of the NRGR is to develop, sustain, enhance, and enrich a centralized national biorepository for collection, storage, manipulation, and distribution of biospecimens and data resources from genetic studies of psychiatric disorders.

The Contractor for the NRGR must have direct experience in providing the scientific community with research resources and services for genetic studies, as well as experience in establishing an appropriate cyberinfrastructure. The Contractor for the NRGR must have a demonstrated capacity to store and distribute the existing collection of biospecimens and associated data (including metadata such as phenotypic data), as well as receive, store, and distribute newly acquired biospecimens and associated data (including metadata and phenotypic data).

Specific areas of scientific expertise required by NRGR include the following:

• Molecular biology, with a primary focus on the Epstein-Barr virus transformation of lymphocytes from fresh blood samples received from national and international sites to create contaminant-free cell lines, and the extraction of high-quality DNA from these cell lines. Additional molecular biology expertise is required in extraction of nucleic acids (DNA and RNA) directly from blood with quality control procedures to assure the integrity and competence of the products in modern genetic assays.

• Tissue and cell culture, with a primary focus on initial isolation, scale-up culture and banking of primary cells from diverse types of tissue samples (e.g., skin punches, hair follicles, olfactory epithelial biopsies).

• Developmental and stem cell biology, with expertise in reprogramming, pluripotent stem cell culture, gene editing, cryopreservation, banking, reconstitution and differentiation of iPSCs with comprehensive quality control capabilities at each step.

• Laboratory information management including receipt of orders and distribution of biologicals with computerized-based inventory management and storage facilities with monitored and alarmed low temperature storage and fail-safe procedures in place.

• Psychiatric clinical data curation, standardization, and harmonization, with a comprehensive knowledge of cross-disorder phenotypic dimensions.

• Computer and information sciences to maintain query of clinical data in NRGR and NIMH Data Archive (NDA; https://nda.nih.gov/) databases, provide tools to support NIH Program tasks associated with registering and monitoring studies, track research outcomes that results from NRGR biosamples and data, and develop systems to support approving and tracking researcher access to samples and the integration of data with other repositories.

SCOPE OF WORK

General 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 below:

There are five main task areas under this contract: 1) Transition of Existing Collection, (OPTION ITEM); 2) Ingress and Management of Biological Samples, Including Receiving, Processing, Storing, Tracking, and Distributing Biological Samples and Associated Data; 3) Biospecimen Extractions, Transformation, Preparations, and Assessments; 4) Customer Service and Outreach; and 5) Transfer-Out of Repository (OPTION ITEM). The Specific Requirements section (below) provides additional detail.

During the Base Period, the Contractor shall provide services under Task Areas 1-4.

During the Option Periods 1-4 (if exercised), the Contractor shall provide services under Task Areas 2-4.

Task Area 5 is an Option Item and may be exercised at the end of Base or any Option period of performance if there is a need to transfer the collection. However, it is anticipated that it would be exercised as part of Option Period 4. If Option Period 4 is exercised, the Contractor shall provide services under Task Area 5.

Specific Requirements:

Optional Task Area 1: Transfer of Existing Collection

1. Transfer-In of Repository https://nda.nih.gov/

In the event that a new Contractor other than the incumbent should win this follow-on contract, it is expected that the new Contractor shall quickly and efficiently transfer 100% of the repository collection, including all data, biological samples, and associated materials from the existing resource without any loss of data or samples and with a minimum of service disruption to users of the repository. This transfer shall occur during the first six months of the Base Year. The total estimated number of biological samples involved in this requirement is approximately 3.5 million, including:

1.4 million LCLs in 1.8 mL glass ampules or plastic cryovials; 300,000 CPLs in 1.8 mL plastic cryovials; 66,000 iPSCs in 1.8 mL plastic cryovials; 1 million aliquots of DNA and 100,000 aliquots of RNA in both tubes and 96-well plates; 750,000 samples of blood plasma; 7,000 urine samples; 40,000 whole blood samples; and 2,000 saliva samples.

These biospecimens are currently stored within a total of forty-five (45) mechanical freezers, fifteen (15) small liquid nitrogen tanks, and twenty-two (22) large liquid nitrogen tanks, currently held at a facility in Piscataway, NJ. It is anticipated that the new Contractor will work closely with the Incumbent to ensure a successful transition.

The new Contractor shall provide services for: 1) pulling, verifying, and packaging each vial for shipment; 2) transporting vials and Government Furnished Property to its facility; 3) offloading, verifying, and storing each vial and Government Furnished Property; and 4) transferring the associated data, 5) if needed, harmonizing the existing associated data structures to the structures used by the Successor Contractor, and 6) acquiring copies of and coming up to speed on the Standard Operating Procedures (SOPs) and other documentation from the Incumbent Contractor. Sample temperatures during normal storage shall be maintained throughout transport; DNA shall be transported in -80°C freezers and LCLs and cryopreserved lymphocytes shall be transferred in liquid nitrogen tanks.

Transfer-in may include coordination of permissions from Institutional Review Boards for certain collections (e.g., if reconsent is needed). If applicable, applicants should include within the body of the proposal an item-based cost estimate for transferring the existing samples of DNA, cell lines, cryopreserved lymphocytes, and linked genotypic and clinical data.

2. NRGR Management Plan

The contractor shall generate an NRGR Management Plan, which shall include:

[1.1] The organizational structure of the contract and identification of the contract leadership team, workstream leads and support staff.

[1.2] Staffing approach that will lead to the successful accomplishments of all proposed General Task Areas.

[1.3] Approach to coordinating the execution of all proposed General Task Areas.

[1.4] Approach to coordinating and collaborating with submitting investigators, network of Contractors at NDA, and NIH staff.

[1.5] Approach to coordinating, directing and effectively managing staff, inclusive of Subcontractors, if a teaming partnership is established, including a conflict resolution plan.

[1.6] A description of the established pipeline for biospecimen and associated data ingress, quality control, management, manipulation, storage, access, and dissemination. This pipeline description will include a diagram of the operation workflow and timeline, including for optional task orders proposed.

[1.7] Continuity of Operations Plan (COOP) for Biospecimen and IT Systems.

The COOP must detail mitigation strategies for any loss of power to the freezers, liquid nitrogen tanks and/or IT systems that will reduce the loss of specimens and/or data.

[1.8] A data and resource sharing plan that includes timelines, format, and mechanisms by which NRGR will share the data (e.g., demographic, diagnostic, clinical, genotypic, and family structure data) and biomaterials (e.g., cell lines and DNA samples) to qualified investigators, in accordance with regulatory requirements, applicable federal, state, and local laws, and NIH and NIMH policies. The NIH Genomic Data Sharing Policy will apply to any large-scale human or non-human genomic data generated under this project, as well as the use of these data for subsequent research (https://sharing.nih.gov/genomic-data-sharing-policy).

The NRGR data sharing plan should minimally include the following elements:

[1.8.1] Mechanisms by which all data and any biomaterials (DNA samples and cell lines, if applicable) are widely distributed to qualified investigators to the scientific community;

[1.8.2] A protocol for wide dissemination of these data and applicable biomaterials;

[1.8.3] A timetable for distribution.

The Management Plan will be reviewed annually.

Services and research resources will be provided to the scientific community by the repository on a fee-for-service basis when appropriate, at competitive prices.

Expectations for biospecimen sharing by NIMH projects and NRGR and support for biospecimen sharing are outlined in the Notice of Biospecimen Sharing Policy for the National Institute of Mental Health, Including Requirements for Induced Pluripotent Stem Cell Resource Development and Sharing (NOT-MH-21-265).

Task Area 2: Ingress and Management of Biological Samples, Including Receiving, Processing, Storing, Tracking, and Distributing Biological Samples and Associated Data

The Contractor for the NRGR shall fulfill the essential functionality of a biorepository, providing 1) services such as the shipping, receipt, cataloguing, banking, and distribution of biospecimens from deidentified human subjects enrolled in NIMH-sponsored genetics studies, and 2) infrastructure to support these services and the ingress, maintenance, organization, and integration of and access to the biospecimens and associated clinical, phenotypic, genetic, and other metadata.

Biospecimens include but are not limited to human-derived saliva, blood, cerebrospinal fluid (CSF), DNA, plasma, biopsied materials, fibroblast cell lines (FCLs), lymphoblastoid cell lines (LCLs), and iPSCs from national and international research projects supported by NIMH. For Task Area 2, the Contractor shall expect to receive 16,000 samples per year, including:

• 13,000 blood samples

• 1,000 saliva samples

• 1,875 externally produced DNA samples

• 25 externally produced fibroblasts

• 100 iPSC lines

The Contractor should have the capacity to manage the ingress, storage, and distribution of up to 50% higher volume of new samples, if necessary (see Option for Additional Quantities).

As of July 2023, the existing NRGR collections releasable to investigators include:

• 46,879 plasma samples

• 110,704 LCLs

• 664 FCLs

• 519 iPSC lines

• 320,834 DNA samples

• 1,703 RNA samples https://grants.nih.gov/grants/guide/notice-files/NOT-MH-21-265.html

• 108,101 cryopreserved lymphocyte samples

Contractor responsibilities as the repository for biospecimens collected through NIMH studies include the following:

[2.1] Provide kits, SOPs, and technical guidance about efficient and effective biospecimen collection and processing methods to registered studies supported by NIMH.

[2.2] Develop and implement a well-defined and executed workflow management plan to track samples during shipping, assign samples to a project-specific service (e.g., genomic/genetic analytic service, cell line establishment), and ensure basic quality control.

[2.3] Coordinate timely shipping and receiving of samples to accommodate the requirements of various scientific protocols and research sites, including sites in foreign countries which may be subject to different local and international shipping regulations and laws, and ensure the viability and integrity of the samples and any downstream products.

[2.4] Provide for the maintenance and storage of the existing NIMH biospecimen collection, as well as new biospecimens to be added each year.

[2.5] Maintain a data warehouse for both legacy studies (i.e., those that have completed data submission to the Biorepository), as well as for ongoing studies (i.e., data submission is in progress).

[2.6] NRGR has historically independently ingressed, curated, stored, and disseminated the data associated with biospecimens submitted to NRGR. The NIMH Data Sharing Policy (NOT-MH-23-100), however, mandates that all raw and analyzed data (including, but not limited to, clinical, genomic, imaging, and phenotypic data) from NIMH studies involving human subjects be deposited to the NIMH Data Archive (NDA), a separate contract-supported entity that serves as the primary data repository for NIMH. To streamline the data submission process for investigators, NRGR data workflows will be integrated so that NRGR data will be submitted, stored, and disseminated through NDA, with NRGR retaining curation responsibilities. Contractors are tasked with working with NIMH program staff, the NIMH COR, and NDA staff to implement an integrated workflow for direct deposition of curated and quality controlled biospecimen-associated phenotypic and clinical data to the NDA, in accordance with the informed consent, relevant local and national laws, and NDA Submission Agreement requirements (https://nda.nih.gov/nda/data-submission-agreement.html), for all biospecimen collections supported by ongoing NIMH studies. This includes:

[2.6.1] Supporting the addition of study-appropriate data dictionaries.

[2.6.2] Linking NDA global unique identifiers (GUIDs) to biospecimen identifiers.

[2.6.3] Coordinating with NDA staff.

[2.6.4] Provide curation of NDA common data elements.

[2.6.5] Establish necessary data security measures for interacting with the data deposited at NDA. FISMA moderate compliance must be achieved within 6 months of award.

[2.7] Following the establishment of an integrated workflow for deposition of data associated with ongoing NRGR studies to NDA as described in [2.6], conduct a census of data from legacy NRGR studies and migrate the legacy data to NDA or another repository, when appropriate. There are 175 legacy studies in NRGR.

[2.8] Ensure all data related to specific subjects will be linked by a unique identifier (linking-ID) which will be used to integrate data from NRGR with associated data (i.e., derived from the same subjects or part of the same study) stored on other public databases (e.g., dbGaP, NDA, federated iPSC registries), with the intent to provide a single entry-point access to all related data.

[2.9] Apply data cleaning procedures and returning all regularized and cleaned data to the repository for distribution, along with curation protocols and metadata.

[2.10] Curate, harmonize and integrate incoming clinical diagnostic data to generate an overall NIMH diagnosis (or diagnoses) for each study participant, based on expertise in clinical psychology and psychiatric instrumentation.

[2.11] Receive, track, and approve access requests to biospecimens and data housed in NRGR.

[2.12] Distribute biospecimens and data to approved users and track distribution.

The Contractor shall expect to distribute at least 12,000 biospecimens a year, mostly comprising genomic DNA samples.

The Contractor is responsible for providing the infrastructure necessary to support NRGR activities, including the following:

[2.13] Facilities that comply with all regulatory requirements, applicable federal, state, and local laws, and current best practices for handling biospecimens, including:

[2.13.1] Storing biospecimens under optimal conditions to minimize loss, damage, or contamination (e.g., monitored and alarmed low-temperature storage).

[2.13.2] Providing security, back-up systems and a plan for disaster recovery, including fail-safe procedures.

[2.14] Laboratory information management system (LIMS) and automated pipelines to ensure efficient and accurate handling and processing of the anticipated daily volume of samples. This system will:

[2.14.1] Maintain high-quality, robust, flexible, and secure information systems to allow detailed tracking of sample receipt, processing, storage and distribution, and rapid retrieval of samples and metadata associated with the samples. This system must have search features, be compliant with HHS Enterprise Performance Life Cycle (EPLC) framework, and be Federal Information Security Modernization Act (FISMA) moderate compliant. FISMA moderate compliance must be achieved within 6 months of award.

[2.14.2] Interface with robotic systems to separate, label, and store biosamples and perform automated sample processing (e.g., DNA extraction).

[2.15] A centralized web-based access portal (https://www.nimhgenetics.org/) to provide a user-friendly, intuitive, and easily navigable web interface for accessing biosample and data resources. Through the centralized web portal, the Contractor will:

[2.15.1] Provide a searchable catalog of available samples and data from various studies.

[2.15.2] Provide open access to summary-level data and restricted access to individual-level data associated with the samples stored in the Biorepository.

https://www.nimhgenetics.org/

[2.15.3] Assure the security, privacy, and confidentiality of the Biorepository data by providing a secure login system with different customizable levels of access.

[2.15.4] Provide comprehensive tools for querying and visualizing data from the centrally integrated databases.

[2.15.5] Provide a web-based process to apply for restricted access to individual-level data and biosamples, including comprehensive on-line instructions and automated tracking of all aspects of the request process.

[2.15.6] Provide the infrastructure for providing both technical and instructional support for all user groups (e.g., naive users, experienced bioinformaticians) of the database and web-portal.

[2.15.7] Provide automated tools for real time tracking and monitoring of sample and associated data submissions, distributions, and utilization of the various resources provided by the Biorepository. Provide a portal for NIH Program Officers to track biospecimen sharing by study.

[2.15.8] Collect and track information on the number and type of samples expected and currently deposited by the study investigator, along with the status of compliance with the data sharing plans.

[2.15.9] Support sample access requests for biosamples by GUIDs.

[2.15.10] Track the outcomes and resulting impact from the use of Biorepository resources, including but not limited to, use metrics of the website tools, newly generated data and publications on mental health research.

[2.15.11] Provide easy cross-referencing of available biosamples with linked data housed in other repositories, such as NDA, dbGaP, or others.

[2.15.11] Provide helpdesk functionality infrastructure, including support for investigators submitting biospecimens and associated data, including submitting biospecimen data to NDA; support for searching for samples, answering technical questions regarding Biorepository processes, or assisting with decisions on ordering. Upon written notice from the CO, the Contractor shall transfer all electronic databases, data management systems, and files as directed by the COR. All data shall be the property of the Government and shall be replicated and disseminated in a transferable format such that any successor Contractor and NIMH customers may use the data after transfer.

Task Area 3: Biospecimen extractions, transformations, preparations, and assessments

The Contractor shall manipulate the biospecimens to generate distributable derivative products and provide descriptive assessment of the samples. Examples of these services are as follows:

[3.1] Processing received blood or tissue samples to extract high-quality, well-characterized whole blood-derived DNA, plasma, whole blood-derived RNA/cDNA, and primary cell cultures (e.g., fibroblasts). This includes capabilities for processing, generating, and storing renewable resources, including generating LCLs via Epstein-Barr virus transformation from approximately 10% and cryopreserved lymphocytes (CPLs) from approximately 70% of received blood collections that are consented for cell lines, respectively; expansion of fibroblasts from skin punches; and expansion of olfactory cells from nasal biopsies.

[3.2] Performing quality control assessment of received biospecimens (e.g., assessing DNA purity, RNA integrity, nucleic acid or cell quantitation).

[3.3] Preparing aliquots of received biospecimens.

[3.4] Expanding received cell lines for storage.

New human iPSC derivation will be required from studies involving either new subject recruitment or leveraging the large collection of cryopreserved source cells (e.g., CPLs) currently banked at NRGR. Contract support is required to use state-of-the-art reprogramming techniques to derive iPSCs internally- and externally-produced donor-derived source cell samples (e.g., skin punches, fibroblasts or peripheral blood mononuclear cells) and provide the option to perform isogenic iPSC line genetic modification, with appropriate quality control. It is expected that approximately 100 iPSC lines will be banked or generated per year. While the percentage of banked vs NRGR-generated lines may vary, for the purposes of proposal development, assume half of the lines will be accepted from external sources and banked and half will be generated by the NRGR. Requirements include:

[3.5] Capabilities for using non-integrating reprogramming factors for “footprint-free” derivation of human source cells to clonal and non-clonal iPSC lines as requested.

[3.6] Capabilities for genetic modification of iPSC lines (e.g., using CRISPR/Cas9 gene editing).

[3.7] Performance of quality control measures on iPSC lines, including but not limited to growth characteristics, pluripotency, clearance of reprogramming transgenes, mycoplasma and sterility, chromosomal and genomic integrity (e.g., digital karyotyping, SNP genotyping to assess copy number variation, exome sequence and/or whole genome sequence).

[3.8] Complete integration with Biorepository functions for managing biosample receipt, processing, banking, and distribution, as well as data management and access. This will include all provenance data linking iPSC lines with both source biosamples and donors.

[3.9] The Contractor is expected to maintain awareness of new tools, techniques, technologies, and approaches in areas applicable to this program. Novel technologies may be adopted and incorporated into the program as they are validated, upon approval by the COR.

The Contractor should have the capacity to manage biospecimen extractions, transformations, preparations, and assessments of up to 50% higher volume, if necessary (see Option for Additional Quantities).

Task Area 4: Customer service and outreach

The Contractor shall provide customer service for the Biorepository, including:

[4.1] Providing timely support, both technical and instructional (e.g., tutorials), for all user groups (e.g., naïve users, experienced bioinformaticians) of the database/web-portal.

[4.2] Staffing a user-friendly customer service interface, such as a help-desk, to provide support to biomedical researchers who submit samples, submit data, search for samples, have technical questions regarding the submission, or who need assistance with decisions on ordering.

The Contractor is also required to publicize the Biorepository collections in a timely manner. Outreach efforts shall include:

[4.3] Publicizing summarized information about the current status of the biosamples and data available on the NRGR website, such as a table detailing for each disorder the number of pedigrees, number of affected sibling pairs, number of affected subjects with DNA available, etc.

[4.4] Promoting awareness of repository services to the scientific community and aiding in recruitment of additional samples for the repository collection when appropriate. These activities should be directed toward scientists and towards the public being served, e.g., those with psychiatric disorders and their friends and families. Examples include:

[4.4.1] Publishing notices and articles in relevant scientific journals that describe specific repository collections or the general purpose and operation of the repository.

[4.4.2] Giving presentations at scientific meetings to represent the repository.

[4.5] Sharing and publicizing the state-of-the-art laboratory standard operating procedures developed for NRGR.

This task order also includes support for Contractor administration and interaction with the government. Activities include:

[4.6] Producing reports as required in the below section, “Reporting Requirements.”

[4.7] Conducting meetings with NIMH program staff. The Contractor shall routinely communicate with the COR and CO, and shall schedule and coordinate teleconferences to discuss repository activities and issues. The Contractor shall organize telephone calls and meetings as needed to manage the project and at the direction of the COR. The Contractor shall prepare minutes following each teleconference call or meeting. The Contractor shall organize one site visit (to the repository site) or one reverse site visit (to the NIH) per year, to include the COR, CO, and approximately 10 advisors to the repository, to be designated by the

COR.

[4.8] The Contractor shall stand up a Genomics Steering Committee (GSC) comprised of NIMH representatives, the Contractors, and at least four external scientists/advisors to be named after the contract is awarded. External advisors will be selected by the Contractors and approved by the COR. The GSC will vote to elect a chair, who will be responsible for developing meeting agendas and chairing meetings. Meetings will be convened at least annually and further on an ad hoc basis around specific issues. Meetings will be conducted virtually via telecommunications platforms like Zoom. The purpose of the GSC is to:

o Advise and provide scientific and operational insight and recommendations on processing milestones, the activities of the Biorepository, and the distribution of data, biospecimens, and services to the wider scientific community.

o Discuss and make recommendations regarding the enhancement of research resources and the facilitation of free and open sharing.

o Provide expertise in undertaking new processing initiatives and incorporating emerging genomic and genetic tools and technologies into Biorepository activities.

o Provide input on whether program activities are aligned with the needs of the broader scientific community for research resources necessary for the genetic analysis of mental disorders.

OPTIONAL TASK AREA 5: Transfer Out of Repository

In the event that the NRGR must be moved from the Contractor’s facility, such as if a new successor contractor is awarded a follow-on contract (“Successor Contractor”) or if NIMH decides to deaccession the collection, the Contractor shall provide transfer-out services.

For Transfer-out, the Contractor shall be responsible for:

[5.1] Preparing for transfer of all the biospecimens in its possession (which includes pulling, verifying, and packaging each vial for shipment) to Successor Contractor or to a NIMH designated storage facility.

[5.2] Providing all data, experimental protocols, and an electronic inventory by individual tube of all of the biospecimens in a common digital format to the COR and Successor Contractor.

[5.3] Bringing any Successor Contractor up to par on the current system.

Upon written notice from the CO, the Contractor shall transfer all biospecimens, electronic databases, data management systems, and files as directed by the COR. All data shall be the property of the Government and shall be replicated and disseminated in a transferable format such that any Successor Contractor and NIMH customers may use the data after transfer.

Option for Increased Quantities – Biospecimen Ingress, Management and Distribution

As demand for contract services may vary, the Contractor shall maintain the capability of expanding throughput to meet a higher volume. Each option for increased quantities may be exercised multiple times within a performance period to fund a higher volume of biospecimen intake or distribution. Each option for additional quantities may be exercised for up to 5% of the estimated annual new biospecimen sample ingress and distribution workload, but not exceeding the ceiling of 50% per performance period.

Option for Increased Quantities – Biospecimen extractions, transformations, preparations, and assessments

As demand for contract services may vary, the Contractor shall maintain the capability of expanding throughput to meet a higher volume. Each option for increased quantities may be exercised multiple times within a performance period to fund a higher volume of biospecimen extractions, transformations, preparations, and assessments. Each option for additional quantities may be exercised for up to 5% of the estimated annual extraction, transformation, preparation, and assessment workload, but not exceeding the ceiling of 50% per performance period.

VI. Other Considerations

A. Government Furnished Property

Unless the resultant contract is awarded to the incumbent provider, all biological samples (approximately 3.5 million biospecimen aliquots are currently collected), data, experimental protocols, and SOPs that compose the current NRGR, as well as NIMH purchased equipment, will be transferred to the new Contractor. This Contractor is responsible for maintaining operations and integrity of all Government Furnished Property.

The Contractor will be required to comply with FAR Part 45, Government Property, and the HHS “Contractors Guide for Control of Government Property,” which will be made available to any resultant Contractor. The Contractor will also be required to account for Government Furnished Information in accordance with Federal Information Security Modernization Act (FISMA)

1. Data and Equipment Rights Should the Government authorize, as a direct cost item under this contract, the purchase of any property, which could possibly include database platforms, software, and other equipment and supplies, or the creation of any informational algorithms, database structures, laboratory procedures and processes, this property shall be titled vested in the Government. Additionally, all data including, but not limited to, DNA preparation logs, phenotypic data, cell line preparation, SNP and microsatellite data, QC data, computer codes for databasing and web representation, experimental protocols, and research tools generated by the Contractor to meet the deliverables of this contract shall remain the property of the Government. As such, this data shall be made available as designated by the COR, including, via public website or controlled website access as directed. The Contractor shall surrender all such materials to the Government or a future Contractor at the time this contract ends (if the contract is not renewed), without additional charges for such surrender. All microsatellite, SNP, and other laboratory data generated by the Contractor shall be provided to the COR and submitting and withdrawing investigators, as requested.

B. Contractor Furnished Property

The Contractor shall be responsible for furnishing all materials, resources, supplies, and personnel necessary to carry out and accomplish their performance obligations under this contract. This includes providing liquid nitrogen tanks and additional -80°C and - 20°C freezers, as needed, to house, transfer, and maintain the entire repository collection.

DELIVERY OR DELIVERABLES

As detailed in the table below, The Contractor shall submit electronic copies of the following deliverables.

Deliverable Date of Submission to

COR

Completion Time for COR Review

Days Contractor has to Deliver the Final Deliverable

A final Management Plan, incorporating any changes or modifications agreed upon by the Government and the Contractor during contract negotiations and the first month of contract performance.

Within one (1) month of contract award

10 business days after receipt

10 business days after COR review

Monthly Progress Reports (MPRs) that specify status updates, accomplishments, problems encountered, problem resolution, unresolved problems, and

3rd day of each month unless it falls during the weekend, then the next business day plans for the next month’s activities for each Task Area. Staff assigned to each workstream should be noted in the MPR.

Biannual Progress Summaries (BPS) detailing the timely processing and yield of sample submissions and requests;

generation of DNA, RNA or cell-lines and iPSC-derivatives from deposited samples; integration of data; federation of data with other databases;

development and implementation of IT systems; and tracking and monitoring of repository use. In the performance period, a Final Report will be submitted in lieu of the last BPS. The Final Report will incorporate a summary of contract activities.

6 months after contract start date and every 6 months thereafter

10 business days after receipt

10 business days after COR review

Details for hosting an annual site visit for NIMH staff.

4 months prior to the site visit date

10 business days after receipt

10 business days after COR review

REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format.

All electronic reports submitted shall be compliant with the Revised 508 Standards, which align with WCAG 2.0 Level A and AA Success Criteria. See this website for full details:

https://www.section508.gov/test/ and this section https://www.section508.gov/test/web-software/. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at:

https://www.hhs.gov/web/section-508/accessibility-checklists/index.html

In addition to the deliverables noted in the section above, the Contractor shall submit the following reports as required by the INFORMATION AND PHYSICAL ACCESS https://www.section508.gov/test/ https://www.section508.gov/test/web-software/ https://www.section508.gov/test/web-software/ https://www.hhs.gov/web/section-508/accessibility-checklists/index.html

SECURITY Article in SECTION H of this contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

[R.1] Roster of Employees Requiring Suitability Investigations: The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including Subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a Federal information system(s). The roster shall be submitted to the Contracting Officer's Representative (COR), with a copy to the Contracting Officer, within 14 calendar days of the effective date of the contract.

[R.2] IT System Security Plan (IT-SSP): The Contractor shall submit the IT-SSP within thirty (30) days after contract award. The IT-SSP shall be consistent with, and further detail the approach to, IT security contained in the Contractor's bid or proposal that resulted in the award of this contract. The IT-SSP shall describe the processes and procedures that the Contractor will follow to ensure appropriate security of IT resources that are developed, processed, or used under this contract. If the IT-SSP only applies to a portion of the contract, the Contractor shall specify those parts of the contract to which the IT-SSP applies. The Contractor shall review and update the IT-SSP in accordance with NIST SP 800- 53A, Guide for Assessing the Security Controls in Federal Information Systems and Organizations, on an annual basis.

[R.3] IT Security Assessment Plan/Report (SAP/SAR): The Contractor shall submit the IT-SAP within thirty (30) days after the contract award. The security assessment must be conducted by the assessor and be consistent with NIST SP 800-53A, NIST SP 800-30, and HHS and NIH policies. The assessor will document the assessment results in the SAR. The NIH should determine which security control baseline applies and then make a determination on the appropriateness/necessity of obtaining an independent assessment.

Assessments of controls can be performed by Contractor, government, or third parties, with third party verification considered the strongest. If independent assessment is required, include statement below. Thereafter, the Contractor, in coordination with the NIH shall conduct/assist in the assessment of the security controls and update the SAR at least annually.

[R.4] Independent Assessment - Due 90 days after the contract award. The Contractor (and/or subcontractor) shall have an independent third-party validate the security and privacy controls in place for the system(s). The independent third party shall review and analyze the Security Authorization package, and report on technical, operational, and management level deficiencies as outlined in NIST SP 800-53. The Contractor shall address all "high" deficiencies before submitting the package to the Government for acceptance. All remaining deficiencies must be documented in a system Plan of Actions and Milestones

(POA&M).

The Contractor shall notify the Contracting Officer's Representative (COR) and Contracting Officer 30 days prior to a change in staffing for positions that require suitability determinations as follows:

[R.5.1] New Employees who have or will have access to HHS Information systems or data: Provide the name, position title, e-mail address, and phone number of the new employee. Provide the name, position title and suitability level held by the former incumbent. If the employee is filling a new position, provide a description of the position and the Government will determine the appropriate security level.

[R.5.2] Departing Employees: 1) Provide the name, position title, and security clearance level held by or pending for the individual; and 2) Perform and document the actions identified in the "Employee Separation Checklist", attached in Section J, ATTACHMENTS of this contract, when a Contractor/Subcontractor employee terminates work under this contract. All documentation shall be made available to the COR and/or Contracting Officer upon request.

The Contractor shall submit a revised/updated Management Plan in the event of a change in any of the Principal Investigators named in the Key Personnel Article in SECTION G of this contract. The revised plan is subject to review and approval by the Contracting Officer.

Additional required reports include the following:

[R.6] Contractor - Employee Non-Disclosure Agreement(s): The Contractor shall complete and submit a signed and witnessed "Commitment to Protect Non- Public Information- Contractor Agreement" form for each Contractor and Subcontractor employee who may have access to non-public Department information under this contract. This form is located at:

https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Documents/Nondisclosur e.pdf.

[R.7] Vulnerability Scanning Reports: The Contractor shall report the results of the required monthly special vulnerability scans no later than 10 days following https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Documents/Nondisclosure.pdf https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Documents/Nondisclosure.pdf the end of each reporting period. This report may be included as part of the Monthly Progress Reports.

[R.8] Section 508 Annual Report: The Contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION C of this contract. The Section 508 Report Template and Instructions for completing the report are available at:

https://www.hhs.gov/sites/default/files/web/508/contracting/technology/section_5 08_annual_report.doc.

[R.9] Invention Reporting: In accordance with contract Article C.3. “Invention Reporting Requirement”, an Annual Invention Utilization Report shall be due on or before the anniversary date of the contract award and a Final Invention Statement will be due on or before the expiration date of the contract.

[R.10] Service Contract Annual Report: In accordance with FAR 52.204-14, “Service Contract Reporting Requirements”, contained in full text in Article I.4. of the contract, the Contractor shall report annually by October 31, for services performed under this contract during the preceding Government fiscal year (October 1 – September 30) the following information to http://www.sam.gov, with an electronic copy to the Contracting Officer: 1) Contract number and, as applicable, order number, 2) The total dollar amount invoiced for services performed during the previous Government fiscal year under the contract, 3) The number of Contractor direct labor hours expended on the services performed during the previous Government fiscal year, 4) Data reported by Subcontractors [if applicable] under paragraph (f) of the subject clause (see full text of clause FAR 52.204-14, “Service Contract Reporting Requirements” in Article I.4. of the contract).

The following reports are required, as applicable:

[R.11] Subcontracting Reports: The Contractor shall submit the following Subcontracting reports electronically via the "electronic Subcontracting Reporting System (eSRS) at http://www.esrs.gov.

[R.11.1] Individual Subcontract Reports (ISR): Regardless of the effective date of this contract, the Report shall be due on the following dates for the entire life of this contract: April 30th and October 30th.

https://www.hhs.gov/sites/default/files/web/508/contracting/technology/section_508_annual_report.doc https://www.hhs.gov/sites/default/files/web/508/contracting/technology/section_508_annual_report.doc http://www.sam.gov/ http://www.esrs.gov/

[R.11.2] Expiration Date of Contract Summary Subcontract Report (SSR): Regardless of the effective date of this contract, the Summary Subcontract Report shall be submitted annually on the following date for the entire life of this contract: October 30th.

For both the Individual and Summary Subcontract Reports, the Contracting Officer/Contract Specialist shall be included as a contact for notification purposes at the following e-mail address: valerie.whipple@nih.gov

OTHER CONSIDERATIONS

Travel:

In accordance with Federal/NIMH travel regulations, the COR can approve travel requests as required to fulfill the work requirements specified by the state of work.

Key Personnel:

The Contractor shall ensure that their staff is appropriately trained in SOP to receive, store, process, prepare, and distribute human blood, DNA, and cell lines and associated data; to adhere to regulations and guidance regarding consent, personally identifiable information, privacy, and security; and to develop the necessary information technology and web-based tools to meet the deliverables of the contract. The Contractor shall provide and assure that within 24 hours (on regular business days) of a consultation request from a COR (or within 48 hours of a consultation request from a repository user), a PhD or MD level scientist with appropriate background knowledge is available for consultation.

The Contractor PI is expected to advise and guide all aspects of the project and its logistics to assure rapid receipt of data and biological samples, and to provide answers to queries from scientists and from the public (e.g., regarding repository content, access, submission, withdrawal, consent, and privacy issues). The Contractor must designate an individual at a senior Project Manager level to manage the activities associated with the repository collection. This senior Project Manager shall be designated as Key Personnel of this contract. The Contractor shall assure that appropriate expertise is available for all aspects of the project, including clinical, genetic, biological sample handling, data management, website development, sample distribution, statistical analysis, accounting, human subjects and human gene discovery regulations, and public outreach.

The PI and Contractor staff shall have extensive and state-of-the-art knowledge of human genetics, molecular biology, cell biology, gene discovery, and human genomics, mailto:valerie.whipple@nih.gov as well as an understanding of genetics applications of bioinformatics. In addition, the PI and contract staff shall obtain appropriate training to maintain expertise (e.g., clinical psychology, psychiatry, and other academic areas pertinent to this project).

Information System Security Plan:

The Contractor shall secure and protect all…