A4_NBB_3_0-Statement_of_Work-October_10_2024.pdf

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

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

The NIH NeuroBioBank Brain and Tissue Repository

Statement of Need and Purpose:

This contract will support a network of human brain and tissue procurement, characterization, processing, and distribution centers (NIH NeuroBioBank Brain and Tissue Repositories), as part of NIH’s strategy to maximize the availability of human brain and nervous system tissues to the research community while simultaneously achieving workflow efficiencies, coordination, and the use of biobanking best practices through a consolidated program management approach.

Background Information and Objective:

The NIH NeuroBioBank (NBB) is a trans-NIH initiative funded by the National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), National Institute on Drug Abuse (NIDA), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the NIH Blueprint for Neuroscience Research. The NBB is currently a network of six collaborative Brain and Tissue Repositories (BTRs) that are federated through a single IT Portal (www.neurobiobank.nih.gov).

The NBB was established in 2013 as part of NIH’s strategy to increase the availability of high-quality, well-characterized, human postmortem brain tissue to support scientific research while simultaneously achieving workflow efficiencies and better coordination of this resource using a consolidated program management approach. In addition to brain and nervous system tissue banking and distribution, the NBB serves to increase public awareness of the contributions of brain donation to improving the understanding of normal brain function and correlates of dysfunction and contributes to the development of best practices for the acquisition, processing, storage, characterization and distribution of human brain and nervous system specimens.

The BTRs support programs that actively recruit and register potential donors with diverse neurodevelopmental, neurological, and neuropsychiatric disorders, as well as individuals with no known brain disorders. Detailed deidentified clinical, phenotypic, and neuropathological data are acquired on donors and specimens by a team of clinicians and listed with inventory on the publicly accessible NBB informatics portal. Requests for specimens are reviewed and approved in a transparent manner and assigned to BTRs for distribution to qualified researchers at institutions around the globe to support biomedical research, and drug development.

The community outreach and communications arm of the NBB is the Brain Donor Project (BDP, https://braindonorproject.org/), which provides information to potential donors, patient advocacy groups, medical examiners, and organ procurement organizations. The BDP refers potential donors to NBB sites for registration and eventual tissue donation upon donor’s death.

Since inception, the NBB has continued to achieve its mission to facilitate research through the democratization of access to high-quality human brain and nervous system specimens by:

• Increasing the availability of specimens for new and emerging technology requirements,

• Contributing to the development of evidence-based biobanking best practices, and

• Increasing the general public’s awareness of brain donation to support research.

http://www.neurobiobank.nih.gov/ https://braindonorproject.org/

Period of Performance:

NIH expects to award multiple cost-reimbursement, term (level of effort) type contracts with a one (1) year base period, four (4) 12-month option years, and optional quantities. Future year funding will depend on each contractor’s prior year performance and the availability of funds.

Base Period: May 1, 2025 – April 30, 2026 Option Period 1: May 1, 2026 – April 30, 2027 Option Period 2: May 1, 2027 – April 30, 2028 Option Period 3: May 1, 2028 – April 30, 2029 Option Period 4: May 1, 2029 – April 30, 2030

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work (SOW) below.

The scope of this SOW covers multiple scientifically detailed daily and long-term responsibilities that are essential for the operations of an efficient human tissue repository, as described below:

• General Task Area 1: Acquire Brains and Tissues from Diverse Postmortem Donors

• General Task Area 2: Process and Optimally Preserve Specimens using Best Practices

• General Task Area 3: Perform Detailed Characterization of Donors and Specimens

• General Task Area 4: Securely Transfer Deidentified Data to a Central Informatics Portal

• General Task Area 5: Distribute Specimens to Qualified and Approved Investigators

• General Task Area 6: Participate in Process Improvement Activities across the Network

• General Task Area 7: Implement an Overall Quality Management Plan

• General Task Area 8: Contribute High Quality Specimens to Support Specialized Initiatives

• General Task Area 9: Coordinate and Perform Genome Sequencing of NBB Specimens

• General Task Area 10: Provide Training in Postmortem Diagnosis of Psychiatric Conditions

• General Task Area 11: Accept Well-Characterized Specimens from Other Brain Banks

[Note 1 to Offerors: General Task Areas 1 through 7 are mandatory and part of the base contract, while General Task Areas 8 through 11 will be exercised as optional quantities].

Contractors shall utilize ethical, legal and policy practices following NIH guidelines concerning informed consent and authorizations for broad and future use of specimens and data, genomics research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html), return of results, and community engagement. All biorepository donor coordinators shall participate in human subjects protection foundational training, such as the free online courses available here:

https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html. Additionally, training in coping strategies and effective communications with potential donors and their families are required for all donor coordinators.

Contractors shall provide and maintain adequate standard operating procedures (SOPs) and protocols for informed consent, tissue retrieval, dissection, processing, tracking, storage, and distribution. These SOPs shall be evidence-based and appropriate for long-term tissue https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html preservation and the maintenance of high tissue integrity. Tissue quality shall be assessed using metrics and protocols that the prevailing evidence and scientific community indicate are most appropriate, such as those described in NCI Best Practices for Biospecimen Resources.

Contractors shall include a description of how they will participate in virtual NBB working group meetings, for example the Diagnostic Categorization, Neuropathology, and the Donor Outreach and Coordination working groups. Contractors will be required to attend virtual and annual in-person NBB network meetings, as well as virtual meetings with stakeholder communities from high priority programs of the NBB.

The Contracting Officer’s Representative (COR), whose role is defined in Section G of the contract, shall monitor the technical aspects of work performance. Contractors will be expected to be responsive and flexible (within the scope of the contract) to evolving research priorities and initiatives as defined by funding institutes and programs.

The NBB is committed to maintaining current and scientifically accurate best practices for human tissue repositories and will continue to solicit input from stakeholders in the biobanking community. As advances occur, Contractors shall propose new state-of-the art procedures in biospecimen preservation and biorepository methodologies to be used for contract performance.

Specific Requirements:

[Note 2 to Offerors: Offerors shall provide a detailed technical approach and include supporting information on prior experience for each of the following Task Areas].

General Task Area 1: Acquire Brains and Tissues from Diverse Postmortem Donors Acquire brain and nervous system tissues from a minimum of 70 postmortem donors per year.

The postmortem interval shall be documented for all donations and should support high tissue quality. To effectively acquire new donors, BTRs shall establish pipelines for community outreach and engagement, recruitment, registration, and follow-up with potential donors, with special emphasis on those with the highest risk factors for relevant diseases. BTRs shall also collaborate with the BDP to register potential donors, and for outreach to disease advocacy groups, medical examiner’s offices, organ procurement organizations, and under-represented populations.

Exclusion criteria for NBB collection include diseases that disrupt the brain’s architecture, such as strokes, and extensive brain cancers, as well as accidental or intended extensive head trauma and prolonged mechanical ventilation prior to the donor’s death.

1. Acquire donors with a variety of neurodevelopmental, neurological, and neuropsychiatric disorders and substance use/addiction, as well as healthy controls, and from diverse geographical catchment areas. NBB program anticipates each BTR will acquire between 70-150 donors per year. Donors shall be comprised of both sexes, aged across the lifespan, and reflect the gender, race, and ethnicity distribution of the United States. Contractors must include a realistic projection for the collection size, disease categories, and race/ethnicity distribution of donors to be acquired based on historical collection data, and outreach methodologies to be employed.

https://biospecimens.cancer.gov/bestpractices/2016-NCIBestPractices.pdf

2. Focus on the collection of brain and nervous system tissues (i.e., spinal cord, peripheral nerves, cerebrospinal fluid), and peripheral tissues (skin, blood, dura, and other organs), as consented to and authorized by the donor’s legal next-of-kin.

3. As requested by the COR, add/change focus of disorders in the collection, acquire specific cases as determined by NIH initiatives, acquire specimens in unique or difficult to reach populations, including children, rare disease populations, minoritized, and underrepresented populations.

4. Participate in outreach activities with the BDP across the NBB network, as well as to patient advocacy groups and underrepresented communities as requested by the COR.

This activity will involve reporting back to the BDP the number of completed referrals, and the number of referrals that completed donations on a quarterly basis.

5. Describe and contribute existing collections (if applicable) for use in the contract (i.e., existing specimens with evidence of high-quality, well-characterized tissues, and provide the quality metrics such as RIN, RINe, 260/280 ratio, tissue pH etc., clinical, and neuropathological, genetic, and other phenotypic characterization metrics.

General Task Area 2: Process and Optimally Preserve Specimens using Best Practices Contractors shall provide a description of their methods for both maintaining specimen quality and ability to track individual specimens and their daughter specimens. Quality control should include gross histological examinations of the brains and other tissues, and molecular analyses including RNA integrity number (RIN or RINe) and analysis of DNA integrity. The Contractor shall describe other proposed quality control assays and provide any relevant data supporting assay validation.

1. Perform macroscopic examination of the brain and other tissues, documenting gross morphological changes, areas of atrophy, swelling, discoloration, and atherosclerotic disease.

2. Perform quality control assessments such as brain weights, tissue pH, RNA integrity, DNA quality, and other quality control measures, such as autolysis assays from at least two poles of the brain. To support assay reproducibility across the network, RNA Integrity measurements (RIN assays) will be performed by an NBB-designated site.

3. Record postmortem interval (PMI) and agonal score, as an index of the tissue quality.

4. Isolate nucleic acids (DNA, RNA) from brain tissues for storage and distribution upon request by researchers.

5. Prepare both fixed and frozen specimens from acquired organs. Prepare coronal slabs from one brain hemisphere (5-10mm thick slabs) using a cutting mold or other agreed upon slabbing devices and fix the other hemisphere in phosphate-buffered formalin or freshly prepared paraformaldehyde.

6. Perform 3D scanning of the hemisphere to be frozen, and 2D imaging and photo-documentation of each slab before freezing. Where equipment is available, perform MRI imaging of the fixed hemisphere.

7. Freeze slabs rapidly after imaging using either dry ice-cooled isopentane, LN2-cooled isopentane or LN2 vapor, followed by vacuum sealing and storage at -80oC or lower.

General Task Area 3: Perform Detailed Characterization of Donors and Specimens Perform detailed characterization of donors and tissues using phenotypic, clinical, serologic, neuropathologic, and toxicologic assessments sufficient to establish or exclude the presence of brain and non-brain disorders. Contractors shall establish a postmortem diagnosis review team to evaluate and integrate the following donor and specimen information, and assign “clinical brain and/or non-brain diagnoses” following NBB guidelines of Confirmed, Investigator Impression, and Insufficient Data categories of the Basis of Clinical Diagnosis (Appendix #1).

1. Conduct interviews of next-of-kin by a clinician or clinical research coordinator:

i. Contractors should propose to conduct semi-structured interviews, using forms such as the Structured Clinical Interview for DSM (SCID) for the interviews. The forms may be available on web applications for informants to complete.

ii. Obtain family history, and date of birth, sex at birth, gender, educational level, race/ethnicity, medical problems, genetic disorders, and mental illness including substance abuse for first-degree relatives, whenever available.

iii. Questionnaires with branching logic may be employed for certain disorders.

iv. Obtain cause and manner of death.

2. Review available medical records and document the following information:

i. Clinical findings and clinical history (provided with the type of diagnostic procedures used to determine clinical brain diagnoses).

ii. Documentation of any discernible pre-agonal medical status.

iii. Time since disease onset and extent (years) of hospitalization when applicable.

iv. Detailed documentation of comorbidities (based on clinical judgment of the assessment team).

v. Psychiatric and neurological history.

vi. Gestational age at birth, if available.

vii. Maternal history, neonatal history (for infant and pediatric donors).

viii. Medications at the time of death and medication history, if available.

ix. Phenotypic information such as cranial MRI findings (deidentified images and/or reports), other radiological reports, results of genetic tests and/or diagnostic evaluations, other clinical notes, and evaluations by specialists.

x. Integrate all available data by qualified personnel (or a consensus diagnosis team) to determine diagnoses using standard schemes such as the International Statistical Classification of Diseases and Related Health Problems (ICD).

3. Perform and record neuropathological, toxicological, and serological assessments:

i. Gross inspection of the base, medial, and lateral surfaces of the brain as well as coronal sections for evidence of any hemorrhage, edema, or other abnormalities.

ii. Neuropathologic evaluation of formalin fixed, paraffin-embedded tissue sections by a neuropathologist, as appropriate for the donor’s age, presenting diagnosis, and preliminary gross pathological evaluation. Perform immunohistochemical assays depending on the clinical diagnosis being evaluated. Minimum guidelines for neuropathological assessments and reporting are provided in Tables 1 and 2.

iii. Acquire high quality digital images of whole neuropathology slides and make data available through a digital pathology sharing resource. This activity, including identifying a central data sharing resource, will be further developed during the contract’s performance period.

iv. Perform serological testing of blood or serum for the following infectious agents:

HIV-1/HIV-2, Hepatitis A/B/C, SARS-Cov2.

v. Postmortem toxicology testing of all acquired tissues will be performed by a NBB-designated central laboratory to identify the presence and quantity of therapeutic, illicit drugs and other pharmacological agents.

General Task Area 4: Securely Transfer Deidentified Data to a Central Informatics Portal The NBB IT infrastructure (https://neurobiobank.nih.gov/) provides a public-facing inventory of available specimens, and donor-associated deidentified data from network BTRs and affiliate sites, and supports inventory searches, requests submission, and tissue distribution workflows.

The IT infrastructure also serves as a central source of information for the research community and the public regarding policies and procedures of NBB BTRs. An image repository that will support image-based search and distribution workflows will be developed during the contract performance period. The long-term goal for the NBB IT infrastructure is to support NIH’s strategic plan for data science, enabling the generation of novel insights through secondary data analysis: https://datascience.nih.gov/nih-strategic-plan-data-science. Contractors shall submit the following information every quarter:

1. Deidentified clinical, phenotypic, serologic, and neuropathologic data on all subjects and specimens to a secure portal using forms and data dictionaries that have been harmonized and validated across the NBB network. Currently, ICD-10 codes are utilized for clinical diagnoses. Data standards are used for neuropathological diagnoses. Efforts to incorporate common data elements, such as those described here:

https://www.commondataelements.ninds.nih.gov/, are underway.

2. Updated tissue inventory, associated data and specimen images on a quarterly basis or as new information become available. Correct identified errors during data submission.

To reduce the number of requests for unavailable specimens, contractors will make good faith efforts to remove depleted inventory from data submissions and contribute to making the NBB inventory an up-to-date system.

3. As development work for the NBB brain image repository progresses, submission of 3D and 2D images of brain hemispheres and slabs will be required following harmonization of how the images are stored and changed as specimens are distributed in real-time.

4. Generate global unique identifiers (GUIDs or pseudoGUIDs) for all donors using the GUID tool in the NIMH Data Archive (https://nda.nih.gov/nda/using-the-nda-guid.html).

GUIDs should be permanently associated with the respective internal subject IDs in the contractor’s Laboratory Information Management System (LIMS).

5. Utilize GUIDs and internal unique identifiers in all data submissions to the NBB IT portal, and work with the NBB Portal IT contractor to ensure BTR data are compatible for upload using standardized data dictionaries as defined by the COR.

6. Participate in technical assistance training on revisions to the data submission process.

https://neurobiobank.nih.gov/ https://datascience.nih.gov/nih-strategic-plan-data-science https://www.commondataelements.ninds.nih.gov/ https://nda.nih.gov/nda/using-the-nda-guid.html

The average time interval between brain recovery and specimen listing on the NBB portal is expected to be 12-18 months. Contractors should seek the COR’s approval and review of cases still pending full characterization and data submission at 24 months post-brain recovery.

General Task Area 5: Distribute Specimens to Qualified and Approved Investigators NBB’s core mission is to increase the availability of clinically annotated high-quality human brain and nervous tissue specimens to the scientific research community. Contractors shall follow NBB policies to support broad sharing of tissues to qualified and approved researchers. Overall, the principle of stewardship to NBB donors and their families, and the guidelines of success, supervision, and significance will be employed in reviewing and approving requests. Requests will be reviewed and approved in a transparent manner by the specimen review committee, and unavailable specimens will be appropriately substituted in collaboration with tissue requestors.

Over the last five years, the NBB network has processed an average of 300 individual requests on an annual basis. Each request has ranged from a few specimens to hundreds of specimens, and usually involve specimens pooled from more than one BTR. Each BTR distributes between 3000-8,000 specimens (fixed and frozen individual pieces of tissue or sections) per year.

[Note 3 to Offerors: Distribution of NBB tissues shall be subject to request approval and MTA execution (Appendix #2) and shall be documented in the request management module for programmatic accounting purposes. Additionally, all communications with tissue requestors about processing and shipments shall be documented in the request management module. Sharing of specimens shall strictly follow NBB guidelines].

1. Provide personnel with training in neuroanatomy to guide advanced brain dissections, and tissue sectioning, as required for brain specimen distribution. Dissected tissue sections/slabs should be shipped in vacuum-sealed bags.

2. Arrange for the shipment of specimens to qualified recipients by overnight shipment and within 30 business days after NBB approval of requests. The Contractor may receive approval from the COR to exceed this timeframe due to a large volume of requests being handled by the BTR or due to the size and/or complexity of any individual request.

All shipping costs and any reasonable handling charges (for complex dissections, large number of slides from fixed, paraffin-embedded blocks, cryosectioning, or additional specimen processing) shall be borne by the tissue requestor.

3. Provide appropriate packaging materials and include information on the safe handling of human biological specimens in every tissue package.

4. Include information about acknowledging the NIH NeuroBioBank Brain and Tissue Repository at (name of contractor’s institution) in all publications resulting from tissue use in the shipping package (please see Appendix #3 for sample language).

5. Obtain appropriate shipping licenses and permits from local, State, Federal and International authorities for the safe distribution of biological specimens, according to current regulatory guidelines.

6. Work with other NBB BTRs to secure and utilize shipment services by established carrier(s) with a proven record for handling medical/clinical specimens in shipping containers with dry ice, or other specialized packaging components, as needed.

7. Utilize secure package tracking system to ensure that all specimens are delivered to the intended recipient in optimal condition (https://biospecimens.cancer.gov/bestpractices/, for minimum acceptable standards).

8. Coordinate with the requestor to confirm that someone will be available to accept and properly store samples before shipping materials.

General Task Area 6: Participate in Process Improvement Activities Across the Network As part of the NBB process improvement and harmonization activities, or as requested for high priority NIH initiatives, Contractors may be required to modify or implement platform specific protocols and perform read-out assays to assess tissue quality. Shared nomenclatures, common data elements, informed consent reviews, and disease-specific structured interview forms may be required as part of these process improvement activities.

1. Collaborate across the NBB network to standardize processes for all aspects of the brain banking workflows, including outreach, remote technician management, donor procurement, dissection, imaging, quality controls, donor and tissue characterization using structured questionnaires, neuropathological assessments, and metadata harmonization.

2. Participate in projects to contribute specimen-associated data and to standardize the consistency of specimens provided to investigators. This is especially important when specimens are pooled from multiple BTRs for the same experiment.

3. Submit a small piece of brain tissue to a centralized location (to be determined at time of award) for RIN and tissue morphology assessments. RIN assays and postmortem toxicology testing are performed centrally for all NBB BTRs.

4. Contribute specimens for genome-wide genotyping and/or whole genome sequencing (WGS) to an NBB-designated site, as funds become available. Genomics data will be archived and shared via the NBB Data Repository in NDA consistent with NIH genomic data sharing policy (https://sharing.nih.gov/genomic-data-sharing-policy).

General Task Area 7: Implement an Overall Quality Management Plan In addition to establishing and maintaining appropriate SOPs, Contractors shall establish a Quality Management Plan (QMP). Contractors shall engage outside consultants with experience in human brain banking (external scientific advisors/consultants) to evaluate the SOPs and the QMP. The consultants shall function in an autonomous manner, separate from technical staff, and report results directly to the Principal Investigator (PI) and/or senior management. Annual reports from the scientific advisor(s)/consultant(s) shall be submitted to NIH with the contract’s annual progress reports.

[Note 4 to Offerors: The QMP shall cover the facility, operations, equipment, and personnel. NBB program staff will perform periodic audits of contractor’s facility and operations in the form of site visits]

The QMP shall include the following processes:

1. An evaluation of staff training in safety and biohazard specimens handling, as well as in human subject’s protection and specimen management protocols.

https://biospecimens.cancer.gov/bestpractices/ https://sharing.nih.gov/genomic-data-sharing-policy

2. The donor and tissue management processes, including donor and legal next-of-kin coordination, the diagnostic consensus review process and the time interval to the confirmation of diagnosis, specimen receipt and thorough inspection; documentation of postmortem interval; specimen processing; monitoring of storage conditions at the box and freezer level; inspection of shipping containers and storage facilities including the central alarm system, air conditioning systems, and the back-up power system; quality data management; requisitioning; and shipping of all requested specimens.

3. Quality control checks for both specimen quality and ability to track individual specimens and their derivations. Quality control reports (submitted quarterly and in the annual progress reports) should include a histological examination of tissue and molecular analyses including pH, RNA integrity number (RIN) and analysis of DNA integrity.

4. Processes and metrics for prospective evaluation of short and long-term specimen integrity. Provide assessments of the biological integrity and viability of the stored specimens, and correlate storage period and storage conditions with specimen degradation and any loss of activity. To the extent possible, industry standard methods should be used and should be consistent with published best practices.

5. Identify key indicators or measures to monitor the specimen management processes to include facility, equipment, operations, and personnel, and define acceptable and non-acceptable limits (upper and lower limits) for all key indicators. Examples of such indicators are:

i. Unidentified and identified specimens versus manifest discrepancies.

ii. Total number of discrepancies.

iii. Data entry or technician processing errors.

iv. Request fulfillments turn-around times.

v. Time taken to complete clinical and neuropathological diagnoses.

vi. Numbers of incoming and outgoing shipments.

vii. Overall productivity (e.g., numbers of published papers using the Bank’s specimens).

viii. Feedback from the scientific research community.

ix. Feedback on interactions with the donor’s next-of-kin.

6. The Offeror shall trend key donor inclusion/exclusion criteria and tissue quality indices and implement corrective actions as deviations beyond the standard limits are observed.

[Note 5 to Offerors: General Task Areas 8 through 11 are optional. Offerors with the required capabilities may propose and include the budget for each year of the contract to perform the optional General Task Areas. These task areas will be exercised as needs arise and as funds become available].

General Task Area 8: Contribute High Quality Specimens to Support Specialized Initiatives This task area will contribute high quality specimens to create a specialized human brain collection supporting NIH initiatives such as the BRAIN Initiative Cell Atlas Network (BICAN -https://braininitiative.nih.gov/research/tools-and-technologies-brain-cells-and-circuits/brain-initiative-cell-atlas-network. The requirements for this collection will be in addition to the general requirements, for example, the need for shorter PMIs, or for neurotypical donors. At the time of task area exercise, contractors will be apprised of any additional requirements, however, the https://braininitiative.nih.gov/research/tools-and-technologies-brain-cells-and-circuits/brain-initiative-cell-atlas-network https://braininitiative.nih.gov/research/tools-and-technologies-brain-cells-and-circuits/brain-initiative-cell-atlas-network general requirements for this task area are shown in appendix 5. Contractors with the required capabilities should include the technical approach and budget for this task area following the requirements in Appendix 5.

General Task Area 9: Coordinate and Perform Genome Sequencing of NBB Specimens To improve on the depth of characterization of NBB subjects and help researchers evaluate genetic contributions to complex disorders of the brain and nervous system, and as NIH funding becomes available, NBB will coordinate genome-wide genotyping or whole genome sequencing of brain tissues from all un-sequenced cases within the NBB inventory. To function as the NBB Genome Sequencing and Data Coordinating Center, Contractors shall propose to perform the following activities:

1. Coordinate sample shipments and track in the laboratory information system:

i. Communicate with NBB sites on sample and metadata requirements.

ii. Provide pre-barcoded kits and shipping materials.

iii. Receive samples from all BTRs, and track using chain of custody approaches.

2. Extract genomic DNA, establish quality metrics, and perform genome-wide genotyping using framework chipsets for samples in a one-time batch of 3000, or 5000:

i. Perform quantitative QC of genomic DNA at every stage of the pipeline.

ii. Following cleaning, securely transfer variant called files to the NBB Data

Repository in NDA.

3. Perform short read whole genome sequencing using the most up to date sequencing platforms for samples in a one-time batch of 3000, or 5000:

i. Prepare libraries and sequence capture for Next Generation Sequencing.

ii. Meet or exceed Illumina’s (or another manufacturer’s platform) recommended minimum sequencing performance specifications: sequencing output per flow cell, quality scores, run times, and sample throughput.

iii. Utilize state of the art computational tools and algorithms for data cleaning.

iv. Provide cloud-based transfer of whole genome sequencing data and associated metadata to the NBB Data Repository in NDA including unique sample identifiers, translation tables, and instrument performance metrics.

General Task Area 10: Provide Training in Postmortem Diagnosis of Psychiatric and/or Neurological Conditions This program will facilitate competency in performing semi-structured informant interviews and create a uniform framework for reaching consensus diagnosis of psychiatric and neurological conditions across the NBB network. This task area seeks Contractors with demonstrated expertise in postmortem diagnosis of psychiatric and neurological conditions and with the ability to train staff at other NBB sites.

1. Collaborate with NBB sites to assess needs and readiness to implement the training program, such as availability of appropriately trained research coordinators or other clinicians with psychology degrees.

2. Provide certified professionals to train in interviewing skillsets, structured interview forms, and procedures for gathering information on various donor-associated parameters for the data collection, as well as neurologists/neuropathologists for diagnosis of neurological disorders.

3. Program should include training in comprehensive psychological and/or neurological autopsy, sufficient to reconstitute the psychosocial and clinical environment of donors from a lifespan perspective.

General Task Area 11: Accept Well-Characterized Specimens from Other Brain Banks NBB program staff are often approached by external brain banks to accept and integrate their specimen inventory into the NBB collection for distribution to the research community. These banks were established and funded over several years by NIH and/or private foundations, and requests for specimen transfer and change in ownership are usually after Principal Investigator retires or following a change in leadership.

This option will assess space availability and surge capacity across the NBB network and will be exercised as the need arises. NIH program staff will manage issues related to MTAs, and the transfer of specimen and data ownership to NIH.

Contractors with space availability in their facilities should propose the following activities and yearly budget to accept and distribute specimens in upright or horizontal -80oC freezers in batches of 5 freezers, up to a maximum of 20 freezers.

1. Work with the external bank to review donation consents and authorizations. Review the diagnoses of cases to be transferred and confirm alignment with NBB requirements.

2. Confirm the cases to be transferred have been appropriately consented, characterized, in high quality, and compatible with NBB protocols.

3. Coordinate and receive -80oC temperature freezers containing well-characterized human brain specimens and arrange the transfer of donor-associated phenotypic, clinical, and neuropathological data.

4. Integrate specimen inventory with existing NBB collection and transfer all available data to the NBB portal for display to the research community, using harmonized formats and diagnosis codes.

5. Manage the distribution of specimens to the research community following approval of requests from the NBB portal.

ADDITIONAL CONTRACT REQUIREMENTS

[Note 6 to Offerors: Offerors shall provide a detailed description of how these requirements will be implemented for contract performance].

A. Standard Operating Procedures

1. The Contractor shall utilize, maintain, and regularly update an SOP manual that states policies and describes all procedures in detail. The SOP manual should be submitted as an appendix to the proposal and will be made available to end-users upon request.

2. Each SOP manual should include the following information:

i. Procedures and documents related to human subjects’ approval, legal next of kin consent process, and consent form elements, and follow up interviews. See Appendix #4 for required consent template language for human genomics data and broad research use.

ii. Requirements for staff training in biospecimen handling policies and procedures, including supplies, methods, and equipment used.

iii. Information about retrieving donor’s records and assessment of diagnoses.

iv. Laboratory procedures for tests performed in-house.

v. Laboratory procedures for processing biospecimens.

vi. Policies and procedures for shipping and receiving biospecimens, including human biospecimen handling instructions to be included.

vii. Policies for managing records and safety programs.

viii. Procedures for administrative, technical, and physical security of infrastructure.

ix. Procedures for information systems security.

x. QA/QC policies and procedures for supplies, equipment, instruments, reagents, labels, and processes employed in sample retrieval and processing.

xi. Emergency biosafety policies and procedures, including the reporting of staff injury and exposure to potential blood-borne pathogens.

xii. Policies and procedures for the investigation, documentation, and reporting of accidents, errors, and complaints.

xiii. Policies, procedures and schedules for equipment inspection, maintenance, repair, and calibration. Include plans for equipment failures or emergency backup storage at different locations in case of catastrophic power outage or other emergency situations.

xiv. Procedures for disposal of medical waste and other biohazardous waste.

xv. Policies and procedures regarding the training of technical and QA/QC staff.

xvi. Information on points of contact and designated backup personnel, including emergency contact numbers.

B. Regulations and Safety Standards

1. Tissues shall be collected in accordance with all applicable state and local laws and Federal regulations.

2. The acquisition and supply of all human specimen material used under this contract shall be obtained by the Contractor in full compliance with applicable Federal, State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States, and no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.

3. Proposals should include written documentation that all human materials obtained for research involving human subjects conducted under this contract, by collaborating sites, or subcontractors identified under this contract, were obtained with prior approval by the Office for Human Research Protections (OHRP) of an Assurance to comply with the requirements of 45 CFR 46 to protect human research subjects.

[Note 7 to Offerors: A blank copy of the IRB approved informed consent/donation authorization form must be included in the SOP manual as an appendix to the technical proposal].

4. Contractors shall provide personnel with protective garments, equipment, training, and sufficient monitoring to assure safe handling of potentially hazardous and infectious human materials. The Contractor shall comply with all applicable health and safety regulations while conducting work set forth herein and with HHSAR 352.223-70. All/any subcontractors shall follow the same regulations. The Contractor shall assure that all personnel are properly trained and have adequate expertise for the roles they will serve under this contract.

5. All donor coordinators and biorepository staff with donors’ next-of-kin-facing tasks shall participate in human research protection foundational training, such the free online trainings available here: https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html.

6. Offeror shall report any accidents regarding exposure, equipment failure resulting in damage to, or loss of tissues, or violations of ethical code of conduct or other breaches of contract terms immediately to the NIDA Contracting Office and the NBB COR.

C. Harmonization of Processes Across the NBB Network

1. Contractors will be expected to utilize, whenever possible, common Standard Operating Procedures (SOPs) with other NBB sites, to minimize variability in tissue quality. In this regard, all sites will be required to make a good faith effort to adopt common and/or harmonized protocols, data structures and methodologies, as directed by the COR.

2. The COR will facilitate this objective by providing a format and venue for discussions on developing consensus documents related to standardized/harmonized protocols, interview and consent forms, and data standards among NBB sites with guidance from the external scientific advisors and NIH program staff.

D. Laboratory Information Management System

[Note 8 to Offerors: A detailed description of the in-house Laboratory Information Management System must be included in the proposal]

1. The Contractor shall provide a secure Laboratory Information Management System (LIMS) suitable for tracking, cataloging, and digitally recording and storing information, including images of specimens received and distributed, as well as images derived from neuropathology slides.

2. The LIMS database shall have the capacity to house donor-associated data and specimen images in a deidentified manner, provide links to samples for each standard portion of tissue and to track all samples, including derived samples via bar codes or sub-IDs (and associated data derived from them).

3. More specifically, for each donor, the LIMS shall hold the following information:

i. Clinical findings and clinical history (provided with type of diagnostic procedure used to determine clinical brain diagnoses).

ii. Documentation of discernible pre-agonal medical status.

iii. Evidence of time since disease onset and extent (years) of hospitalization when applicable.

iv. Detailed documentation of prioritized comorbidities (clinical judgment of assessment team).

v. Psychiatric history.

vi. Gestational age at birth.

vii. Maternal history, neonatal history (for infant and pediatric donors).

https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html https://www.hhs.gov/ohrp/education-and-outreach/human-research-protection-training/human-research-protection-foundational-training/index.html

viii. Gender, race, ethnicity.

ix. Cause and manner of death.

x. Medications at the time of death (ATOD) and medication history, if available.

xi. Neuropathological evaluation that is appropriate given the donor’s age, presenting diagnosis, and preliminary pathological evaluation.

xii. Phenotypic information such as cranial MRI findings (deidentified images and/or reports), other radiological reports, results of genetic tests and/or diagnostic evaluations, other clinical notes, and evaluations by specialists.

xiii. Review of clinical data by expert consultants to determine diagnoses based on standard classification schemes such as the ICD-10.

xiv. Family history information such as date of birth, education level, ethnicity, medical problems, genetic disorders, and mental illness including substance abuse for first-degree relatives, when available.

4. The LIMS shall include information about specimens distributed (types and number), up to date inventory, and information about requests turnaround times from request approval on the NBB portal to tissue distribution. See Reporting Requirements (below).

5. Information from the Contractor’s database shall be securely transferred to the NBB IT portal on a quarterly basis or as new information becomes available.

E. Facilities and Equipment

[Note 9 to Offerors: A detailed description of the contractor’s facility to be devoted to the project must be included in the technical proposal].

1. Contractors shall provide sufficient floor space and ultra-low freezer capacity to store and maintain all tissues and derivatives acquired under this contract, including allowing for future program expansion based upon donor accruals. If options are exercised (and as collection sizes increase), additional space and freezer capacity may be required beyond the base contract’s performance period.

2. Additional storage and processing capacity for non-frozen material, including fixed tissues. The Contractor must demonstrate an adequate facility and infrastructure in place at the time of award for contract performance.

3. Provide designated laboratory work area(s) of sufficient size and capacity, including a biosafety cabinet or negative pressure room for human tissue dissection. Facility should also have capacity to accommodate sectioning equipment and other instruments necessary for specimen preparation, such as cryostats, digital cameras, and computer.

4. A climate-controlled facility with the capacity to maintain room temperatures of 19-22°C when all equipment is operating with sufficient back up power to maintain 19-22˚C in a power failure until power is restored or until samples can be relocated to another facility.

5. Sufficient back-up freezer space to accommodate the failure of at least two freezers.

Complete transfer of the contents of a freezer shall occur within 2 hours of an initial freezer failure.

6. Adequate electrical power to accommodate all mechanical freezers, the central alarm system, and the air conditioning system. Provide adequate, on-site back-up power to handle complete electrical power failure 24 hours a day, seven days a week. All freezers, air conditioners and the central alarm system shall be electrically monitored so that should the power fail, complete back-up power (capable of continuous operation for up to 48 hours) shall be immediately available.

7. Security measures that ensure the facility and equipment are protected against fire, flooding, other environmental hazards, and intrusion.

8. Secure dedicated office spaces for record/file keeping, administrative, system, and data management activities. The Contractor must comply with all applicable laws related to the protection of personally identifiable information.

9. An On-site Monitoring System with the following capabilities:

i. A central, 24-hour per day, computerized alarm system for monitoring all freezer and storage facility conditions, which provides an immediate audible alarm, beeper, and cell phone triage alert.

ii. Response to a freezer/power failure with acceptable time intervals from notification of the problem to physically moving the samples to the back- up freezer.

iii. Weekly testing of the alarm system and monthly tests on the back-up electrical system. Include the results of these tests in the Quarterly Progress Reports.

iv. Maintenance of a log of regular inspections and a summary of inspection records, including problems encountered and actions taken, in the Annual Progress Reports.

F. Transition/Relocation to a Third-Party Site

It is unknown whether a Transition or Relocation will be required during or at the end of the contract performance period. All offerors shall include a plan to transition or relocate the repository to a designated third-party site, as requested by the Government. All Government property shall be subject to the provisions of FAR PART 45-Government Property.

1. The Contractor shall include an initial Transition Plan in the proposal. This plan should address the logistics and methodology involved in a transition (i.e., transfer of all Government property, including specimens, protection of specimens during transfer, and data transfer) and provide an estimated cost/budget based upon a transition at the end of the base period. This proposal shall be organized and catalogued with sufficient details to support an orderly transition to a successor Contractor or a third party.

2. With each Annual Report, the Contractor shall provide successive updates to the Transition Plan. For example, the first Annual Report for year 1 will update the initial transition plan for a projected potential transition at the end of year 2, the second Annual Report will update the Plan for a potential transition at the end of year 3, etc.

3. At any time during the contract at the request of the COR, the Contractor shall update the most current Transition Plan and submit a Final Transition Plan for approval. The Final Transition Plan shall include recommended steps (with a detailed cost estimate) to sustain and continue the activities provided for in the contract, during a transition period prior to contract expiration, and shall include delivery of all contract-related items to a third-party designee. Contract-related items include the following:

i. All donor tissue samples acquired during the contract.

ii. All computerized data files and software systems (with documentation and specifications) including specimen inventory files, specimen batches in queue for commitment or shipment, data entry files, active specimen discrepancy files (information shall be provided in electronic format and transferred in a secure manner as determined by NIH IT and the Contractor).

iii. All hard copy files of freezer management and maintenance, correspondence files, archived activity files for incoming and outgoing shipments.

iv. All other Government-Furnished Property. Verification of equipment performance standards shall take place prior to the transfer.

G. Contract Options

The contractor shall demonstrate flexibility to perform all Options specified in their contract, if exercised by the Government. The following Options will be included in the contract:

1. Option to extend the performance period:

i. The Government may unilaterally exercise the option to extend the contract’s performance period in accordance with the terms and conditions listed in the contract.

ii. This option will extend repository services, as described in the SOW, on an annual (12-month) basis beyond the first contract year.

iii. Unless the contract is modified, the final expiration date of the contract including all optional extensions is five (5) years after the date of award.

2. Option for additional quantities of…