A7_-_IDIQ_Contract_Statement_of_Work__080724.pdf

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

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

STATEMENT OF WORK (SOW) FOR BASE CONTRACT 08/07/2024

ARTICLE C.1. – STATEMENT OF WORK

GENERAL INFORMATION

Title of Project:

Phase I Clinical Trials for Development of Small Molecule and Biologics Therapeutics

Background Information and Objectives:

General

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the Federal agency whose primary mission is to seek fundamental knowledge about the nature and behavior of living systems and apply that knowledge to enhance health, lengthen life, reduce illness and disability, and conduct, support, and make medical discoveries that improve people’s health and save lives. The National Institute of Neurological Disorders and Stroke (NINDS) is an institute within the NIH that conducts research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological disease.

The National Institute of Neurological Disorders and Stroke (NINDS) has the need for a full service, turn-key phase I clinical trials operations and facility for the development of novel therapeutics. This full-service facility will support a full range of services from protocol development through submission of a final clinical study report.

The term therapeutics will include investigational agents developed by the National Institutes of Health (NIH) and its grantees and/or partners (henceforth known as the “Contributor(s)”) and provided to the NINDS for collaborative development as well as investigational agents supported by and through the NINDS. This includes the NIH Blueprint Neurotherapeutics Network https://neuroscienceblueprint.nih.gov/, the NINDS Ultra-rare Gene-based Therapy (URGenT) Network https://www.ninds.nih.gov/Current-Research/Research-Funded- NINDS/Translational-Research/urgent-network, the NIH Helping to End Addiction Long-term (HEAL) initiative https://heal.nih.gov/ or other programs as needed. The Phase I clinical trial investigational agents to be assessed may include small molecules and large biologic molecules (i.e., peptides, oligonucleotides, proteins, or other biologics). The results of these Phase I clinical trials will be the basis to advance candidate compounds for further clinical development (i.e., additional Phase I, Phase II/III clinical trials), and submitted ultimately to the FDA in support of a New Drug Application (NDA) or Biologics License Agreement (BLA) submission.

https://neuroscienceblueprint.nih.gov/ https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network https://heal.nih.gov/

NIH Drug Development Programs

This contract supports NIH drug development projects for the NIH Blueprint Neurotherapeutics Network program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), and other extramural or intramural NIH drug discovery and development programs.

The NIH Blueprint Neurotherapeutics (BPN) network (https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-neurotherapeutics-bpn-network) is a consortium comprised of the NIH Office of the Director and 14 NIH Institutes and Centers (ICs) that support neuroscience research. BPN provides neuroscience researchers with funding and access to a full range of industry-style drug development services and expertise.

The program, originally focused on small molecules, was launched for projects requiring medicinal chemistry optimization, pharmacokinetics (PK), drug manufacturing and formulation, Investigational New Drug (IND)-enabling toxicological studies support through Phase I clinical testing and has recently been expanded to include the development of biological therapeutics for neurological diseases (BPN-Biologics).

(https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics).

The URGenT program (https://www.ninds.nih.gov/Current-Research/Research-Funded- NINDS/Translational-Research/urgent-network) has been established by the NINDS to support the development and clinical evaluation of therapeutics to address ultra-rare genetically based neurological disorders. The network will provide neuroscience researchers with funding and access to a full range of industry-style biologics development services and expertise and in the future may expand to include other NIH institutes. The program is intended to rapidly advance patient-customized therapeutics through manufacturing, preclinical toxicology testing, and evaluation in Phase I clinical studies.

The HEAL-PTDP program (https://heal.nih.gov/) is a multi-IC initiative that has been established by the NIH to support preclinical optimization and development of safe, effective, and non-addictive therapeutics to treat pain. The goal of the program is to accelerate the optimization and development of promising therapeutics to Phase I clinical trials and readiness for Phase II clinical studies. The scope of this program includes optimization and early development activities, IND-enabling studies, development of a pharmacodynamic (PD)/ target engagement biomarker, assembly and filing of an IND application, and Phase I clinical testing. This is a milestone-driven phased cooperative agreement program involving participation of NIH program staff in the development of the project plan and monitoring of research progress.

Ordering Period:

This indefinite-delivery indefinite quantity (IDIQ) contract includes a ten-year ordering period.

It is anticipated that the period of performance, including options, for some task orders (TOs) will extend multiple years past the end of the IDIQ ordering period. However, under FAR Clause 52.216-22, the Contractor shall not be required to make any deliveries under this contract after three years past the end of the IDIQ ordering period unless otherwise agreed to in writing by both parties.

https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-neurotherapeutics-bpn-network https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-neurotherapeutics-bpn-network https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network https://heal.nih.gov/

SCOPE OF WORK

Scope:

The scope of activities to be performed by the Contractor include the provision of a Phase I clinical research unit, the conduct of Phase I clinical trials of therapeutics, and the provision of a full range of services to support the clinical trials for investigational small molecules and biologics, including but not limited to peptides, oligonucleotides, proteins or other biologics, and reporting of the results to regulatory agencies.

These trials shall be designed to develop or assess tolerated dose range, the dosing regimen, safety profile and PK parameters. At the request of the Government, the trials may include PD measures, and evaluation of biological effects and early signs of efficacy. All clinical trials shall be carried out in a timely fashion and in compliance with all FDA regulations and International Conference on Harmonization (ICH) Good Clinical Practices (GCP) guidelines.

Technical Requirements:

The Contractor shall initiate work only when authorized by issuance of an approved task order.

At contract initiation, the Contractor will be responsible for participating in a kickoff meeting and providing a contract-level project management plan (PMP). The Contractor shall only provide additional services if they are subsequently issued one or more task orders for individual clinical projects of investigational agents. It is anticipated that these task orders will be awarded through a competitive, Task Order Requests for Proposals (TORFP) process, will be cost-reimbursement/completion, fixed price, OR a combination of both, and will have variable periods of performance. NINDS anticipates issuing up to 2-10 TORFPs during each year of the contract.

The actual number of TORFPs issued will depend upon programmatic needs and funding availability and may vary from year to year.

The Contractor shall perform all activities associated with the conduct of Phase I clinical trials.

Task Orders issued for “Clinical Projects” will consist of a base requirement for “Protocol Development and Trial Preparation” and include a quality-type option for “Clinical Trial Implementation”. Required activities are defined below and are to be considered general Technical Requirements that will be executed following issuance of individual Task Order awards. Each individual Task Order award will also define specific and additional technical requirements as appropriate for that Task Order Statement of Work.

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 actions outlined below:

Contract Initiation

The Contractor shall:

i. Conduct a kick-off meeting to review the contract requirements, timelines, milestones, and deliverables; discuss the Contractor’s technical approach and project management plan;

and identify any anticipated difficulties in completing the contract requirements

ii. Provide a contract-level Project Management Plan (PMP) describing general procedures and processes of the vendor. (This isn’t trial-specific information; that is required below as part of the clinical project.) The contract PMP must be a single, well-organized document or folder that clearly connects document elements with the sections below. The PMP shall address and include, at a minimum, the following:

a. General standard operating procedures (SOPs) for the conduct of Phase I clinical trials and for all other integrated and collaborating services (such as pharmacy, database management, bioanalytic, statistical analysis plans etc.)

b. Personnel listing including their roles and responsibilities

c. General policies on human subject considerations (e.g., federal wide assurance

(FWA), procedures for managing medical emergencies on-site, reporting of adverse events (AEs), serious adverse events (SAEs), unexpected adverse events, hospitalizations and procedures for prompt reporting of SAEs in compliance with FDA regulations and NIH policies)

d. General data management procedures and systems planning

e. General pharmacy management procedures for receiving, storing and dispensing investigational agents

f. Clinical and laboratory quality monitoring procedures

g. General procedures for preventing, identifying, handling, reporting and resolving protocol deviations

h. Quality control plans and procedures

i. Demonstration for independence of oversight including quality assurance procedures

j. Protocols for protection of Contributors’ intellectual property and data procedures

k. Archival plans for securing completed trial data according to regulatory requirements

l. Contingency planning

m. Training: For human subject protection (HSP) or current Good Clinical Practices

(cGCP), plan for training of technical staff, clinicians and/or scientists designated by the Contractor on techniques, methods, and best practices relevant to the conduct of clinical trials carried out under the IDIQ contract. Must also include any other relevant or mandatory trainings for the contract.

Base Requirement: “Protocol Development and Trial Preparation” This requirement includes activities up to trial initiation. Continuation of trial activities is covered by the “Clinical Trial Implementation” quantity option.

i. Conduct Teleconferences and Meetings for the following. Set up meetings with all applicable participants. Prepare and share agendas and slides 24-48 hours prior to the meetings. Prepare minutes of all site visits and teleconferences/webinars for submission to the COR for review and approval within 5 business days after the meeting.

a. Task Order kick-off meeting to review the contract requirements, timelines, milestones, and deliverables; discuss plans and approaches and identify any anticipated difficulties in completing the contract requirements.

b. Ad hoc Site Visits: Host a one-day meeting as requested by COR and/or CO. It is anticipated that this will occur no more than once or twice per trial.

c. Ad hoc teleconference as requested by the COR and/or CO

ii. Finalize a protocol and submit to NINDS and the Sponsor/Contributor for review and approval in compliance with the timelines specified within the task order. Provide all necessary documentation for the proposed clinical trial to the contributor required to secure the IND approval (e.g., Form FDA 1571, Form FDA 1572) and work with Contributors to submit documents for all requisite regulatory approvals (e.g., IRB and FDA submissions). Prepare the informed consent form (ICF) that contains appropriate reference to the NINDS Privacy Act system germane to data collection for awarded task orders and all other protocol specific supporting documents (e.g., subject recruitment advertisements), and submit the final protocol, any protocol amendments, ICF and other documents to the institutional review board (IRB) for review and approval.

iii. Prepare protocol amendments and modifications as required:

a. Upon COR approval, the Contractor shall submit the amended protocol and ICF to the lRB for review and approval

b. The Contractor shall provide the amended protocol to the COR and the Contributor/Sponsor

c. Upon IRB approval, the amended protocol and revised ICF shall be archived in the master regulatory file

d. The PMP, case reports forms and other supporting documents will be modified to reflect the protocol amendments; and

e. If necessary, the PI or designee shall conduct a training session describing the protocol amendment and its impact on clinical trial procedures and assessments

iv. Throughout the process essential regulatory documents as specified in ICH guideline should be generated and stored in files/folders and be available for monitors and for use in the subsequent quantity option when executed. Essential regulatory documents may include but are not limited to signed IRB approved protocol, informed consent form and advertisement for subject recruitment; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, conflict of interest declaration, indemnification/insurance documents, Form FDA 1571, Form FDA 1572.

These and all relevant data/documents must be maintained with compliance with all Information Technology preparedness, security, and compliance with contract requirements e.g., FISMA and 508 of the Rehabilitation Act of 1973, as amended by the Workforce Investment Act of 1998.

v. Prepare and deliver a trial-specific Project Management Plan (PMP) within 60 calendar days after task order award and before dosing of the first subject. The PMP must be a single, well-organized document or folder that clearly connects document elements with the sections below. The PMP shall address and include, at a minimum, the following:

a. Clinical Quality Management Plan (CQMP): consisting of, at a minimum, the following: acceptance criteria for each deliverable, procedures and process controls for each deliverable, roles and responsibilities of personnel involved, and assurance that the established procedures and processes are followed. Timelines must be included in the plan. Develop, maintain, update, and submit the CQMP to the COR for approval. Update the CQMP annually, or as specified by the COR. CQMP shall be contractor-specific as well as site-specific. Upon request of the COR/NINDS, provide summary statements about the contractor QC/QA findings that demonstrate utilization of the CQMP

b. Project-specific standard operating procedures (SOPs) for the conduct of Phase I clinical trials and for all other integrated and collaborating services

c. Personnel listing including their roles and responsibilities to include an organizational chart

d. Human subject considerations (e.g., federal wide assurance (FWA), initial and continuing human subject training/education for personnel, data and safety monitoring plan, consenting procedures, procedures for managing medical emergencies on-site, reporting of adverse events (AEs), serious adverse events (SAEs), unexpected adverse events, hospitalizations, and procedures for prompt reporting of SAEs in compliance with FDA regulations and NIH policies)

e. Data Safety and Monitoring (DSM) plan including an Independent Safety Monitor in accordance with NIH guidelines and policies for DSM for review and approval by the IRB https://www.ninds.nih.gov/funding/apply-funding/application-support-library/clinical-research-guidelines/ninds-guidelines-monitoring-clinical-trials

f. Training program for clinicians, clinical site staff, data management staff and other support staff in the protocol procedures with every task order protocol in order to ensure reliability of evaluation, treatment, and assessment procedures

g. Recruitment and retention plan (e.g., enrollment of a diverse subject pool, including women and minorities, rate of subject accrual, subject retention, plans for deficient enrollment). Enrollment data shall be collected and reported according to current federal laws and policies.

h. Data management procedures and systems planning that is in compliance as specified with the contract terms and conditions including but not limited to development of database and case report forms (CRFs) using NINDS common data element where applicable https://www.commondataelements.ninds.nih.gov/#

i. Data collection, data monitoring, data safety review https://www.ninds.nih.gov/funding/apply-funding/application-support-library/clinical-research-guidelines/ninds-guidelines-monitoring-clinical-trials https://www.ninds.nih.gov/funding/apply-funding/application-support-library/clinical-research-guidelines/ninds-guidelines-monitoring-clinical-trials https://www.commondataelements.ninds.nih.gov/

j. Plan and timeline for development of the statistical analysis plan (SAP)

k. Pharmacy management procedures for receiving, storing and dispensing investigational agents; also, to be included a procedure for randomization and if appropriate stratification of eligible subjects

l. Bioanalytical method development plan

m. Blinding plan, including during pharmacy, clinical and data management activities, as appropriate

n. Clinical and laboratory quality monitoring procedures

o. Procedures for preventing, identifying, handling, reporting, and resolving protocol deviations

p. Quality control plans and procedures

q. Establishment and demonstration for independence of oversight including quality assurance procedures

r. Protection of Contributors’ intellectual property and data procedures

s. Archival plans for securing completed trial data according to regulatory requirements

t. Contingency planning

u. Plan for quality control and quality assurance, e.g., monitoring plans, data quality plans and audits; and

v. Training: For human subject protection (HSP) or current Good Clinical Practices (cGCP), develop, implement, and provide training to technical staff, clinicians and/or scientists designated by the Contractor on techniques, methods, and best practices relevant to the conduct of clinical trials carried out under the IDIQ contract. Maintain a log of the date and recipients for HSP and GCP training. Prior to the training program’s execution, ensure the training program is consistent with HHS policy.

w. Close-out plan

vi. Regulatory preparations and compliance:

a. Register the clinical trial in the National Library of Medicine’s Clinical Trials registry

(http://www.clinicaltrials.gov); Data will be shared according to federal laws and policies.

b. Ensure all requisite regulatory approvals are in place (e.g., IRB and FDA submissions) including that the investigational agent has appropriate FDA clearance (i.e., IND) confirming the agent’s suitability for testing in humans prior to initiating recruitment in compliance with all NIH policies, FDA regulations and International Conference on Harmonization (ICH) Good Clinical Practices (GCP) guidelines http://www.clinicaltrials.gov/

c. Obtain any necessary Material Transfer Agreement (MTA) from Contributor/Sponsor

d. Throughout the studies essential regulatory documents should be generated and stored in files/folders and be available for monitors and at the end of the studies all essential regulatory documents at the clinical research unit should be placed in the master regulatory file for archiving. Regulatory documents may include but are not limited to: IRB approved protocol, ICF and advertising; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, indemnification/insurance documents, Form FDA 1572, investigational agent shipment receipts, etc. During the conduct of the clinical trial, all new relevant information/data must be appended to the essential documents as it becomes available

e. Ensure that the conduct of the clinical trials is performed in compliance with all FDA and ICH GCP regulations and guidelines

f. Prepare a complete clinical study report in submission ready format for FDA unless otherwise specified. Additionally, the IND report for annual filing requirements to the IND application, as needed

g. Ensure the confidentiality of all clinical records and information about subjects enrolled in the clinical trial conforms to all Privacy Act requirements (https://www.justice.gov/opcl/privacy-act-1974 and https://www.hhs.gov/hipaa/for-professionals/index.html). This acquisition will require the Contractor to do one or more of the following: design, develop or operate a system of records on individuals to accomplish an agency function. Therefore, the Contractor shall comply with the Privacy Act of 1974 as amended at 5 U.S.C. 552a, FAR Clause 52.224-2, applicable agency regulations, and provisions of the NIH Privacy Act System of Record Notice (SORN) applicable to work under this contract. The Privacy Act SORN applicable to this contract is System No. 09-25- 0200, Clinical, Basic and Population-based Research Studies of the NIH, HHS/NIH/OD. The SORN is attached and made a part of this contract.

Violation of the Act may involve the imposition of criminal penalties. Information and records obtained from subject volunteers who have consented to participate in performance of work under this contract will be subject to the provisions of the Privacy Act. The Contractor shall explain to participants exactly how information is to be collected, the purpose and use for which the information is being collected and how the information will be protected pursuant to the Privacy Act of 1974 (P.L. 93-

579) and accompanying Privacy Act System Notice made a part of this contract, both of which are applicable to the performance of work under this contract. All participants must be made to understand, through use of the informed consent form and careful education, that the extent of their participation is entirely voluntary and that they may provide all, some, or none of the information which the Contractor is intending to collect. Upon completion of each clinical trial, the system of records generated in performance of that study shall be disposed of in accordance with instructions to be furnished by the COR.

https://www.hhs.gov/hipaa/for-professionals/index.html https://www.hhs.gov/hipaa/for-professionals/index.html

vii. Bioanalytical Development Perform assay development, qualification, and validation concurrent with protocol development for bioanalytical evaluation of clinical samples to have bioanalytical assays ready prior to clinical protocol implementation. This includes small molecules and biologics.

a. Provide the bioanalytical assay validation plan to the COR and the

Sponsor/Contributor prior to initiating the clinical protocol.

b. Complete validation and provide the bioanalytical validation report to the COR and the Sponsor/Contributor. The report may be submitted in the bioanalytical laboratory’s standard format, as long as every item listed in the FDA Bioanalytical Method Validation guidance documents has been addressed, all described results are included with the report, all described statistical analyses have been conducted, and a summary table listing the pass or failure of each of the validation criteria is included.

c. For clinical trials, the validation report must be submitted, reviewed, and approved by NINDS prior to initiation of any clinical enrollment.

viii. Database Build

a. As required for the conduct of the trial specified in the Task Order, the Contractor shall develop and validate a database for the clinical trial

b. The Contractor shall provide any required licenses, software or dictionaries for the database

Quantity Option “Trial Implementation”

i. Conduct Teleconferences and Meetings for the following. Prepare minutes of all site visits and teleconferences/webinars and submit to the COR for review and approval within 5 business days of the meeting.

a. Clinical Trial Initiation meeting to review the trial protocol, timelines, milestones, and deliverables.

b. Ad hoc Site Visits: Host a one-day meeting as requested by COR and/or CO. It is anticipated that this will occur no more than once or twice per trial.

c. Ad hoc teleconference as requested by the COR and/or CO

A) Protocol Implementation: Compliance and Oversight The PMP developed in “Protocol Development and Trial Preparation” shall be followed and documents updated as needed. Regulatory compliances shall also be maintained and updated as needed following the preparations made in the “Protocol Development and Trial Preparation” period.

i. Clinical Trial Initiation

The Contractor’s clinical trial team and support staff shall participate in a clinical trial initiation meeting at the Contractor’s clinical research facility. The Contractor shall provide an invitation to NINDS and the Contributor/Sponsor to participate in person or via video conferencing. Prepare and deliver a summary report of the initiation meeting to include but not be limited to the agenda and the list of participants

ii. Protocol Amendments as required:

a. Prepare all protocol amendments and modifications. Prepare all modifications to the PMP or other documents as a result of the amendments.

b. Upon COR approval, the Contractor shall submit the amended protocol and ICF to the lRB for review and approval

c. The Contractor shall provide the amended protocol to the COR and the

Contributor/Sponsor

d. Upon IRB approval, the amended protocol and revised ICF shall be archived in the master regulatory file

e. The PMP, case reports forms and other supporting documents will be modified to reflect the protocol amendments; and

f. If necessary, the PI or designee shall conduct a training session describing the protocol amendment and its impact on clinical trial procedures and assessments

iii. Protocol and trial-site Oversight:

a. Oversee and ensure adherence to the protocol all clinical activities conducted at the clinical research facility and all collaborating sites including research pharmacy, clinical laboratory, data management center, imaging center and subcontracting sites; and

b. Ensure that each participant: meets protocol entry criteria; has given informed consent and has undergone all the screening and baseline assessments as specified in the protocol

c. Develop and implement remedial/corrective actions to address site performance problems and issues identified through the clinical-site monitoring process.

iv. For each Task Order protocol:

a. Track subject enrollment and adherence to defined recruitment goals

b. Review and assess participant data as specified within the data management plan, protocol requirements and/or quality assurance requirements. For example:

i. Promptly provide all data reports for monitor review prior to start of dose escalation decisions

ii. Monitor continuously for the validity and integrity of the accumulating data

iii. Monitor continuously protocol adherence and compliance with current

ICH GCP guidelines, DHHS Protection of Human Subjects regulations (45 CFR Part 46) and FDA regulations and report all protocol deviations

iv. Report of any serious adverse events and/or unexpected adverse events to FDA, IRB, and COR

v. Report all performance-related issues and proposed resolutions or corrective actions taken; and

vi. Database summary tables for monitoring and tracking purposes throughout the course of the clinical trial including subject enrollment updates

c. Update clinicaltrials.gov as required by NIH policy and Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801)

v. Data Management and Quality Control:

a. Maintain and update the clinical database throughout the trial

b. Modify the database to support any protocol amendments that are implemented during the conduct of the clinical trial, as required; and

c. Provide quality control to ensure initial data entry within 24 hours and to correct or issue a data query within 48 hours and inform promptly the clinical research staff of any missing, incomplete, and erroneous data

vi. Audit Compliance The NINDS at their discretion may undertake an audit of the Contractor’s facility including all collaborating sites. The Contractor shall make available all facilities, records and files related to any activity under the contract. The Contractor shall submit a report describing the implementation of the corrective actions.

B) Investigational Agents and Clinical Specimens

i. Investigational Agent:

a. Maintain inventory records of investigational agent in accordance with the pharmacy SOPs

b. Maintain documentation that the investigational agent will be stored and quarantined under appropriate conditions in the research pharmacy according to the sponsor and regulatory requirements for small molecules and biologics; and

c. Mechanism for the return and/or destruction of investigational material

ii. Clinical Specimens

a. Ensure collection, processing, labeling, temporary storage under appropriate conditions and management of all collected biological specimens

b. Ensure shipping of biological specimens for testing and/or repository deposition, as specified in the protocol, in compliance with current Good Laboratory Practice (cGLP), cGCP and domestic laws and regulations. Maintain clear chain of custody; ensure reporting of deviations and sample labeling issues.

c. Conduct protocol-required testing (including but not limited to screening, safety, and human anti-human (HAHA) laboratory testing); and

d. Maintain current Clinical Laboratory Improvement Amendment certification (http://www.cms.gov/clia/ and The Joint Commission approval (http://www.jointcommission.org/)) or local equivalent, as appropriate

C) Clinical Trial Analysis, Close-out, and Final Clinical Trial Reporting

i. Close-out and Analysis Following the last subject’s completion of clinical trial procedures including any outpatient follow- up visits, the Contractor shall:

a. Continue to monitor any residual safety concerns (i.e., AEs & SAEs) until complete resolution

b. Complete data editing/cleanup

c. Finalize and lock the database

d. Conduct the statistical analysis as described in the PMP

e. Deliver the locked deidentified database in agreed upon format (e.g., R, SAS, SPSS, ASCII) and schedule as requested by the COR;

f. Provide to the COR with the final enrollment report according to current federal laws and policies

g. Provide annual IND reports to the FDA and the COR within 60 days of the anniversary date the IND went into effect for as long as the IND remains open, or as recommended by current FDA guidance; and

h. Register trial results in clinicaltrials.gov within 3 months of the trial completion date unless otherwise directed by the COR http://www.cms.gov/clia/ http://www.jointcommission.org/

ii. Completion:

a. Prepare for archiving the final dataset and all associated clinical trial records.

Clinical trial records are considered case report forms and detailed documentation necessary to assess the final dataset with specific codes for all variables including all transformation that have been created (i.e., data dictionary);

b. Prepare and deliver draft and final clinical study report; the study report must be in a format suitable for submission to the FDA; and

c. Archive the final locked dataset with de-identified data for each clinical trial conducted under each task order in an agreed upon format (e.g., R, SAS, SPSS, ASCII) that is readily usable by NINDS, Contributor/Sponsor or NINDS designee.

D) Facilities, Equipment and Other Resources

The Contractor shall be responsible for the adequacy and availability of all facilities, equipment, and other resources necessary for the conduct of a clinical trial which may include but is not limited to the following.

i. Provide Inpatient Clinical Research Facility:

a. Accreditation with a national or state accreditation board for the conduct of clinical trials

b. Areas to allow for waiting, check-in and discharge

c. Examination rooms to allow for protocol-related assessments

d. Standard clinical support services for inpatient care, twenty-four hours/day, seven days/week

e. Capability to recruit healthy volunteers and target populations

f. Adequate and secure computing resources for communication and data management (e.g., entry editing, quality control)

g. Adequate and secure electronic access to the data management center

h. Emergency care and a definitive plan for management of life-threatening adverse events including on-site resuscitation equipment and hospitalization procedures in the event a participant requires these services

i. Adequate equipment, staff, and services for performing routine safety evaluations (e.g., vital signs, ECG), precisely timed phlebotomy, collection of cerebrospinal fluid (CSF), urine and other bodily fluids for PK/PD trials and processing of PK and PD samples and administration of investigational agents (small molecules or biologics by different routes of administration including but not limited to oral, intravenous (infusion and bolus), subcutaneous, intramuscular and intrathecal routes.

j. Capabilities for the collection of cerebrospinal fluid (CSF) via lumbar puncture or with a temporary in-dwelling catheter if required by the TORFP

k. Ability to provide experienced research staff to perform cognitive testing, using paper or computer-based systems

l. Staff with expertise in the conduct of Phase I clinical trials including but not limited to physicians, pharmacologists, clinical specialists, registered research nurses, study coordinators, clinical research associates, research assistants, Independent Safety Monitor(s) (ISM) and research pharmacists

m. Access to clinical specialists in the therapeutic areas covered by NINDS, the NIH Blueprint Neurotherapeutics Network and NIH HEAL Initiatives for additional safety assessments that may be required in select clinical trials, such as ophthalmology exam or detailed neurologic examination; and

n. Pharmacovigilance capabilities for composition of serious adverse event reports and narratives

ii. Provide cGLP Clinical Laboratory Facility:

a. Adequate space for the processing and temporary storage of biological specimens

b. Adequate facilities and equipment for conducting protocol-required tests and assays such as PK and specialty PD assays on blood, plasma, CSF or other body fluids and tissues

c. Secure, on-site sample storage facilities at room temperature, 4, -20 and -80 degrees Celsius

d. Clinical laboratory support services with provisions of 24 hours/day testing if required by the protocol

e. Adequate and secure electronic access to the data management center; and

f. Have current certification and licensure for the performance of biological specimen assays and analyses

iii. Provide Research Laboratory Facility:

a. Adequate space and equipment for the processing, temporary storage, and shipment of biological specimens

b. Adequate facilities and equipment for conducting protocol-required tests and assays such as PK and specialty PD assays on blood, plasma, CSF or other body fluids and tissues

c. Capabilities to design and validate PK, PD and biomarker assays

d. Secure on-site sample storage facilities at room temperature, 4, -20 and -80 degrees Celsius

e. Adequate and secure electronic access to the data management center; and

f. Have current certification and licensure for the performance of biological specimen assays and analyses

iv. Provide Clinical Imaging Facility:

a. Adequate and secure electronic access to the data management center

b. Adequate facilities and equipment for conducting protocol-required imaging procedures for diagnosis or special safety evaluations, including echocardiogram, computerized tomography (CT), magnetic resonance imaging (MRI), proton emission tomography (PET), electromyography (EMG), and electroencephalography (EEG)

c. Electroretinography (ERG)

d. Have current certifications and licensures for the performance of imaging procedures

v. Provide Research Pharmacy Facility:

a. Research pharmacist with expertise in the preparation, distribution, and storage of investigational agents (biologics and small molecules) for Phase I clinical trials

b. Limited cGMP capability for compounding and manipulations such as over encapsulation

c. Adequate space for processing, storing, and dispensing investigational agents under appropriate conditions

d. Adequate and secure electronic access to the data management center; and

e. Have current accreditation and certification for the performance of pharmacy services

vi. Provide Data Management Center:

a. Adequate computing resources to support data collection activities

b. Personnel knowledgeable about data management activities and operations including but not limited to data management planning and reporting, performance reporting, quality assurance and administrative support

c. Clinical data warehousing capabilities/facilities in order to provide a centralized, integrated system for data storage, analysis, reporting and ad hoc query of clinical data

d. Data management capabilities necessary to support the conduct of Phase I clinical trials, such as case report form (CRF) design, data dictionary development, database programming, data base design and development in compliance with Good Clinical Practice (GCP) guidelines and Clinical Data Interchange Standards Consortium (CDISC)

e. Provide other facilities and equipment, as may be specified by the task order protocols (e.g., biosafety laboratory facilities in compliance with Federal and state regulations); and

f. Personnel knowledgeable about data security

CONTRACT MANAGEMENT

The Contractor shall provide a Principal Investigator (PI) who is primarily responsible and accountable for the overall implementation of the awarded contract, who serves as the central contact for scientific and technical aspects of the contract, who will serve as the lead on the trials as defined by the FDA (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilities-protecting-rights-safety-and-welfare-study-subjects), and one who has significant experience in the conduct of Phase I clinical trials.

The Contractor shall provide project, technical, and quality management in support of the entire contract to successfully operate, coordinate, communicate, and integrate all activities during the performance of all Task Orders, including those carried out by subcontractors. For project management, the Contractor shall provide its own core team to ensure project planning, execution, delivery of reports, and accurate and timely communication with the NIH Contracting Officer (CO), Contracting Officer’s Representative (COR), and contributors.

The Contractor shall have a designated head Program Manager as the point of contact for the contract. If work will be subcontracted, the Contractor shall also provide a Subcontract management plan (SMP) for how subcontracted work will be executed, including but not limited to how qualified subcontractors will be identified, how studies will be scheduled to meet NIH timelines, and how subcontractor work will be managed and overseen.

The Contractor shall provide project management support for the overall administration of the contract; and development, tracking and management of all TOs issued under this contract. The Contractor’s project management support staff shall work in coordination with designated federal staff and will be responsible for performing all the non-inherently governmental activities associated with administration of this contract.

The Contractor shall provide an investigative team with all the required core expertise including but not limited to principal investigator, attending physician, clinical pharmacologist, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilities-protecting-rights-safety-and-welfare-study-subjects https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilities-protecting-rights-safety-and-welfare-study-subjects regulatory specialist, statistician and project manager, medical writing, research associates, information security technicians, data manager, data management support staff, research pharmacists, bioanalytical specialist, and other personnel with Phase I clinical trial expertise. The Government expects the Contractor to provide the majority of the services at its own institution. The Contractor shall provide trial subjects, established facilities and the clinical research infrastructure, with the appropriate number and mix of clinical, laboratory, technology, and support personnel to conduct these clinical trials.

All clinical trials to be conducted under this contract must be completed as per the protocols developed and finalized for each trial requirement. Time duration for a clinical trial from recruitment initiation to the last subject’s protocol exit is estimated to be approximately 7 months for a SAD clinical trial and 10 months for a MAD clinical trial but may be longer for example for therapeutics with a long half-life, or for biological agents.

Special Requirements:

a. CONFIDENTIALITY

All data provided to the Contractor and developed by the Contractor under this contract must be treated confidentially. The data to be treated confidentially is associated not only with the certain “discreet” investigational agents which are not available to the public, but with all agents (Materials) submitted for testing through the program. Under no circumstances are chemicals or drugs or any information associated with these chemicals or drugs, including the data generated under this contract, to be released or divulged without prior written approval of the NINDS COR.

The Government requires that all data accumulated under the contract be immediately available for its review and that provisions are made to maintain confidentiality of all data. Authority to release data may be granted only by the CO together with the COR and must be in writing.

The Contractor shall use Materials supplied by Contributors under this contract only for contract-related research. The Contractor shall not publish any data generated from Contributor’s Materials submitted for testing under the contract, without written approval of the COR and Contributor. Toxicity and safety data for compounds/biologics shall be disclosed only to the COR and the Contributor and may only be disclosed to other parties at the written direction of the COR.

b. INTELLECTUAL PROPERTY

The testing of agents through this contract may result in intellectual property. To facilitate the Contributors’ further development and eventual commercialization of their investigational agents, the NIH has sought a Determination of Exceptional Circumstances (DEC) to the Federal Acquisition Regulation (FAR) for this contract. The DEC enables the Contributors to retain control of the intellectual property created related to their investigational agents through this contract, thereby increasing the likelihood of commercializing of potential new therapies. The intellectual property policies established under the DEC are described in detail in Department of Health and Human Resources Acquisition Regulation (HHSAR) 352.227-11 Patent Rights—Exceptional Circumstances (Sept. 2014) and HHSAR 352.227-14 Rights in Data—Exceptional Circumstances (Sept.

2014) hereby made a part of any resultant contract in Section I.

To summarize:

Class 1: Subject Inventions that require use of the Material.

Class 2: Subject Inventions that could utilize the Material but are not limited to the Material.

Class 3: Subject Inventions that do not fall into Class 1 or Class 2 above.

The DEC contains the clause HHSAR 352.227-14 Rights in Data-Exceptional Circumstances (Sept. 2014), also made a part of any resultant contract under Section I, to ensure that proprietary data provided to the Contractor are used only for the purpose of the contract, and that data generated under the contract are not disclosed until there has been reasonable time for the applicable party to prepare and file a patent application, if appropriate.

c. SUPPLY AND PURITY OF THE INVESTIGATIONAL AGENTS:

1) For some trials, use of controlled substances may be required; the Contractor and/or its subcontractor must be licensed by the Drug Enforcement Administration (DEA) to procure, receive, and handle schedule I-V compounds. The Contractor and/or its subcontractor must demonstrate that it possesses the required DEA registration before beginning any such work.

2) At the end of the requested studies the Contractor shall transfer any stored investigational agents to a location designated by the COR or shall dispose of it in an approved manner based on industry standards when directed by the COR to do so.

d. DATA SECURITY, STORAGE, ACCESS AND TRANSFER TO NINDS

1) Access to all investigational therapy, data, or other materials provided by the Government as well as all reports, summaries, data descriptions, generated tables and/or testing results derived in performance of this contract shall be restricted pursuant to the terms of HHSAR 352.227-14 Rights in Data—Exceptional Circumstances (Sept. 2014) not this FAR clause. The Contractor is not allowed any internal use or through outside contract to study, manipulate, copy, remove, publish, and/or release any information on any data provided by the Government and/or generated under this contract without the prior written approval of the CO and the COR. Further, any request for such approvals must be submitted in writing by the Contractor to the COR and CO.

When the data are not at the contract site, e.g., when data are being securely transmitted, mailed or delivered to NIH, the Contractor must ensure that the data are covered with the statement, "Privileged Communication of Data -- Property of the U.S. Government” and take appropriate measures to assure safe transmission. The contract number and title shall also be included on such transmissions. Any unexpected or notable observation discovered during evaluation of investigational compounds or resultant from reviews or other summary data collected must be immediately reported to the COR. All such information and conclusions and raw data are deliverables and therefore the sole property of the U.S. Government.

2) Computers shall have the latest operating system, web browser, anti-virus software, and security patches installed with automating updating enabled.

3) The Contractor shall store all raw data (i.e. CRF, data storage media, etc.) for the performance period of the contract. At the end of the performance period of the contract, the Contractor shall transfer program data to a location designated by the

NINDS COR.

4) The Contractor shall submit all deliverables to an NINDS secured, provisioned website. The Contractor must maintain a current list of each contract staff who will be accessing this website. For access to the NINDS provisioned website, the Contractor must implement NIH sponsored, or NIH approved, Federated login solutions. Some NIH approved solutions include no-cost social media solutions, and upon request, NINDS can provide a current list of the sponsored and/or approved solutions. The Contractor shall be responsible for the setup and support of the chosen Federated login solution.

e. INSURANCE

The Contractor and all collaborating sites participating in the conduct of approved protocols shall provide sufficient malpractice insurance and indemnification for trial related injuries to volunteers. The Government will not provide third party liability insurance.

NOTE: The Government will not provide medical care or financial compensation for research-related injuries to clinical trial volunteers.

f. SECTION 508 COMPLIANCE HHS Section 508 and Accessibility Standards Section 508 of the Rehabilitation Act, as amended by the Workforce Investment Act of 1998 (P.L. 105-220) requires that when Federal agencies develop, procure, maintain, or use information and communication technology (ICT), it shall be accessible to people with disabilities.

Federal employees and members of the public who have disabilities must have access to, and use of, information and data that is comparable to people without disabilities.

All products, platforms and services delivered as part of this work statement that are ICT, or…