A20_Sample_TO1_SOW_4-30-2024_final.pdf

SAMPLE TASK ORDER #00001

STATEMENT OF WORK

4/30/2024

PROJECT TITLE: Screening of investigational agents through the NINDS Preclinical Screening Platform for Pain (PSPP)

A. BACKGROUND INFORMATION AND OBJECTIVES

The National Institutes of Neurological Disorders and Stroke (NINDS) established the Preclinical Screening Platform for Pain (PSPP) in response to the National Institutes of Health (NIH) Helping to End Addiction Long-term (HEAL) Initiative. The HEAL Initiative (https://heal.nih.gov/) is a trans-NIH effort to fast-track basic, translational, and clinical research in the field of addiction and pain to address the national opioid crisis. The goal of the PSPP is to foster the development of non-opioid, non-addictive treatments for all types of pain conditions. As part of the NIH HEAL Initiative, the PSPP will provide pain researchers from the academic, industry, and government communities with a centralized resource for profiling small molecules, biologics, natural products, and devices for their potential as pain therapeutics. Researchers with promising non-opioid, non-addictive therapeutics for pain (here and after Contributors) will be invited to submit small molecules, biologics, natural products, and devices (here and after referred to as “assets”) to the PSPP for evaluation. These assets will be evaluated to determine if they are non-opioid, non-addictive, and effective in models of pain.

The Contractor shall provide profiling of potentially viable assets submitted through the PSPP. NINDS will send assets to the Contractor in a blinded fashion (Contractor is blinded to structure, target, asset owner), and the Contractor shall perform evaluation through the progressive testing funnel established in collaboration with NINDS staff and the PSPP External Consultant Board (ECB). The evaluation will entail (1) in vitro studies for determining functional activity at known human targets of drugs of abuse, and safety signals(2) in vitro models of pain, (3) testing models of tolerability and/or side effect liability shall also be performed to determine therapeutic index (4) series of acute and chronic pain models. (5) Target engagement studies where appropriate. (6) Additional testing in models of abuse liability, in vivo, shall also be investigated to evaluate the assets for addictive potential. The Contractor shall provide resources and expertise in not only the execution of existing models, but also in establishing new in vivo pain models to create a standardized panel of preclinical pain models and endpoints that shall be used to evaluate potential efficacy as well as the side effects and abuse liability of Contributor-submitted investigational agents. The Contractor shall evaluate the efficacy, pharmacokinetics, side effects and abuse liability of new investigational agents, perform in vitro pharmacological profiling and determine target selectivity, execute formulation research studies and establish Absorption, Distribution, Metabolism and Excretion (ADME) profiles of candidate agents submitted to the NINDS by Contributors. The Contractor in their own facilities or through subcontractors shall https://heal.nih.gov/ also provide the complete array of in vitro and in vivo assays to evaluate the potential side effects, drug abuse liability, in vitro pharmacological profiling and target selectivity, ADME profiling, formulation research studies, and pharmacokinetic studies of the investigational agents.

The goal of the NIH programs served by this contract is to bring new drugs to market. To this end, a Determination of Exceptional Circumstances (DEC) to the Federal Acquisition Regulation (FAR) for this contract is required. The DEC enables the Contributors to retain control of the intellectual property for investigational agents evaluated through the

PSPP.

B. SCOPE

The Contractor shall provide evaluation of Contributor’s investigative agents, including small molecules, biologics, natural products, and devices for their potential as non-opioid, non-addictive therapeutics. The PSPP will evaluate investigational agents in vitro and in vivo to determine they are non-opioid, metabolically stable compounds that show promise in established and newly developed models of pain. The scope of the contract also includes activities focused on interpretation of efficacy data including the evaluation of abuse liability and potential motor or sensory side effects. Other activities include in vitro target selectivity profiling assays, ADME profiling, formulation research, pharmacokinetic studies and target engagement studies. The Contractor shall demonstrate in-house expertise in the in vivo evaluation of investigational agents using animal models related to a variety of pain conditions including but not limited to headache. In addition, the Contractor shall be able to adapt, develop, validate and establish new models to support the PSPP mission to sustain the changing priorities of the program and the state of the art for existing models.

C. TECHNICAL REQUIREMENTS AND PERFORMANCE AREAS

C.I. TECHNICAL REQUIREMENTS:

The Government will be responsible for providing the following:

• NIH staff. The NINDS Contracting Officer (CO) and Contracting Officer Representative

• (COR) will oversee the PSPP contract. The COR will approve platform design, investigational agent testing progression and provide feedback to the Contractor on PSPP strategies and project design, in consultation with the Contributors and NIH External Consultant Board (see below).

• Contributors with bioactive investigational agents (small molecules, biologics, natural products, and devices) will be the source of the test agents. All interactions between the Contractor and Contributors will be mediated and managed by the COR.

• Access to reports of pharmacokinetic (PK) and PD assays if available.

• Additional scientific information on the analogs as needed to execute the services under this contract.

• The NIH will utilize external consultants to assist the COR in reviewing proposals, reports, and data produced by the Contractor.

• Information Technology (IT) system. The NIH will establish a SQL database for entering, searching, downloading, the data under this contract. The Contractor shall be responsible for entering the data that they generate into this database. NINDS will provide training on how to use the IT system and technical support.

The Contractor shall be required to demonstrate a platform of a wide-range of established and validated models of pain conditions and in-house expertise for evaluating new investigational agents and devices in models of pain conditions.

The Contractor shall provide a platform of in vivo testing in models to cover the broad spectrum of pain conditions to measure efficacy, abuse liability and neurologic, sensory, or motor side effects of investigational agents (small molecules, biologics, natural products, and devices). The Contractor shall also demonstrate capabilities in the areas of supportive in vitro pharmacological screening against opioid receptors and other molecular targets associated with off-target effects, ADME profiling, formulation research, pharmacokinetic, target engagement and bioanalytical studies. Evaluation of new investigational agents will be conducted under the following three performance areas:

1) In vivo testing in pain conditions, abuse liability and side effects assessment models, including supporting studies or establishing new pain-related models to support the evolving requirements of the PSPP as needed;

2) In vitro pharmacological profiling against opioid receptors and/or other molecular target(s)

3) of safety; and

4) ADME and formulation studies as well as PK assessment, target engagement and bioanalytical testing of samples.

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 conduct services in the following Performance Areas.

C.I.a. PERFORMANCE AREAS

PERFORMANCE AREA 1: IN VIVO TESTING IN PAIN CONDITIONS, ABUSE LIABILITY

AND SIDE EFFECTS MODELS

Objective: The Contractor shall establish, using existing and proposed models, a testing platform and conduct in vivo studies by administering PSPP-supplied investigational agents to assess efficacy, side effects, and abuse liability.

Technical requirements: The Contractor shall furnish all necessary services, qualified personnel, materials, equipment, and facilities to perform the following in vivo testing studies:

a) A battery of in vivo testing studies to assess efficacy including but not limited to models of acute, inflammatory, and neuropathic pain and/or unspecified pain condition-related model(s) which have been established and validated in rodents or non-rodent species.

b) In vivo abuse liability testing studies established and validated in rodents and/or nonrodent species including but not limited to non-human primates.

c) In vivo testing to assess efficacy in pain conditions-related models that can be tissue and/or organ and/or system and/or condition and/or disease specific pain models, including but not limited to headache, fibromyalgia pain, post-surgical pain, visceral pain, osteoarthritis pain, diabetic pain, bone cancer pain, chemotherapy-induced pain, postherpetic neuralgia pain, established and validated in rodents and non-rodent species including but not limited to non-human primates.

d) In vivo side effects testing studies in an established and validated model in rodents or non-rodent species including but not limited to non-human primates to assess confounding sensory and motor neurons-related activities.

e) Demonstrate the ability to create, modify, validate, and implement additional in vivo testing models in rodents and non-rodent species including but not limited to non-human primates as requested.

f) Elucidating the target engagement (TE) level of pharmacotherapeutic investigational agents in in-vitro, in-vivo and ex vivo studies can consist of direct and indirect biological markers/pathways measuring the level of agent-target interactions which include but are not limited to receptor occupancy studies, gene profiling, metabolic changes, protein and phosphor protein changes, electrophysiology, microdialysis, tissue morphological evaluation, reporter in vivo or in in vitro models.

The Contractor in coordination with the NINDS data management representative should coordinate a seamless transfer of detailed information on material and methods, experimental design and rationale supporting the proposed studies, raw data and analyzed data (% inhibition, dose response curves, ED50 or any measurement of agonist or antagonist activity), mathematical and statistical method(s) of analysis into the NINDS database.

TESTING ESTIMATIONS FOR LEVEL OF EFFORT BUDGETING (PERFORMANCE

AREA 1):

Although the exact numbers and mix of experiments will depend on numbers of Contributor agents and efficacy demonstrated by them, for estimating purposes it is assumed the Contractor shall be responsible for evaluating in a battery of pain, safety and abuse liability models, using a starting cohort of approximately 12 agents during the base period and approximately 12-15 agents for each subsequent funding options 1-4 and approximately 7 agents should services be extended for up to 6-months pursuant to FAR Clause 52.217-8 (Table 1). All in-vivo studies are subject to either a 4-point dose-response one time point or a single dose time course. All in-vivo assays should utilize Sprague Dawley rats as subjects, unless agreed upon or directed otherwise by the COR. Any proposed substitutions of strain of rat or of mice as subjects in in-vivo assays should be justified. All studies are performed using a single route of administration.

Because the estimated number of agents will most likely fluctuate to meet the NINDS’s needs during each performance period, the estimated quantities shown below are for cost estimating purposes only.

Table 1: Estimated agents and tests number for Performance Area 1

PERFORMANCE AREA 2: IN VITRO PHARMACOLOGICAL PROFILING

Objective: The Contractor shall provide in vitro pharmacological profiling of proposed investigational agents to evaluate molecular interaction with opioid receptors, other targets of abuse liability and other biological molecular targets known to elicit adverse events or induce off-target liabilities as well

Technical Requirements: The Contractor shall furnish all necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to perform the following in vitro profiling of the investigational interventions submitted:

a) Binding or functional assays for opioid receptors including Mu-opioid, Delta-opioid, and Kappa-opioid receptors.

b) Binding or functional assays for other biological targets. The assays available should include but are not limited to the following:

a. Adenosine receptor A2A,

b. α1A-adrenergic receptor, α2A-adrenergic receptor, β1-adrenergic receptor, β2-adrenergic receptor,

c. Cannabinoid receptor CB1, Cannabinoid receptor CB2,

d. Cholecystokinin A receptor,

e. Dopamine receptor D1, Dopamine receptor D2,

f. Endothelin receptor A,

g. Histamine H1 receptor, Histamine H2 receptor,

h. Muscarinic acetylcholine receptor M1, Muscarinic acetylcholine receptor

M2, Muscarinic acetylcholine receptor M3,

i. 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT3,

j. Vasopressin V1A,

k. Acetylcholine receptor subunit α1 or α4,

l. Voltage-gated calcium channel subunit α Cav1.2,

m. GABAA receptor α1 Benzodiazepine site,

n. Potassium voltage-gated channel subfamily H member 2; hERG,

o. Potassium voltage- gated channel KQT-like member 1,

p. NMDA receptor subunit NR1,

q. Voltage-gated sodium channel subunit α Nav1.5,

r. Acetylcholinesterase,

s. Cyclooxygenase 1; COX1, Cyclooxygenase 2; COX2,

t. Monoamine oxidase A,

u. Phosphodiesterase 3A, Phosphodiesterase 4D,

v. Lymphocyte-specific protein tyrosine kinase,

w. Dopamine, Noradrenaline, and Serotonin transporters,

x. Androgen receptor and Glucocorticoid receptor.

The in vitro assays above can utilize purified preparations of cell-membrane or protein from recombinant or tissue sources that expresses the molecular target of interest at a single test concentration (for example: 10-100 μM final concentration in duplicate) and/or multiple concentrations establishing concentration–response curves.

In addition, new and evolving in vitro functional evaluation studies of human pain relevant preparations such as dorsal root ganglion (DRG) assays that can evaluate potential efficacy, in vitro, for pain related targets.

The Contractor shall provide detailed information on material and methods, experimental design and rationale supporting the proposed studies. The Contractor shall coordinate a seamless transfer of raw and analyzed data (% inhibition, concentration response curves, inhibitory binding affinity, EC50 or any measurement of agonist or antagonist activity), mathematical and statistical method(s) of analysis into the NINDS database.

TESTING ESTIMATIONS FOR LEVEL OF EFFORT BUDGETING (PERFORMANCE

AREA 2):

Although the exact numbers and mix of experiments will depend on numbers of Contributor agents and efficacy demonstrated by them, for estimating purposes it is assumed the Contractor shall be responsible for evaluating test agents in In vitro pharmacological screening using a starting cohort of approximately 20 agents during the base period and approximately 20 agents for each subsequent funding options 1-4 (Table 2). Because the estimated number of agents will most likely fluctuate to meet the NINDS’s needs during each performance period, the estimated quantities shown below are for cost estimating purposes only.

Table 2: Estimated agents and tests number for Performance Area 2

PERFORMANCE AREA 3: ADME AND FORMULATION STUDIES AS WELL AS PK

ASSESSMENT AND BIOANALYTICAL TESTING OF SAMPLES

Objective: The Contractor shall conduct in vitro and/or in vivo ADME and formulation studies as well as PK studies to assess blood and tissue (including brain) levels of novel investigational agents supplied by the PSPP to support in vivo efficacy studies testing.

Technical requirements: The Contractor shall furnish all necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to perform the necessary ADME and formulation as well as PK studies. As requested by the COR the Contractor shall develop a study protocol including a timeline for study initiation and completion and plan and execution of the following studies:

a) In vitro and/or in vivo ADME studies including but not limited to solubility, permeability assessment, P-glycoprotein efflux, CYP profiling, clearance in rodents and/or non-rodent species including but not limited to non-human primates’ liver microsomes and hepatocytes.

b) Formulation studies to identify best suitable formulation for dosage in animals via a specified route of delivery including intravenous, intraperitoneal, oral and other route of administrations.

c) Single dose and multiple dose pharmacokinetic studies in rodents, dogs, non-human primates, and/or other species.

d) Plasma and tissue sample analysis for test agent.

e) Elucidating the target engagement (TE) level of pharmacotherapeutic investigational agents in in-vitro, in-vivo and ex vivo studies can consist of direct and indirect biological markers/pathways measuring the level of agent-target interactions which include but are not limited to receptor occupancy studies, gene profiling, metabolic changes, protein and phosphor protein changes, electrophysiology, microdialysis, tissue morphological evaluation, reporter in vivo or in in vitro models.

The Contractor in coordination with the NINDS data management representative should coordinate a seamless transfer of material and methods, experimental design, bioanalytical methods, formulation methods, all raw data, analyzed data, statistical data and method(s) of analysis pertaining to the outlined studies into the NINDS database.

TESTING ESTIMATIONS FOR LEVEL OF EFFORT BUDGETING (PERFORMANCE

AREA 3):

Although the exact numbers and mix of experiments will depend on numbers of Contributor agents and efficacy demonstrated by them, for estimating purposes it is assumed the Contractor shall be responsible for evaluating test agents in ADME/ Formulation and Pharmacokinetic studies, using a starting cohort of approximately 15 agents during the base period and approximately 15 agents for each subsequent funding options 1-4 (Table 3). Because the estimated number of agents will most likely fluctuate to meet the NINDS’s needs during each performance period, the estimated quantities shown below are for cost estimating purposes only.

Table 3: Estimated agents and tests number for Performance Area 3

C.2. 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 Contracting Officer’s Representative (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 shall be disclosed only to the COR and may only be disclosed to other parties at the direction of the COR.

b. INTELLECTUAL PROPERTY The testing of agents in the PSPP 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 the PSPP, thereby increasing the likelihood of commercializing of potential new therapy alternatives to opioids.

The intellectual property policies established under the DEC are described in detail in HHSAR 352.227-11 Patent Rights—Exceptional Circumstances 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 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.

D. ADDITIONAL REQUIREMENTS

D.I. ANIMAL FACILITY - shall be accredited by or registered as follows:

1. The Contractor and any subcontractor shall be fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International or equivalent and maintain that accreditation for the duration of the contract. Information about AAALAC accreditation is available at www.aaalac.org.

2. The Contractor shall submit an approved Animal Welfare Assurance for the Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW) (http://grants.nih.gov/grants/olaw/olaw.htm), Office of the Director, NIH, as required by Section I-43-30 of the Public Health Service Policy on Humane Care and Use of Laboratory Animals. The Contractor shall maintain such assurance for the duration of this contract, and any subcontractors performing work under this contract involving the use of animals shall also obtain and maintain an approved Animal Welfare Assurance.

3. The Contractor and any subcontractor shall comply with the Public Health Service (PHS)

4. Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/phspol.htm) and conduct work in compliance with recommendations established in the Guide for the Care and Use of Laboratory Animals (http://www.nap.edu/openbook.php?record_id=5140).

5. The Contractor’s Institutional Animal Care and Use Committee (IACUC) shall approve all animal procedures under this contract.

D.II. ANIMAL REQUIRMENTS:

The Contractor shall comply with the HHSAR clause 352.270(5)(b), Care of Live Vertebrate Animals. All available animal handling and safety assurances and related laboratory inspections shall be provided to the COR on an annual basis throughout the period of the contract and such assurances must also be accessible when required. Any violations of protocol resulting in issues, warnings http://grants.nih.gov/grants/olaw/olaw.htm http://grants.nih.gov/grants/olaw/references/phspol.htm http://www.nap.edu/openbook.php?record_id=5140 or the need for corrective measures shall be reported immediately in writing to both the COR and Contracting Officer. All relevant explanations related to the nature of the violation as well as planned remedy or actions need to accompany the report.

1. Animal Sources and Strains: Animal species and strains shall be specified by the COR for each investigational intervention and should be used from the same supplier throughout this contract. Testing in female animals shall also be required on specified investigational agents as specified by the NINDS

COR.

2. Data Integrity and Controls: The Contractor shall establish controls to ensure consistency of the data. Source of animal supplies shall not be changed without advanced permission of the COR and validation of appropriate drug standards.

3. Animal Facility Treatments: No insecticides, such as chlorinated hydrocarbons or methylenedioxyphenyl compounds shall be used in animal facilities because of their effects on hepatic drug metabolism enzymes.

Bedding for animal cages shall not contain any substances that alter the animal's microsomal enzymes or that produce other adverse effects.

D.III. RIGOR:

The Contractor shall refer to Article H.2., of the Contract and the NIH Rigor and Reproducibility webpage (https://www.nih.gov/research-training/rigor-reproducibility) for guidance on implementing enhanced rigor in study designs and data reporting as appropriate or as directed by the NINDS COR.

D.IV. SUPPLY AND PURITY OF THE INVESTIGATIONAL AGENTS:

1) The supply and purity of the investigational agents shall be the responsibility of the COR and the Contributor sources of test submissions. The COR shall supply the Contractor with available information on storage and physicochemical properties of the investigational agents when it is available from owners (PSPP Contributors) of the investigational agents. In addition, any available toxicological data concerning handling of investigational agents shall be made available to the Contractor.

2) The Contractor shall be required to confirm and/or determine the purity of investigational agents when applied using reasonable standard analytical tools including melting point, nuclear magnetic resonance (NMR), infrared (IR), and potency and report any discrepancy between batches to ensure continuity of different batches of candidate investigational agents. Noted discrepancies shall be reported to the COR who will attempt to find resolution.

3) The Contractor must be licensed by the Drug Enforcement Administration (DEA) to receive and handle schedule II-V compounds. In addition, the Contractor must either possess, or demonstrate the ability to obtain a DEA registration for Schedule I controlled substances.

4) Investigational agents will usually be submitted to the Contractor blinded for testing to maintain rigor and protect intellectual property rights of the PSPP Contributor. For DEA scheduled investigational agents that cannot be shipped blinded it shall be the Contractor’s responsibility to establish a procedure for blinding the technical staff that will conduct testing.

5) Contractor shall be responsible for proper storage of investigational agents as directed by the COR. Most investigational agents shall be stored at 4°C but some shall require - 20°C, -80°C and/or in a desiccator.

6) At the end of the end of 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.V. DATA SECURITY, STORAGE, ACCESS AND TRANSFER TO NINDS

D.V.1. Test Data and Programmatic Information Storage, Access and Data Transfer.

NINDS shall maintain a Structured Query Language (SQL) database that can be accessed by authorized contract personnel using NINDS assigned individual passwords. Pertinent information about the database and its operation follows.

1) The database shall store all test data generated by Contractors and any sub-contractors. Test sites can access the database using current versions of commonly used web browsers such as IE, Mozilla, and Chrome.

2) Test sites are required to upload raw data and test results contemporaneously within 15 days of completion of tests ordered by the

3) Enable the COR to communicate with test site to provide Test Orders.

4) Test sites shall not be able to edit historical data. Historical data can be edited by contacting the COR providing reasons for the edit, and the nature of the edits needed. COR will respond in a timely manner, within 5 calendar days, to Edit requests. Once COR approves an edit, he / she shall task appropriate NINDS staff to make the changes in the database.

5) The database shall also store programmatic information deemed useful by NINDS.

D.V.2. Data Security:

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 NINDS Contracting Officer and the COR.

Further, any such approvals must be submitted in writing by the Contractor to the COR and Contracting Officer. 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, raw data are deliverables and therefore the sole property of the U.S. Government.

2) All computers, software and databases used by the Contractor in the performance of this Contract shall be FISMA compliant. 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. laboratory notebooks, 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

E. DELIVERABLES

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

https://www.hhs.gov/web/section-508/contracting/technology-products/product-accessiblitytemplate/index.html under "Vendor Information and Documents." Additionally, when submitting electronic reports and forms the offeror shall ensure they fully conforms to the applicable Revised 508 Standards prior to delivery and before final acceptance.

E.I. TECHNICAL DELIVERABLES

1) Protocol manual describing established and validated in vivo pain models in any animal species. This shall be due within 60 days after contract award in an electronic format.

2) Protocol manual describing in vitro and or in vivo methods, test preparations, relevant mathematical calculations and formula derivations. This shall be due within 60 days after contract award in an electronic table format.

3) Protocol manual describing newly established and validated in vivo pain models in any animal species. This shall be due within 30 days after completion of the validation of the experimental study according to the COR specifications.

4) Preliminary Data Reports - After completion of the in-life portion of the study, the Contractor shall prepare a preliminary data report, to be submitted within 10 calendar days from the end of in-life portion of the study. Within 20 calendar days of submission of the data report, the Contractor shall submit a full draft report for review and comment by the COR. After receipt of COR comments, raw data and a final study report shall be delivered and /or transferred to a specified NINDS-Data base.

5) Final Data Reports - The Contractor in coordination with the NINDS data management representative shall coordinate a seamless transfer of raw https://www.hhs.gov/web/section-508/contracting/technology-products/product-accessiblitytemplate/ https://www.hhs.gov/web/section-508/contracting/technology-products/product-accessiblitytemplate/ and analyzed data, statistical and method(s) of analysis into the NINDS database within 1 week of finalization on study reports.

6) Comprehensive Summary Reports – As directed by the NINDS COR, a comprehensive report of all PSPP studies shall be completed within 45 days after final test results are submitted for each asset. Other less comprehensive summaries for “pilot studies and special projects” shall have a 30-day completion requirement for each separate candidate selected.

7) Quarterly Progress Reports – Quarterly Progress Reports for all testing summaries shall be provided in an approved electronic format to the COR. Quarterly Reports shall comprise of:

a) a summary of all testing performed in the performance period;

b) status of all projects under development (i.e., new model development, pilot studies), problem areas and any performance delays encountered or that may impede future performance;

c) list of comprehensive summary reports in preparation or completed during the reporting period and

d) solutions to identified problems encountered during the reporting period if any. The first reporting period consists of the first full three months of performance including any fractional part of the initial month. Thereafter, the reporting period shall consist of three full calendar months. Reports shall be due on or before the 10th calendar day following each reporting period. The Contractor shall send two copies of the Quarterly Progress Reports, one to the COR and one copy to the Contracting Officer, NINDS.

8) Conference Call Summaries- The Contractor shall be required to generate and deliver summaries of all conference calls conducted in performance of work under the contract. The summary shall consist of a bulleted list of decisions made and action items identified on the call. These summaries shall be sent via e-mail to all participants within 48 hours of each call. The exact number and timing for such calls will depend on the specifics and circumstances surrounding each individual project.

9) Final Progress Report/ Summary of Salient Results - Upon final completion of the contract/task order, the Contractor shall deliver a comprehensive final report to the CO and COR that briefly summarizes all the projects initiated over the course of the contract and their outcomes. This final report should also summarize lessons learned that may be applicable to future NIH opioid alternatives initiatives. The Contractor will also be required to prepare and submit, with the final report, a summary of salient results achieved during the performance of the contract. This report will be required on or before the expiration date of the contract.

E.II ADMINISTRATIVE AND REGULATORY REPORTS

1) Reporting of Financial Conflict of Interest (FCOI) - All reports and documentation required by 45 CFR Part 94, Responsible Prospective Contractors including, but not limited to, the New FCOI Report, Annual FCOI Report, Revised FCOI Report, and the Mitigation Report, shall be submitted to the Contracting Officer in electronic format. Thereafter, reports shall be due in accordance with the regulatory compliance requirements in 45 CFR Part 94. 45 CFR Part 94 is available at:

https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-94, Management and reporting of financial conflicts of interest for complete information on reporting requirement (Reference subparagraph g. of the INSTITUTIONAL RESPONSIBILITY REGARDINGINVESTIGATOR FINANCIAL CONFLICTS OF INTEREST Article in SECTION H of this contract.)

2) Service Contract Reporting Requirements for Indefinite-Delivery Contracts - In accordance with FAR 52.204-14, “Service Contract Reporting Requirements”, contained in full text in Article I.4. of the contract, the Contractor shall report annually by October 31, for services performed under this contract during the preceding Government fiscal year (October 1 – September 30) the following information to http://www.sam.gov, with an electronic copy to the Contracting Officer:

i. Contract number and, as applicable, order number.

ii. The total dollar amount invoiced for services performed during the previous Government fiscal year under the contract.

iii. The number of Contractor direct labor hours expended on the services performed during the previous Government fiscal year.

iv. Data reported by subcontractors [if applicable] under paragraph (f) of the subject clause (see full text of clause FAR 52.204-14, “Service Contract Reporting Requirements” in Article I.4. of the contract).

https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-94 http://www.sam.gov/

3) Subcontract Reporting Requirements - The Contractor shall submit the individual and summary subcontract reports as required and as set forth in Section H. These reports shall be submitted via the "electronic Subcontracting Reporting System (eSRS) at http://www.esrs.gov.

4) Invention Reporting Requirement - All reports and documentation required by

HHSAR Clause 352.227-11, Patent Rights—Exceptional Circumstances (September 2014) including, but not limited to, the invention disclosure report, the confirmatory license, and the Government support certification, shall be directed to the Division of Extramural Inventions and Technology Resources (DEITR), OPERA, OER, NIH, 6705 Rockledge Drive, Suite 310, MSC 7980, Bethesda, Maryland 20892-7980 (Telephone:

301-435-1986). In addition, one copy of an annual utilization report, and a copy of the final invention statement, shall be submitted to the Contracting Officer.

5) Section 508 Annual Report - The contractor shall submit an annual Section 508 report in accordance with the schedule set forthby the Contracting Officer (CO)/Contracting Officer's Representative (COR). The Section 508 Report Template and Instructions for completing the report are available at:

http://www.hhs.gov/web/508/contracting/technology/vendors.html under "Vendor Information and Documents."

E.III. INFORMATION TECHNOLOGY REPORTS

Information Security and Physical Access Reports

The Contractor shall submit the following reports as required by the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of the contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

1) Roster of Employees Requiring Suitability Investigations (Monthly IT

Roster) - The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a Federal Information System(s). The initial roster shall be submitted to the COR, with a copy to the CO, within 14 calendar days after contract award. Monthly IT Roster reports shall be submitted thereafter. The monthly IT roster reports are due 5 calendar days after the end of each monthly reporting period. (Reference INFORMATION AND PHYSICAL ACCESS SECURITY Article) http://www.esrs.gov/

2) Contractor-Employee Non-Disclosure Agreement(s) - The Contractor shall complete and submit a signed and witnessed "Commitment to Protect Non-Public Information - Contractor Agreement" form for each Contractor and Subcontractor employee who may have access to non-public Department information under the contract. Reference INFORMATION AND PHYSICAL ACCESS SECURITY Article)

3) Reporting of New and Departing Employees - The Contractor shall notify the Contracting Officer's Representative (COR) and Contracting Officer within five working days of staffing changes for positions that require suitability determinations as follows:

I. New Employees who have or will have access to HHS

Information systems or data: Provide the name, position title, e-mail address, and phone number of the new employee.

Provide the name, position title and position sensitivity level held by the former incumbent. If the employee is filling a new position, provide a description of the position and the Government will determine the appropriate security level.

II. Departing Employees: 1) Provide the name, position title, and position sensitivity level held by or pending for the individual; and 2) Perform and document the actions identified in the Employee Separation Checklist", attached in Section J, ATTACHMENTS of this contract, when a Contractor/Subcontractor employee terminates work under this contract. All documentation shall be made available to the COR and/or Contracting Officer upon request. (Reference INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)