Attachment 1 - SOW NINDS PK studies.pdf

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

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

NINDS Division Translational Research – Rodent Pharmacokinetic (PK) Testing Services

Statement of Need and Purpose:

The National Institute of Neurological Disorders and Stroke (NINDS) requires plasma and brain sample analysis and rodent pharmacokinetic (PK) testing for the purposes of new therapeutics developments.

Background Information and Objective:

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people.

The NIH Blueprint Neurotherapeutics Network (BPN) is part of NIH Blueprint for Neuroscience Research, a collaborative framework that includes the NIH Office of the Director together with eleven NIH Institutes and Centers, that support research on the nervous system. The BPN was launched to enable neuroscientists in academia and biotechnology companies to develop new drugs for nervous system disorders.

NIH BPN has a series of collaborative drug discovery and development projects focused on supporting preclinical optimization and development of safe, effective, and non-addictive small molecule and biologic therapeutics to support their eventual use as therapeutics for nervous system disorders. These projects will be developing therapeutic candidates through an iterative process of lead optimization, in vitro and in vivo testing. A component of this process will be the conduct of in vivo pharmacokinetic (PK) assessment of small molecules and biologics (e.g, peptides, etc). The Contractor shall conduct rodent PK studies to assess blood and tissue (primarily brain) levels of a novel test article supplied by the Principle Investigator (PI) or the Project Team in order to support lead optimization and preclinical pharmacokinetic efforts under the NIH BPN program.

Period of Performance:

The period of performance shall be a 12 month period effective at time of award, anticipated to be:

Base Period: August 19, 2024 - August 18, 2025

SCOPE OF WORK

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

Base:

• Rodent plasma and brain samples analysis testing for 2 compounds

• Two rodent pharmacokinetic studies

Option 1*:

• One rodent pharmacokinetic studies

*Option 1 may be exercised up to five (5) times during the 12-month period of performance.

Specific Requirements:

1. Rodent Plasma and Brain Samples Analysis for 2 Compounds (Base Requirement) The Contractor shall analyze plasma and tissue samples supplied by the BPN to measure levels of two test articles being studied to support pharmacokinetic assessment. Each of the two (2) compounds has 16 plasma samples and 13 brain samples. Samples will be collected off-site, as a component of in vivo activity studies conducted by the investigators.

2. Rodent Pharmacokinetic Studies (Base and Option 1) The Contractor shall conduct pharmacokinetic testing, administering BPN - supplied test articles to rodents (e.g., rat or mouse) and assessing blood concentrations of test article at various time points and calculating standard PK parameters.

Designs for the mouse or rat PK study are presented below.

a. Mouse Pharmacokinetic Study Design

• Blood (plasma) collected via retro orbital sinus stick and/or cardiac puncture last time point (prefer volume of 50-60 ul if possible since C57 mouse is smaller than CD1 mouse or other strains)

• Dose levels will be determined at the time of protocol development based on available information on the test article.

Group Test Compound Dose Route Subgroup No. of

Animals Plasma Collection (hr.)

1 Compound A

TBD

iv A 3 0.083, 0.5 iv B 3 0.25, 1 iv C 3 2, 4 iv D 3 6, 8

2 Compound

A TBD

po A 3 0.25, 0.5 po B 3 0.75, 1 po C 3 2, 4 po D 3 6, 8

• For the purposes of quotation development, assume that C57/BL6 mice will be used and a bioanalytic method is not available. The expected LLOQ is 1ng/mL for plasma (or value applicable to biologic test article).

b. Rat Pharmacokinetic Study Design

Group Test Article

Dose (mg/kg) Route No. of

Animals Plasma Collection

1 Compound B TBD iv 3 10 time points

2 Compound B TBD po 3 10 time points

• Blood (plasma) collected via jugular catheters. Blood will not be collected from the catheter used to administer the dose formulation.

• Route of administration will be iv/po.

• Dose levels will be determined at the time of protocol development based on available information on the test article.

• Plasma will be collected on after dose administration for 10 time points (e.g., pre-dose, 0.083, 0.25, 0.5,1, 2, 4, 6, 8 and 24).

For the purposes of quotation development, assume that a bioanalytic method is not available and must be developed. The expected LLOQ is 1ng/mL for plasma and 5ng/mL for brain.

GOVERNMENT RESPONSIBILITIES

The Government will provide investigational agents that will be provided by either the Government via a third party Contractor or contributor. The Contractor shall comply with FDA regulations and Contractor’s standard operating procedures for handling investigational agents.

Receipt, handling, storage and disposition of investigational agents will be in compliance with Contractor’s Standard Operating Procedures and in compliance with FDA regulations. At the request of the Government, investigational agents may be returned as instructed by the COR at any time.

REPORTING REQUIREMENTS AND DELIVERABLES

The Government will initiate the testing with the submission of a testing request form which will include available information on the test article to be evaluated. After completion of the in-life portion of the study, the Contractor shall estimate Pharmacokinetic parameters of the test articles or samples using WinNonlin (Phoenix software, Pharsight). The Contractor shall prepare an excel file and submit it as a data report for each study requested by the Contracting Officer’s Representative (COR) within 4 weeks or less of receiving of compounds or samples for bioanalysis

Deliverable/Description Quantity Due Date Test/Study Report An excel file shall be submitted as the data report

1 e-copy to the

COR

Less than 4 weeks from receiving the compounds for PK studies and 3 weeks for bioanalysis from receiving the

OTHER CONSIDERATIONS

Travel:

Not applicable.

Regulatory Compliances and Safety Requirements:

The Contractor shall obtain, prior to the start of any work under this contract, an approved Animal Welfare Assurance from 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. The Contractor shall also be fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. Information about AAALAC accreditation is available at www.aaalac.org. The Contractor’s Institutional Animal Care and Use Committee (IACUC) shall approve all animal procedures under this Purchase Order.

Data Rights:

It is expected that all data generated on the compounds or samples will be held confidential and provided only to the Government and the party supplying the compounds for testing. As standard methods will be used in the proposed assays and studies, it is not anticipated that new patents will be generated in the course of this contract.

The Contractor shall guarantee strict confidentiality of the information/data that it is provided by the Government during the performance of the purchase order. The Government has determined that the information/data that the Contractor will be provided during the performance of the contract is of a sensitive nature and shall not be released, disclosed, or otherwise disseminated to any person, organization, etc., except as otherwise directed by the Government.

Section 508—Electronic and Information Technology Standards:

The contractor shall comply with Section 508 of the Rehabilitation Act (29 U.S.C. § 794d), as amended by the Workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998. All tasks for testing of functional and/or technical requirements must include specific testing for Section 508 compliance, and must use NIH approved testing methods and tools.

samples or the contractor can propose an appropriate alternative deadline Report of Unexpected Event

1 e-copy to the

COR

Notification within 6-8 hours of the event

Publications and Publicity:

Contractor will ensure protection of the Government Sponosored Studies. Contractor shall not publish any articles as a result of fulfilling this requirement.

Disclosure of the information/data, in whole or in part, by the Contractor can only be made after the Contractor receives prior written approval from the Contracting Officer. Whenever the Contractor is uncertain with regard to the proper handling of information/data under the contract, the Contractor shall obtain a written determination from the Contracting Officer.

Confidentiality of Information:

All data and the results emanating from or generated on the compounds or samples provided by the Government, along with any data compiled, are considered confidential based on the pre-existing agreements that the NINDS has established with compound sponsors. The contract restricts and prohibits the Contractor’s right to use, release to others, reproduce, distribute or publish data or other information resulting from testing/evaluations performed under purchase order. Such data shall not be releasable under the Freedom of Information Act (FOIA) as it is considered proprietary, i.e., trade secrets, and, therefore, could be determined to be exempt from FOIA. Restricted access to data and materials will be maintained at the Contractor’s facility in a secured manner. Special notices or other safeguards will be affixed to any packages containing such data.

The Government will initiate the testing with the submission of a testing request form which will include available information on the test article to be evaluated. After completion of the in-life portion of the study, the Contractor shall estimate Ph...