Attach 3 SOW PK Base Final.pdf

Attachment 1 – Statement of Work (SOW) PK IDIQ Base 11/19/2020

Statement of Work PK IDIQ Base

Title: Preclinical Pharmacokinetic and Pharmacology Evaluations of Agents Being Developed for Cancer Patients

Independently and not as an agent of the Government, the Contractor shall furnish all of the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as required to perform the work stated below in accordance with laboratory protocols developed by the National Cancer Institute’s (NCI) Contracting Officer’s Representative (COR).

SCOPE

The Contractor shall characterize the pharmacokinetics and other pharmacological properties of investigational and approved agents being developed for the treatment of cancer.

TASKS

Compounds under evaluation will vary in their stage of development and in their requirements for evaluation. Therefore, Task Orders specific for each compound (or series of compounds) will be awarded to perform one or more of the following tasks as specified on the individual task order, such as:

1. Implement and validate analytical methodologies that are sufficiently sensitive, specific, and reproducible for measurement and quantitation of assigned test agents (e.g., drug-like small molecules and well-characterized biologicals) and their metabolites in body fluids and/or tissues of animals and tissues of humans at therapeutic and/or toxic concentrations.

2. Conduct pharmacokinetic evaluations in animals (e.g., mice, rats, tumor-bearing rodents, optionally larger animals) to support early lead and candidate drug characterizations. Various routes of administration (e.g., intravenous, oral, intraperitoneal, subcutaneous, continuous infusion, etc.)

may be utilized. Studies may include collection of multiple blood samples to obtain plasma or serum and, in some studies, collection of urine, feces, tissues or tumor samples. Detailed experimental protocols will be developed by the COR and if needed, modified following input from the contractor.

3. Utilize established analytical methods/protocols to determine concentrations of test agents in various matrices (cell extracts, media, plasma, urine, bile, saliva, tumors, and normal tissues) that may be obtained from:

(a) Pharmacokinetic evaluations conducted under item 2 above

(generated in-house);

(b) Other Government laboratories; and/or

(c) human materials/samples from clinical trials (de-identified of patient Personally Identifiable Information or PII)

4. Use state-of-the-art modeling software to fit concentration vs. time data

(for plasma and possibly tissues) to suitable non-compartmental and/or compartmental pharmacokinetic models and calculate relevant pharmacokinetic parameters (e.g., half-life, volume of distribution, area under the curve, clearance, etc.) for a given agent and route of administration.

5. Calculate systemic bioavailability for various routes (e.g., oral, ip, sc) and determine (as requested) if bioavailability is dose-dependent. Calculate mass-balance parameters when sufficient data are collected.

6. Determine the suitability of standard formulation strategies for the administration of test agents to animals by the desired route and at the desired dose level(s).

7. Determine the in vitro plasma protein binding and stability of test agents in biological fluids and tissues using standard techniques.

8. Carry out pharmacokinetic-pharmacodynamic (PK-PD) study protocols using tumor-bearing mice and collect plasma, tissue, and/or tumor samples for drug level determinations and analysis of specified pharmacodynamic endpoints.

9. Utilize standard mass spectroscopic techniques to characterize the metabolites and/or degradation products of test agents present in blood, plasma, urine, and/or other fluids. The extent of metabolite characterization will be specified by the NCI COR in the Task Order.

10. Characterize the plasma and tissue pharmacokinetics of major metabolites.

11. Store samples generated in-house or received from other laboratories under suitable conditions and ship samples to other laboratories upon request by the NCI COR.

The Contractor shall adhere to the following requirements for all task orders issued under the base contract:

A. PROJECT MANAGEMENT

Unless otherwise specified in an individual task order, the Contractor shall engage in the following project management tasks:

1. Task Order Initiation Meeting and/or Teleconference:

a. Within 10 calendar days after the effective date of the Task Order or before the start of any tasks, the Contractor shall plan for and participate in an Initiation Meeting or Teleconference to review the Task Order requirements and timelines, discuss Task Order technical plans and approaches, and identify any anticipated problems/obstacles to completing the Task Order requirements. The Task Initiation Meeting shall be attended by Contractor key personnel (including subcontractor personnel as appropriate), the COR, and other representatives at the discretion of the COR (e.g., CO, Subject Matter Experts, investigator representatives).

2. Progress Review Meetings and Teleconferences

a. The Contractor shall plan and participate in Progress Review Meetings or Teleconferences, which shall be attended by Contractor key personnel (including subcontractor personnel as appropriate), the COR, the Contracting Officer, and other individuals designated by the COR (e.g., Subject Matter Experts, investigator representatives), as necessary or as issues arise. The purpose of these meetings/teleconferences shall be to review and discuss:

1) ongoing and planned activities, protocols, and associated data;

2) timelines for task initiation and completion, submission of data, and other information;

3) any problems or deficiencies identified with respect to the accuracy, timeliness, and completeness of data submitted; and

4) any other matters relevant to the technical and financial administration of the task.

b. Key personnel or other senior staff coordinator(s) shall be available for ad hoc meetings/teleconferences with the COR immediately upon a meeting request.

B. HEALTH AND SAFETY PLAN

Each agent provided to the contractor will be considered potentially hazardous. Therefore, all necessary precautions must be taken to protect personnel and the environment against possible exposure to the agents being tested. The Contractor shall perform all work associated with this contract in accordance with all applicable Federal, State and local regulations including transportation and disposal of hazardous waste.

C. ACCESS TO DATA

The Government requires that all data accumulated under the projected contracts be immediately available for its review and those provisions are made to maintain confidentiality of all data. Authority to release data may be granted only by the Contracting Officer together with the COR and must be in writing. Upon request, individual animal data should be provided to the COR in a format that allows integration into Developmental Therapeutics Program (DTP) databases. Excel or other tab delimited file formats for are acceptable.

Other formats will be considered but compatibility shall be confirmed.

D. Section 508 – ICT Accessibility Requirements

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.

Products, platforms and services delivered as part of this work statement that are ICT, or contain ICT, must conform to the Revised 508 Standards, which are located at 36 C.F.R. § 1194.1 & Apps. A, C & D, and available at https://www.access-board.gov/guidelines-and-standards/communications-and-it/about-the-ict-refresh/final-rule/text-of-the-standards-and-guidelines Section 508 Conformance (as outlined in the attached Word document) of electronic documents shall be determined or confirmed by successful completion and submission of the relevant checklists and acceptance by NCI. Fillable versions of the GSA Section 508 Create Accessible Products may be downloaded at https://www.section508.gov/create and/or HHS’s Making Files Accessible shall be provided to the selected offeror upon initiation of this contract. NCI retains the right to confirm the accessibility and Section 508-conformance of vendor submitted documents and to return them for remediation, at no cost to the National Cancer Institute but at the contractor’s expense.

Any and all reports (including monthly and ad-hoc reports) shall be formatted for Section 508-conformance and accessibility for persons with disabilities.

Instructions may be found at HHS Making Files Accessible and at GSA Section508.gov Create Accessible Digital Products. The respective checklists from either of these sites will be considered acceptable.

All reports required herein shall be submitted in electronic format.

All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at: http://www.hhs.gov/web/508/index.html under "Making Files Accessible."

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