Draft PK SOW 10.22.2020.pdf

Attachment 1 – Draft SOW 10/22/2020

Statement of Work

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. All 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.