2020 PK Recomp Attach 1 SOW.pdf

Attachment 1 – Draft SOW

Statement of Work

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

A. 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 to be developed in conjunction with the NCI COR (Government).

Compounds under evaluation will vary in their stage of development and in their requirements for evaluation. Therefore, Task Orders specific for each compound will be developed by the COR and the Contractor to perform one or more of the following:

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 molecule and well-characterized biologicals) and their metabolites in body fluids and/or tissues of animals and 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 jointly by the COR and 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;

(b) Other Government-sponsored laboratories

(c) Human clinical trials

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 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.

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.

B. SAMPLE TASK ORDERS

The following sample Task Order Requests are typical of the work that may be requested and are appended to this solicitation:

1. Kick-off Meeting with NCI Staff

2. Pharmacokinetic and Bioavailability Studies of Anticancer Compounds in

Mice.

3. Pharmacokinetic-Pharmacodynamic-Efficacy Study of Anticancer

Compounds in Tumor-Bearing Mice.

4. Analytical Support for animal pharmacology Studies with Selected

Anticancer Agents

5. Determination of [NSC #] in Plasma and Urine Samples from an NCI-supported Human Phase I Clinical Trial.

Technical and business responses should be provided in your proposal, according to the specific instructions included in each sample Task Order.

Note that Task Orders 2-5 are for informational and evaluation purposes only

– no actual awards will be made. For Task Order 1, it is anticipated that a Task for participation in a kick-off meeting with the NCI will be made at the time of award of all contracts resulting from this solicitation.

C. GOVERNMENT-FURNISHED PROPERTY/SUPPLIES

1. Mice, rats, and any other animals will be purchased by the contractor under this contract as specified by the COR.

2. The Government will furnish the test articles and some of the control articles used in the assigned work. Most vehicle components for compound dosing will be purchased by the Contractor.

3. Available analytical chemistry information including chemical identity data and methodology for dose concentration analysis, plasma drug analysis, formulation information, available literature, etc. will be supplied by the Government.

D. HUMAN SUBJECTS

It is hereby understood and agreed that research involving human subjects shall not be carried out under this contract, and that no material developed, modified or delivered by or to the Government under this contract, or any subsequent modification of such material will be used by the Contractor or made available by the Contractor for use by anyone other than the Government for experimental or therapeutic use involving humans without the prior written approval of the Contracting Officer. However, refuse human materials such as blood, serum, plasma, bone marrow, liver, kidney, other tissues, etc. may be necessary for use on this contract.

E. HUMAN MATERIALS

Human samples will be coded and anonymized such that the donors cannot be identified. The Contractor is responsible for any local IRB approvals required for work with human samples as described herein and for implementation of, and adherence to, all federal, local, and institutional policies regarding the occupational health and safety of personnel working with animal and/or human plasma, urine, or other tissues.

The acquisition and supply of all human specimen material used under this contract shall be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States, and no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material. The Contractor shall receive written documentation that all human materials obtained as a result of research carried out by collaborating sites were obtained with prior approval by the Office for Human Research Protections (OHRP) of an Assurance to comply with the requirements of 45 CFR 46 to protect human research subjects. This restriction applies to all collaborating sites without OHRP-approved Assurances, whether domestic or foreign, and compliance must be ensured by the Contractor.

Provision by the Contractor to the Contracting Officer of a properly completed "Protection of Human Subjects Assurance Identification/IRS certification/Declaration of Exemption", Form OMB No. 0990-0263(formerly Optional Form 310), certifying IRS review and approval of the protocol from which the human materials were obtained constitutes the written documentation required. The human subject certification can be met by submission of a self designated form, provided that it contains the information required by the "Protection of Human Subjects Assurance Identification/IRS Certification/Declaration of Exemption", Form OMS No.

0990-0263(formerly Optional Form 310).

F. 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.

G. 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 DTP databases. Excel or other tab delimited file formats for are acceptable. Other formats will be considered but compatibility shall be confirmed.

H. CONFIDENTIALITY OF INFORMATION

Certain data provided to the Contractor under this contract must be treated confidentially. The data to be treated confidentially is associated with certain discreet compounds that are not available to the public. When compounds are assigned to the Contractor, these discreet compounds will be identified by the letter “D” as a prefix to the compound NSC number. Under no circumstances are chemicals or drugs or any information associated with these chemicals or drugs to be released or divulged without prior written approval of the NCI COR.