Attach 8 STO No. 5 Final.pdf

RFP 75N91021R00007

Attachment 8 – Sample Task Order #5 (11/20/20)

SAMPLE TASK ORDER #5

STATEMENT OF WORK

NOTE: THIS IS ONLY AN SAMPLE TASK ORDER REQUEST FOR PROPOSAL. WHILE A RESPONSE IS REQUIRED AS PART OF YOUR SUBMISSION AS REFERENCED IN SECTION L OF THE RFP, NO ACTUAL

TASK ORDER AWARD WILL BE MADE IN RESPONSE TO THIS SAMPLE TASK ORDER.

TORFP No: _#5__

Order Title: Pharmacokinetics and Bioavailability Evaluations of Selected Anticancer Compounds in Mice

Type of Order: Fixed Price type task order Period of Performance: One year from date of award

A. Statement of Work/Protocol/Project Description:

The purpose of this Task Order is to characterize the plasma pharmacokinetics and bioavailability of candidate anticancer compounds in mice as outlined below.

For the base task:

1. Develop and/or adapt a standard LC-MS/MS bioanalytical approach for quantification of a small drug-like molecule in mouse plasma. A “generic” assay platform is acceptable and validation to full FDA bioanalytical guidance is not required. Potential internal standards will be provided if available. A lower limit of quantitation (LLOQ) of <5 ng/mL is desirable.

2. Carry out the appended protocol for mouse PK and bioavailability evaluations with one small-molecule, drug-like compound to be provided by NCI. Note for costing purposes that the protocol specifies 2 dose groups, two routes of administration, 8 time points, and 3 mice/time point, for a total of 48 plasma samples to be generated for analysis.

3. Pharmacokinetic data analysis should include standard non-compartmental modeling to determine Cmax(po), C0(iv), Tmax, AUC0∞, AUClast, CL, and t½, Vss, and %F for each compound.

For Options 1 - 5:

1. For each Option task exercised, the contractor shall perform PK-bioavailability evaluations as above and per the attached protocol for one additional small-molecule, drug-like compound per Option. Assume all compounds will be different. Minor adjustments to the protocol that should not affect cost or schedule (e.g., routes of administration, specific sampling times) may be made.

Options are considered additional quantities, are not directly related to predetermined dates, and may be exercised at any time within the Task Order period of performance.

B. Deliverables:

The following deliverables will be required for the base task and each option exercised:

1. A final protocol signed by the PII shall be provided to the COR prior to initiation of each PK study. A proposed study schedule should be indicated on the cover page. Evidence of IACUC approval of the protocol should also be provided.

2. Preliminary Data File: Results of each study and data analysis performed (c vs. t data and derived PK parameters, with plots as appropriate) shall be provided to the COR in an agreed upon tabular format (Excel) within two weeks of receipt of the finalization of the protocol.

3. Final Data File: The Preliminary Data File shall be updated to include an outline of methods used (analytical conditions and validation, formulation, etc.), results of any sample or PK re-analysis, and any changes requested by the COR. All information should be formatted on separate tabs in Excel. The Final Data File shall be due two weeks after receipt of comments on the Preliminary Data File.

4. Monthly Reports: Monthly Technical Progress Reports are required for this task order. These reports shall include: 1) a summary of progress on the study during the past month, 2) whether or not the project is on schedule, and (3) whether any problems were encountered in the collection, handling or processing of data, including resolution of the problems.

The reporting period shall consist of each calendar month. The first report shall cover the period consisting of the first full calendar month following the effective date of the task order and any fractional part of the initial month. Reports shall be due on or before the 15th of each month following the end of each reporting period. A Monthly Study Progress Report shall not be submitted when the Final Report is due.

5. A narrative final report (e.g., Word document) will NOT be required for this Task Order.

C. Evaluation Factors:

The evaluation criteria found in Section M of the ID/IQ RFP will govern the evaluation of responses received to this Sample Task Order Request for Proposals or TORFP (see Section M). In an actual TORFP competed under any resultant IDIQ contract, study-specific evaluation criteria will be provided in this section. Per the RFP, options will be evaluated in accordance with FAR 52.217-5.

D. Order Response Due Date: Responses to this Task Order shall be included in your technical and business proposals for this RFP.

E. Attachment- Protocol for Sample Task Order #5

SAMPLE PROTOCOL

TASK ORDER #5

PHARMACOKINETICS AND ORAL BIOAVAILABILITY OF NSC [TBD] IN MALE MICE

SPONSOR: Toxicology and Pharmacology Branch

Developmental Therapeutics Program

Division of Cancer Treatment and Diagnosis National Cancer Institute National Institutes of Health Bethesda, Maryland 20892

COR: TBD

CONTRACT NUMBER: TBD

CONTRACTOR: TBD

PRINCIPAL INVESTIGATOR: TBD

STUDY DIRECTOR: TBD

PROPOSED IN-LIFE PHASE:

Start: TBD

Finish: TBD

I. OBJECTIVE

The objective of this protocol is to characterize the plasma pharmacokinetics and oral bioavailability of NSC [TBD] in male mice.

II. MATERIALS AND METHODS

A. Test Article and Vehicle:

1. Name of Test Article:

NSC TBD (drug-like small molecule)

2. Name of Vehicle:

TBD in conjunction with the COR

3. Characterization and Documentation of Methods of Synthesis, Fabrication or Derivation:

a. Test Article:

Compound identity, strength, quality, stability and purity as well as documentation of methods of synthesis, fabrication or derivation are the responsibility of the NCI. Sufficient quantity of drug shall be reserved for archiving from each lot and shipment used.

b. Vehicle:

The vehicles are stable throughout the date of expiration on the container labels when stored according to the manufacturer’s instructions.

B. Test System:

1. Species, Strain Supplier and Test System Justification:

CD-1 mice or other acceptable strain obtained from an approved commercial supplier will be used in this evaluation. This is an accepted species to support studies of compounds used or intended for use in humans.

2. Initial Age, Sex and Weight:

On the first day of dosing, the weight ranges of mice will be approximately 18 to 22 grams and the mice will be approximately 5 to 7 weeks of age. Only males will be used.

3. Care and Housing:

General procedures for animal care and housing will be in accordance with The Guide for the Care and Use of Laboratory Animals, National Research Council, 2011 and the U.S. Department of Agriculture through the Animal Welfare Act (7 USC 2131), 1985 and Animal Welfare; Standards incorporated in 9 CFR Part 3, 1991. Appropriate caging and bedding or cage board (not cedar or pine chips) will be used. No contaminants should be present in the bedding which could interfere and affect the results of the evaluation. Environmental parameters will be set to maintain conditions specified in the facility SOPs. Environmental conditions will be within specified limits for at least 90 percent of observations.

4. Diet and Water Supply:

Diet is to be certified, commercial, dry rodent chow provided ad libitum. Water source will be the public supply given ad libitum. No contaminants will be present in the feed or water which could interfere and affect the results of the evaluation.

5. Quarantine:

All mice will be quarantined for a minimum of 5 days prior to baseline measurements.

No prophylactic or therapeutic treatment will be administered during the quarantine period. Only healthy animals will be placed on test.

6. Animal Identification:

All mice will be given a unique identification number for this evaluation by ear tag or other approved method.

C. Experimental Design

1. Randomization:

In order to obtain groups that are comparable by weight, all mice will be randomly assigned from the colony to each treatment group using a computer-based body weight stratification procedure.

2. Group Assignments:

After randomization, 12 male mice will be assigned to each of two dose groups as follows:

Group Cpd. Route Dose (mg/kg)

Conc. in Formulation

(mg/mL)

Dose Volume (mL/kg) Sub-group No. of

Animals

Blood (Plasma)

Collection Timepoint

(min)

1 NSC

TBD IV TBD TBD 5

A 3 5, 120 B 3 15, 240 C 3 30, 480 D 3 60, 1440

2 NSC

TBD PO TBD TBD 10

A 3 15, 240 B 3 30, 360 C 3 60, 480 D 3 120, 1440

3. Route of Administration and Reason for Choice:

The test compound will be given as a single intravenous bolus or oral gavage dose in order to characterize its pharmacokinetics and bioavailability in mice.

4. Formulation Preparation:

To be specified for iv and oral administration to mice.

5. Dosing Procedure:

On Day 1, each mouse in a given dose group will receive formulated test article either by iv injection (tail vein) or oral gavage. The dose volume will be 5-10 mL/kg of body weight. The amount of drug administered to each mouse will be based on each animal’s most recent individual body weight.

6. Measurements:

a. Clinical signs:

The mice will be observed during the blood sampling period and any adverse clinical signs recorded.

b. Body Weight:

Individually weigh all mice prior to dosing on Day 1.

c. Sample Collection for Plasma Drug Levels:

Whole blood samples (target volume of 200 µL) will be collected from 4 cohorts of 3 mice each from each group via the retro-orbital sinus (or other IACUC approved method). Mice in each cohort will be stagger-sampled twice to obtain the eight timepoints indicated below and in the table above. Mice will be anesthetized and blood will be collected according to established laboratory SOPs. Blood will be placed into tubes containing the anticoagulant K- EDTA.

Target blood collection time points:

Group 1 (iv): 5, 15, 30, 60, 120, 240, 480, and 1440 minutes after dosing.

Group 2 (oral): 15, 30, 60, 120, 240, 360, 480, and 1440 minutes after dosing.

Actual collection times will be recorded.

Blood samples will be placed on wet ice until centrifuged to obtain plasma.

Plasma samples will be transferred into appropriately labeled tubes and placed on dry ice until stored in a freezer set to maintain at least -70 ºC.

e. Necropsy Procedure:

Necropsy is not required in this protocol.

d. Bioanalytical and Pharmacokinetic Analysis:

A bioanalytical method for the compound in mouse plasma will be identified and implemented using standard LC-MS/MS approaches. Analytical sensitivity should be as great as possible (ideally < 5 ng/mL). Full validation to FDA guidelines is not required for this analysis.

Total number of samples for quantification of test article in plasma:

8 timepoints x 3 mice/timepoint x 2 groups = 48 samples

Pharmacokinetic data analysis should include (at a minimum) standard non-compartmental modeling to determine Cmax(po), C0(iv), Tmax, AUC0∞, AUClast, CL, and t½, Vss, and %F.

III. QUALITY ASSURANCE

A. Type of Evaluation This evaluation will not require compliance with the FDA Good Laboratory Practice Regulations.

B. Standard Operating Procedures

All operations pertaining to this evaluation, unless specifically defined in this protocol, will be performed according to the standard operating procedures of the laboratory and any deviations will be documented.

C. Protocol Amendments

All changes in or revisions of an approved protocol and the reasons therefore will be documented, signed, and dated by the Project Director/Project Manager and the NCI COR. Amendments will be maintained with the protocol. Verbal approval for changes in the protocol may be granted by the NCI COR, but a written amendment will follow.

IV. REPORTING AND DISCUSSION OF DATA

A. A signed final protocol shall be provided to the COR prior to initiation of each PK study.

B. Preliminary Data File: Results of each study and data analysis performed (c vs. t data and derived PK parameters, with plots as appropriate) shall be provided to the COR in a tabular format (Excel) within two weeks of receipt of the test article.

C. Final Data File: The Preliminary Data File shall be updated to include an outline of methods used (analytical conditions and validation, formulation, etc.), results of any sample or PK re-analysis, and any changes requested by the COR. All information should be formatted on separate tabs in Excel. The Final Data File shall be due two weeks after receipt of comments on the Preliminary Data File.

D. A narrative final report (e.g., Word document) will NOT be required for this Task Order

Protocol Approvals:

Project Director:

(Date)

Project Manager:

NCI COR:

Actual collection times will be recorded.