SOW.pdf

RFP/N01-CM-07014-39

January 2010

Statement of Work

“Preclinical Pharmacokinetic and Pharmacological Studies of Anticancer and Other Therapeutic Agents”

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 Statement of Work as presented below:

1. Develop (or adapt) and validate appropriate analytical methodology which is sufficiently sensitive, specific, and reproducible to allow measurement and quantitation of assigned test agents (e.g., small molecule therapeutics and well-characterized biologicals) and metabolites in body fluids and/or tissues of animals and humans at therapeutic and/or toxic concentrations.

2. Conduct pharmacokinetic studies in animals (e.g., mice, rats, optionally larger animals) using various routes of administration (e.g., intravenous, oral, intraperitoneal, subcutaneous, continuous infusion, etc.). Studies will include collection of multiple blood samples by suitable methods to obtain plasma or serum and, in some studies, collection of urine, feces, and tissue and/or tumor samples.

3. Utilize suitable analytical methods to determine concentrations of test agents in biological samples (e.g., plasma, urine, bile, saliva, and tissues) provided by:

(a) Pharmacokinetic studies conducted under item 2 above;

(b) The Government from other laboratories. The ability to receive and work with human samples is desirable but not required. 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.

4. Use modern modeling software to fit concentration vs. time data (for plasma and possibly tissues) to appropriate 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. Calculate systemic bioavailability for various routes (e.g., oral, ip, sc) and determine if bioavailability is dose-dependent. Calculate mass-balance parameters if sufficient data are collected.

5. Determine the solubilities of test agents as required in solvents and other formulations suitable for parenteral and/or non-parenteral administration to animals.

6. Conduct in vitro plasma protein binding and stability studies of test agents in biological fluids, model systems, and tissues.

RFP/N01-CM-07014-39

January 2010

7. Conduct in vitro studies to assess (a) the permeability of test agents through biological membranes and (b) the metabolism of test agents by human and animal liver preparations, cells, or purified enzymes to characterize the pathways responsible for metabolite formation and to compare these processes across species.

8. Determine the structures of metabolites and/or degradation products of test agents present in blood, plasma, urine, and/or other fluids. Characterize the plasma and tissue pharmacokinetics of major metabolites.

. 9. Store samples generated in-house or received from other laboratories under suitable conditions and ship samples to other laboratories upon request.