STATEMENT-OF-WORK-fluorocellobiose.pdf

NIH/OD/OLAO/OA

Statement of Work (SOW) Office of Acquisitions

11/19/2013

Statement of Work

TABLE OF CONTENTS

1.0 Introduction 2

1.1 Background 2

1.2 Scope 2

1.3 Objectives 2

2.0 Requirements 3

2.1 Tasks 3

2.2 Deliverables 3

2.3 Schedule 4

2.4 Assumptions 4

3.0 Government Furnished Property 4

4.0 Security Requirements 4

1.0 INTRODUCTION/OVERVIEW

The purpose of this project is to obtain toxicity testing of a new PET ligand which is required for the Investigational New Drug (IND) application as per the FDA requirements. The new ligand will be tested by the contractor in their facilities and the final report of any detected toxicity or lack thereof will be provided to the NIH to be included in the IND application packet. The testing will be performed under Good Laboratory Practice (GLP) conditions.

1.1 BACKGROUND

The National Institutes of Health (NIH) main campus is located in Bethesda, Maryland.

As part of the U.S. Public Health Service under the Department of Health and Human Services, NIH is the Federal Government’s primary biomedical research agency. Within NIH, the Clinical Center is a research hospital providing medical services for patients participating in human research protocols. The Clinical Center provides patient facilities and services for clinical investigations by the NIH Institutes, conducts research in related areas and supervises residency and other training programs.

Radiology and Imaging Sciences (RIS) Department provides imaging services for Clinical Center patients participating in research protocols conducted by the various NIH institutes. Services include planar x-ray, fluoroscopy, mammography, interventional radiology and computed tomography (CT) scans.

The Center for Infectious Disease Imaging (CIDI) is a cooperative initiative between Radiology and Imaging Sciences at the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases (NIAID). CIDI was established in 2009 to perform basic science, translational, and clinical research on the imaging features of infectious disease, including CT, nuclear medicine, MRI, ultrasound, radiography, and optical modalities.

These efforts comprise a new initiative at NIH to advance the knowledge of radiology-pathology-virology correlation with clinical translation in the study of infectious disease and emerging pathogens.

The Hammoud lab is part of CIDI, with a main focus of development and validation of fungal imaging ligands in animal models that can be translated to patients. An IND application will be submitted regarding a recently developed fungal specific ligand (18F- Fluorocellobiose).

1.2 SCOPE

Under the contract, the Clinical Center at NIH expects the performance of a single dose, single species Toxicity Study in Rats with 14-day Recovery for a proposed PET ligand (Fluorine-18-Fluorocellobiose). The results of this study will be provided to the FDA as per the Center for Drug Evaluation and Research (CDER) requirements. This is a necessary step for the Investigational New Drug (IND) application.

1.3 OBJECTIVES

The objective of this study is to determine potential toxic effects and to identify potential target organs of toxicity, if possible, for the toxicity endpoints examined following a single intravenous (iv) bolus administrations of a novel radiotracer given to Sprague Dawley rats.

Additionally, maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) of the tracer in rats may be established. Information from this study may be used to determine the suitability of the proposed human dose and is required for a successful IND application.

2.0 REQUIREMENTS

2.1 TASKS

Tasks to be performed by the contractor:

1. Development of analytical chemistry methods in order to assess the level of the drug in the dose formulation administered to the rats for toxicity testing. Homogeneity (analysis of top, middle, bottom of formulation) concentration verification and stability will be evaluated.

2. Validation of the chemistry methods of determining concentration in dose formulations administered to the rats.

3. Intravenous Dose Toxicity Study in Sprague Dawley Rats performed in accordance with the U.S. FDA “Good Laboratory Practice for Nonclinical Laboratory Studies” (GLP). Male and female Sprague Dawley rats will receive a single dose at 1000x human dose based on expected human dose of test article or vehicle via bolus intravenous (iv) injection. Mortality/morbidity evaluation of the rats will be conducted at least once daily. Clinical observations will be performed daily (Days 1-15) and prior to euthanasia, or more often if warranted by clinical signs. Clinical pathology (hematology and clinical chemistry) parameters will be determined from surviving animals prior to necropsy (Day 3 and 15). Necropsy will be performed on all surviving animals on Days 3 (Main) and 15 (Recovery). Organ weights and weight ratios will be determined from selected tissues. Histopathology evaluations will be performed for recommended tissues. Gross lesions observed at necropsy will be evaluated. Target tissues and lesions will be evaluated for all rats. The slides will be evaluated by a Board-Certified Veterinary Pathologist.

2.2 DELIVERABLES

Primary Deliverables:

Draft and final Reports of the results of the toxicity study will be provided to the NIH Clinical Center (Dr Dima Hammoud) within a predetermined period from last necropsy. The contractor will be responsible for providing FDA Submission ready files. Those include the following:

1. All relevant Standard for “Exchange of Nonclinical Data (SEND) for nonclinical data” (SEND) datasets

2. define.xml (version 2.0)

3. Study Data Reviewer’s Guide (which includes statement that the data accurately reflects final report).

The NIH Clinical Center will be responsible to provide comments on the SEND datasets within 3 months of the delivery of the Final SEND package.

2.3 SCHEDULE

The project will be performed at the contractor’s facility. The estimated period of performance for the project is a maximum of 12 months following receipt of the completed Authorization Form signed by an authorized representative of the NIH Clinical Center, receipt of any study materials to be provided by NIH Clinical Center, and initial payment.

2.4 ASSUMPTIONS

None.

3.0 GOVERNMENT FURNISHED PROPERTY

No government-furnished property will be provided to the contractor.

4.0 SECURITY REQUIREMENTS

No unique security requirements will be associated with contract performance.