Draft statement of work.docx

CDC Draft Statement of Work

STATEMENT OF WORK

Title of Project: Assess the Safety of a Microneedle Patch for Vaccination Against Rotavirus When Given Intradermally for Four (4) Administrations in Rats (GLP compliant).

C.1 Background and Need – Despite the introduction of two live oral rotavirus vaccines into the routine national immunization in many countries, rotavirus remains a major cause of severe diarrhea and a major killer among children, particularly in low-income countries. The two licensed oral rotavirus vaccines, RotaTeq and Rotarix, are effective in preventing severe diarrhea among children in developed and middle income countries, but are much less effective in developing countries. In addition, both vaccines are generally safe but are associated with a low risk of diarrhea and intussusception among infants who receive the first dose of vaccine. To improve the safety and efficacy of oral rotavirus vaccines, CDC scientists have developed a proprietary inactivated rotavirus vaccine (IRV) technology (new human strains and a novel method for rotavirus inactivation) and demonstrated the immunogenicity in small animals (mice, rats and guinea pigs) and protective efficacy in piglets of this IRV by intradermal (ID) administration using an innovative dissolving microneedle (MN) patch. MN provide a simple and painless method to administer vaccines without using hypodermic needles. They are inexpensive to manufacture and may not need the cold chain, a major advantage for immunization campaigns in the developing world.

To help advance MN technology, CDC entered an agreement with a contract manufacturing organization (CMO) to manufacture IRV bulk material and awarded a contract to another CMO to fabricate IRV microneedle patch under Good Manufacturing Practice (GMP) conditions. CDC now is requesting a purchase requisition with a contract research organization (CRO) that will allow the company to assess preclinical toxicology and safety of this IRV MN patch in rats in accordance with regulatory requirements. Establishment of IRV preclinical safety will help advance this vaccine for testing in phase I trial in humans and further clinical development towards the licensure. The advance on a simplified and heat-stable vaccine delivery technology could revolutionize immunization programs and save more lives among children throughout the world.

C.2 Project Objective –

The objectives of this project will be to assess the safety of an IRV MN patch for vaccination against rotavirus when given intradermally for four (4) administrations in rats (GLP compliant).

The specific deliverables will be to:

1) Prepare a toxicology protocol for IRV MN patch in accordance with regulatory requirements.

2) Prepare and seek approval for an animal protocol from local IACUC, and

3) Conduct GLP preclinical toxicology and perform all laboratory analyses to establish the safety and immunogenicity of IRV MN patch in rats.

C.3 Scope of Work

CRO will provide a detailed study protocol for the study. The company will seek approval of the study from their Institutional Biosafety Committee, and Institutional Animal Care and Use Committee in compliance with all applicable federal regulations.

CRO will conduct toxicology and perform evaluation in rats as follows:

1. Mortality and moribundity: 2x daily (within one hour on dosing days)

2. Detailed clinical observations: once weekly

Specifically, CRO will assess the safety of candidate vaccine by checking local tolerance at injection sites, determining food consumption, body weight and body temperature, testing clinical chemistry/hematology and various organs in rats, and performing histopathology, and other lab assays.

C.4 Technical Requirements –

CRO is required to utilize established GLP-compliant facilities for this preclinical toxicology study. Vendor is familiar with the CDC’s programs, its approaches and data. In addition, the company has expertise and understands issues in the testing of vaccines for use in humans and in the preparation of documentation related to animal toxicology and human clinical trials.

CRO has experience and expertise in providing preclinical toxicology services and has established an excellent track record in the area of vaccine research and development. The provider’s investigators have sensitivity to the issues of rotavirus vaccines and an infrastructure that would enable them to conduct this study in a timely manner and with complete follow up. The investigators also have all materials, reagents and assays in place to complete all required laboratory tests.

The provider will work with scientists at CDC to conduct animal toxicology experiments, analyze the data and prepare a final report after completion of the experiment. The final report will include the results and report from immunogenicity study to be done and provided by CDC. The provider will provide CDC scientists with reports and documentation to support IND submission and phase I clinical trial in humans throughout the contract and 30 days after completion of the contract.

C.5 Reporting Schedule –

Provide monthly updates and a final report 30 days after completion of the project

C.6 Special Considerations –

NA

C.7 Government Furnished Property

CDC will not furnish property, but will provide the vendor with vaccines and necessary laboratory support and consultation.

C.8 References –

CDC may provide a study outline if requested.

C.9 Deliverables – The vendor shall provide the following deliverables to the Project Officer by the dates reflected below.

All electronic files should be delivered in MS Word format and provided via e-mail.