RFQ 75D301-22-Q-74545 Attachment 1 - Statement of Work.docx

RFQ 75D301-22-Q-74545

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 is now seeking a contract research organization (CRO) 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 (Good Laboratory Practice (GLP) compliant).

The specific deliverables will be to:

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

(b) Prepare and seek approval for an animal protocol from local Institutional Animal Care and Use Committee (IACUC).

(c) 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 contractor 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:

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

(b) 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 Period of performance The period of performance is no more than one year from the date of award.

C.5 Technical Requirements CRO is required to utilize established GLP-compliant facilities for this preclinical toxicology study. Vendor 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 contractor will work with scientists at CDC to conduct the animal toxicology experiment, analyze the data, and prepare a report after completion of the experiment. The contractor’s report will include the results and a report from an immunogenicity study that will be conducted by CDC and provided by CDC to the contractor. The contractor will provide an interim report to CDC nine months after the award date, after which CDC will provide feedback and comments. The contractor will then provide a final report no later than twelve months after the award date. The contractor will provide CDC scientists with a final report and associated documentation to support investigational new drug (IND) submission and phase I clinical trial in humans.

C.6 Regulatory Compliance Animal use conducted under this contract shall be in compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the current edition of the “Guide for the Care and Use of Laboratory Animals (the Guide), the Animal Welfare Act and Regulations (Title 9 Code of Federal Regulations part 1), and all applicable local, state, or other federal regulations.

The contractor and any subcontractors shall have an approved Animal Welfare Assurance on file with the Office of Laboratory Animal Welfare (OLAW) at the time of contract award.

Accreditation of the contractor by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) is preferred.

If animal species regulated by the United States Department of Agriculture (USDA) are involved in a contract, the contractor shall be registered with the Secretary of Agriculture of the United States in accordance with the following Federal regulations: 7 U.S.C. 2136 and 9 CFR sections 2.25-2.28, respectively.

The contractor and/or subcontractors must submit an IACUC-approved protocol for CDC ACUPO/IACUC review prior to award, which includes the following items as required by the Public Health Service Policy on Humane Care and Use of Laboratory Animals (section IV.D.1.):

(a) identification of the species and approximate number of animals to be used;

(b) rationale for involving animals, and for the appropriateness of the species and numbers used;

(c) a complete description of the proposed use of the animals;

(d) a description of procedures designed to assure that discomfort and injury to animals will be limited to that which is unavoidable in the conduct of scientifically valuable research, and that analgesic, anesthetic, and tranquilizing drugs will be used where indicated and appropriate to minimize discomfort and pain to animals; and

(e) a description of any euthanasia method to be used in accordance with the most recent version of the AVMA Panel on Euthanasia Guidelines.

C.7 Reporting Schedule Provide monthly updates by e-mail, an interim report, and a final report.

C.8 Government Furnished Property CDC will not furnish property, but will provide the vendor with vaccines and necessary laboratory support and consultation.

C.9 References A draft study outline is provided in Appendix 1.

C.10 Deliverables The vendor shall provide the following deliverables to the Contracting Officer’s Representative (COR) and Project Officer by the dates reflected below.

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

C.11 Travel No travel is authorized.

C.12 Place of performance The place of performance is the contractor’s facility(ies).

C.13 Contracting Officer’s Representative (COR) and Project Officer.

The Contracting Officer’s Representative (COR) is:

[To be provided after award]

The Project Officer is:

[To be provided after award]

Appendix 1. Draft study outline.

Repeat-Dose Vaccine Toxicity Study in Rats with a 2-Week Recovery

Compliance: GLP- compliant

Species: Wistar rats

Number of animals: 30 males and 30 females

Route of administration: intradermal application of microneedle patch

Dosing Frequency: Day 1, 15, 29, 43 (n+1 design)

Sacrifice times: 2 days and 2 weeks after the fourth administration (to be confirmed)

Sacrifice

Recovery sacrifice (~2 week)

5M/5F

5M/5F

Dose formulation confirmation: not needed, patches will be supplied, use as is.

Dose stability and homogeneity: not needed, patches will be supplied.

Cage-side clinical observations

Mortality/moribundity/distress/pain: twice daily General health: Post-dose within one hour and daily thereafter during study

Noninvasive method is preferred.

Modified Draize assessment preferred

Clinical Chemistry

Standard parameters Prestudy, 2 days after first administration, 2 days after the last administration and at recovery sacrifice

Prestudy, 2 days after first administration, 2 days after the last administration and at recovery sacrifice

Standard Ophthalmology

Prestudy and within the last weeks prior to sacrifice (terminal and recovery)

Necropsy (gross pathology)

Full necropsy (terminal and recovery)

Standard list (including injection sites and draining lymph nodes)

Organ weights

Following organs at terminal and recovery sacrifice

Brain, heart, kidneys, liver, lungs, ovaries with oviducts, pituitary, prostate, seminal vesicles, spleen, thyroid with parathyroid, thymus, testes, uterus

Histopathology

Standard histopathology panel (terminal and recovery sacrifices)

Assay for antibodies against virus and/or assay specifically evaluating neutralizing antibodies.

*Immunogenicity: CDC lab has validated assay in place and will perform neutralization assays.