Attachment_3_-_SOW.pdf

ATTACHMENT 3:

CONTRACT STATEMENT OF WORK

EVALUATION AND TESTING SERVICES (ETS) FOR VACCINES AND OTHER

BIOLOGICS FOR INFECTIOUS DISEASES

RFP-NIAID-DMID-75N93024R00019

1) BACKGROUND AND INTRODUCTION

Research supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives.

The NIAID Division of Microbiology and Infectious Diseases (DMID) supports extramural research for the investigation, control and prevention of diseases caused by all infectious agents other than HIV. Support for basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics is provided through a variety of research grants and contracts as described in the following link:

https://www.niaid.nih.gov/research/resources?search=dmid.

The development and introduction of new vaccines and biologics against potential agents of bioterrorism, drug-resistant pathogens, emerging and re-emerging infectious diseases, as well as infectious diseases prevalent in resource-limited countries remain a high public health priority. To assist in filling these public health gaps, NIAID requires a product development-oriented program to provide preclinical development support for multiple vaccine and biologic candidates.

The services shall be directed at infectious diseases including, but not limited to:

• Biodefense pathogens and toxins);

• emerging and reemerging infectious diseases;

• antimicrobial resistant and multi drug resistant infections;

• other bacterial infections;

• fungal infections;

• viral infections other than HIV; and

• parasitic diseases.

The contracts will focus on supporting development and introduction of new vaccines and biologics as medical countermeasures against infectious diseases. To assist in filling these public health gaps, NIAID requires a coordinated evaluation and testing services program to provide preclinical, non-clinical, and clinical testing support for multiple vaccine and biologic candidates that emerge from academia, the private sector, or other sources. The suite https://www.niaid.nih.gov/research/resources?search=dmid of testing services will encompass those activities commonly associated with the testing of vaccine and biologic products for infectious disease required for regulatory submissions to the Food and Drug Administration (FDA), such as Investigational New Drug (IND) and/or Biologic License Applications (BLA), but excludes the conduct of a clinical trial. NIAID recognizes that a single contracting organization or institution may not have the full spectrum of expertise or facilities required to perform all activities needed, nor have expertise in the wide array of candidate products to be assessed. Consequently, NIAID anticipates awarding multiple indefinite delivery/indefinite quantity (IDIQ) contracts to organizations that best meet the overall qualifications needed to fulfill the technical requirements of the four Task Areas of this solicitation. All Offerors must submit separate proposals to Task Area A and at least one other Task Area (from Task Areas B, C and/or D). Offerors must submit one proposal per Task Area proposed. If submitting to all four Task Areas, you are required to submit four separate proposals. Offerors may propose to extend internal expertise and resources by including the expertise and resources of other organizations or persons through subcontracts, partnerships, consortia agreements, and/or use of consultants. However, an awarded Contractor shall be responsible for ALL work performed and shall be responsible for project planning, initiation, implementation, management and communication;

evaluation, selection, and management of subcontractors; and for all deliverables specified in this contract and each awarded Task Order for the following Task Areas.

Task Area A – Administrative Activities and Management Support Activities (required for all proposals) Task Area B – Assay Development, Clinical and Non-clinical Sample Testing Task Area C – Non-clinical Immunogenicity and Efficacy Testing Task Area D – Safety and Toxicity Testing including specialty toxicology

This solicitation is a third recompetition originating with a NIAID award of a single contract in 2012 and in 2018 to Battelle Memorial Institute that provided a suite of product development services using the IDIQ contract mechanism. Under the previous solicitations it was anticipated that a single contract would be awarded for all Task Areas. Since the contract’s inception, NIAID has awarded multiple Task Orders for five specific activities that included administration or management of the contract, assay development, immunogenicity and efficacy testing, clinical and non-clinical sample testing, and safety and toxicology testing. Within the scope of the 2012 and 2018 contracts, testing of various vaccines against Ebola was performed, resulting in the data provided to facilitate the filing for the Ebola vaccine that was EMA approved in 2020. Work on the contract(s) was used for the FDA filing for the Biotrax vaccine against anthrax, and continues for the evaluation of the liquid versus lyophilized AV7909. More recently, the contract was used to test various formats of anti-SARS-CoV-2 vaccines in animal models, testing of samples from human vaccine trials in the live SARS-CoV-2 neutralization assay and to provide toxicology data for a combination of SARS-CoV-2 monoclonal antibodies. The contract(s) have supported the testing of more than 75 vaccine/biologic products spanning 21 pathogens.

The purpose of this solicitation is to recompete a NIAID resource, Contract Number HHSN272201800013I. While the overall suite of services provided is comprehensive, the intent is to provide individual gap-filling services on a case-by-case basis for a diverse collection of vaccine candidates and other biologics, rather than carry a single product candidate through an entire preclinical development pathway. These services are intended to help a wide variety of investigators in a broad number of scientific areas obtain critical data needed to acquire additional funding, gain prospective partnerships (either for further development or to support Phase I/II/III clinical trials), fulfill regulatory requirements, and complete studies needed to apply for an IND and enter Phase I/II/III clinical trials.

However, since the 2012 and 2018 soliciations a wide array of vaccine and biologic formats have evolved, as well as new formats for assessing immune function that are difficult to encompass within a single contract organization. Sample Task Orders are provided in the RFP solely to evaluate offeror responses and capabilities. Offerors must respond to Task Area A and to any combination of other three Task Areas, and Offerors will only be considered for Task Area(s) that they include in their proposal. Each successful Contractor will be awarded a base award for limited contract initiation activities. Individual Task Orders for specific tasks will be issued after award of the Contract. In case of multiple Offerors in a Task Area, all Offerors will be provided a Request for Task Order Proposal and offered the opportunity to submit a Task Order Proposal.

Sample Task Order solicitations are provided in the RFP solely for evaluative purposes and do not represent actual work being solicited at this time. Task Order solicitations for actual work will be issued either at or after the award of the Contract.

2) SCOPE

Contracts awarded from this solicitation will provide the capacity and capability for evaluation and testing services to support preclinical, non-clinical, and clinical studies for validated candidate vaccines and other related biologics when such products emerge from investigator-initiated research studies or other sources identified by NIAID Program staff.

3) GENERAL TASK ORDER REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below.

The Contractor shall be required to carry out, either directly, or through its partners, collaborators, subcontractors, and/or consultants, the Scope and Activities defined in the following four Task Areas. All Offerors must submit separate proposals to Task Area A and at least one other Task Area (from Task Areas B, C and/or D). Offerors must submit one proposal per Task Area proposed. If submitting to all four Task Areas, you are required to submit four separate proposals. The NIAID Contracting Officer’s Representative (COR), the Contracting Officer (CO) and NIAID Subject Matter Experts (SMEs) will collaborate with the Contractor in all awarded Task Orders. Technical Requirements will be defined in the individual Task Orders.

The following requirements shall apply to each Task Order:

A) TECHNICAL

1) Provide the expertise, availability, and technical capabilities to address the SOW in each Task Area.

2) Provide the expertise, availability, and technical capabilities to address the SOW as requested in the Sample Task Order(s).

B) PROJECT MANAGEMENT

1) Provide and implement plans for overall project management to coordinate and integrate activities conducted under the Task Order to meet all Technical Requirements. Clearly delineate all the roles and responsibilities of personnel and site(s) involved on the Task Order and any preparation and/or planning to be done prior to performance of the tasks.

2) Task Order Initiation Meeting and/or Teleconference: Within 10 calendar days after the effective date of the Task Order or before the start of any tasks, plan for and participate in, an Initiation Meeting or Teleconference to review the Task Order requirements and timelines, discuss Task Order technical plans and approaches, and identify any anticipated problems/obstacles to completing the Task Order requirements. The Task Order Initiation Meeting shall be attended by Contractor key personnel (including subcontractor personnel as appropriate), the COR, the designated NIAID SMEs, the Contracting Officer, and the product third party investigator(s)/developers.

3) Project Management Plan: The Contractor shall provide a Task Order Project

Management Plan (PMP) to the COR within 30 calendar days after the effective date of the Task Order award, delineating proposed project management of all proposed tasks, as described in Reporting Requirements and Deliverables.

4) The Contractor shall develop, monitor, and modify the timelines, tasks, budgets, objectives and milestones as discussed with, and/or prioritized by, the COR before and during the performance of activities under the Task Order, and prepare regular updates to the schedule on a monthly basis.

5) Monthly Progress Reports: The Contractor shall submit to the Contracting Officer and to the COR electronic copies of Monthly Progress Reports covering the work accomplished during each reporting period, as described in Reporting Requirements and Deliverables.

6) The Contractor Principal Investigator (or equivalent) shall be responsible for overall compliance with quality requirements, project management and communication, tracking performance, monitoring and reporting on project status and progress, and recommending modifications to project requirements and timelines, including projects undertaken by subcontractors.

7) Key personnel or other senior staff coordinator(s) shall be available for ad hoc meetings/teleconferences with the COR within at least 24-48 hours of a meeting request.

8) Progress Review Meetings and Teleconferences:

a. The Contractor shall plan and participate in Progress Review Meetings or Teleconferences, to be attended by Contractor key personnel, the COR, and designated NIAID SMEs, the Contracting Officer, and/or the third party investigator(s), as necessary, at regular mutually-agreed upon intervals or as issues arise. The purpose of these meetings/teleconferences shall be to review and discuss:

i. Ongoing and planned activities, protocols and associated data, and associated task-linked budget;

ii. Timelines for task initiation and completion, submission of data and other information;

iii. Any problems or deficiencies identified with respect to the accuracy, timeliness and completeness of data submitted; and

iv. Other matters relevant to the technical and financial administration of the task order.

b. The Contractor shall:

i. Prepare and distribute agenda and background materials no later than two business days in advance to all meeting attendees.

ii. Organize, coordinate, and record minutes for the above meetings. Provide meeting minutes to the COR for review within three business days post-meeting.

iii. Monitor and routinely report progress and expenditures, including expenditure burn rate with respect to progress to COR and CO.

iv. Provide a detailed development plan, timeline and task-linked budget, and update as needed to COR and CO.

v. Establish reliable electronic communication links with NIAID for sharing word processing, data files, and product timelines in a format that is compatible with software used by NIAID. The Contractor shall be responsible for maintaining compatibility with software applications used by NIAID. When specific formats/templates are required, they will be developed in consultation with and/or provided by the COR.

C) QUALITY MANAGEMENT

As outlined in the Task Order:

1. The Contractor shall be responsible for the quality and regulatory compliance of the materials and documentation generated per the SOW. The study protocols and reports shall be required to meet stated quality standards specified in each Task Order including non-GLP, GLP and Animal Rule studies. The Contractor shall provide a Quality Management Plan that includes management responsibilities, resources, training program, oversight of all outsourced operations, and communication processes, including timelines, and is submitted as part of the Reporting Requirements and Deliverables.

2. The Contractor shall be responsible for the control of outsourced or subcontracted activities. The Contractor shall have a quality system oversight program that ensures stage-specific compliance of the outsourced activities. The quality system oversight program must include establishing a Quality Agreement with the subcontractor that clearly delineates the responsibilities of both the Contractor and the subcontractor and describes communication processes including timelines. The Quality Agreement must cover Organization & Personnel, Training, Facilities, Equipment, SOPs, Test Systems, Good Documentation Practice, Study Protocols/ Amendments, Deviations/Investigations, Challenge Material/Reagents, Data Management/Computer Systems, Subcontractors, Reporting, Data/Specimen/Sample Handling, Archiving, Access to Data, and Audits. When requested, the Contractor shall provide the draft and/or final Quality Agreements to NIAID.

3. The Contractor shall conduct routine site monitoring visits and “for cause” audits of the subcontractor facility(ies) required for performance of the contracted work, upon approval by the government. The Contractor audit team shall include representatives of the government on an as needed basis determined by NIAID.

D) FACILITIES, EQUIPMENT AND OTHER RESOURCES

As outlined in the Task Order:

1. The Contractor shall provide facilities, equipment, space, training and other resources to conduct work with hazardous biological materials in compliance with all Federal and NIH regulations, in accordance with the following guidelines where applicable:

a. “Biosafety in Microbiological and Biomedical Laboratories”, Centers for Disease Control and Prevention and the National Institutes of Health, Sixth Edition 2020 (https://www.cdc.gov/labs/BMBL.html)

b. Federal Guidelines for Research involving Recombinant and Synthetic Nucleic Acid Molecules

(https://osp.od.nih.gov/policies/biosafety-and-biosecurity-policy#tab2/)

c. Federal Guidelines for Research involving Select Biological Agents or Toxins at (https://www.selectagents.gov/regulations/index.htm) https://www.cdc.gov/labs/BMBL.html https://osp.od.nih.gov/policies/biosafety-and-biosecurity-policy#tab2/ https://www.selectagents.gov/regulations/index.htm

2. The Contractor shall provide facilities, equipment, space and other resources to conduct work in a manner to prevent cross-contamination with other materials.

3. All personnel, equipment and facilities shall be compliant with applicable regulatory agency requirements in effect throughout the entire period of performance. The Contractor shall maintain Quality Assurance documentation to support adherence to these areas.

E) STORAGE AND SHIPPING

As outlined in the Task Order, the Contractor shall:

1. Be responsible for the overall management and conduct of the receipt, storage, retrieval, packaging and shipping of products, materials, and specimens, including obtaining appropriate licenses and permits.

2. Be responsible for retrieval, packaging, and shipping of materials to various domestic and international locations. Detailed shipping instructions will be supplied at the time of shipment. When appropriate, a documented shipping procedure compatible with CGXP (Current Good Clinical, Laboratory or Manufacturing Practices) regulations is to be established and followed. Temperatures maintained during shipping and storage shall be captured and documented. Packaging shall adhere to U.S. and international standards.

3. Store products, materials, and test samples at the specified temperature range and conditions in a secure area. Specific temperature ranges include, but are not limited to, liquid nitrogen, -70°C +/- 10°C, -20°C +/-10°C, 2-8°C, room temperature.

4. Monitor the conditions in all controlled temperature chambers and document, as appropriate, for the level of regulatory compliance under which each product is produced. Specific procedures should be proposed by the Contractor and will be reviewed/approved by COR.

5. Qualify or validate temperature chambers as proposed by the Contractor and reviewed/approved by the COR.

F) TRANSITION

The Contractor shall ensure an orderly, secure, and efficient transition of contract-related materials and activities to the Government, or a third party, as designated by the COR, at the completion of the specified Task Order. Contractor shall deliver to the Government or its designee the following items:

1. All data obtained from all work;

2. All products remaining from the work;

3. Any critical reagents, test results, references or materials developed under each Task

Order, and

4. All files pertaining to each Task Order.

5. It is expected that the Contractor shall provide appropriate documentation of the work performed to include in regulatory submissions.

4) DESCRIPTION OF INDIVIDUAL TASK AREAS

A. TASK AREA A - ADMINISTRATION AND MANAGEMENT SUPPORT

ACTIVITIES

1. Scope of Task Area A

The scope of this Task Order includes administrative and management functions performed by the Contractor in support of NIAID’s contract entitled “EVALUATION AND TESTING

SERVICES (ETS) FOR VACCINES AND OTHER BIOLOGICS FOR INFECTIOUS

DISEASES” which occurs independent of other specific Task Orders to be awarded under the contract.

Requirements for Task Area A include:

a. Contract Initiation Meeting Plan and participate in the initial contract initiation meeting to be held in Rockville, Maryland, the Contractor’s vicinity, or as a virtual meeting as designated by the government. The contract initiation meeting is to be attended by the Contractor Principal Investigator and other relevant key Contractor technical and business staff, the COR and his/her designees, and the Contracting Officer and/or his/her designees.

b. General Requirements For All Task Area A Meetings

i. Prepare and distribute agenda and background materials no later than two business days in advance to COR and CO.

ii. Organize, coordinate, and record minutes for the above meetings. Provide meeting minutes to the COR for review within three business days of the meeting.

iii. Provide travel and per diem funds for all in person meetings, as necessary for participants, including the Principal Investigator and Project Manager(s).

c. Electronic Communications: Establish reliable electronic communication links with NIAID for sharing word processing, data files, and product timelines in a format that is compatible with software used by NIAID. The Contractor shall be responsible for maintaining compatibility with software applications used by NIAID. When specific formats/templates are required, they will be developed in consultation with, and/or provided by, the COR.

d. Site Visits/ Audits: Conduct site visits and/or audits for the purpose of assessing of capabilities, quality systems and procedures for any subcontracting sites.

Deliverables and Reports - As Described In “Reporting Requirements and Deliverables”

Task Order Project Management Plans (PMPs): The Contractor shall provide a Draft and Final Task Order Project Management Plan (PMP). The Task Order PMP shall include task order requirements and deliverables, timelines in Gantt charts or other COR approved format, and shall discuss Task Order technical plans and approaches, and identify any anticipated problems/obstacles to completing the Task Order requirements.

This PMP shall include a separate financial section containing a task linked budget.

Quality Management Plan (QMPs): The Contractor shall have a Quality Management Plan (QMP) that includes management responsibilities, resources, training program, oversight of all outsourced operations, and communication processes. The quality system oversight program for subcontractors must include establishing a Quality Agreement with the subcontractor that clearly delineates the responsibilities of both the Contractor and the subcontractor and describes communication processes.

Task Order Initiation Meeting: The Contractor shall provide a draft and final presentation separated into a technical and administrative presentations to the COR and CO two days in advance of the meeting. The technical presentation shall review the Task Order PMP. The technical presentation will also address plans to share information and communicate with NIAID and third-party product innovators. A second administration meeting between the Contractor and NIAID may be included to address financial and contractual issues.

Meetings: The Contractor shall prepare and distribute agenda and background materials two days in advance of and during the meetings, manage calendar invites and teleconference systems during the meetings, and provide minutes and final presentation documentation after the meeting to all meeting attendees. If requested in task order, provide travel and per diem for in-person meetings.

Invoices: The contract shall submit invoices as defined in article G.4.

Public Information: Copies of publications, abstracts, presentations, press releases, and any other information prior to public dissemination shall be provided to the COR in draft and final form.

B. TASK AREA B: Assay Development, Clinical and Non-clinical Sample Testing

1) Scope of Task Area B:

The scope of Task Area B includes the design, development, qualification and validation (if needed) of in vitro and in vivo assays as needed for characterization and testing of a vaccine, vaccine component, or other biologic products. This Task Area also includes testing clinical and non-clinical samples provided from internal and external sources.

Note: Designing, reviewing, and performing non-clinical and clinical studies is outside of the scope of this Task Area.

Requirements for Task Area B include:

The Contractor shall:

a. Manage the overall conduct of test/assay assessment and development for vaccines, vaccine components, and other biologic products.

b. Develop a detailed project plan, task-linked budget, and Gantt chart for

NIAID approval prior to initiating any work.

c. Develop, optimize, qualify and, as needed, validate assays for evaluation of animal/human innate and adaptive immune responses to infectious organisms, prophylactics and therapeutics.

d. Prepare documentation for assay development, qualification, validation (if needed) and regulatory submissions.

e. Develop, produce, procure, and characterize assay reagents and required components.

f. Conduct tasks in accordance with quality oversight that is appropriate to the phase of product development; under the appropriate level of biocontainment (BSL-2, BSL-3, BSL-4); and within all applicable and current federal, state, and local laws, codes, ordinances and regulations, as well as all Public Health Service (PHS) Safety and Health provisions.

g. Manage the overall design and conduct of clinical and non-clinical sample testing for vaccines and other biological products.

h. When needed, transfer established assays from other laboratories under a technology transfer agreement. Perform appropriate assay transfer, development, qualification, and as needed, validation of assays.

i. When needed, transfer assays established by the Contractor to an external laboratory. Monitor appropriate assay transfer, development, qualification, and as needed, validation of assays.

j. Conduct receipt and management of samples using an electronic inventory system.

k. Perform analysis of clinical and non-clinical samples, including high-throughput analysis.

l. Submit results from assays performed electronically into a specimen tracking and data management web site designated by the NIAID.

m. Maintain control of the assay, the reagents and the data as appropriate for the level of regulatory compliance as stated in the Task Order(s), including:

i. Reagent change control,

ii. Monitoring and maintenance of system suitability criteria,

iii. Statistical analysis of assay data to ensure assay stability for the length of the study, and

iv. Investigations of assay deviations.

n. Deliver to NIAID or its designee (e.g., a third party, such as the product sponsor) within 30 days of the completion of each Task Order, or after completion of specific activities within the Task Order, as designated by the COR, the following items:

i. Assay protocols, Task Order developed SOPs and Reports.

ii. Development, qualification and validation reports with all related raw data attached as appendices or made available for NIAID review.

iii. Technology transfer packages.

iv. Critical assay reagents and components specific to the assay and required for successful technology transfer.

v. All products resulting from work performed under the contract, such as vaccine, vaccine components, adjuvants, assay components, and associated data.

C. TASK AREA C: Non-clinical Immunogenicity and Efficacy testing

1. Scope of Task Area C:

The scope of activities under Task Area C includes designing and performing IND-enabling immunogenicity and efficacy testing for products using established animal models and supporting assays needed in the conduct of immunogenicity and efficacy studies This scope includes testing performed under FDA and International Council for Harmonisation (ICH) guidelines..

2. Requirements for Task Area C:

The Contractor shall:

a. Manage the overall design and conduct of immunogenicity and efficacy testing for vaccines, vaccine components, and other biologic products.

b. Develop a detailed project plan, task-linked budget, and Gantt chart for NIAID approval prior to initiating any work.

c. Assess and/or design assays, as needed, prior to use in preclinical studies.

d. Perform IND-enabling preclinical immunogenicity evaluation of vaccines.

i. Design preclinical studies to assess the immune response, such as antigen-specific antibody levels, neutralizing antibody levels, and cell mediated immune responses in immunized animals, as well as determining passive transfer protection in non-immunized animals.

ii. Evaluate all required assays to measure the immune response and pathogen specific analyses and perform appropriate qualifications and as needed, validations.

e. Perform preclinical efficacy studies on the product using established animal models and assays. Perform efficacy testing concurrent with, or subsequent to, immunogenicity studies.

f. Conduct tasks in accordance with quality oversight that is appropriate to the phase of product development; under the appropriate level of biocontainment (BSL-2, BSL-3, BSL-4); and within all applicable and current federal, state, and local laws, codes, ordinances and regulations, as well as all PHS Safety and Health provisions. The Contractor shall be responsible for the acquisition, care, and housing of animals in an appropriate level bio-containment facility, and ensuring all work is conducted in accordance with the Animal Welfare Act and Public Health Service Policy on Humane Care and Use of Laboratory Animals ,(https://olaw.nih.gov/policies-laws/phs-policy.htm) including the implementation of an animal care and use program and an animal use protocol approval process.

g. Deliver to NIAID or its designee (e.g., a third party, such as the product sponsor) within 30 days of the completion of each Task Order, or after https://olaw.nih.gov/policies-laws/phs-policy.htm https://olaw.nih.gov/policies-laws/phs-policy.htm https://olaw.nih.gov/policies-laws/phs-policy.htm https://olaw.nih.gov/policies-laws/phs-policy.htm completion of specific activities within the Task Order, as designated by the COR, the following items:

i. all documents and data obtained from efficacy studies;

ii. all non-proprietary animal model data for the purpose of sharing with the scientific community to minimize redundant animal model development efforts and to maximize the use of government and Contractor resources;

iii. all vaccines, vaccine components, products, adjuvants, or other materials remaining from these studies; and

iv. all samples generated in the course of performance of the contract, as specified by the COR.

D.TASK AREA D: Safety and Toxicity Testing including specialty toxicology

1. Scope of Task Area D:

The scope of activities under Task Area D includes designing and performing IND-enabling Good Laboratory Practice (GLP) compliant testing of products as required prior to initiating human clinical trials. The scope also includes preliminary non-GLP studies.

Requirements for Task Area D:

The Contractor shall:

a. Manage the overall design and conduct of safety toxicity testing for vaccines and other biological products.

b. Develop a detailed project plan, task-linked budget, and Gantt chart for NIAID approval prior to initiating any work.

c. Perform IND-enabling preclinical safety and toxicity studies and studies for special populations for vaccines and other products; perform preclinical safety evaluation including but not limited to:

i. Systemic toxicity. Preclinical studies shall include dose-ranging studies of systemic toxicity, as well as toxicity to potential target organs, including hematopoietic and immune systems.

ii. Local site reactivity studies to include detailed clinical observations and histological evaluation of tissue at the injection or application site, or other visible lesions from biopsies or term necropsy samples.

iii. Biodistribution/Integration. In the case of specific products, such as nucleic acid based and some vector-based vaccines, perform studies to determine the biodistribution of the product. If the product persists above threshold levels in a tissue, perform an integration analysis.

iv. Genetic toxicity. In the case of specific products, such as nucleic acid based and some vector-based vaccines, a pivotal GLP preclinical study shall focus on assessment for the potential of the vaccine nucleic acid to recombine with endogenous host DNA sequences and integrate into host chromosomes. Studies designed to address the potential for integration shall use the most sensitive methods available.

v. Tumorigenicity studies. Tumorigenicity studies may be required under certain conditions; for example, if the preclinical genetic testing demonstrates evidence of integration activity and/or broad tissue distribution.

vi. Reproduction toxicity studies. Reproduction toxicity studies shall be performed prior to the use of products in pregnant women. Such studies shall include, for example, fertility, general reproductive performance, teratogenicity and developmental toxicity.

vii. Other studies. Includes other toxicity/safety studies and evaluation of vaccine components, adjuvants, alternate formulations, and delivery systems.

d. Provide all data, information, records, and all other documents required for the writing and submission of Master File, Investigator’s Brochure, and IND submission or for submission to other non-U.S. regulatory authorities to the COR or to a COR-designated third party. Provide information pertaining to the composition, manufacture, and quality control of the product as appropriate for particular investigations carried out under an IND.

e. Conduct tasks in accordance with quality oversight that is appropriate to the phase of product development; under the appropriate level of biocontainment (BSL-2, BSL-3, BSL-4); and within all applicable and current federal, state, and local laws, codes, ordinances and regulations, as well as all PHS Safety and Health provisions. The Contractor shall be responsible for the acquisition, care, and housing of animals in an appropriate level bio-containment facility, and ensuring all work is conducted in accordance with the Animal Welfare Act and Public Health Service Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/phspol.htm), including the implementation of an animal care and use program and an animal use protocol approval process.

f. Deliver to the NIAID COR or its designee (e.g., a third party, such as the product sponsor) within 30 days of the completion of each Task Order, or after completion of specific activities within the Task Order as designated by the COR, the following items:

http://grants.nih.gov/grants/olaw/references/phspol.htm

i. data and documents obtained from safety, biodistribution, and toxicity studies;

ii. all records, samples, and histology/microscopy slides, as indicated under GLP, Animal Rule and cGMP or other applicable regulatory guidelines;

iii. all products, adjuvants or other materials remaining from these studies;

and

iv. all products resulting from work performed under the Task Order, such as vaccine, vaccine components, adjuvant, or assays, including associated data.

[END OF STATEMENT OF WORK FOR CONTRACT]