StatementofWork.pdf

RFP NIAID-DMID-NIHAI2010092 ATTACHMENT 3

Statement of Work May 13, 2011 Page 1

ATTACHMENT 3: STATEMENT OF WORK

Evaluation and Testing Services for Vaccines and Other Biologics for Infectious Diseases

RFP-NIAID-DMID-NIHAI2010092

A. 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 of 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. DMID also supports an array of research resources and services to assist investigators, including programs that provide or make available genomic data and technologies; organisms and state-of-the-art reagents; biocontainment facilities; and preclinical and clinical translational research services (http://www3.niaid.nih.gov/research/resources/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, the NIAID requires a coordinated evaluation and testing services program to provide preclinical, nonclinical, and clinical testing support for multiple vaccine and biologic candidates that emerge from academia, the private sector, or other sources. The suite of testing services will encompass those activities commonly associated with the testing of vaccine and biologic products for infectious disease required for Investigational New Drug (IND) application and/or Biologic License Application (BLA). Consequently, DMID recognizes that to obtain the full spectrum of expertise or facilities required to perform all activities set forth in this solicitation, individual organizations will likely need the expertise and resources of other organizations or persons through consortia agreements, partnerships, subcontracts, and/or consultants. The 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.

The purpose of this solicitation is to establish a NIAID resource entitled “Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases” that provides a suite of preclinical, nonclinical, and clinical testing services for vaccines and other biologic products. While the overall suite of testing services is comprehensive, the intent is to provide individual services on a case-by-case basis for a diverse collection of vaccine and biological product candidates, 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 trials), fulfill regulatory requirements, and complete studies needed to http://www3.niaid.nih.gov/research/resources/dmid�

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Statement of Work May 13, 2011 Page 2 apply for an IND and enter Phase I/II/III trials.

DMID anticipates awarding a single Indefinite Delivery/Indefinite Quantity (ID/IQ) contract that provides a guaranteed minimum award to the organization or consortium that best meets the overall qualifications needed to fulfill the technical requirements of this solicitation. Sample Task Orders are provided in the RFP solely to evaluate offeror responses and capabilities. Task Orders for specific tasks will be issued after award of the Basic Contract.

B. SCOPE AND TASK AREA ACTIVITIES

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 tasks below. The Contractor shall be prepared to develop a response to individual Task Orders as they are assigned and to specify the methods it will employ in accomplishing the key components of each Task Order.

The Contractor shall provide DMID with a broad and flexible range of proactive and developmentally-oriented capabilities to provide testing services to support preclinical, nonclinical, and clinical studies for promising products when such products emerge from investigator-initiated research studies or other sources identified by DMID Program staff.

These testing capabilities support early feasibility through Phase III clinical studies to 1) provide the ability to combine, develop, test, evaluate and refine different evaluation and testing technologies from multiple developers; 2) create capacity for the evaluation and testing of candidate vaccines and other biologics for infectious diseases and/or related toxins; 3) increase the Federal Government’s response to emerging disease threats; and 4) improve surge capabilities. The Contractor shall also provide appropriate documentation and support for pre-IND, IND, and BLA submissions.

Specific Task Orders will depend on the status of the candidate(s) as part of an overall product development plan and/or regulatory submission plan to the FDA. DMID will issue a Task Order Request for Proposal after determination of a specific need that is appropriate to the Statement of Work. The Contractor shall be prepared to develop a response in which the Contractor specifies the methods it will employ in accomplishing the key components of each Task Order and the associated costs. The needs, funding, product maturity and timelines of the product as specified in the Task Order establishes requirements for compliance with current Good Laboratory Practices (GLP) and current Good Manufacturing Practices (cGMP) [21 CFR Parts -11, -58, -210, -211, -600].

For the purposes of this contract, the following definitions shall apply:

• Vaccine – An antigenic preparation used to render an organism immune to an infectious disease by inducing or increasing immunity for prophylaxis and/or therapy.

Vaccine products include but are not limited to synthetic peptides, recombinant proteins, nucleic acids, viral-like particles, vector-based vaccines, as well as live, modified, killed, and/or attenuated bacteria, viruses, and other organisms.

• Vaccine Component – An antigen-enhancing substance (i.e. adjuvant) or a delivery system (i.e. needle free dermal patch) that is used during dose administration to enhance the immune response of a vaccine.

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• Other Biologic – Therapeutic preparation made from living organisms or the components of living organisms and are most likely regulated by the Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER). Biologics include but are not limited to allergenics; antitoxins; blood and blood products; and cellular and gene therapy products. For the purposes of this contract, challenge material for non-clinical, preclinical, and clinical trials will also be included in the definition of biologics.

The services shall be directed at the following:

• diseases caused by pathogens and toxins on the National Institute of Allergy and Infectious Diseases (NIAID) Category A, B, and C Priority Pathogens list ( http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/ Pages/CatA.aspx)

• emerging and re-emerging infectious diseases;

• antimicrobial resistant and multi-drug resistant infections;

• other bacterial infections;

• fungal infections;

• viral infections excluding HIV; and

• parasitic diseases.

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 five Task Areas. Task Orders may address one Task Area or multiple Task Areas. Technical Requirements will be defined in the individual Task Orders. The Scope and Activities for Task Orders awarded under this ID/IQ contract include the following:

TASK AREA 1: ADMINISTRATIVE, MANAGEMENT, AND TECHNICAL SUPPORT

ACTIVITIES

It is estimated that one Task Order will be assigned under this Task Area.

The Task Order will be a cost-reimbursement, term (level of effort) with a Base Period of 12 months and multiple Options to extend the Base Period of Performance in 12-month increments up to a total of 10 years to continue the same requirement.

1. Scope of Task Area 1:

The scope of Task Area 1 includes the below described functions performed by the Contractor as part of the general administrative, management, and technical support activities that are not Task Order-specific.

2. Activities for Task Area 1:

a. Ad Hoc, Annual and Technical Advisory Meetings – Organize and convene meetings of the principal investigators and key personnel of Task Orders and/or Contractor worksites and organize teleconferences and meetings as requested by the COTR.

b. Training and Workshops – Provide training and/or exchange of information to government staff and/or Program-designated third parties via workshops or http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx� http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx�

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Statement of Work May 13, 2011 Page 4 other venues for preclinical planning, Good Manufacturing Practices (GMP), product characterization and other activities that support vaccine and biologic product development.

c. Ad Hoc Reporting and Requests for Information- Prepare and submit ad hoc reports throughout the performance period of the Task Order. Examples of ad hoc reports include a compiled final audit report, project planning reports for active Task Orders, and summary reports of manufacturing activities and costs across all Task Orders.

TASK AREA 2: ASSAY DEVELOPMENT

1. Scope of Task Area 2:

The scope of Task Area 2 includes the design, development, qualification and validation of in vitro and in vivo assays as needed for characterization and testing of a vaccine, vaccine component, or other biologic. Other activities under this task area include method assessment/feasibility studies, method comparability studies, redevelopment or improvement of existing assays, and technology transfer of assays to/from other facilities.

The Contractor shall 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.

2. Activities for Task Area 2:

a) Manage 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, qualify and validate analytical methods for evaluation of the product, product potency, lot release, in vivo safety, immunogenicity, efficacy, and other preclinical, nonclinical, and clinical evaluations in compliance with applicable GLP and cGMP regulations.

d) Develop, qualify and validate assays for evaluation of animal/human innate and adaptive immune responses to infectious organisms, prophylactics and therapeutics.

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e) Prepare documentation for assay development, qualification, validation and regulatory submissions.

f) Develop, produce, procure, and characterize assay reagents and required components.

g) Deliver to the Government or its designee (Agency COTR or third party such as the product sponsor) within a mutually agreed upon period prior to the completion of each Task Order, or after completion of specific activities within the Task Order, the following items:

i. Assay protocols, 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 of the contract such as vaccine, vaccine components, adjuvants, assay components, and associated data.

TASK AREA 3: IMMUNOGENICITY AND EFFICACY TESTING

1. Scope of Task Area 3:

The scope of activities under Task Area 3 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 trials. This scope includes testing performed under FDA and ICH guidelines for Animal Rule.

The decision regarding which animal species to be used and any requirements for specific pathogen free (SPF) animals shall be made jointly by the COTR and the Contractor, with the COTR having final authority. The decision whether these studies will be performed in compliance with GLP (21 CFR 58) will be determined by the COTR and identified in the Task Order.

The Contractor shall 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

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2. Activities for Task Area 3:

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 assays 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 and perform appropriate qualifications and validations.

iii. Conduct testing consistent with relevant FDA guidelines.

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. Deliver to the Government or its designee (Agency COTR or third party such as the product sponsor) within a mutually agreed upon period prior to the completion of each Task Order, or after completion of specific activities within the Task Order, 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 use of government and contractor resources;

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

iv. all products of the contract, such as vaccine, vaccine components, adjuvant, or assays, including associated data.

TASK AREA 4: CLINICAL AND NONCLINICAL SAMPLE TESTING

1. Scope of Task Area 4:

The scope of activities under Task Area 4 includes testing clinical and non-clinical samples provided from internal and external sources to support

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Statement of Work May 13, 2011 Page 7 these studies. This scope includes providing reagent control, assay control, assay monitoring, and statistical review to support the conduct of the analysis. (Note: Designing, reviewing, and performing non-clinical and clinical studies is outside of the scope of this task area.)

The Contractor shall 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.

3. Activities for Task Area 4:

a. Manage the overall design and conduct of Clinical and Nonclinical Sample

Testing for vaccines and other biological products.

c. Assess assays prior to use in these studies.

d. When needed, establish assays developed by other laboratories under a technology transfer agreement.

e. Perform appropriate assay transfer, development, qualification, and validation of assays

f. Perform analysis of clinical and nonclinical samples, including high throughput analysis.

g. 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.

h. Deliver to the Government or its designee (Agency COTR or third party such as the product sponsor) within a mutually agreed upon period prior to the completion of each Task Order, or after completion of specific activities within the Task Order, the following items:

i. all documents and sample data obtained from the assay(s);

ii. all raw data or access to all raw data on the study site as required by the

Task Order(s);

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iii. all non-proprietary assay data for the purpose of sharing with the scientific community to minimize redundant efforts and to maximize use of Government and Contractor resources;

iv. all reagents, samples, products, or other materials remaining from these studies; and

v. all products from a Task Order such as assay SOPs, including associated data.

TASK AREA 5: SAFETY AND TOXICITY TESTING

1. Scope of Task Area 5:

The scope of activities under Task Area 5 includes designing and performing IND-enabling Good Laboratory Practice (GLP) compliant testing of products as required prior to initiating human clinical trials. This scope includes testing of candidate products for safety and toxicity by in vitro tests, small animals studies, and studies in non-human primates as required by the FDA. This scope also includes any additional testing required by the FDA which may include biodistribution studies and reproductive toxicology studies. These studies shall be performed in accordance with GLP regulations (21 CFR 58).

The Contractor shall 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

2. Activities for Task Area 5:

a. Manage the overall design and conduct of Safety Toxicity Testing for vaccines and other biological products.

c. Perform IND-enabling preclinical safety and toxicity studies. For vaccines and other products, perform preclinical safety evaluation including:

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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 DNA and some vector-borne 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 DNA and vector-borne vaccines, a pivotal GLP preclinical study shall focus on assessment for the potential of the nucleic acid vaccine 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, and records required for the writing and submission of Master File, Investigator’s Brochure, and all other documents related to IND submission or for submission to other non- U.S. regulatory authorities to the COTR or to a COTR-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. Deliver to the Government or its designee (Agency COTR or third party such as the product sponsor) within a mutually agreed upon period prior to the completion of each Task Order, or after completion of specific activities within the Task Order, the following items:

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

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ii. all records, samples, and histology/microscopy slides, as indicated under GLP and current Good Manufacturing Practice (cGMP) guidelines

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

iv. all products of the Task Order, such as vaccine, vaccine components, adjuvant, or assays, including associated data.

[END OF STATEMENT OF WORK FOR BASIC CONTRACT]