Attachment 3 - Statement of Work.pdf

ATTACHMENT 2: PARENT CONTRACT STATEMENT OF WORK (SOW)

INTERVENTIONAL AGENTS SAFETY AND PHARMACOKINETIC SERVICES (IASPS)

75N93024R00003

BACKGROUND AND INTRODUCTION

The National Institute of Allergy and Infectious Diseases (NIAID), an Institute of the 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. Within this remit, the NIAID Division of Microbiology and Infectious Diseases (DMID) supports extramural research for the investigation, control, and prevention of infectious diseases. DMID support for basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics is provided through research grants and contracts. DMID also provides 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. This solicitation concerns safety and pharmacokinetics services support provided as preclinical services.

To meet the demands for interventional agent product development, NIAID awarded eight (8) contracts in 2018 that provided preclinical product development capabilities in five technical Task Areas using the Indefinite Delivery, Indefinite Quantity (IDIQ) contract mechanism (Contracts HHSN272201800001I to - 8I). The purpose of the current solicitation is to ensure the product development planning, safety, toxicology, and pharmacokinetics activities of this valuable NIAID resource continue to be offered with the intent of supporting product development services that will propel new products forward. The preclinical development resource is intended to be applied on a case-by-case basis for diverse interventional agent product candidates rather than to carry a single product candidate through the entire preclinical development pathway. These services are intended to help a wide variety of investigators in several scientific areas obtain critical data needed to attract additional funding, gain prospective partnerships (either for further development or to support clinical trials), fulfill regulatory requirements, and complete necessary studies to satisfy regulatory requirements.

The development and introduction of new therapeutic products against potential agents of bioterrorism, drug-resistant pathogens, emerging and re-emerging infectious diseases, as well as infectious diseases prevalent in resource-limited countries remains a high public health priority. To assist in filling these public health gaps, the NIAID requires a nontraditional, proactive, and product development-oriented program to provide preclinical and non-clinical development support for promising therapeutic candidates that emerge from academia, the private sector, or other sources. The suite of services will encompass those activities commonly associated with the development of interventional products for infectious disease required for New Drug Applications (NDA), Biologic License Applications (BLA), and/or Investigational New Drug (IND) applications.

For the purposes of this contract, an Interventional Agent is a chemical or biological agent for control of diseases caused by pathogens or toxins. The provided services shall be directed at the following:

• Diseases caused by pathogens and toxins on the National Institute of Allergy and Infectious Diseases (NIAID) Emerging Infectious Diseases/Pathogens list (https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens) https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens

• Emerging and re-emerging infectious diseases

• Antimicrobial-resistant and multi-drug-resistant infections

• Bacterial infections

• Fungal infections

• Viral infections

• Parasitic diseases

NIAID anticipates awarding multiple Indefinite Delivery, Indefinite Quantity (IDIQ) contracts to organizations that demonstrate capability to fulfill the technical requirements of at least one (1) of the technical Task Areas listed below (Section 3) plus required Task Area F. A contract may be awarded to an organization proposing to fulfill any number or combination of the technical Task Areas plus Task Area F.

The Government anticipates making awards to those organizations with the best qualifications in each Task Area. Subpar evaluation in one technical Task Area will not exclude the organization from or negatively impact consideration for award in another Task Area. Organizations will be considered for contracts only in the Task Area(s) they include in the 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 after the award of the Parent Contract.

SCOPE

The Interventional Agents Safety and Pharmacokinetic Services (IASPS) program provides for preclinical/nonclinical services and activities required for the development of interventional products for infectious disease including IND, NDA, or BLA for advanced products. The scope of this solicitation does not include animal efficacy studies involving infectious particles or pathogens.

GENERAL TASK ORDER REQUIREMENTS

Independently, and not as an agent of the Government, the Offeror 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 Offeror shall be prepared to develop a response to individual Task Orders or activities under the Task Area as they are assigned and to specify the methods it will employ in accomplishing the key components of each Task Order.

The Technical Requirements have been assembled into the following Task Areas:

Technical Task Areas:

Task Area A - Product Development Planning and Education Task Area B - Non-GLP in vitro Preclinical Safety Studies Task Area C - Non-GLP in vivo Preclinical Microbiological, Safety, Toxicology, and Pharmacokinetic Services Task Area D - GLP Preclinical Microbiological, Safety, Toxicology, and Pharmacokinetics (PK) Services Task Area E – Commercial Off-the-Shelf Screening for Absorption, Distribution, Metabolism, and Excretion (ADME), Safety, and Pharmacokinetics (PK) Task Area F- Contract Kick-Off Meeting - REQUIRED

All offerors must propose Task Area F, and at least one Task Area from Task Areas A-E.

NIAID recognizes that a single organization or institution may not have the full spectrum of expertise or facilities required to perform all activities set forth in the Statement of Work. Offerors may need to be supported to a certain extent by the expertise and resources of other organizations or persons through subcontracts, partnership or consortia agreements, and/or use of consultants. However, Offerors 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.

NIAID will issue a Request for Task Order Proposal (RTOP) after the determination of a specific need which will be articulated in a Statement of Work (SOW) included in the RTOP. Specific activities within the Task Areas will depend on requirements developed by NIAID in conjunction with the status of the individual interventional agents as part of an overall product development plan. The Offer shall develop a response including a technical proposal in which the Offer specifies the scientific approach and methods it will employ to accomplish the key components of the RTOP and a business proposal detailing the associated costs or pricing structure as appropriate to the Task Order type. Compliance with applicable parts of 21 CFR (e.g. Good Laboratory Practices, and Electronic Records) may be required as determined by needs, funding, product maturity, and timelines of the product as specified in the Task Order.

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

Therapeutic - A drug (synthetic or natural product) or a biotechnology product (e.g., monoclonal antibody) intended for use in the cure, mitigation, or treatment of disease.

The following requirements shall apply to each Task Area, except for Task Area F, as part of general administrative, management, and technical support activities that are not Task Order specific:

PROJECT MANAGEMENT

The Offeror shall designate a Principal Investigator who will 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.

The Offeror shall provide a Project Management Plan (PMP) to the Contracting Officer’s Representative (COR) delineating the proposed project management of all proposed tasks including:

• Project Management

• Project Organization

• Roles and Responsibilities and Staffing Plan

• Project Deliverable Tracking

• Subcontract Management (if applicable)

• Communication Approach

• Risk Management Approach

• Quality Management Approach

• Technical Approach and protocols

• Project Monitoring and Control

• Schedule including Gantt chart(s)

• Budget: task-linked budgets that separate costs for each milestone to facilitate tracking and reporting costs about progress made and activities accomplished

• Project Reports

• Action Item Tracking

The Offeror shall provide Individual Study Plans: For each task order, develop an Individual Study Plan describing in detail the technical plan for how the Task Order requirement will be achieved by the Offeror.

Task Orders with multiple objectives may require more than one Individual Study Plan. Draft Individual Study Plans may be reviewed by COR-designated Subject Matter Experts (SMEs) or third parties. Draft Individual Study Plans are required to be reviewed by the COR for comments and revision. After receipt of the COR comments, revise the drafts and submit them for COR review and acceptance.

The Offeror shall provide a Draft and Final Study Report: develop and prepare draft and final study reports following the completion of each study. Each should contain data tables, and data summaries, and be audited by the quality assurance unit when GLP is required. Draft Individual Study Reports may be reviewed by COR-designated SMEs or third parties. Draft Individual Study Reports are required to be reviewed by the COR for comments and revision. After receipt of the COR comments, revise the drafts and submit a final version for COR review and acceptance.

The Offeror shall provide ad hoc reports as requested by the COR throughout the performance period of each Task Order. Examples of ad hoc reports include a compiled final audit report, project planning reports, summary reports of activities and costs, interim study reports or a complete list of accurate and updated information on subcontract activities.

The Offeror shall develop, monitor, and modify the timelines, tasks, budgets, objectives, and milestones as discussed with the COR and CO before and during the performance of activities under each Task Order.

The Offeror shall provide planning and logistics for all meetings required by the contract. The Offeror shall prepare and distribute meeting agendas and background materials in advance of each meeting, conduct the meeting and record detailed and technically literate notes of the meeting, and provide meeting minutes to include summaries of all discussions, decisions and action items. Each Task Order RTOP will designate the required delivery schedule for meeting agendas and minutes

The Offeror shall organize and participate in a contract initiation meeting and participate in an annual contract review meeting. These meetings shall be attended by the Principal Investigator and other relevant key Contractor technical and business staff, the COR and COR designees, and the Contracting Officer (CO) and CO designees.

The Offeror shall organize and participate in Progress Review Meetings, to be attended by Contractor key personnel, to include business representatives as needed, (including subcontractor personnel as appropriate), the COR, the designated Subject Matter Experts (SMEs), the Contracting Officer, as necessary, and the investigator representatives, as necessary, at regular intervals or ad-hoc as designated in each Task Order RTOP. The purpose of these meetings is to review and discuss planned activities, emerging or ongoing issues, technical progress, financial progress, and contracting issues.

The Offeror shall organize and participate in ad hoc meetings including key personnel and the COR within three days of a meeting request made by the COR or CO.

The Offeror shall establish reliable electronic communication links with NIAID for sharing word processing, data files, and product timelines in a format that is compatible with the 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. Document types may include preliminary candidate information documents such as draft project plans, project timelines, Gantt charts, reports, publications, abstracts, protocols, audit reports, meeting agendas, meeting minutes, SOPs, preclinical studies, and safety data, process development, GLP reports, pre-IND package and meeting documents, Toxicology Safety Data, IND supporting documentation, and other Government documentation and deliverables.

QUALITY MANAGEMENT

The Offeror shall ensure the quality and regulatory compliance of the services, materials, and documentation generated per this SOW. The products will be required to meet stated quality standards specified in each Task Order. The Offeror shall have a quality management plan that includes management responsibilities, resources, training program, oversight of all outsourced operations, and communication processes including timelines.

The Offeror shall establish and maintain control of outsourced activities. A quality system oversight program that ensures stage-specific GLP compliance for the outsourced activities if supporting a GLP deliverable. The quality system oversight program must include establishing a Quality Agreement with any subcontractor that clearly delineates the responsibilities of both the Contractor and the subcontractor and describes communication processes including timelines. The Quality Agreement must cover personnel, production and process controls, facilities, equipment, laboratory controls, training, materials management, packaging and labeling, records and documentation, deviations, Corrective and Preventative Action (CAPA) and Out of Specification (OOS). When requested, the Contractor shall provide the draft and/or final Quality Agreements to the government.

STORAGE AND SHIPPING

The Offeror shall provide the overall management and conduct of the receipt, storage, retrieval, packaging, and shipping of products, materials, and specimens, including obtaining appropriate licenses and permits.

The Offeror shall 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 +/-5°C, 2-8°C, and room temperature.

The Offeror shall ensure the conditions in all controlled temperature chambers shall be monitored and documented as appropriate for the level of regulatory compliance required by the Task Order. Specific procedures should be proposed by the Contractor and will be reviewed/approved by COR.

The Offeror shall ensure temperature chambers shall be qualified or validated as proposed by the Contractor and reviewed/approved by the COR.

The Offeror shall perform retrieval, packaging, and shipping of materials to various domestic and international locations. Detailed shipping instructions will be supplied.at he time of a needed shipment.

When requested, a documented shipping procedure compatible with GMP 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.

TRANSITION

The Offeror 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 each Task Order. The Contractor shall deliver to the Government or its designee all data obtained from all work, all products remaining from the work, any critical reagents, test results, references, or materials developed under each Task Order, and all files pertaining to each Task Order.

DESCRIPTION OF INDIVIDUAL TASK AREAS

Refer to the Sample Task Orders under each Task Area under Attachments 2 – 6. Refer to only those Task Area requirements for which an offeror will be proposing.

The Offeror shall perform the Scope and Activities defined in each of the following Task Areas to which they are applying and receive an award. Agency CORs and Subject Matter Experts (SMEs) will participate in all awarded Task Orders under each Task Area. Technical Requirements will be defined in the individual Task Order RTOP.

A. Task Area A: Product Development Planning and Education

Scope of Task Area A

Task Area A supports products by review, evaluation, or development of Product Development Plans (PDP) or their individual components, with respect to feasibility of design, development, manufacture, assay development, stability, preparation for clinical trials to include required documents, materials, and data for IND. This Task Area also supports conducting, reviewing, and evaluating technical feasibility or regulatory compliance of planned preclinical or nonclinical studies. Task Area A supports the development of Section 508-compliant educational materials including white papers, technical reviews, technical guidance documents, classes, and workshops.

Technical Requirements for Task Area A

1. Conduct an evaluation of and prepare a report regarding the current status and overall scientific feasibility of a project as determined by: 1) product development history including all current scientific documents related to the project, laboratory notebooks, publications, and any ancillary documentation, plus all regulatory documentation; and 2) the manufacturing feasibility and traceability of all project reagents and substances.

2. Develop and/or update Preclinical or Product Development Plans (PDP) for candidate products in collaboration with the Product Investigator and COR. Plans shall include regulatory, preclinical, clinical, nonclinical, and manufacturing activities to be undertaken for a product and an estimated budget. Anticipated minimum timelines for the completion of tasks related to the activity shall be provided via the use of Gantt charts or other appropriate project management tools.

3. Develop Individual Study Plans for designated therapeutics and related studies needed to achieve desired outcomes for the product.

4. Develop informational reports for COR-designated services, products, processes, and/or technologies using a literature review of scientific and industry publications. Utilize public databases for identifying and comparing potential products and prepare reports of product characteristics that can be used to identify and support the selection and prioritization of candidate therapeutic or diagnostic products.

5. Plan and provide for the training and/or the exchange of information pertaining to product development, including GMP, GLP, preclinical services, process development, and/or activities supporting the development of interventional agents to Government staff and/or COR-designated third parties via workshops.

B. Task Area B: Non-GLP in vitro Preclinical Safety Studies

Scope of Task Area B

The scope of this Task Area is to test candidate interventional agents in in vitro preclinical microbiological and safety studies.

Technical Requirements

1. Perform in vitro microbiological assays to determine the candidates with properties considered most amenable to drug development and to determine safety and metabolism in in vitro systems, e.g., metabolic, and permeability assays.

2. Develop methods and perform analytical tests to characterize interventional agents in various carriers in support of in vitro studies.

3. Perform in vitro Preclinical Studies, including:

a. Biotransformation assays

b. Cytotoxicity of compounds for actively dividing mammalian cells

c. All other in vitro safety and pharmacology assays and studies that may be required for a particular interventional agent

C. Task Area C: Non-GLP in vivo Preclinical Microbiological, Safety, Toxicology, and Pharmacokinetic Services

Scope of Task Area C

The scope of this Task Area is to perform preclinical safety, toxicity, and pharmacokinetic studies of interventional agent candidates in relevant small and large animal models. This activity includes all such non-GLP in vivo tests that are needed for drug development, toward the IND. The Contractor is responsible for the acquisition, housing, and care of animals, and must provide access to an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited (or equivalent) animal facility and the capacity (appropriate cage space, etc.) as required to fulfill the required services.

1. Overall management and the conduct of technology transfer activities where appropriate.

2. Prepare drug dosage forms for various routes of delivery (i.e., oral, IV, IP) to be used in the in vivo studies.

3. Develop methods and perform analytical tests to characterize interventional agents in various carriers in support of in vivo safety, pharmacokinetic studies, and other preclinical evaluations.

4. Perform in vivo preclinical safety, toxicology, and pharmacokinetics studies, including:

a. Determination of maximum tolerated dose and no observed adverse effect levels (NOAEL)

b. Customizable PK-Determination of relevant pharmacokinetic parameters: either, more than a single compound, and/or more than two dosages (either dose amount or route of delivery) for small animals; or at least a single dosage, in higher species

c. Single and repeated dose toxicity studies

d. Toxicokinetic parameters

e. Bioavailability studies

f. Behavioral pharmacology (e.g., functional observational battery, locomotor activity, convulsant activity, gastrointestinal motilities-time potentiation, etc.

g. All other safety and pharmacology studies that may be required for a particular interventional agent candidate

5. Provide all data, information, and records to contribute to the writing and submission of the relevant sections of the Investigator’s Brochure, and all other documents related to IND submission, or FDA submission, such as SEND data, when requested, by the COR. Retain all records, samples, and histology/microscopy slides.

D. Task Area D: GLP Preclinical Microbiological, Safety, Toxicology, and Pharmacokinetic Services

Scope of Task Area D

The scope of this Task Area is to perform preclinical safety, toxicity, and pharmacokinetic studies of interventional agent candidates against in vitro, or relevant small and large animal models. This activity includes all such tests that are required to support clinical use in humans. Testing must be sufficient to meet requirements for IND/NDA/BLA filing and shall be performed under Good Laboratory Practice (GLP requirements (21 CFR 58). The Contractor is responsible for the acquisition, housing, and care of animals, and must provide access to an AAALAC-accredited (or equivalent) animal facility and the capacity (appropriate cage space, etc.) as required to fulfill the required services.

1. Overall management and the conduct of technology transfer activities where appropriate.

2. Prepare drug dosage forms for various routes of delivery (i.e., oral, IV, IP) to be used for the in vivo studies.

3. Determination of relevant pharmacokinetic parameters: Develop methods and perform analytical tests to characterize interventional agents in various carriers in support of in vivo safety, pharmacokinetic studies, and other preclinical evaluations.

4. Perform preclinical microbiological, safety, preclinical, and toxicity studies.

5. Perform in vitro microbiological assays to determine the candidates with properties considered most amenable to drug development and to determine safety and metabolism in in vitro systems, e.g., AMES, metabolic, and permeability assays; tissue cross reactivity, TCR.

6. Perform 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.

7. Perform in vitro and in vivo preclinical Safety, toxicology, and pharmacokinetics studies, including:

a. Determination of maximum tolerated dose and NOAEL

b. Determination of acute and subchronic toxicity

c. Single and repeated dose toxicity studies

d. Toxicokinetic parameters

e. Bioavailability studies

f. Absorption, distribution, metabolism, and excretion studies

g. Genotoxicity testing

h. Carcinogenicity testing if relevant for a therapeutic candidate

i. Reproductive toxicity studies

j. Biotransformation assays conducted in vitro

k. Cytotoxicity of compounds for actively dividing mammalian cells (e.g., IC50)

l. Immunotoxicity studies to determine the toxicity of candidate compounds to the immune system, or other specialized target organ systems

m. Behavioral pharmacology (e.g., functional observational battery, locomotor activity, convulsant activity, gastrointestinal motility, sleep-time potentiation, etc.

n. All other safety and pharmacology assays and studies that may be required for a particular interventional agent candidate

8. Retain all records, samples, and histology/microscopy slides, as indicated under GLP guidelines.

9. The Contractor shall permit routine and “for cause” audits of their own facilities required for the performance of the contracted work, or of its technical capabilities, technical performance, or documentation to evaluate compliance with domestic and non-domestic laws and regulations for GLP guidance as per US FDA regulations and guidance and NIAID policies, and the terms and conditions of the Task Order and Parent Contract. The audit team will be determined by the government and the Contractor shall make available appropriate staff and all necessary records for audits.

10. The Contractor shall conduct routine and “for cause” audits of the subcontractors’ or vendors’ facility(s) required for the performance of the contracted work, or of the technical capabilities, technical performance, or documentation to evaluate compliance with domestic and non-domestic laws and regulations for GLP guidance as per US FDA regulations and guidance and NIAID policies, and the terms and conditions of the Task Order and Parent Contract. The Contractor audit team shall include representatives of the government as determined by the government and the Contractor shall ensure availability of all appropriate Contractor and Subcontractor staff and all necessary records for audits.

11. Monitor compliance with corrective and remedial actions to confirm that appropriate actions have been taken. Provide interim and final prime and subcontractor audit reports to the COR and the Contracting Officer on the implementation of corrective and remedial actions and the resolution of all issues identified during the auditing process. Distribute a copy of the final audit reports to the audited organization’s representative and NIAID. Ensure the confidentiality of this information and prohibit it from being released inappropriately to third parties. Submit to other non-U.S. regulatory authorities to the COR or a COR- designated third party as required.

12. Provide all data, information, and records to contribute to the writing and submission of the relevant sections of the Investigator’s Brochure, and all other documents related to IND, or needed for submission to FDA or other non-U.S. regulatory authorities to the COR or a COR- designated third party.

E. TASK AREA E: Commercial Off-the-Shelf Screening for Absorption, Distribution, Metabolism, and Excretion (ADME), Safety, and Pharmacokinetics (PK)

Scope of Task Area E

Task Area E provides non-GLP in vitro and in vivo screening style assays for Adsorption, Distribution, Metabolism, and Excretion (ADME), Safety, and Pharmacokinetics (PK) in a fixed format requiring minimal customization or protocol development. The scope of Task Area E animal studies includes small animal PK and tolerability studies using traditional routes of administration and standard timepoints and bioanalysis. Task Area E does not include the following: (1) Good Laboratory Practice (GLP) studies of any kind; (2) Non-GLP animal studies requiring protocol development, customization, large animals or non-traditional species, non-traditional routes of administration, extended observation or data collection periods, or multiple dosing per animal.

1. Provide standardized, non-GLP screening assays with some limited flexibility in protocol customization to provide rapid turn-around and efficient use of limited compound supply.

2. Rapidly develop bioanalytical Liquid Chromatography (LC) - Mass Spectrometry (MS)/MS assays for a wide variety of chemotypes expected from the submitted compounds using standard HPLC columns and generic gradients and mass spec conditions to provide compound detection in sample matrices appropriate for the in vitro and PK assays.

3. Assess compound physical properties and ADME and safety profiles using standard industry-wide in vitro screening assays.

4. Perform screening assays for PK properties in rodents or other small animals to assess plasma (and limited tissue) drug concentrations using industry-standard routes of administration (Intravenous (IV), Oral (PO), Intraperitoneal (IP), and Subcutaneous (SC)) and provide a summary of results.

5. Perform tolerability in rodents or other small animals using industry-standard routes of administration (IV, PO, IP, SC). Report the observed Maximum Tolerated Dose (MTD), acute toxic symptoms, autonomic effects, clinical signs, or mortality observed up to 72 hours post-test article administration.

F. Task Area F (REQUIRED): Contract Kick-Off Meeting

Scope of Task Area F

The Contractor shall plan and participate in the contract kick-off meeting.

Requirements

1. Plan and participate in the parent contract kick-off meeting.

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

3. Record minutes and provide the minutes to the COR for review within three business days of the meeting.

4. Establish reliable electronic communication links with NIAID for sharing text and 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 or provided by the COR.

End of Statement of Work