Attachment 3 - Statement of Work.pdf

ATTACHMENT 2: PARENT CONTRACT STATEMENT OF WORK

Interventional Agents Chemistry Services (IACS)

75N93024R00002

1) 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. These services are provided through Indefinite Delivery, Indefinite Quantity (IDIQ) contracts.

In order to meet the demands for interventional agent product development, NIAID awarded eight

(8) IDIQ contracts (HHSN272201800001I to -8I) in 2018 that provided preclinical product development capabilities in five technical Task Areas including product development planning, medicinal chemistry, manufacturing, non-infected animal studies, and ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity). The purpose of the current solicitation is to continue the medicinal chemistry and manufacturing parts of this valuable NIAID resource with the intent of supporting product development services that will propel new products forward. The other services provided by the 2018 IDIQ contracts are subject of a separate solicitation (Preclinical Safety and Pharmacokinetic Services for Interventional Agents RFP-NIAID-DMID- 75N93024R00003) and those services are not part of this solicitation.

Chemistry underpins all stages of product development by providing the materials required at each stage of development for studies supporting advancement to the next stage of development. The Interventional Agents Chemistry Services resource is intended for case-by-case support of diverse interventional agent product candidates rather than for carrying a single program through multiple stages of the preclinical development pathway. These services are intended to help a large number and variety of investigators to 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.

Investigators work with NIAID program officers to access the services through an online request portal. Through these interactions the program officers develop requirements in conjunction with the investigators that reflect the program development needs at the time. These requirements become the basis of the Statement of Work (SOW) of a Request for Task Order Proposal (RTOP) which is issued as a solicitation to all awardees (the contractor “pool”) of the Task Area to which the RTOP is issued. Contractors in the pool then submit technical and cost proposals against the work in the RTOP and these proposals are evaluated by the responsible NIAID staff. The proposal determined to be the best value to the government is awarded, provided funds are available.

Contractors in the pool are not involved in the development of the requirements, however, they may receive inquiries from the Contracting Officer (CO), in the form of a Request for Information (RFI) in regard to technical capabilities in some cases.

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 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 development support for promising therapeutic candidates that emerge from academia, the private sector, or other sources. The full suite of services, of which the services in this solicitation are a part, will encompass those activities commonly associated with the development of interventional products for infectious disease required for New Drug Application (NDA), Biologic License Applications (BLA) and/or Investigational New Drug (IND) applications. Consequently, NIAID 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, or consultants.

For the purposes of this contract an Interventional Agent is a chemical or biological agent for control of an infectious disease caused by a pathogen or toxin (e.g., botulinum toxin). The provided services shall be directed at the following:

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

• Emerging and re-emerging infectious diseases

• Antimicrobial resistant and multi-drug resistant infections

• Other 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 plus required Task Area A. A contract may be awarded to an organization proposing to fulfill either or both of the technical Task Areas plus Task Area A.

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. A Task Order solicitation for Task Area A is provided and this Task Order will be awarded at the time of parent contract award. Sample Task Order solicitations for Task Areas B and C are provided in the https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens

RFP solely for evaluative purpose and do not represent actual work being solicited at this time. Task Order solicitations for actual work will be issued after award of the Parent Contract.

2) SCOPE

The Interventional Agents Chemistry Services (IACS) program provides a broad and flexible range of chemistry and manufacturing capabilities to support infectious disease programs from the Lead Optimization stage through Preclinical Development, IND submission, and subsequent clinical and nonclinical studies. The IACS Contractors shall assist NIAID staff in providing all support and required documentation needed for preclinical/nonclinical activities related to IND, NDA, or BLA for advanced products. The scope of this solicitation does not include biological studies of any kind, except as they may pertain to production or qualification of product materials delivered under this contract.

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 tasks below. The Contractor 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 and Support Task Areas:

Task Area A – Contract Kick-Off Meeting - REQUIRED Task Area B - Non-GMP Chemistry Task Area C - GMP Manufacturing, Formulation, Fill and Finish

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

Specific activities within the Task Areas will depend on requirements developed by NIAID in conjunction with individual programs as part of an overall product development plan. NIAID will issue a Request for Task Order Proposal (RTOP) after determination of a specific need which will be articulated in a Statement of Work (SOW) included in the RTOP. The Contractor shall develop a response including a technical proposal in which the Contractor 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., Part 58: Good Laboratory Practices (GLP), Parts 210, 211: current Good Manufacturing Practices (GMP) and Electronic Records) may be required for tasks performed under Task Area C concerning GMP Drug Substance (DS) synthesis or Drug Product (DP) manufacturing. No GLP studies will be performed under this contract, however, materials intended for use in GLP studies may be produced under this contract.

This RFP requires the Offeror to respond in the form of a technical proposal to a fictional individual sample Task Order for each technical Task Area to which they are applying. Each sample technical proposal should include a technical approach and specify the methods to be employed in accomplishing the key components of the sample Task Order solicitation.

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 aggregate of Task Areas A, B and C in the SOW. However, the Offeror shall be able to perform all work delineated in each individual Task Area to which the Offeror proposes. All offerors must propose to Task Area A and at least one Task Area from Task Areas B and C. Offerors will only be considered for award in the Task Areas to which the Offeror proposes. Contractors may need to be supported to a certain extent by the expertise and resources of other organizations or persons through consortia agreements, partnerships, subcontracts, or consultants. In such cases, the Contractor shall remain responsible for all work performed, project planning, initiation, implementation, management, and communication. The Contractor is responsible for evaluation, selection, and management of any subcontractors, consultants or partners and for all deliverables specified in this contract and each awarded Task Order.

For the purpose of this solicitation a “meeting” may be virtual, or in-person at NIAID or the Contractor site, unless explicitly stated otherwise.

The following requirements shall apply to each Task Area, with the exception of Task Area A, as part of general administrative, management, and technical support activities that are not Task Order-specific:

PROJECT MANAGEMENT

The Contractor 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 Contractor shall provide a Project Management Plan (PMP) to the Contracting Officer’s Representative (COR) delineating 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

• 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 with regard to progress made and activities accomplished

• Project Reports

• Action Item Tracking

The Contractor 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 Contractor. 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 (SME) or third parties. Draft Individual Study Plans are required to be reviewed by the COR for comment and revision. After receipt of the COR comments, revise the drafts and submit for COR review and acceptance.

The Contractor shall provide Individual Study Reports: For each task order, develop and prepare an Individual Study Report following the completion of each study. Each report should contain chemical schemes, procedures, graphical and tabular characterization data, data tables, data summaries, discussion of results and be audited by the quality assurance unit when GMP is required. Draft Individual Study Reports may be reviewed by COR-designated Subject Matter Experts (SME) or third parties. Draft Individual Study Reports are required to be reviewed by the COR for comment and revision. After receipt of the COR comments, revise the drafts and submit a final version for COR review and acceptance.

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

The Contractor shall provide planning and logistics for all meetings required by the contract. The Contractor 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 Contractor 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, 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 Contractor 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 Contractor shall 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. Chemical schemes should be in Chemdraw Format. The Contractor shall be responsible for maintaining compatibility with software applications used by NIAID. When specific templates are required, they will be developed in consultation with 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 synthesis and material safety data, process development manufacturing reports, GMP manufacturing reports, pre-IND package and meeting documents, IND supporting documentation, and other Government documentation and deliverables.

QUALITY MANAGEMENT

The Contractor shall ensure the quality and regulatory compliance of the materials and documentation generated during execution of Task Orders under this contract. The products will be required to meet stated GMP quality standards in each Task Order, if so specified. The Contractor shall have a quality management plan that includes management responsibilities, resources, training program, oversight of all outsourced operations, and communication processes including timelines.

The Contractor shall establish and maintain control of outsourced activities. A quality system oversight program that ensures GMP compliance for the outsourced activities if supporting a GMP deliverable shall be in place. 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 personnel, production and process controls, facilities, equipment, laboratory controls, training, materials management, packaging and labeling, records and documentation, deviations, Corrective and Preventive Action (CAPA) and Out-of-Specification (OOS). When requested, the Contractor shall provide the draft and final Quality Agreements to the government.

STORAGE AND SHIPPING

The Contractor shall manage the receipt, recording, storage, retrieval, packaging and shipping of products, reagents, and materials, including obtaining appropriate licenses and permits.

The Contractor 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 Contractor 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 by the COR.

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

The Contractor shall perform retrieval, packaging, and shipping of materials to various domestic and international locations as indicated by the COR and requirements of each Task Order. Detailed shipping instructions will be supplied at the time of shipment in conjunction with a specific Task Order. When appropriate, 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 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 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.

4) DESCRIPTIONS OF INDIVIDUAL TASK AREAS

The full Scope of this SOW is divided into technically distinct Task Areas. The Contractor shall perform the Scope and Activities defined in each Task Area to which the Contractor has been awarded. Task Orders on the parent IDIQ contract will be issued for a single Task Area and the requirements of any single Task Order will not exceed the requirements of the Task Area for which it was issued as defined below. CORs and Subject Matter Experts (SMEs) will collaborate with the Contractors in all awarded Task Orders under each Task Area. Technical Requirements for specific tasks will be defined in individual Task Order RTOPs issued to Contractors after award of this IDIQ. The Scope and Activities for each Task Area are:

A. TASK AREA A (required): Contract Kick-Off Meeting

Scope of Task Area A

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

Requirements for Task Area A

1. Planning and participating in the parent contract initiation 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 for the COR for review within three business days of the meeting.

4. Establishing 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.

B. TASK AREA B: Non-GMP Chemistry

Scope of Task Area B

The scope of Task Area B includes activities required for the route optimization, process development, and synthesis of a synthetic intermediate, lead, or preclinical candidate, and may include acquisition or purchase of compounds from a third-party source, such as a commercial vendor. Activities under this Task Area include technology transfer of synthesis schemes and procedures between third party facilities and contractors as specified in each Task Order.

Technical Requirements for Task Area B

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

2. Synthesis and/or purchase of non-GMP grade bulk intermediates, compounds, or therapeutic agents.

3. Synthesis and/or purchase of chemical analogs of a given lead compound or scaffold in singleton or library format in quantities sufficient for biological and biochemical testing.

4. Route optimization, including route design, reaction optimization and production of a demonstration batch, to enable late-stage diversification of a medicinal chemistry route or large scale synthesis of a target compound or therapeutic agent.

5. Compound storage, partitioning and shipping to third-party recipients.

C. TASK AREA C: GMP Manufacturing, Formulation, Fill and Finish

Scope of Task Area C

The scope of Task Area C includes formulation development for clinical or advanced preclinical studies; current Good Manufacturing Practices (cGMP)-compliant synthesis of Drug Substance (DS), cGMP-compliant manufacturing of Drug Product (DP) consistent with relevant FDA guidelines; provision of all required documentation including documentation required for IND filing; product release testing required for human clinical use; and DP stability testing required during clinical trials. The Contractor shall be responsible for directing and ensuring the successful technology transfer of all materials, assays, methods and procedures as required for the successful performance of the activities. The focus of this task area will be for discrete small molecule drugs, including those derived from fermentation. Biological drugs and complex or poorly defined mixtures are excluded.

Technical Requirements for Task Area C

1. Overall management and the conduct of technology transfer and cGMP production activities.

2. Acquire, store, and distribute cGMP material under appropriate conditions.

3. Develop a detailed project plan, budget and Gantt chart in consultation with the COR for the synthesis or manufacture of each designated product prior to undertaking cGMP production.

4. Develop and perform analytical methods to characterize interventional agents in various carriers in support of product characterization, in vivo safety, pharmacokinetic studies and other non-clinical evaluations.

5. Perform product release testing required for clinical use and to provide a Certificate of Analysis.

6. Develop cGMP-compliant synthesis and manufacturing processes and procedures.

7. Manufacture drug product materials in a variety of dosage forms, including, but not limited to, liquid, tablets, capsules, trans-dermal, sterile injection, in compliance with cGMP.

8. Conduct formulation development studies to enhance solubility, stability, and other measurable physical parameters.

9. Perform cGMP-compliant lot release and stability studies to support regulatory submission.

10. Perform fill and finish, package, label, store and ship drug substance and drug products.

11. Establish and maintain an inventory of all lots of materials that have been produced, and store in accordance with regulatory guidelines. Maintain controlled storage of samples at appropriate temperatures, including liquid nitrogen, and with monitoring for equipment failure.

12. Receive, store, ship and inventory products, reagents, records, and any other materials associated with the products, and provide them to the COR or COR designee upon request.

13. Provide all data, information, and records to contribute to the writing and submission of the Chemistry, Manufacturing and Controls (CMC) Information, Master File, and all other documents related to IND or NDA submission or for submission to other non-U.S. regulatory authorities to the COR or to a COR-designated third party.

14. Provide information pertaining to the composition, manufacture, and quality control of the interventional agent as appropriate for particular investigations carried out under an IND.

15. Establish, implement, and oversee product specific stability programs that comply with FDA and/or ICH guidelines for cGMP manufactured drug product materials intended for human use.

16. If activities are subcontracted or outsourced, the Contractor shall conduct routine and “for cause” audits of the subcontractors’ or vendors’ facility(s) required for performance of the contracted work or of the technical capabilities, technical performance or documentation (e.g.

reports, data reports) for the purpose of evaluating compliance with US FDA regulations as well as NIAID and NIH policies and the terms and conditions of the Task Order. The Contractor audit team shall include representatives of the government as determined by the Government and shall request that appropriate staff and all necessary records are available for audits.

17. Monitor compliance with corrective and remedial actions to confirm that appropriate actions have been taken. Provide interim and final audit reports to the COR and the Contracting Officer on implementation of corrective and remedial actions and the resolution of all issues identified during the auditing process. Distribute a copy of final audit reports to the audited organization’s representative. Ensure the confidentiality of this information and prohibit it from being released inappropriately to third parties.

End of Parent Contract Statement of Work