JnA_and_Attachments_1-4_Redacted.pdf

(INDs), New Drug Applications (NDAs), and Biologic License Applications (BLAs); and (2) first-in-human studies in limited circumstances.

Therapeutic clinical candidates that reach this stage should be attractive to biotechnology and pharmaceutical companies to take into clinical development.

A critical step towards that goal is conducting safety evaluations on candidate therapeutics through toxicology studies. Contractors conduct these toxicology studies on candidate therapeutic compounds for NCATS and DPI under these four awarded IDIQ contracts. Through the issuance of task orders under the IDIQ contracts, these contractors perform essential in-vitro and in-vivo IND/NDA/BLA-enabling safety studies for small and large molecules. In addition, in-vitro tests and in-vivo exploratory studies are carried out to aid therapeutic target evaluation, lead optimization, and compound selection processes on a case-by-case basis. The overall goal is to bring new drugs to market faster that are safe, effective treatments for patients.

Beginning in 2010, DPI obtained these services through a contract between the National Cancer Institute (NCI) and contractor . In 2016, DPI planned new contracts within NCATS to meet these needs, resulting in the following four (4) multiple award IDIQ contracts awarded under Solicitation No. N01TR-17-2002:

Contract Number HHSN271201700014I Contractor Name: SRI International (SRI) Ordering Period: April 21, 2017 to April 20, 2022 Contract Minimum: $6,500 Contract Maximum: $19,961,960

Contract Number HHSN271201700015I Contractor Name: Battelle Memorial Institute (Battelle) Ordering Period: April 21, 2017 to April 20, 2022 Contract Minimum: $6,500 Contract Maximum: $19,961,960

Contract Number HHSN271201700016I Contractor Name: IIT Research Institute (IITRI) Ordering Period: April 21, 2017 to April 20, 2022 Contract Minimum: $6,500 Contract Maximum: $19,961,960

Contract Number HHSN271201700017I Contractor Name: Lovelace Biomedical & Environmental Research Institute (LBERI) Ordering Period: April 21, 2017 to April 20, 2022 Contract Minimum: $6,500 Contract Maximum: $19,961,960

To date, the total dollar amount obligated across all four (4) contracts is $16,644,658 under the following task orders:

Task Order No. 75N95019F00089 / HHSN271201700014I Contractor Name: SRI Title: “Non-Clinical Safety Assessment of VK4-116 to Support Human Patients Afflicted with Severe Pain Disorders” Period of Performance: 08/01/2019 to 07/31/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100001 / HHSN271201700015I Contractor Name: Battelle Title: “Non-Clinical Safety Assessment of CTI-1601 to Support ATAXIA Indication” Period of Performance: 09/30/2017 to 03/31/2019 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100002 / HHSN271201700015I Contractor Name: Battelle Title: “Single I/V, 13-Hour Infusion, Cardiovascular and Pulmonary Safety Pharmacology Study of HBN-1 in Telemetered Gottingen Minipigs using Latin-Square Cross Over Design” Period of Performance: 07/01/2018 to 08/15/2019 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. 75N95019F00088 / HHSN271201700015I Contractor Name: Battelle Title: “Non-Clinical Safety Assessment of VK4-116 to Support Human Patients Afflicted with Severe Pain Disorders” Period of Performance: 08/07/2019 to 02/06/2021 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100001 / HHSN271201700016I Contractor Name: IITRI Title: “Non-clinical Safety Assessment of sPIF to Support Chronic GVHD Indication” Period of Performance: 09/30/2017 to 09/30/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100002 / HHSN271201700016I Contractor Name: IITRI Title: “28 Day IV Toxicity Study of AXER-204 in Rats” Period of Performance: 06/30/2018 to 08/30/2019 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100003 / HHSN271201700016I Contractor Name: IITRI

Title: “Single PO Dose Cardiovascular and Pulmonary Safety Pharmacology Study of Metarrestin in Telemetered Beagle Dogs using Latin-Square Cross Over Study Design” Period of Performance: 07/15/2019 to 01/30/2019 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100004 / HHSN271201700016I Contractor Name: IITRI Title: “sPIF 3 Month Subcutaneous Toxicity Studies in Dogs and Mice” Period of Performance: 08/31/2018 to 07/31/2019 Obligated Amount:

Fair Opportunity Given: Excepted on the basis of being a logical follow-on to previous awarded task order HHSN27100001 /

HHSN271201700016I.

Task Order No. HHSN27100005 / HHSN271201700016I Contractor Name: IITRI Title: “Non-Clinical Safety Assessment of BPN14770 to Support Pediatric Population with Fragile X Syndrome” Period of Performance: 09/07/2018 to 04/30/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. 75N95019F00090 / HHSN271201700016I Contractor Name: IITRI Title: “GLP 28 Day Toxicity Study of ACT-1 When Applied Topically to Eyes Twice Daily for 28 Days in Dogs with a 14 Day Recovery Period” Period of Performance: 09/01/2019 to 08/15/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. 75N95019F00091 / HHSN271201700016I Contractor Name: IITRI Title: “Non-Clinical Safety Assessment of Acoziborole (SCYX- 7158) to Support Human African Trypanosomiasis (HAT or “Sleeping Sickness”)” Period of Performance: 09/01/2019 to 08/31/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100001 / HHSN271201700017I Contractor Name: LBERI Title: “Non-clinical Safety Assessment of PTH-RM/L Y2561553 to Support Hypoparathyroidism Indication” Period of Performance: 09/15/2017 to 03/14/2019 Obligated Amount:

Fair Opportunity Given: Yes, competed.

Task Order No. HHSN27100002 / HHSN271201700017I Contractor Name: LBERI Title: “Non-Clinical Safety Assessment of TTHX1114 to Support Fuchs Endothelial Corneal Dystrophy IND Application” Period of Performance: 09/17/2018 to 06/15/2020 Obligated Amount:

Fair Opportunity Given: Yes, competed.

3. Description of the supplies or services required to meet the agency’s needs (including the estimated value).

a. Project title. “CRO Support for NCATS In Vitro and In Vivo Toxicology Studies”

b. Project description.

See Attachment 1 – Statement of Work (SOW) for a full description of the requirement.

Requirement type.

Research & development (R&D) R & D support services Support services (non-R&D) Supplies/equipment Information technology (IT) Construction Architect-engineer (A & E) services Design-build Other (specify): ____________________

Type of action.

New requirement Follow-on

Other (specify): Modifications to IDIQ contracts to increase the maximum dollar amount of services the Government will acquire under these contracts.

Proposed contract/order type.

Firm-fixed-price Other fixed-price (specify, e.g., fixed-price award-fee, fixed-price incentive-fee): __________

Cost-plus-fixed-fee Other cost reimbursement (specify, e.g., cost-plus-award-fee, cost-plus-incentive-fee): ___________ Time and materials

Indefinite delivery (specify whether indefinite quantity, definite quantity, or requirements): ___________

Other (specify): ___________ Completion Form Term form

Acquisition identification number.

Proposed bilateral modifications to IDIQ contracts to increase the contract ceilings:

Mod. No. P00003 to Contract No. HHSN271201700014I Mod. No. P00004 to Contract No. HHSN271201700015I Mod. No. P00003 to Contract No. HHSN271201700016I Mod. No. P00004 to Contract No. HHSN271201700017I

c. Total estimated dollar value and performance/delivery period. This action is to increase the IDIQ contract maximum dollar amount of services the Government will acquire under these contracts; however, no funds will be immediately obligated with this action. The contract maximum dollar amount of services the Government will acquire under these contracts will be increased to $39,804,016, but the total IDIQ ordering period/period of performance will remain unchanged from April 21, 2017 to April 20, 2022.

4. Identification of the statutory authority permitting other than full and open competition.

This acquisition is conducted under the authority of 41 United States Code (U.S.C.) 3304(a)(1) as set forth in Federal Acquisition Regulation (FAR) 6.302-1.

This acquisition is conducted under the authority of section 4202 of the Clinger-Cohen Act of 1996.

This acquisition is conducted under the authority of the Services Acquisition Reform Act of 2003 (41 U.S.C. 428a).

5. Demonstration that the proposed contractor(s) unique qualifications or the nature of the acquisition requires use of the authority cited.

a. Name and address of the proposed contractor(s).

SRI International (SRI) 333 Ravenswood Avenue Menlo Park, CA 94025-3493

Battelle Memorial Institute (Battelle) 505 King Avenue Columbus, OH 43201-2693 competition would also require duplication of direct labor costs for time spent by new contractor staff (scientific, information technology, and administrative) to develop documentation, reports, and internal processes to support this project.

Based on the history of performance under these contracts, it is estimated new contractors, once started, would need approximately 6 months to become established to operate efficiently under this project.

Furthermore, the new task orders under this project will be cost-plus-fixed-fee and focus on Technical Area 3: In-Vivo Toxicity Testing from the SOW (See pages 5-6 of Attachment 1) which involves animals; as a result, new contractors would need the following in place before they could perform this work:

Adequate and suitable accounting and estimating systems for recording costs;

Compliance with HHS information access security standards including:

applying approved security configurations to information technology (IT) that is used to process information on behalf of HHS, adhering to all NIH configuration standards and policies, configuring computers that contain HHS data with the latest applicable United States Government Configuration Baseline (USGCB), encrypting equipment and sensitive information stored and/or processed by such equipment in accordance with HHS and FIPS 140-2 encryption standards, and configuring systems to allow for periodic HHS vulnerability and security configuration assessment scanning;

Registration with the Secretary of Agriculture of the United States in accordance with 7 U.S.C. 2136 and 9 CFR 2.25 through 2.28 for any contract involving animal-related activities where the species is regulated by the United States Department of Agriculture;

Access to an animal facility with an active Animal Welfare Assurance;

Evidence that the offeror has an Animal Care and Use Committee and an approved Animal Welfare Assurance on file with the NIH Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW); and

Facilities in compliance with the Food and Drug Administration's (FDA) Good Laboratory Practice Regulations (GLP). Official written documentation of GLP compliance must demonstrate regulations are currently being met and list recently conducted GLP compliant safety studies.

Additionally, the original independent government cost estimate (IGCE) for this project dates from an acquisition plan fully signed on January 21, 2016, and included consideration of anticipated budgets during the 5-year ordering period (2017-2022); however, the budget for NCATS has increased substantially in each fiscal year since 2016 as follows:

NCATS FY 2016 Budget: $685,417,000 https://ncats.nih.gov/about/center/budget/past#fy2016

NCATS FY 2017 Budget: $705,903,000 https://ncats.nih.gov/about/center/budget/past#fy2017

NCATS FY 2018 Budget: $742,354,000 https://ncats.nih.gov/about/center/budget/past#fy2018

NCATS FY 2019 Budget: $806,373,000 https://ncats.nih.gov/about/center/budget/past#fy2019

NCATS FY 2020 Budget: $832,888,000 https://ncats.nih.gov/about/center/budget

Since 2016, the annual budget for NCATS has increased by $147,471,000, or 21.52%, from $685,417,000 to $832,888,000. Consequently, it is possible to significantly expand testing to more compounds and accelerate moving small molecule and biologic drug candidates forward in the drug development pipeline.

Modification of these IDIQ contracts can be completed in less than thirty days so expanded testing can begin immediately; whereas, the alternative of conducting a new acquisition for R&D services would require a minimum lead time of 12 to 16 months, duplication of costs, additional time for new contractors to develop efficient operation, and require a shift of significant time and effort from acquisition staff toward related pre-award activities. This would be an unacceptable delay in fulfilling the executive agency's needs. The goal of NCATS is to get more treatments to more patients more quickly, and modifying these IDIQ contracts to increase the contract ceilings is the most effective way to support this goal.

10. Listing of sources, if any, that expressed, in writing, an interest in the acquisition. We received no responses to the pre-solicitation notice published on beta.sam.gov, and no other sources have expressed an interest, in writing, in the proposed acquisition.

11. Statement of the actions, if any, the agency may take to remove or overcome any barriers to competition before any subsequent acquisition for the required supplies or services. There are future plans to acquire these same services by re-competition beginning in fiscal year 2021, and new IDIQ contracts for these services are expected to be awarded on or around April 21, 2022.

12. Program office certification.

This is to certify that the portions of this justification that have been developed by the undersigned program office personnel, including supporting information and/or data verifying the Government’s minimum needs, schedule requirements and other rationale for other than full and open competition, are accurate and complete.

Official Name & Title Signature Date

Project Officer Pramod Terse, Ph.D.

Toxicologist, Division of Preclinical Innovation, Therapeutic

Pramod S.

Terse -S

Digitally signed by Pramod S. Terse -S Date: 2020.05.08 09:41:08 04'00'

Official Name & Title Signature Date

Development Branch, NCATS

Project Officer’s

Immediate Supervisor

Donald Lo, Ph.D., Director, Division of Preclinical Innovation, Therapeutic Development Branch, NCATS

Head of the Sponsoring

Program Office

Anton Simeonov, Ph.D., Scientific Director, Division of Preclinical Innovation, NCATS

13. Contracting Officer Certification.

This is to certify that the justification for the proposed acquisition has been reviewed and that to the best of my knowledge and belief the information and/or data provided to support the rationale and recommendation for approval is accurate and complete.

Official Name & Title Signature Date

Contracting Officer/Branch

Chief

Scott Bredow, Contracting Officer, NIDA

14. Chief of the Contracting Office and Head of the Contracting Activity signature(s).

Official Name & Title Signature Date

Chief of the Contracting

Office

Chris Belt, Director, Office of Acquisitions, NIDA

Head of the Contracting

Activity

Diane Frasier, Director, Office of Acquisitions and Logistics Management

(OALM), NIH

Donal d C.

Lo -S

Digitally signed by Donald C. Lo -S Date:

2020.05.08 12:33:10 -04'00'

Anton M.

Simeonov -S

Digitally signed by Anton M.

Simeonov -S Date: 2020.05.08 18:50:16 -04'00'

Scott A.

Bredow -S

Digitally signed by Scott A. Bredow -S Date: 2020.05.11 09:26:40 -04'00'

Christophe r J. Belt -S

Digitally signed by Christopher J. Belt -S Date: 2020.05.11 10:44:58 -04'00'

Nancy M.

Norton - S

Digitally signed by Nancy M.

Norton -S Date:

2020.05.13 08:49:05 -04'00'

15. Competition Advocate signature.

Official Name & Title Signature Date

Competition Advocate

Jodi B. Black, PhD, MMSc, Deputy Director, Office of Extramural Research, NIH

Jodi B.

Black -S

Digitally signed by Jodi B. Black -S Date: 2020.05.17 15:10:48 -04'00'

Statement of Work

I. Introduction/Background

Researchers nationwide and across the globe face common barriers in translational research that can delay the development of new interventions for patients in need. The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) studies translation on a system-wide level as a scientific and operational problem to accelerate the development of treatments and preventive strategies for a wide range of diseases. Within NCATS, the Division of Pre-Clinical Innovation (DPI) plans, conducts and uses both internal and contract resources to advance collaborative research projects across the pre-clinical phases of the translational science spectrum.

Contracted organizations provide manufacturing, pharmacology, toxicology, regulatory, and clinical operations services to DPI to assist with probe and assay development, lead selection and optimization, and Investigational New Drug (IND)-, New Drug Application (NDA)-, and Biologic License Application (BLA)-directed studies.

II. Goals and Objectives

Safety assessment of therapeutics and diagnostics is an important component of the drug and device discovery and development efforts in DPI. These assessments play a pivotal role in determining and evaluating therapeutic targets; selecting and optimizing leads; and establishing first in human starting doses, dose limiting toxicities, safety/pharmacodynamic biomarkers and therapeutic indexes.

The overall goal of this project is to support safety evaluations that are of interest to NCATS and other NIH institutes/centers by conducting various toxicology studies.

Through the issuance of Task Orders, (TO) Contractors will be required to help identify, develop, and perform in-vitro and in-vivo IND/NDA/BLA-enabling safety studies for small and large molecules. In addition, in-vitro tests and in-vivo exploratory studies will be carried out to aid therapeutic target evaluation, lead optimization, and compound selection processes on a case-by-case basis.

Therapeutic modalities may include new and repurposed chemical entities and biological products (e.g. monoclonal antibodies, enzymes, gene vectors, etc.).

III. Requirements

A. General Requirements

1. All work under these contracts shall be monitored by the Government Contracting Officer's Representative (COR), whose position is defined in Section G of this contract.

2. When tasked to work on a project via a TO, Contractors shall work with the COR, Contracting Officer (CO), and other stakeholders identified by the COR, to deliver a comprehensive project plan, including work breakdown structures, timelines, key milestones and deliverables, Go/No-Go decision points, resource allocation, budget, and a risk mitigation plan.

3. Contractors shall arrange for site visits and independent audits as requested by the COR. Audits may be requested to assure Contractor and subcontractor

Attachment 1 facilities and all planned procedures meet FDA-required drug development (GLP) standards. Contractors shall ensure all contractor and subcontractor records and staff are available in response to site visits or study-specific audits, and provide interim and final audit reports to the COR.

4. Contractors shall, upon request by the COR, submit any Standard Operating Procedures (SOPs), method descriptions, and references to be used in the implementation of the studies. Contractor confidential SOPs will be treated as confidential and information release can be discussed with the contractor.

5. As needed, Contractors shall provide facilities such as animal rooms, compound or biological sample storage, equipment, resources, and capability to successfully complete study specific tasks.

6. Contractors shall provide project management for its own core team to ensure project planning, execution, delivery of reports, accurate and timely communication with the COR, CO, and other stakeholders. The Contractor's core team leader shall attend program team meetings on biweekly basis either in person or via teleconferencing. During these meetings, the Contractor shall report project progress and provide input and feedback to the program team. The Contractor shall send the materials needed for these meetings to the COR at least one day in advance of the meeting. The material needed shall include an update on status of all ongoing studies, data generated and interpretations of data, any quality control issues, and the status of budget when requested.

7. Contractors will be required to maintain a system of records for all TOs awarded.

Contractors must meet the following data management requirements:

a. Develop, implement, and maintain data management systems to support all assigned studies and drug projects.

b. Develop, implement and maintain secure in-house data management capabilities and equipment to submit, compile, store, collate, analyze, track and retrieve data, structures, results, specimens, reagents, biological agents, drug product produced and released, documents generated in product development, and data received from other compound screening activities performed by third parties. This database will contain confidential/ proprietary information that shall not be used for data-mining purposes by the contractor or subcontractors.

c. Ensure secure electronic communications, including email, word processing and transmission of data files, between the contractor, NCATS staff, subcontractors and consultants. Organize, maintain, and transfer information on protocols and test results and provide electronic copies of all reports to the COR. All electronic deliverables shall be in compliance with Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d)

d. Provide all data, information, and records required for the writing and submission of the Drug Master File, Investigator's Brochure, Investigational New Drug Application(IND), and all other documents related to IND/ Non- Disclosure Agreement(NDA)/Biologiclicense Application(BLA) submission and maintenance to the COR, CO, or designated third party.

e. Provide all equipment and operational systems to maintain the confidentiality of data received from NCATS or third parties and data generated within the scope of the contract. [Note: The Government reserves the right to have complete access to those files relevant to NCATS studies in databases, provide access to third parties, and to transfer all rights and custody to a successor contractor.

8. The Contractor shall immediately contact the COR if there are any adverse or problematic research results or difficulties with studies that would impact the development success of the project or endanger the timeline. This communication shall include proposed solutions according to its risk mitigation plan by the Contractor.

9. The contractor may not begin working on activities that are not within the scope of the awarded the TO or SOW without CO approval.

10. At least 45 days prior to task order expiration, the Contractor shall provide the COR with a proposed Transition Plan for an orderly and complete transition/relocation of the task order resources to a successor Contractor or to the Government. The plan shall include details on the relocation/disposition of:

unused materials and supplies; manuals and directories developed by the contract; all contract-developed database programs, entries, and files; and all other government property not listed. Upon written direction by the Government, the Contractor shall transfer all Government property as directed, and fully cooperate with any successor Contractor and the Government to ensure an efficient transfer.

B. Regulatory Compliances and Safety Requirements

1. The Contractor shall develop experimental protocols in consultation with the COR and conduct studies using established techniques, study parameters, and statistical methods of data analysis in accordance with current FDA GLP regulations for nonclinical laboratory studies (21 CFR Part 58) and International Conference on Harmonisation (ICH) Guidelines. Investigators will use the technical reports as part of an IND or Radioactive Drug Research Committee (RDRC) application for human studies. As such, it is required that the format and content of the technical report conform to the highest scientific standards.

2. It is expected that during the contract term the Contractor will maintain compliance with current GLP regulations, and provide documentation to the COR of any FDA data audits and inspections (i.e., reports and responses to issues raised) in a timely manner. If it is determined that problems are encountered with the assays or documentation because GLP conditions were not met or maintained, the Contractor shall repeat the assay at no additional cost to the Government.

3. In the event that data quality issues arise in any of the tests performed under the NCATS contract due to Contractor performance issues or negligence, the Contractor shall cooperate fully with the COR to resolve the issues, and if necessary repeat specified tests or data analyses at no additional cost to the Government. In the event that compound quality control or assurance issues in a given experimental study cannot be resolved between the Contractor and COR, a scientific advisory group, comprised of Government staff and expert consultants chosen by the COR shall be asked to review the data and make recommendations to resolve the issues.

4. For studies involving animals only the Contractor is expected to have available the following species for use in the in vivo studies: rodents (rats or mice), dogs (purpose bred Beagle dogs), rabbits, non-human primates, and other animal models (as appropriate). The animals shall be obtained from an AAALAC-accredited registered breeder (Association for Assessment, Accreditation, and Laboratory Animal Care, U.S. Department of Agriculture (USDA).

5. For studies involving animals only the Contractor shall obtain, prior to the start of any work under this contract, an approved Animal Welfare Assurance from the Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW) (http://grants.nih.gov/grants/olaw/olaw.htm), Office of the Director, NIH, as required by Section I-43-30 of the Public Health Service Policy on Humane Care and Use of Laboratory Animals.

6. For studies involving animals only the Contractor shall maintain such assurance for the duration of this contract, and any subcontractors performing work under this contract involving the use of animals shall also obtain and maintain an approved Animal Welfare Assurance. The Contractor shall also be fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. Information about AAALAC accreditation is available at www.aaalac.org. The Contractor's Institutional Animal Care and Use Committee (IACUC) shall approve all animal procedures under this contract.

7. All candidate therapeutics and any known human safety data for storage and handling shall be supplied to the Contractor directly by the sponsor or through the COR. Obtaining any other equipment, chemicals, or other materials shall be the responsibility of the Contractor.

8. Each agent will be considered potentially hazardous. Therefore, all necessary precautions must be taken to protect personnel and the environment against possible exposure to the agents being tested. The Contractor shall perform all work associated with this contract in accordance with all applicable Federal, State and local regulations including transportation and disposal of hazardous waste.

C. Specific Requirements

To accomplish the goals and objectives of this project, services under the Technical Areas described below are required.

1. Technical Area 1: Administrative Reporting Requirements

The Contractor shall perform activities related to the overall administration of the contract. Specific services to be performed under this Technical Area include the fulfillment of administrative reporting and deliverable requirements.

Administrative Reporting Requirements reporting and deliverable requirements are outlined in Sections C, F, and H of this Request for Proposals and include:

- Reporting of Financial Conflict of Interest (FCOI)

- Information Security and Physical Access Reporting Requirements

- Service Contract Reporting for Indefinite-Delivery Contracts

- Invention Reporting Requirement

- Subcontracting Reports (applicable only if the prime contractor is a large business)

2. Technical Area 2: Exploratory and Genetic Toxicology

The Contractor shall perform efforts associated with planning, conducting and reporting on in-vitro toxicity testing (GLP and non-GLP) with limited in-vivo capabilities as described by each individual TO in accordance with approved protocols. At the direction of the COR, the Contractor shall perform toxicity evaluations in two areas including, but not limited to, the following:

a. In-vitro assays: Mitochondrial toxicity, Phospholipidosis and steatosis assay, Hemolysis assay, Lysosomal Trapping assay (to assess the test-article effect of lysosomotropism), Membrane integrity assay, Oxidative stress assay, Apoptosis assay, hERG assay, Ames assay, Mouse lymphoma assay, Chromosomal aberration assay.

b. In-vivo assays: Micronucleus Assay and Single Cell Gel Electrophoresis assay (COMET) assays. In-vivo studies under this technical area may include:

animal dosing; formulation and biological fluid analysis; clinical observations;

clinical pathology; and histopathology evaluations.

As needed, Contractors may be asked to complete only a portion or full studies, e.g. biological sample and histopathology analysis.

Upon completion of a study under Technical Area 2, the Government may require that all study documentation including, but not limited to, laboratory notebooks, source documents, monitoring logs, regulatory documents, observations or notations of activities and all reports and records necessary for the evaluation and reconstruction of the research study, as well as databases on disk or tape, be placed in secure storage for a period of up to 5 years. During this period, the contractor will be responsible for the integrity and organization of the material and its confidentiality. At the end of this period, all reference material, data files, etc. will be transferred or disposed of per instructions of the COR.

3. Technical Area 3: In-Vivo Toxicity Testing

The Contractor shall perform efforts associated with planning, conducting, and reporting on approved in vivo toxicology studies (GLP and non-GLP), as directed by each individual TO in accordance with approved protocols. At the direction of the COR, the Contractor shall perform toxicity evaluations, including but not limited to, the following:

a. In-vivo general toxicology and safety pharmacology studies (via oral, IM, IV, SC, IT, ocular, IP, etc.) for IND/NDA/BLA-enabling toxicology packages

i. Non-GLP range finding studies in rodent and non-rodent species

ii. GLP studies in rodent (with FOB and Micronucleus/comet assays either built-in or conducted stand-alone) and non-rodent species

iii. Single-dose safety pharmacology studies (pulmonary, cardiovascular) in relevant species

iv. Reproductive toxicology studies

v. Carcinogenesis studies in rodent and non-rodent

b. In-vivo exploratory assays: Common non-GLP exploratory toxicology studies in rodent and non-rodent species to aid therapeutic target evaluation, lead optimization and compound selection.

In-vivo studies under this technical area will include, but not be limited to: animal dosing; formulation and biological fluid analysis; clinical observations; clinical pathology; and histopathology evaluations.

As needed, Contractors may be asked to complete only a portion or full studies, e.g. biological sample and histopathology analysis.

Upon completion of a study under Technical Area 3, the Government may require that all study documentation including, but not limited to, laboratory notebooks, source documents, monitoring logs, regulatory documents, observations or notations of activities and all reports and records necessary for the evaluation and reconstruction of the research study, as well as databases on disk or tape, be placed in secure storage for a period of up to 5 years. During this period, the contractor will be responsible for the integrity and organization of the material and its confidentiality. At the end of this period, all reference material, data files, etc. will be transferred or disposed of per instructions of the COR.

This is a U.S. General Services Administration Federal Government computer system that is "FOR OFFICIAL USE ONLY." This system is subject to monitoring. Individuals found performing unauthorized activities are subject to disciplinary action including criminal prosecution.

Attachment 3

REGULATORY AUTHORITY

The resultant modifications will include all applicable provisions and clauses of the Federal acquisition Requlation (FAR) in effect through the Federal Acquisition Circular (FAC) 2005-05 with effective date 03-30-2020.

STATUTORY AUTHORITY

This acquisition is conducted as non-competitive under the authority of 41 U.S.C.

3304(a)(1) under provisions of the statutory authority of FAR Subpart 6.302-1.

DESCRIPTION

Background Researchers nationwide and across the globe face common barriers in translational research that can delay the development of new interventions for patients in need. The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) studies translation on a system-wide level as a scientific and operational problem to accelerate the development of treatments and preventive strategies for a wide range of diseases. Within NCATS, the Division of Pre-Clinical Innovation (DPI) plans, conducts and uses both internal and contract resources to advance collaborative research projects across the pre-clinical phases of the translational science spectrum. Contracted organizations provide manufacturing, pharmacology, toxicology, regulatory, and clinical operations services to DPI to assist with probe and assay development, lead selection and optimization, and lnvestigational New Drug (IND)-, New Drug Application (NDA)-, and Biologic License Application (BLA)-directed studies.

Goals and Objectives Safety assessment of therapeutics and diagnostics is an important component of the drug and device discovery and development efforts in DPI. These assessments play a pivotal role in determining and evaluating therapeutic targets; selecting and optimizing leads; and establishing first in human starting doses, dose limiting toxicities, safety/pharmacodynamic biomarkers and therapeutic indexes.

The overall goal of this project is to support safety evaluations that are of interest to NCATS and other NIH institutes/centers by conducting various toxicology studies.

Through the issuance of Task Orders, (TO) Contractors will be required to help identify, develop, and perform in-vitro and in-vivo IND/NDA/BLA-enabling safety studies for small and large molecules. In addition, in-vitro tests and in-vivo exploratory studies will be carried out to aid therapeutic target evaluation, lead optimization, and compound selection processes on a case-by-case basis.

Therapeutic modalities may include new and repurposed chemical entities and biological products (e.g. monoclonal antibodies, enzymes, gene vectors, etc.).

The project includes the following tasks:

Administrative Reporting Requirements: The Contractor shall perform activities related to the overall administration of the contract. Specific services to be performed under this Technical Area include the fulfillment of administrative reporting and deliverable requirements.

Exploratory and Genetic Toxicology: The Contractor shall perform efforts associated with planning, conducting and reporting on in-vitro toxicity testing (GLP and non-GLP) with limited in-vivo capabilities as described by each individual TO in accordance with approved protocols. At the direction of the COR, the Contractor shall perform toxicity evaluations in two areas including, but not limited to, the following:

In-vitro assays: Mitochondrial toxicity, Phospholipidosis and steatosis assay, Hemolysis assay, Lysosomal Trapping assay (to assess the test-article effect of lysosomotropism), Membrane integrity assay, Oxidative stress assay, Apoptosis assay, hERG assay, Ames assay, Mouse lymphoma assay, Chromosomal aberration assay.

In-vivo assays: Micronucleus Assay and Single Cell Gel Electrophoresis assay (COMET) assays. In-vivo studies under this technical area may include: animal dosing;

formulation and biological fluid analysis; clinical observations; clinical pathology; and histopathology evaluations. As needed, Contractors may be asked to complete only a portion or full studies, e.g. biological sample and histopathology analysis.

In-Vivo Toxicity Testing: The Contractor shall perform efforts associated with planning, conducting, and reporting on approved in vivo toxicology studies (GLP and non-GLP), as directed by each individual TO in accordance with approved protocols. At the direction of the COR, the Contractor shall perform toxicity evaluations, including but not limited to, the following:

a. In-vivo general toxicology and safety pharmacology studies (via oral, IM, IV, SC, IT, ocular, IP, etc.) for IND/NDA/BLA-enabling toxicology packages

i. Non-GLP range finding studies in rodent and non-rodent species

ii. GLP studies in rodent (with FOB and Micronucleus/comet assays either built-in or conducted stand-alone) and non-rodent species

iii. Single-dose safety pharmacology studies (pulmonary, cardiovascular) in relevant species

iv. Reproductive toxicology studies

v. Carcinogenesis studies in rodent and non-rodent

b. In-vivo exploratory assays: Common non-GLP exploratory toxicology studies in rodent and non-rodent species to aid therapeutic target evaluation, lead optimization and compound selection.

In-vivo studies under this technical area will include, but not be limited to: animal dosing;

formulation and biological fluid analysis; clinical observations; clinical pathology; and histopathology evaluations. As needed, Contractors may be asked to complete only a portion or full studies, e.g. biological sample and histopathology analysis.

Period of Performance The IDIQ contracts proposed for modification have an ordering period of April 21, 2017 to April 20, 2022.

CLOSING STATEMENT

This synopsis is not a request for competitive proposals and the Government is not committed to award a contract pursuant to this announcement.. However, interested parties may respond by identifying their interest, submitting capability statements, and or submitting objections to the proposed contract modifications. The Government will consider responses; however, a determination by the Government to proceed with the proposed IDIQ contract modifications is solely within the discretion of the Government.

All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov. In addition the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response.

A determination by the Government not to compete these proposed IDIQ contracts based upon responses to this notice is solely within the discretion of the Government.

The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

All responses must be received by 12:00 p.m. Eastern Daylight Time, Wednesday, April 22, 2020, and reference notice number 75N95020R00025. Responses must be submitted electronically to Mark McNally, Contract Specialist, at mark.mcnally@nih.gov.

Fax responses will not be accepted.

Contracting Office Address:

National Institutes of Health National Institute on Drug Abuse Office of Acquisitions c/o 3WFN MSC 6012 301 N Stonestreet Ave Bethesda, MD 20892

All responsible sources may submit a capability statement which shall be considered by the agency.