Redacted JOFOC 1700014C.pdf

Attachment 3

Justification for Other than Full and Open Competition

“Source Selection Information – see FAR 2.101 and 3.104”

1. Identification of the agency and contracting activity.

a. Federal agency and contracting activity. Department of Health and Human Services

(DHHS), National Institutes of Health (NIH)

b. Sponsoring organization. National Institute of Allergy and Infectious Diseases (NIAID), Division of Acquired Immunodeficiency Syndrome (DAIDS), Office of Policy and Clinical Research Operations (OPCRO), Clinical Research Resources Branch (CRRB)

c. Contracting Officer’s Representative (COR) information.

COR name:

Mailing address:

E-mail address:

Telephone number:

2. Nature and/or description of the action being approved.

a. Acquisition purpose and objectives.

The acquisition related to this Justification for Other than Full and Open Competition (JOFOC) is the acquisition of additional level of effort under the current contract (Contract No. HHSN272201700014C), entitled, “NIAID/Division of AIDS: Regulatory Support Center”. The purpose of this contract is to provide regulatory expertise and support to operate and manage the DAIDS Regulatory Support Center (RSC), to provide a wide range of clinical research activities and programs for DAIDS, including the delivery of regulatory services for unanticipated DAIDS clinical research projects that may be required in response to emerging needs or public health emergencies.

b. Project background.

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), conducts and supports research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. The mission of DAIDS, NIAID, is to bring an end to the HIV/AIDS epidemic by increasing the basic knowledge of the pathogenesis and transmission of HIV, to support the advancement of therapies for HIV infection and its complications, and to support the development of HIV/AIDS vaccines and other prevention measures. NIAID/DAIDS, henceforth referred to as DAIDS, supports extramural Clinical Trials Networks, investigator-initiated clinical trials, and partners with other Government and private organizations, in order to accomplish DAIDS’s scientific objectives. Through grants and contracts, DAIDS sponsors Phase I, II, III and IV clinical trials to evaluate the safety and efficacy of therapeutics, vaccines, and other preventive modalities. The DAIDS global clinical trial portfolio includes approximately 440 active protocols, 73 active INDs, 300+ network study sites in 22 countries, and collaborations with 60 pharmaceutical companies. As the IND Application Sponsor for a large number of DAIDS-funded clinical trials, DAIDS is required to ensure compliance with applicable regulations, including Title 21 Code of Federal Regulations (CFR) Part 312, Human Subjects Protection Title 45 CFR Part 46, and ICH E6(R2) International Conference on Harmonisation-Good Clinical Practices (ICH-GCP).

A contract (number HHSN272201700014C) for “NIAID/Division of AIDS: Regulatory Support Center (RSC)”, was awarded as a restricted competition (small business set-

DocuSign Envelope ID: B46DEABA-D333-4560-AF63-41DC11C9E78E aside) to Technical Resources International, Inc., 6500 Rock Spring Drive, Suite 650, Bethesda Maryland 20817. A term type/level of effort contract was awarded for the delivery of 91,077 direct labor hours per year. The total value of the contract, including all options, was $79,104,240. The contract includes options for the extension of the term for a total performance period of 7 years from August 15, 2017 through August 14, 2024, and quantity options for increases in the level of effort during the term of the contract. The purpose of the contract is to provide comprehensive regulatory support to: 1) perform DAIDS-funded and DAIDS-sponsored domestic and international clinical trial research; 2) provide training in key functions of clinical trial research to DAIDS staff, investigators, and collaborators; and 3) maintain all contract-associated data and records in the DAIDS Enterprise System (DAIDS-ES) and NIAID-Clinical Research Management System (N- CRMS), including the electronic submission of required regulatory information.

A JOFOC was subsequently approved by Richard Ikeda, NIH Competition Advocate, on May 9, 2019, for additional level of effort to address unanticipated increases in contract activity. This resulted in the following increases to term Options 2-6 and were incorporated into the contract via Modification #6 on October 15, 2019. As a result of Modification #6, the total contract value was increased by $17,518,057, from $79,104,240 to $96,622,297.

Please note that the funds for Option 2 were partially de-obligated under Modification #9, in the total amount of $800,000, as a result of a cost underrun. As a result of Modification #9, the total contract value was decreased by $800,000, from $96,622,297 to $95,822,297.

On August 12, 2020, in response to the COVID-19 pandemic, the contract was modified to procure regulatory support services (these activities are within the existing scope of the contract) for a sponsored DAIDS COVID-19 clinical trial entitled “A5401: Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt Out COVID)” also known as ACTIV- 2. This clinical trial is one of the studies identified by Operation Warp Speed (OWS) to move towards identifying a therapeutic for COVID-19 as quickly as possible. The support provided to date includes: 1) expedited clinical trial protocol registration of research sites to verify that clinical sites have received the necessary applicable Regulatory Entity/Approving Entity approvals and documentation required by regulatory authorities; 2) preparation and submission of regulatory filings, such as IND submissions, LOAs, protocol amendments and appendicies to the FDA; 3) negotiation and development of clinical trial agreements and 4) technical and project management services to support NIAID COVID-19 clinical research. A total of 24,369 direct labor hours were added to the contract to address this COVID-19 requirement. The total estimated cost-plus award fee of the contract was increased by $2,363,306 to cover performance from August 15, 2020 - August 14, 2021. This was incorporated into the contract via Modification #11 on August 12, 2020. As a result of Modification #11, the total contract value was increased by $2,363,306, from $95,822,297 to $98,185,603.

At this time, both the complexity as well as quantity of requirements for full clinical trial support services for ACTIV- 2 have significantly increased based on “real time” clinical trial implementation data as well as evolving scientific requirements.

Specifically, these significant increases of key clinical trial activity drivers include:

Increase in number of protocol documents, including additional IND submissions, Letters of Amendments, protocol amendments for protocol updates and new appendices to the Food and Drug Administration (FDA). The RSC has assumed responsibility for additional (27% increase) study arms than originally scoped, resulting in a 55% increase in number of protocol versions/amendments to the FDA.

Increased number of clinical research sites. The RSC has assumed responsibility for significantly more clinical research sites (172% increase) than originally scoped, resulting in significantly more expedited protocol registration activities.

238% increase in period of performance of study than originally scoped.

10% increase in number of study products than originally scoped.

Therefore, based on these considerably increased requirements, detailed above, as well as the overall complexity of the clinical trial requirements, the Government intends to acquire additional level of effort from the contractor, on a sole source basis, in order to provide the support needed for the completion of the ACTIV-2 study. As a result, the level of effort under the base requirement (Options 4-6) will be increased as follows:

An increase of 28.69 FTEs (from 68.58 FTEs to 97.27 FTEs) during Option 4/Year 5 (04/15/21-04/14/22)

An increase of 32.82 FTEs (from 64.45 FTEs to 97.27 FTEs) during Option 5/Year 6 (04/15/22-04/14/23)

An increase of 32.56 FTEs (from 63.45 FTEs to 96.01FTEs) during Option 6/Year 7 (04/15/23-04/14/24)

A Total Increase of 94.07 FTEs (Options 4-6/Contract Years 5-7)

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

The Contractor shall provide regulatory support services for the DAIDS extramural clinical trial research portfolio. In addition to the options to extend the term of the contract (Options 1-6), Options for Increased Level of Effort for Unanticipated Increases in Demand (Options 7-34) are also within the scope of the contract. The total contract value, including all Options, is $98,185,603.

a. Project title. “NIAID/Division of AIDS: Regulatory Support Center (RSC)”.

b. Project description.

The purpose of this contract is to provide regulatory expertise and support to operate and manage the NIAID/DAIDS RSC, to provide a wide range of clinical research activities and programs for DAIDS, including the delivery of regulatory support services for unanticipated DAIDS clinical research projects that may be required in response to emerging needs or public health emergencies. The DAIDS RSC provides comprehensive regulatory support to:

1) perform DAIDS-funded and DAIDS-sponsored domestic and international clinical trial research; 2) provide training in key functions of clinical trial research to DAIDS staff, investigators, and collaborators; and 3) maintain all contract-associated data and records in the DAIDS Enterprise System (DAIDS-ES) and NIAID-Clinical Research Management System (N-CRMS), including the electronic submission of required regulatory information.

Activities include support for: 1) Assisting with the development of SOPs, quality assurance quality control plans, training, meetings with Health Authorities; 2) Reviewing document for regulatory compliance and preparing and filing new regulatory (such as INDs); 3) Safety and Pharmacovigilance activities including safety reporting; 4) Database and website operation and maintenance; 5) Tracking all protocol registration materials; 6) Maintaining clinical and study related information in the NIAID Clinical Research Management system;

7) Assisting with preparing, negotiating, and finalizing Clinical Trial Agreements; 8) Assisting with human subjects protection related issues and ClinicalTrials.gov requirements;

and 9) Assisting with technical regulatory and administrative review of clinical documents (such as protocols and consent forms).

This contract ensures, through the provision of a variety of regulatory support services and standardized approaches, that DAIDS adequately meets its regulatory Sponsor obligations.

Without this critical infrastructure initiative, DAIDS cannot carry out its core mission of performing clinical trial research in HIV/AIDS treatment and prevention. The regulatory requirements that this research is subject to originates from a variety of sources, including the Office of Human Research Protection (OHRP) and various international Ministries of Health. The support provided by the RSC contract enables DAIDS staff to coordinate and direct the numerous regulatory tasks in support of all its network and non-network clinical trial research, both domestic and international.

DAIDS, with support from the RSC, interacts with research stakeholders consisting of, but not limited to: treatment, prevention, and vaccine clinical investigators and their institutions, statistical and data analysis centers, operational centers, OHRP, the Fogarty International Center (FIC), non-U.S. regulatory authorities, the bio-tech and pharmaceutical industries, domestic and international organizations involved in HIV/AIDS-related research, patients with HIV/AIDS and their advocates, populations at risk for HIV infection and their advocates, and NIH scientific and administrative personnel.

The original Performance Work Statement for Contract No. HHSN272201700014C is attached to this document as a reference (Attachment A).

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): New Work Modification

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): Cost-Plus-Award-Fee

Time and materials Indefinite delivery (specify whether indefinite quantity, definite quantity, or requirements): ___________ Other (specify): ___________ Completion Form Term form

Acquisition identification number: HHSN272201700014C

c. Total estimated dollar value and performance/delivery period. The total estimated dollar value for this acquisition is [See Attachment B – Independent Government Cost Estimate (IGCE) for this JOFOC] for the period from April 15, 2021 through April 14, 2024.

The table below provides a breakdown for the additional funds needed for this contract by Option period.

Option Period of Performance Estimated Cost Option 4 04/15/2021–04/14/2022 Option 5 04/15/2022-04/14/2023 Option 6 04/15/2023-04/14/2024 Total

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.

Only one responsible source and no other supplies or services will satisfy agency requirements.

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).

Technical Resources International (TRI), Inc.

6500 Rock Spring Drive, Suite 650 Bethesda, MD 20817

b. Nature of the acquisition and proposed unique qualifications of the contractor(s).

The objective of this acquisition is to provide funding to cover an increase the level of effort of the existing contract to allow the Contractor to continue providing specific clinical trial support services (these activities are within the existing scope of the contract) for ACTIV-2. These services include 1) expedited clinical trial protocol registration of research sites; 2) preparation and submission of regulatory filings, such as IND submissions, LOAs, protocol amendments and appendicies to the FDA;

3) negotiation and development of clinical trial agreements; and 4) technical and project management services to support NIAID COVID-19 clinical research.

As mentioned above, at this time, both the complexity as well as quantity of requirements for full clinical trial support services for ACTIV- 2 have significantly increased based on “real time” clinical trial implementation data as well as evolving scientific requirements. Specifically, the following significant increases of ACTIV-2 key clinical trial activity drivers include:

Increase in number of protocol documents, including additional IND submissions, Letters of Amendments, protocol amendments for protocol updates and new appendices to the FDA. The RSC has assumed responsibility for additional (27% increase) study arms than originally scoped, resulting in a 55% increase in number of protocol versions/amendments to FDA.

Increase in number of clinical research sites. The RSC has assumed responsibility for significantly more clinical research sites (172% increase) than originally scoped, resulting in significantly more expedited protocol registration activities.

238% increase in period of performance of study than originally scoped.

10% increase in number of study products than originally scoped.

With the decision to utilize the RSC contract on August 12, 2020, to provide the required support services for ACTIV-2, the RSC remains uniquely positioned to: a) continue its full-service support for ACTIV-2, and b) assume this additional level of effort. TRI is currently, successfully executing critical regulatory support services for the ACTIV-2 trial. TRI’s experience and processes under the contract have resulted in finely tuned processes and systems which would need to be transitioned in an intricate manner to prevent any disruption. For example, the contract plays a role in planning, coordinating, and executing an expedited protocol registration process to enable the streamlined assessment and government approval of clinical research sites for participation in the study. This specialized expedited registration function is essential to rapidly increase the number of clinical research sites to effectively enroll the large number of participants required to successfully conduct the ACTIV 2 protocol. No other source can immediately provide these expedited essential services which require extensive knowledge and expertise in DAIDS-specific business procedures, the NIAID Clinical Research Management System computer database and to rapidly interface with the ACTG network. Any alternate vendor would need extensive demonstrated experience with using NCRMS components including: Master Contact, Protocol Management, Protocol Registration, Protocol Development Tracking, and Investigational New Drug Application Management. The RSC has over a decade of experience successfully using these highly specialized NIAID/DAIDS modules.

The COVID-19 pandemic continues to grow at an alarming rate and has catastrophically affected the health and economic stability of the world. To combat this global threat and to prevent the further spread of the coronavirus, NIAID must continue to execute a rapid, efficient and scalable response. The work related to this JOFOC is critical to continue the Phase 2 and 3 testing of lifesaving COVID-19 therapeutics. If a new contractor, with no institutional history, no established relationships, no established processes, and no experience/operational knowledge base was required to integrate its activities, de novo, into this existing, highly complicated, regulatory support network, there would be an immediate fracturing of these already established systems/processes/ communication pathways. Additionally, due to the tight integration of current system requirements, the introduction of a new contractor would impose a significant disruption to even existing operations. Any impedance/disruption would, in turn, jeopardize the continuation of ACTIV 2; impact the rights, safety and well-being of the clinical trial subjects; and diminish the quality and integrity of the clinical trial data.

6. Description of the efforts made to ensure that offers are solicited from as many potential sources as practicable. Indicate whether a FedBizOpps notice was or will be publicized as required by FAR Subpart 5.2 and, if not, which exception under FAR

5.202 applies:

A Research and Development Sources Sought Notice (Attachment C) was posted on the System for Award Management (Beta.Sam.Gov) website for a period of 15 days on December 31, 2020 with responses due by January 19, 2021. This notice described the work being sought by NIAID and requested capability statements from potential sources. Further information regarding the responses received from this notice are provided below, under item 10.

A Presolicitation Notice (Attachment E) was posted on the Beta.Sam.Gov website for a period of 15 days on January 21, 2021 with responses due by February 5, 2021. This notice described the work being sought by NIAID, stated NIAID’s intent to negotiate with the present Contractor on a sole source basis, under the authority of FAR 6.302-1 and HHSAR 306.302-1, and provided responsible sources with the opportunity to express their interest by submitting a capability statement. Further information regarding the responses received from this notice are provided below, under item 10.

7. Determination by the Contracting Officer that the anticipated cost/price to the Government will be fair and reasonable.

The Independent Government Cost Estimate (IGCE) [Attachment B] was developed using knowledge of this type of work, as well as the historical costs of the current contract. In addition, the Contracting Officer will obtain certified cost and pricing data, to establish a fair and reasonable price for the services being acquired, as required by FAR 15.403-4. Finally, the Contracting Officer will conduct a cost analysis and cost realism analysis, as part of the proposal analysis. Negotiations will be conducted if needed to ensure that the proposed costs are fair and reasonable for performance of the proposed work. A field audit will not be performed, as it is not considered necessary because NIAID has historical cost data to assist in the analysis of the proposed costs.

8. Description of the market research conducted (see FAR Part 10) and the results, or a statement of the reasons market research was not conducted.

The NIAID performed market research by: (a) issuing a sources sought notice (Attachment C) and a pre-solicitation notice (Attachment E), in Beta.Sam.Gov, as described in item 6., above, and item 10., below (a copy of each notice and the evaluation of each capability statement received in response to each notice, are attached to this document); and (b) contacting knowledgeable acquisition and program officials in Government and industry regarding market capabilities. As a result of the foregoing, it was determined that there is only one responsible source (Technical Resources International, Inc.) and no other supplies or services will satisfy agency requirements.

Due to the complex nature of NIAID/DAIDS ACTIV-2 trial and the urgent public health need for a COVID-19 therapeutic, this work can only be completed using the current contractor. Attempting to bring in a new contractor would result in a significant disruption to critical services and could jeopardize participant rights, safety and data integrity. Moreover, this scenario would likely result in further loss of life by depriving the nation of a therapeutic during an unprecedented pandemic.

9. Any other facts supporting the use of other than full and open competition.

In addition to the above, the COR and Contracting Officer believe that there would be duplication of cost by awarding this work to another organization. The estimated duplication is and was derived from a review of the costs billed to date for study start up.

10.Listing of sources, if any, that expressed, in writing, an interest in the acquisition.

As stated above, under item 6, a Research and Development Sources Sought Notice (Attachment C) was posted on the System for Award Management (Beta.Sam.Gov) website for a period of 15 days on December 31, 2020 with responses due by January 19, 2021 (a copy of the notice is attached to this document). The notice requested capability statements from potential sources. Capability Statements were received from organizations, by the closing date of January 19, 2021. The Contracting Officer’s Representative (COR) reviewed the capability statements received and determined that none of the offerors could provide all services required by the Performance Work Statement. As stated above, it was determined that there is only one responsible source (Technical Resources International, Inc.) and no other supplies or services will satisfy agency requirements. Due to the complex nature of NIAID/DAIDS ACTIV-2 trial, the full integration of RSC staff, processes and data systems with DAIDS processes as well as the urgent public health need for a COVID-19 therapeutic, this work can only be completed using the current contractor. Attempting to bring in a new contractor would result in a significant disruption to critical services and could jeopardize participant safety and data integrity. Finally, attempting to bring in a new contractor would result in a catastrophic disruption of the ACTIV-2 trial, this scenario would likely result in further loss of life by depriving the nation of a therapeutic during an unprecedented pandemic.

Any disruption to the ACTIV-2 trial would be disastrous. The COR’s evaluation of each capability statement received in response to this notice is attached to this document (See Attachment D).

A Presolicitation Notice (Attachment E) was published on the Beta.Sam.Gov website for a period of 15 days on January 21, 2021 with responses due by February 5, 2021. This notice described the work to be performed, stated NIAID’s intent to negotiate with the present Contractor on a sole source basis, under the authority of FAR 6.302-1 and HHSAR 306.302-1, and provided responsible sources with the opportunity to express their interest by submitting a capability statement. Capability Statements were received from organization, by the closing date of February 5, 2021. The Contracting Officer’s Representative (COR) reviewed the capability statement received and determined they could not provide all services required by the Performance Work Statement. As stated previously, due to the complex nature of NIAID/DAIDS ACTIV-2 trial, the full integration of TRI staff, processes as well as the existing/fully existing TRI/ACTIV-2 regulatory support systems as well as the urgent public health need for a COVID-19 therapeutic, this work can only be completed using the current contractor. Attempting to bring in a new contractor would result in a catastrophic disruption to the ACTIV-2 trial and would also jeopardize participant rights, safety and data integrity while ultimately delaying the delivery of a COVID-19 treatment. The COR’s evaluation of each capability statement received in response to this notice is attached to this document (Attachment F).

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.

The contract will be re-competed prior to the expiration date of the current contract, in order to have a new contract in place by 4/14/2024.

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.

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 , Contracting

Officer, OA, NIAID

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

Chief of the Contracting Office

, Director

OA, NIAID

Head of the Contracting Activity

OALM, OM, NIH

15. Competition Advocate signature.

Competition Advocate

Attachments:

Attachment A – Performance Work Statement Attachment B - Attachment C – Sources Sought Notice Attachment D –

Attachment E – Presolicitation Notice Attachment F –

Official Name & Title Signature Date Contracting Officer’s Representative

, Branch Chief

CRRB, OPCRO, DAIDS, NIAID

Contracting Officer’s Representative Immediate Supervisor

, Director

OPCRO, OD, DAIDS, NIAID

Head of the Sponsoring Program Office

DAIDS, NIAID

Performance Work Statement 1 ATTACHMENT dated December 21, 2015

ATTACHMENT : PERFORMANCE WORK STATEMENT NIAID/

DIVISION OF AIDS: REGULATORY SUPPORT CENTER

1) BACKGROUND AND INTRODUCTION

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), conducts and supports research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. The mission of the Division of AIDS (DAIDS), NIAID, NIH, is to bring an end to the HIV/AIDS epidemic by increasing basic knowledge of the pathogenesis and transmission of HIV, supporting the advancement of therapies for HIV infection and its complications, and supporting the development of HIV/AIDS vaccines and other prevention measures. NIAID/DAIDS, henceforth referred to as DAIDS, supports extramural Clinical Trials Networks, investigator-initiated clinical trials, and partners with other Government and private organizations to accomplish the Division’s scientific objectives. Through grants and contracts, DAIDS sponsors Phase I, II, III and IV clinical trials to evaluate the safety and efficacy of therapeutics, vaccines, and other preventive modalities. This contract will be used primarily to support DAIDS activities. However, this contract may be used to support other NIAID programs as necessary to help accomplish our mission.

DAIDS acts as study sponsor for clinical trials that meet the requirements to be conducted under Health Authority (HA) oversight (U.S. Food and Drug Administration [FDA] and others as appropriate), of Investigational New Drug (IND) studies, as well as those studies that do not meet these requirements (non-IND). As of May 2015, there are 61 active INDs containing 117 protocols (86 active), and 1342 clinical research sites (718 domestic, 624 international) with trials being conducted in 64 (22 active) different countries. As the IND sponsor for a large number of DAIDS-supported clinical trials, there is an established requirement for DAIDS to provide regulatory support for these clinical trials to ensure compliance with applicable regulations, including Title 21 Code of Federal Regulations (CFR) Parts 11, 50, 54, 56, 312, and 314 and Title 45 CFR Part 46.

Clinical trials must also be conducted in accordance with the International Conference on Harmonisation (ICH) Guidelines: E2A Clinical Safety Data Management and E6 Good Clinical Practices (GCP), and country-specific regulatory requirements. In order to provide regulatory support services for DAIDS clinical research and clinical trials, on April 15, 2010, a seven-year contract [Contract No.: HHSN272201000013C] was awarded to Technical Resources International, Inc. to operate the Regulatory Support Center (RSC).

The purpose of this solicitation is to continue clinical regulatory and technical support services for DAIDS-supported clinical trials and clinical research and to meet evolving regulatory and scientific needs.

DAIDS has several systems and processes that provide resources for regulatory support:

The NIAID-Clinical Research Management System (N-CRMS) is a comprehensive information system that supports many of the clinical research management and oversight responsibilities of DAIDS.

Data Management Center (DMC): Each of the DAIDS Clinical Trial Networks have associated DMCs. The DMC collects, manages, and analyzes data from clinical trials and epidemiological studies. The HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network (HPTN), the Microbicide Trials Network (MTN), the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) are

Performance Work Statement 2 ATTACHMENT supported by the Statistical Center for HIV/AIDS Research & Prevention (SCHARP). The AIDS Clinical Trials Group (ACTG) is supported by Frontier Science & Technology Research Foundation, Inc. (FSTRF).

The DAIDS protocol registration process verifies that sites have received the necessary Institutional Review Board (IRB)/ Ethics Committee (EC) and other applicable Regulatory Entity (RE)/Approving Entity (for example, ministry of health, national regulatory agency, in-country drug control council, national IRB/EC, or other government agency) approvals and have provided to DAIDS all documentation pertaining to investigator qualifications and responsibilities that are required by U.S. Federal regulations and NIH. The DAIDS protocol registration process also verifies that site-specific informed consent (IC) forms contain the necessary information to comply with U.S. Federal regulations.

DAIDS RSC public website http://rsc.tech-res.com/default.aspx

2) SCOPE

The Contractor shall operate and manage the NIAID/DAIDS Regulatory Support Center (RSC) to provide comprehensive clinical regulatory and administrative support services for NIAID-supported clinical trials and clinical research, both domestic and international.

3) TECHNICAL REQUIREMENTS

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Performance Work Statement (PWS) as stated herein. Specifically, the Contractor shall:

A. General Requirements Optimize efficient achievement of the Performance Requirements and Performance Standards listed in the PWS. The requirements below affect all other task areas of the PWS.

1. Develop, maintain, and implement DAIDS RSC Standard Operating Procedures (SOPs) used by DAIDS and Contractor personnel to carry out all RSC regulatory support responsibilities. SOPs shall be reviewed, and modified by the Contractor, and approved by the Contracting Officer’s Representative (COR). Within 14 business days of receipt of comments from the COR and other designated DAIDS staff, electronic versions of the SOPs shall be made available by the Contractor to appropriate DAIDS staff. Electronic SOP versions shall be posted by the Contractor on the secure password protected/limited access RSC website.

2. Use various information systems:

a. NIAID-Clinical Research Management System (N-CRMS): The N-CRMS is a comprehensive information system that supports many of the clinical research management and oversight responsibilities of DAIDS. The Contractor shall use the following N-CRMS components: Master Contact, Protocol Management, Protocol Registration, Protocol Development Tracking, Investigational New Drug Application Management, Clinical Site Monitoring, Adverse Experience Reporting System, Adverse Experience Processing System, and others as designated by the COR.

Performance Work Statement 3 ATTACHMENT

b. FDA Electronic Submissions Gateway (ESG): For electronic submission of documents to the FDA http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/default.ht m

c. NIAID interface for electronic Common Technical Document (eCTD) publishing

d. ClinicalTrials.gov website: (http://clinicaltrials.gov)

e. NIAID clinical trial networks’ Data Management Centers (DMCs)

3. Complete all tasks in compliance with all applicable U.S. and in-country regulations as well as NIH, NIAID, and DAIDS policies and procedures.

4. Interface with the appropriate entities, and comply with the format of the deliverable output(s) and timelines, which include review and approval by DAIDS staff.

5. Provide support for operational meetings and teleconferences with HA and DAIDS collaborators: Prepare draft formal meeting request and briefing packets as well as meeting minutes, final documents should incorporate all DAIDS’ comments;

and track action items as directed by the COR and per DAIDS-provided timelines.

For meetings with HA, follow all applicable rules, regulations and guidances as well as DAIDS SOPs.

6. Provide support for training related to tasks under this contract, such as safety reporting and protocol registration.

a. The Contractor shall provide any or all of the following support as directed by the COR: administrative and logistical support, develop, conduct, and assess effectiveness of the training and develop and administer tests approved by the COR.

b. Training may be conducted in a variety of ways, for example, in-person, web-based or pre-recorded.

c. Training may be provided to a variety of NIH, contractor and collaborator staff at a variety of venues or at a location provided by Contractor.

d. Training may also be targeted to address recurring problems at certain clinical research sites and across sites.

7. Other Support:

a. Provide other administrative support such as development of technical templates, copying, posting, tracking, delivery (paper copy and electronic) and distribution of documents (using various mechanisms), tracking status of projects, and providing reports such as Monthly highlights within 10 business days following each monthly reporting period, as directed by the

COR.

b. Provide Help Desk/customer service support for tasks under this contract during normal business hours (Monday through Friday, 8:00 am-5:00 pm Local Time).

c. Provide pertinent information to other DAIDS contractors and collaborators (such as information related to safety report identification).

B. IND and other Regulatory Support Provide technical and administrative support, in compliance with HA and DAIDS timelines, to DAIDS staff for the processing and maintenance of a variety of U.S. and non-U.S. DAIDS-held regulatory filings and related regulatory activities. Support

Performance Work Statement 4 ATTACHMENT shall include the following and other related tasks as directed by the COR. For clinical trials involving non-DAIDS sponsorship, the Contractor may be responsible for carrying out a subset of the following functions.

1. Preparation of Regulatory Filings Draft, prepare, publish, distribute and track complete and accurate documents for DAIDS-sponsored regulatory filings in accordance with all applicable U.S. and in-country regulations, and NIH and DAIDS templates and relevant SOPs (see https://ecollab.niaid.nih.gov/readingroom/DAIDSRSC) and DAIDS-determined timelines. Publish eCTD-compliant documents and convert non-compliant documents to a compliant format using NIAID-provided eCTD software for submission to DAIDS-held INDs through the U.S. FDA ESG as directed by DAIDS.

2. Regulatory Submissions Submit DAIDS-approved documents to national HA (such as U.S. FDA). Prepare and deliver Submission Status Summary Reports, Status Summary Reports of IND Annual Reports, and other regulatory documents and reports as directed by the COR.

3. Additional Support Services

a. Obtain, duplicate, and distribute Investigators’ Brochures (IBs), IB updates, package inserts, and updates to HA and to relevant organizations and relevant personnel per DAIDS-approved SOPs.

b. Distribute DAIDS documents to relevant organizations and personnel per DAIDS-approved timelines.

c. Maintain paper copy and electronic files of all HA (e.g., FDA) correspondence and submissions for DAIDS-sponsored clinical trials.

d. Provide technical assistance in the development and implementation of regulatory strategies and approaches for design and submissions to the FDA and other regulatory health authorities.

e. Maintain and update data in relevant N-CRMS components. Ensure that systems are in alignment with and support current DAIDS business processes, and conform to DAIDS business rules and data standards, and are fully integrated within the N-CRMS architecture.

f. Provide, use, support and maintain desktop configurations that satisfy NIAID security requirements to access the NIAID eCTD system.

C. Safety and Pharmacovigilance Assist DAIDS staff with safety and pharmacovigilance activities within timeframes that meet all applicable requirements and conform to DAIDS SOPs, such as:

1. Safety Reporting and Safety Information Distribution Prepare and distribute safety-related information:

a. Receive, process, evaluate, triage, prepare and distribute Adverse Experience Safety Reports (i.e., Serious Adverse Events [SAEs] and/or Expedited Adverse Events [EAEs]) reported by sites participating in DAIDS-supported clinical activities. Use the N-CRMS DAIDS Adverse Experience Reporting System (DAERS). Include review by the DAIDS Medical Officer.

b. Prepare interim and final Adverse Experience Safety Reports with a Compliance Statement in appropriate formats to meet applicable timelines and that include all information required by all applicable regulations and DAIDS SOPs.

Performance Work Statement 5 ATTACHMENT

c. Generate and maintain periodic (daily, weekly, monthly and ad hoc) status reports for compliance with Adverse Experience Safety Reporting requirements, contractor performance, etc.

d. Distribute Safety Information such as Safety Memoranda, Safety Reports, Safety Notices, Package Inserts, IBs with a summary of changes (if available), Data and Safety Monitoring Board (DSMB) reports, other serious safety information (e.g., DAIDS Safety Alerts, information from company collaborators) and DAIDS policy notices. Provide instructions to clinical research sites on site responsibilities related to the disseminated safety information.

2. Pharmacovigilance and Safety Data Code, reconcile and analyze safety data:

a. Provide Medical Dictionary for Regulatory Activities (MedDRA) coding of safety data as specified by the COR;

b. Participate in the cross-center consistency check activity (to ensure that adverse experience data are coded consistently and uniformly) and in relevant Working Groups as directed by the COR;

c. Conduct two-way reconciliation of Safety Data with DMCs per DAIDS-approved timelines;

d. Implement ICH E2B Compliance of Safety reports and other safety data outputs;

e. Assist DAIDS in performing ongoing analyses of safety data (to include AE data from DMCs);

f. Support weekly and ad hoc electronic data interchange of safety data reported to the RSC, to the central database of each DAIDS HIV/AIDS Clinical Trials Network (such as Network DMCs);and

g. Collaborate with DAIDS to implement weekly and ad hoc electronic data interchange of AE data reported on case report forms (CRFs) received by DAIDS-supported DMCs to DAIDS.

3. Other RSC Safety Office Support Services Provide other support as directed by the COR (generate status reports, respond to requests for information, assist in other projects, etc.) per DAIDS-approved timelines. The Contractor shall:

a. Prepare and submit to the COR and other DAIDS staff a daily report on status of 7-day and 15-day IND Safety Reports as well as Adverse Experience/Safety reports to other HA;

b. For IND annual reports and other periodic reports, compile accurate, complete data, reconciled with DMC data;

c. Generate SAE/EAE summary reports for specific studies, study agents, and by type of SAE/EAE;

d. Prepare and provide monthly and quarterly safety summary reports to each HIV/AIDS Clinical Trials Network by study and study agent;

e. Respond to queries on pharmacovigilance and the safety databases;

f. Provide support for DAIDS projects such as performing literature searches, summarizing literature reviews, gathering country-specific safety reporting requirements, and developing country-specific safety data reporting process documents.

Performance Work Statement 6 ATTACHMENT

g. Develop, implement and maintain quality assurance/ quality control (QA/QC) procedures.

D. RSC Website and Information Systems Maintain, and update an N-CRMS-independent RSC government-labeled website and other RSC-related databases/applications that will interact with the DAIDS clinical research system, with Network DMCs and the NIAID Office of Cyber Infrastructure and Computational Biology (OCICB). All infrastructure and software lifecycle activities associated with the N-CRMS will be performed by the N-CRMS contractor.

Specifically, the Contractor shall:

1. RSC Databases/Information Systems Maintain the RSC related databases/applications to Government requirements for scheduling, tracking, reporting, storage, modification, transmission, and disposition of all work and work products generated under this contract. These databases/applications shall provide for the following features and capabilities:

a. Generation of customized reports on a broad range of RSC functions and the status of specific regulatory activities.

b. Analysis of and reporting on the use of RSC resources and time required to complete regulatory requirements, etc., as directed by the COR.

c. Appropriate backup systems to restore the data and functionality.

2. RSC Website Maintain and update a reliable, secure and user friendly RSC Government-labeled website that serves as an information source for DAIDS staff, DAIDS-supported clinical investigators and other clinical, operations and data management staff.

The website shall be independent of the N-CRMS and house and provide easy access to all required documents as directed by the COR.

E. Coordinate and Collaborate with NIAID Clinical Research Management System (N-CRMS) or Alternative Information Technology System Contractor:

1. Coordinate and collaborate with the N-CRMS contractor staff in order to assure efficient systems and data integration in support of DAIDS. Enter, update and facilitate interchange of RSC information with the relevant N-CRMS systems, or if necessary into an alternative DAIDS clinical research system as directed by the COR and in compliance with all applicable standards, regulations and policies.

2. As needed, adapt local/internal Contractor data management systems and develop/deploy data interchange mechanisms required to receive, store and exchange data with and from the N-CRMS, or alternative, in accordance with specifications provided by the COR (e.g., N-CRMS specified software Application Programming Interfaces (APIs), eXtensible Markup Language (XML)-based web services, XML Schema Definitions (XSD), RDBMS, .NET Framework, UDDI, IIS, Internet Explorer, Service Oriented Architecture (SOA), Design Patterns, Frameworks and Templates, Microsoft Office, web browsers, etc., including specific versions thereof). The Contractor shall adhere to these guidelines and standards on a continuous basis.

3. Provide input in identifying requirements and specifications for new functionality within the N-CRMS system, or alternative, and adapt to new system features implemented by DAIDS.

Performance Work Statement 7 ATTACHMENT

F. Protocol Registration

1. Receive, process, and track all protocol registration materials supporting DAIDS

IND and non-IND studies in compliance with DAIDS SOPs and DAIDS-approved timelines.

2. Provide support to DAIDS staff for protocol registration by maintaining electronic registration records in N-CRMS Protocol Registration to ensure that all clinical research sites conducting DAIDS–supported and/or-sponsored clinical research do so in compliance with all applicable regulations governing human subjects protection and the use of investigational drugs, biologics and/or devices as well as NIH, NIAID, and DAIDS SOPs and policies and in compliance with DAIDS SOPs and DAIDS-approved timelines. Support includes but is not limited to the following:

a. Receive, process, review and track all protocol registration documentation (i.e., IRB/EC documents, site IC forms);

b. Prepare and distribute protocol registration reports to DAIDS staff and collaborators;

c. Provide instructions to DAIDS clinical research sites on site responsibilities related to protocol registration requirements;

d. Notify appropriate DAIDS staff and collaborators of protocol registration approvals; and

e. Provide other support as directed by the COR (generate status reports, respond to requests for information, assist in other projects, etc.).

G. Clinical Study Information

1. Receive, post, distribute, and track draft and final versions of protocols, protocol amendments, and related information submitted to DAIDS using the N-CRMS Protocol Management (PM) module to DAIDS staff and collaborators to meet DAIDS-approved timelines.

2. Track and enter protocol statuses, milestones, and event changes during the lifecycle of DAIDS-supported clinical trials/studies into N-CRMS.

3. Maintain an up-to-date electronic document library with copies of study-related documents per DAIDS SOPs.

4. Abstract data elements from the clinical documents and enter into the N-CRMS per DAIDS-approved timelines.

5. Enter and update information in N-CRMS Master Contact (MC) module per DAIDS-approved timelines. This includes contact information for DAIDS staff and collaborators, such as pharmacies, laboratories, pharmaceutical companies and other personnel.

6. Detect and resolve discrepancies in data entered into N-CRMS.

H. Clinical Trial Agreements (CTAs) and Other Research Agreements

1. Provide support to DAIDS, in compliance with limitations imposed by the Federal

Guidelines on Inherently Governmental Functions and NIH Policy on Relations with the Office of General Counsel, for the preparation, negotiation, finalization, distribution and tracking of CTAs and other research agreements (e.g., Confidential Disclosure Agreements) using DAIDS-approved templates.

2. Maintain records of CTAs and other agreements, track the documents and negotiation milestones in the N-CRMS Protocol Development Tracking module, and provide status reports as directed by the COR.

Performance Work Statement 8 ATTACHMENT

I. Human Subjects Protection (HSP) Provide assistance to the DAIDS staff in the review of sample informed consent (SIC) documents and their translations, and maintenance and distribution of informed consent (IC) templates.

1. Review SIC documents at various stages of protocol development as well as site-specific IC forms, for the following:

a. compliance with all applicable international, Federal regulations, NIH, and DAIDS policies and all in-country requirements for studies outside of the U.S.,

b. consistency with IBs and/or package inserts

c. consistency with the protocol

2. Translate SIC documents to other languages as directed by the COR.

3. Maintain and distribute to applicable parties all DAIDS IC templates used to prepare the SICs for all protocols sponsored by DAIDS. Maintain the templates on the RSC website.

J. DAIDS Scientific Review Committees (SRCs) Provide administrative, technical and scientific support for the SRCs used by DAIDS for programmatic and regulatory review of clinical documents (such as protocols and SIC documents)…