CSS W81XWH21R0078-02-2FEB2021-Changes.docx

W81XWH21R0078-02

This is a combined synopsis/solicitation for commercial items prepared in accordance with Federal Acquisition Regulation (FAR) Subpart 12.6, Streamlined Procedures for Evaluation and Solicitation for Commercial Items, in conjunction with the policies and procedures for solicitation, evaluation and award prescribed in FAR Part 15-Contracting by Negotiation, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and no other solicitation will be issued. The solicitation number is W81XWH21R0078.

The solicitation is issued as a Request for Proposals (RFP). Provisions and clauses in effect through Federal Acquisition Circular 2021-02 are incorporated. It is the offeror’s responsibility to be familiar with the applicable clauses and provisions. The clauses may be accessed in full text at: https://www.acquisition.gov/far/.

The NAICS Code is 541990, with a small business size standard of $16.5 million. The requirement is full and open with no set-aside restrictions.

The contract shall be a single award Indefinite-Delivery Indefinite-Quantity (IDIQ) contract with an ordering period of five (5) years plus five (5) one-year optional periods. All services to be ordered under this contract shall be set forth in individual task orders. The base contract will not be funded. Funds will be obligated on task orders written against this contract.

The minimum guarantee is $1,000,000 over the life of the contract. The anticipated maximum ceiling amount for this requirement is $95,000,000 for the entire ordering period.

PERFORMANCE WORK STATEMENT

PERFORMANCE WORK STATEMENT (PWS)

For Regulated Activities Support

Original Date: 22 Dec 2020

Revised Date: 7 Jan 2020

Title: REGULATED ACTIVITIES SUPPORT

Requiring Activity/Agency Name: Office of Regulated Activities (ORA), U.S. Army Medical Research and Development Command (USAMRDC)

1.0 Scope: The scope of this contract is for (1) regulatory consultation, (2) regulatory oversight, and (3) Contract Research Organization (CRO) support to include administrative, financial, clinical, nonclinical, manufacturing and regulatory support for drugs, biologics, and devices within an integrated product team framework as specified in the performance work statement (PWS). Work performed under this contract is deemed to be non-personal and severable in nature.

2.0 Background:

The USAMRDC is committed to develop safe and effective medical products for the Warfighters. In order to accomplish that mission, products must be developed using approaches that are compliant with all relevant regulations and ensure the protection of human subjects used in research.

USAMRDC is the Army's premier medical materiel developer responsible for medical research, development, acquisition, and medical logistics management. The USAMRDC's expertise in these critical areas helps with establishing and maintaining the capabilities the Army needs to fight and win on the battlefield. Currently, the USAMRDC medical research laboratory subordinate commands (subcommands) execute the science and technology programs to investigate medical solutions for the battlefield with a focus on various areas of biomedical research, including military infectious diseases, combat casualty care, military operational medicine, medical chemical and biological defense, and clinical and rehabilitative medicine. The Command manages a large extramural research program with numerous contracts, assistance agreements, cooperative research and development agreements, and other transactions to provide additional science and technology capabilities from leading academic, private industry, and other government organizations.

The USAMRDC subordinate laboratories and Military Health System (MHS) facilities that conduct, contract, sponsor, support, or manage the Department of Defense (DoD)’s medical product research and development research are entrusted with the responsibility of working with the Sponsor’s representative and the ORA to ensure data and reported results are credible and accurate, the rights and confidentiality of trial subjects are protected, and study integrity is maintained.

On 16 January 2018, the Commanding General, USAMRDC, designated ORA as a stand-alone office with direct reporting to the Deputy Commanding General, USAMRDC.

ORA provides regulatory support for DoD drug, biologic, device, and combination products from product concept to products in the advanced development pipeline (Phase 1-3). ORA currently maintains over 80 Investigational New Drug (IND) applications, 11 Master Files (MF), 2 Emergency Use Authorizations (EUAs), 1 Biologics License Application (BLA), and 3 New Drug Applications (NDAs). In FY19, The Surgeon General, Department of the Army (TSG-DA) had over 105 medical product development efforts with approximately 30 active studies and 339 submissions including 80 annual reports, 39 response to FDA request for information, 22 information amendments, 4 initial IND applications, 4 final clinical study report, and 3 original applications (NDA). Products include biologics, blood products, drugs, orphan drugs, and some devices. ORA support services include regulatory strategy and advice, data management, pharmacovigilance, biostatistics, product technical services and support, clinical monitoring, regulatory, publishing, and submissions to the Food and Drug Administration (FDA). Support is provided by a combination of civilian personnel, on-site Contractor personnel, and off-site Contractor personnel. The level of civilian and on-site contract support remains relatively stable; however the number of tasks and amount of support required vary based on the number of ongoing projects and the requirements for those projects.

3.0 Objective: The primary objective of this contract is to provide administrative, financial, regulatory, clinical, nonclinical, manufacturing, product accountability and quality support for drugs, biologics, and devices to support the medical product development mission as is necessary to facilitate full program coordination, management, policy development, execution, and oversight across all of ORA.

4.0 General Information:

4.1 Ordering Period

The estimated ordering period for this contract is (actual dates will be specified in the contract at time of award):

Base Period – Date of Award through 60 months of performance.

Option Period 1 – Expiration of Base Period through 12 months of performance.

Option Period 2 – Expiration of Option Period 1 through 12 months of performance.

Option Period 3 – Expiration of Option Period 2 through 12 months of performance.

Option Period 4 – Expiration of Option Period 3 through 12 months of performance.

Option Period 5 – Expiration of Option Period 4 through 12 months of performance.

4.2 Place of Performance

The Contractor may be required to perform at the Government’s facility, located at Fort Detrick, MD 21702, or the Contractor’s facility; this will be defined at the task order level. Contractor personnel (including those performing off-site) may be required to attend meetings in person at locations that include but are not limited to Fort Detrick, Walter Reed Army Institute of Research (WRAIR), other facilities, or via teleconference as specified by Government at the task order level. The Government will provide at least 24 hours notice when requesting in person Contractor attendance.

Contractor personnel working off-site shall be required to obtain a Personal Identity Verification (PIV) Card in order to use ORA Electronic Document Management System (EDMS) Livelink for document storage and/or delivery and USAMRDC intranet and extranet (i.e., SharePoint). In order to get the publishing output and/or remediate documents, all work must go through EDMS, which can only be accessed with a PIV Card. Users are not required to come to Fort Detrick or any military facility to get the PIV card and reader. However, they shall be required to take Information Awareness training, and provide the completed IdenTrust Forms Packet to the USAMRDC Enterprise Information Technology Project Management Office.

4.3 Hours of Operation

The Contractor shall be available to conduct business, Monday through Friday during the core business hours of 0900 – 1500 Eastern Time, except recognized Federal holidays (see PWS section 4.4) or when the Government facility is closed due to local or national emergencies, administrative closings, or similar Government directed facility closings. For on-site support, alternate work sites and/or telecommuting requests will be addressed at the task order level. At the task order level, on-call support may be required.

4.4 Recognized Federal Holidays

The Contractor is not required to perform services on the following recognized Federal Holidays:

New Year’s Day Dr. Martin Luther King Jr.’s Birthday Washington’s Birthday Memorial Day Independence Day Labor Day Columbus Day Veterans Day Thanksgiving Day Christmas Day

4.5 Type of Contract

This is an indefinite-delivery indefinite-quantity (IDIQ) Contract. Task orders issued under the IDIQ may be firm-fixed-price or time-and-materials.

4.6 Contracting Officer’s Representative (COR)

The COR for this contract shall be assigned via a separate appointment letter. The Task Order COR (TO-COR) for each task order issued under this contract shall be assigned via a separate appointment letter at the task order level. The COR monitors all technical aspects of the contract and assists in contract administration. The COR is authorized to perform the following functions: assure that the Contractor performs the technical requirements of the contract; perform inspections necessary in connection with contract performance; maintain written and oral communications with the Contractor concerning technical aspects of the contract; issue written interpretations of technical requirements, including Government drawings, designs, specifications; monitor the Contractor's performance and notify both the Contracting Officer (KO) and Contractor of any deficiencies; coordinate availability of Government furnished property; and provide site entry of Contractor personnel. A COR appointment letter will issued to the COR, a copy of which will be sent to the Contractor, stating the responsibilities and limitations of the COR, especially with regard to changes in cost or price, estimates or changes in delivery dates. The COR is not authorized to change any of the terms and conditions of the base contract or resulting task orders.

The COR/TO-COR will have ten (10) business days to review draft deliverables and make comments. The Contractor shall have five (5) business days to make corrections. Upon receipt of the final deliverables, the COR will have two (2) business days for final review prior to acceptance or providing documented reasons for non-acceptance. Should the Government fail to complete the review within the review period, the deliverable will become acceptable by default, unless prior to the expiration of the ten (10) business days the Government notifies the Contractor in writing to the contrary. The final submission should be deemed approved if the Government has not rejected it in 30 calendar days.

The COR will have the right to reject or require correction of any deficiencies found in the deliverables. In the event of a rejected deliverable, the Contractor will be notified in writing by the COR of the specific reasons for rejection. The Contractor shall have five (5) workdays to correct the rejected deliverable and return it per delivery instructions.

5.0 Performance Requirements:

The Office of Regulated Activities (ORA) provides regulatory and clinical support for the life cycle development of FDA-regulated medical products sponsored by The Surgeon General, Department of the Army, as well as other studies of interest to the Department of Defense Sponsored by other organizations. ORA has a requirement for contract services to provide various levels of support as defined below to enable product development of medical products, enable submissions to the FDA, and ensure all Code of Federal Regulations (CFR) Sponsor responsibilities are met in a manner consistent with FDA guidance and industry best practices.

This contract requires a mix of consultation, oversight and contract research organization services (CRO), support in the following areas listed below.

· Regulatory Business Support

· Planning, Programming, Budgeting, and Execution

· Administrative Support

· Regulatory Management

· Regulatory Project Management

· Regulatory Affairs

· Clinical Trial Management

· Clinical Trial Monitoring

· Data Management

· Biostatistics

· Pharmacovigilance

· Investigational Product and Chemistry, Manufacturing, and Controls

· Nonclinical Support

· Medical Writing

· Regulatory Operations

· Publishing

· Document Control

· Quality

· Training

· Document Translation

The term “support” throughout this document refers to any activity (nonclinical, manufacturing, and clinical) required to meet any FDA Sponsor requirement, including but not limited to 21 CFR and International Council on Harmonisation (ICH) guidelines; applicable DoD and Army regulations (AR), directives, policies, and procedures; and, in some cases, industry standards for the development of medical products to include drugs, vaccines, devices, and combination products. Support may include preparing, developing, writing, reviewing, editing, evaluating, implementing, executing, archiving, or any combination thereof as described in the task order. The Contractor shall provide support at the consultation, oversight, or CRO full support level as specified in the task order.

Consultation support includes providing subject matter expertise regarding drug, biologic, device, and/or combination product development strategies and activities using knowledge of 21 CFR, FDA guidance documents, ICH documents, and/or industry standards as appropriate. Consultation support may include but is not limited to the review of protocols, other regulatory documents, and nonclinical and manufacturing product development activities to determine compliance with the FDA regulations, guidance documents, and other best practices. On an as needed basis, the Contractor may provide peer review of the Congressionally Directed Medical Research Program clinical trial proposals. The Government anticipates 50 regulatory projects (e.g. clinical, nonclinical, and manufacturing) will require regulatory consultation support each year.

Oversight support deals with the Sponsor’s responsibilities as defined in Army Regulation 40-7, 21 CFR, ICH, and either Government standard operating procedures or Contractor standard operating procedures that have been reviewed and approved by the Government. Oversight support includes providing coordination, direction, review, and evaluation of regulatory documents, which individually and collectively serve to demonstrate compliance with Good Clinical Practices and all other applicable regulatory requirements and permit evaluation of the quality of the data produced. Consultation includes liaising with appropriate functional areas, including internal and external stakeholders, to obtain missing information/data required to accomplish the assigned tasks; providing a written plan/gap analysis in the form of a checklist to ensure that regulatory deliverables are in compliance with all applicable regulations, and have input from the technical subject matter experts such that the appropriate levels of FDA compliance requirements/expectations are met; and ensuring the safety of study subjects using the Government’s risk-based decision making process. The Government estimates approximately 50 regulatory projects (e.g. clinical, nonclinical, and manufacturing) will require regulatory oversight each year. These are typically TSG-DA Sponsored products in which the bulk of regulatory deliverables are produced by a CRO.

Contract Research Organization (CRO) Full Support includes coordination, management, development, execution, documentation, review, and evaluation of clinical, nonclinical, and manufacturing activities, as appropriate. Full support includes provision of a written plan in the form of a checklist that includes gap analyses and the necessary regulatory oversight to ensure that regulatory deliverables are in compliance with all federal and state codes, Army regulations as defined in AR 40-7, and harmonization standards, are in accordance with either Government standard operating procedures or Contractor standard operating procedures that have been reviewed and approved by the Government, as determined by the Government, and ensure audit readiness. The Government estimates 10-15 ongoing clinical studies (typically Phase 1 and 2) will require full regulatory support each year. Other than active clinical trials the Government estimates that approximately 30 projects that will require full support for Regulatory Science and Regulatory Operations support, 30 projects will require full support for Clinical Trial Management, and 20 projects that will require full support for Investigational Product Management Support.

At all levels of support, the Contractor shall ensure that all tasks listed below are performed in accordance with FDA regulations and guidance and DoD, Army, USAMRDC, and ORA regulations, policies, and procedures. All tasks described below may require support in the development of contracting strategies and documents, including procedures and policies. For specific acquisition and product development projects and programs, Contractor personnel shall become familiar with and understand the DoD 5000 and the associated acquisition processes and procedures, as well as USAMRDC tailoring of those policies through the Decision Gate (DG) process.

Task 5.1 Regulatory Business Support:

The Contractor shall provide regulatory support (consultation, oversight, or full support) to the ORA Business Office and work closely with the ORA subject matter experts to provide regulatory business and project management support. Personnel supporting these tasks shall be knowledgeable of and able to apply project management skills and FDA product development requirements to facilitate required tasks and interactions with multiple customers, internal and external to ORA, for the development of medical products.

Sub-Task 5.1.1 Planning, Programming, Budgeting, and Execution:

The Contractor shall provide financial management support for Planning, Programming, Budgeting, and Execution (PPBE) applying the pertinent laws, regulations, policies, procedures, and work processes to requirements for product development. It is important to note that ORA operates on a cost reimbursable basis, so there is a large emphasis on budget preparation and tracking. PPBE support includes but is not limited to the following

· Provide financial planning for regulatory business functions including analysis of workload and resource planning

· Assist with support plan development and coordinate with ORA subject matter experts through email and workspace collaboration in EDMS and SharePoint; coordinate and facilitate required interactions with multiple regulatory customers via email and teleconference

· Assist in the establishment, maintenance, and facilitation of processes within established manuals and handbooks to include the analysis of support needed by external customers

· Provide business metrics tracking. Track and report support plan and agreement outputs, financial execution status, progress against agreements, and personnel requirements against plans

· Coordinate and consolidate financial input from the applicable financial systems on obligation and disbursement status of the organization’s product portfolio into monthly financial reports; provide status briefing on the funds and other essential financial indicators; provide input for the current, annual, and future years Program Objective Memorandum (POM); provide periodic updates to financial plans, including planned release schedules and noting current fiscal year activity; submit reports used to brief senior management and external funding organizations; and assist in clearing obligations prior to fund expiration

· Provide and analyze programmatic planning, budget formulation, cost estimation, and execution data reports

· Provide assistance with product-specific medical materiel development budget formulations, justifications, and oversight monitoring (cost, schedule, performance); prepare cost estimates for ORA services/functions for technology base or advanced development products, which includes tracking hours for ORA deliverables against product estimates

· Draft agreements (e.g., clinical trial agreements, quality management plans, protocols, etc.) that identify the scope, roles, responsibilities, tasks, and deliverables to be performed by ORA and/or its delegated parties

· Facilitate strategy development to produce integrated, all-inclusive regulatory support proposals for the total lifecycle of the projects

· Monitor the acquisition process in designated data systems and ensure contracts, grants, or other agreements are funded as outlined

· Maintain project and grant/contract financial reports (planned expenditures to invoiced expenditures) and coordinate with funding chain personnel in other organizations or commands

· Prepare budget advisory council forms, executive summaries (EXSUMs), and purchase requests

· Maintain all budget estimates and actual hours spent supporting products

· Maintain product support data, including direct product support versus indirect full-time equivalent percentages for the organization staff

Sub-Task 5.1.2 Administrative Support:

The Contractor shall provide administrative support to the ORA and serve as the subject matter expert on administrative related tasks. Examples of support include but are not limited to the following

· Maintain ORA calendars, personnel contact information, and emergency contact information in organized spreadsheets

· Prepare and review documents IAW Army regulation and ORA policies and procedures

· Use the Defense Travel System to assist with and track travel according to Army policy in organized spreadsheets

· Provide administrative support for the Sponsor’s Protocol Review Board (PRB) to include but not limited to receiving protocol packages, scheduling meetings, coordinating schedules, communicating with PRB members and other ORA personnel, and using the EDMS

· Assist with and ensure new staff is properly in-processed IAW USAMRDC and ORA policy and by updating applicable Organizational Charts/Rosters and Contact Lists

· Participate in administrative meetings, prepare and/or disseminate associated information and guidance to personnel, and render assistance in the interpretation, implementation, and operation of administrative processes

· Coordinate and schedule ORA meetings, seminars, trainings, ceremonies, video teleconferences, Defense Connect Online sessions, etc.), prepare and/or disseminate the associated information when requested, alert staff to impending meetings and appointments, and be able to de-conflict meetings and other events

· Serve as ORA’s accountability representative during building evacuations

· Archive documentation in EDMS, OneNote, SharePoint, the Army Records Information Management System (ARIMS) or other system

· Track and document all taskers assigned to ORA, and, when requested, collect data by the designated suspense date

· Account for durable property according to applicable local policies

· Act as the liaison with other branches and divisions to assure coordination and commonality of effort in specific program areas and maintain an informal administrative communication network

· Use Microsoft Word, PowerPoint, Excel, and Outlook

· Perform a variety of other administrative support services, to include but not limited to controlling visitor access; answering telephones; filing, faxing and copying documents, creating business cards, and receiving office supplies and equipment, and maintenance of records in accordance with Army and ORA policy

Task 5.2 Regulatory Management:

The Contractor shall provide regulatory support for performing activities to ensure compliance with all FDA Sponsor responsibilities, including 21 CFR 312.

Subtask 5.2.1 Regulatory Project Management:

The Contractor shall provide project management support to coordinate the planning, executing, monitoring, controlling, and closing of regulatory projects. Regulatory project management support includes but is not limited to the following

· Prepare and maintain project risk management plans

· Identify and mitigate cost, schedule, and performance risks

· Develop strategies for the efficient execution of regulatory projects, which include product development, specific regulatory submissions, and/or clinical trials

· Coordinate project status and review meetings and prepare, distribute, and maintain meeting agendas and minutes

· Prepare and maintain Gantt charts for projects

Subtask 5.2.2 Regulatory Affairs:

The Contractor shall ensure compliance with FDA Sponsor responsibilities, serve as a subject matter expert for regulatory strategy, to include identifying and mitigating risk, and provide support to integrated project teams and working groups for submissions to and communications with the Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, and Center for Devices and Radiological Health submissions. Regulatory Affairs support includes but is not limited to the following

· Provide subject matter expertise on all regulatory matters related to assigned regulatory projects; ensure ORA leadership and the sponsor’s representative are kept current on the progress of the program through periodic reports

· Provide regulatory support to an integrated product team or working group, which includes working with the team members, advising the team of any FDA-related activities and issues, and attending meetings, updating ORA leadership and the sponsor’s representative through routine reports

· Lead the development of a written regulatory strategy

· Create and maintain Target Product Profiles

· Identify and mitigate regulatory risk through a project Risk Register

· Serve as the primary contact with the FDA; review, analyze, and respond to FDA communications and meetings by the regulatory deadline

· Lead the development, organization, and structure of regulatory submissions and meeting minutes in EDMS

· Coordinate, prepare, write, review, obtain, maintain, and archive the required documents for regulatory submissions in EDMS

· Assist in writing and/or reviewing abstracts, papers, and publications, which shall be written in collaboration with the study team members and submitted to all appropriate approval authorities

· Confirm the need for registration, based on regulation and Army policy, and provide regulatory support for data entry and quality assurance of ClinicalTrials.gov information/entries, a Web-based resource that provides information on publicly and privately supported clinical studies on a wide range of diseases and conditions

· Review and provide critical regulatory feedback on acquisition milestone decision briefings, progress reviews, and other acquisition documents

Subtask 5.2.3 Clinical Trial Management:

The Contractor shall provide regulatory support for clinical trial project management, clinical development strategies, execution of clinical trials, and provision of clinical site training. Clinical trial project management includes but is not limited to the following

· Manage single site and multicenter clinical studies both inside and outside the continental United States; manage other entities supporting the conduct of clinical trials to ensure all sponsor required trial monitoring is conducted and all deliverables are received, providing updates to ORA leadership and sponsor’s representative through Gantt Charts or other acceptable tracking tool

· Develop and maintain a document inventory/version control log, which is used to document the version numbers, dates, sponsor approval date, institutional review board approval date, and any additional approval information for study protocols, informed consent forms, clinical monitoring plans, recruitment advertisements, diary cards, and any other pertinent study document; collect and file essential regulatory documents in accordance with ICH E6

· Write, review, and/or revise trial specific standard operating procedures or study specific procedures, including standard operating procedures for specific research, pharmacokinetic assays, or other testing not described in the trial procedure manual

· Provide regulatory inspection notifications and any report generated from an inspection or external audit to the sponsor

· Review and revise protocols, informed consent forms, and other study related documents to include the initial versions and amendments. This is including, but not limited to the informed consent, Investigators Brochure, source documents, study procedures manual, study specific procedures, pharmacy manual, FDA Form 1572, clinical trial agreement(s), and transfer of regulatory obligations documentation (FDA Form 1571 listing the obligations transferred).

· Coordinate, lead, or participate in study working groups, which include protocol development working groups, risk assessment groups, product or manufacturing working groups, and other working groups established by the integrated product team, and write or review the associated minutes

· Assist in writing and/or reviewing abstracts, papers, and publications, which shall be written in collaboration with the study team members and submitted to all appropriate approval authorities

· Enter data into and comply with the current regulatory and Army requirements of ClinicalTrials.gov, a Web-based resource that provides information on publicly and privately supported clinical studies on a wide range of diseases and conditions

· Prepare and/or review sample handling instructions to include volume of the sample, tube or container for collecting the sample, sample collection time points, special instructions for processing and storing samples, instructions on how and where to ship specimens, and documentation requirements for sample accountability, which may be part of Trial Procedure Manuals or stand-alone instruction manuals, standard operating procedures, or study specific procedures

· Develop study specific grading criteria, and use them to conduct viability assessments during site qualification visits to document whether or not a proposed clinical site and principal investigator meet the requirements for execution of the proposed clinical trial

· Prepare and/or review a final sample accountability log, which documents the disposition of all samples collected during the study and shall include the subject number, type of sample, and location of the sample (laboratory, storage unit identification, box number) for any samples remaining in storage

· Maintain and file monitoring and clinical trial management correspondence files, which includes emails and letters between the clinical monitor or clinical trial manager and the Sponsor that contain important clinical trial decisions or instructions

· Assist in investigator selection, which includes documenting the qualifications and experience of the investigator with, at a minimum, the curriculum vitae, current Good Clinical Practices and Human Subjects Protection training certificates, and the medical license (if applicable)

· Assist in monitor selection, which includes documenting the monitor’s qualifications and experience

· Collect and file essential regulatory documents in accordance with ICH E6

Subtask 5.2.4 Clinical Trial Monitoring:

The Contractor shall provide clinical trial monitoring to ensure all sponsor required trial monitoring is conducted and all deliverables are provided according to 21 CFR 312 and ICH. Clinical trial monitoring includes but is not limited to the following

· Develop a Clinical Monitoring Plan and monitor single site and multicenter clinical studies both inside and outside the continental United States; when required, conduct centralized monitoring activities to include remote review of electronic source documents, electronic Case Report Forms (CRFs), trends, and metrics in order to identify and mitigate safety and data quality risk issue(s), prepare Clinical Monitoring Reports and file in the sponsor’s regulatory file.

· Prepare protocol deviations and violation and non-compliance reports

· Provide remote evaluation of the study data, carried out by a team including central monitors, medical reviewers at a location other than the sites at which the clinical investigation is being conducted.

· Prepare/review calibration and maintenance records, which are records kept at the clinical site that document the calibration and maintenance of all applicable equipment utilized during the execution of the clinical trial including laboratory equipment, and ensure equipment is adequate, current, and accessible and annotate this information in monitoring reports for the sponsor’s regulatory file

· Prepare and/or review shipment records, which include shipping documentation for investigation products, biological samples, and if applicable, other study supplies provided to the clinical sites

· Prepare and/or review laboratory sample analysis reports

Subtask 5.2.5 Data Management:

The Contractor shall provide support for regulatory data management according to the applicable regulations, guidance, and standards using a Government and/or Contractor, as determined by the Government, 21 CFR Part 11 compliant clinical data management system. Data management support includes but is not limited to

· Develop a Data Management Plan, which is a comprehensive document developed to describe all data management activities and their processes and implementation during pre-study conduct, study conduct, and study closure and that reflect Good Data Management Practices based on good Clinical Data Management Practices, Good Clinical Practices, and ICH guidelines.

· Develop CRFs, which are a series of questionnaire forms used as a data collection instrument for accurately and completely capturing the data required by the clinical protocol, that meet the FDA submission requirements and conform to Clinical Data Interchange Standards Consortium (CDISC)/Clinical Data Acquisition Standard Harmonization (CDASH) standards and Study Data Tabulation Model (SDTM) controlled terminology

· Develop and maintain study-specific database, CDASH annotated CRFs, which are the blank CRFs with the markings of the corresponding CDASH variable names, variable labels, data type and length, associated code lists, and data domains. The CDASH Annotated CRFs shall reflect the raw data extracted from the Clinical Data Management System and prior to the transformation into the SDTM datasets

· Develop database specifications, which describe all of the study-specific design, testing, and validation requirements, following CDISC/CDASH standards and SDTM Controlled Terminology

· Perform and document database testing and validation (initial production release and post go-live), which consists of a plan describing the User Acceptance Testing and validation processes/procedures of the study-specific database, testing scripts/documents, and validation documentation and is in place prior to the initial database production release and all subsequent database modifications during the study conduct

· Develop technical support plans that include end user support and the development, modification, maintenance, testing, and validation of the protocol-specific Electronic Data Capture (EDC) database throughout the life of the trial

· Develop database training support plans, which describe the required trainings that shall be provided to end users, and the associated training materials, which may include but are not limited to agendas, course syllabi, attendance sign-in logs, etc.

· Create data listings and reports (e.g., metrics) that pertain to data management activities during study conduct

· Provide completed medical coding reports using Medical Dictionary for Regulated Activities and World Health Organization Drug Dictionary per the FDA and industry guidance, completed CRFs and related queries and audit trail reports, which document resolved queries during study conduct and closure and all database changes, the reasons data were changed/updated, timestamps (date and time), and who made the changes during study conduct and closure activities

· Provide documentation of how study data will be cross-checked and the outcome of the evaluation to ensure quality and accuracy before the study database is locked

· Document data reconciliation through a written report, which indicates that for data where the same data points are collected in more than one source, the applicable CRFs data in the Clinical Data Management System have been reconciled with data in the other system (to include but not limited to, the serious adverse event system and/or the external laboratory databases), prior to database lock

· Provide final raw data in SAS format compliant with CDASH and applicable CDISC standards prior to the transformation to SDTM datasets

· Provide other essential data management documents (e.g., medical coding conventions/guidelines, self-evident corrections), which are documents deemed necessary by the data management team to be important in describing data management activities

· Collect and validate laboratory data in an electronic and analyzable format and in compliance with CDISC

· Collect and manage data according to the applicable FDA regulations, FDA guidance, ICH, CDISC/CDASH Standards, and Good Clinical Data Management Practices

Subtask 5.2.6 Biostatistics:

The Contractor shall provide biostatistical support and deliverables that meet the applicable regulations, guidance, and standards, including industry standards (clinical and nonclinical). Biostatistical support includes but is not limited to the following

· Prepare, update, and maintain all versions of statistical analysis plans

· Prepare, update, and maintain all versions of statistical programming validation plans, and all versions of statistical programming validation reports; Develop and provide statistical program formats used in the statistical programs (all versions)

· Prepare, update, and maintain all versions of randomization plans including randomization list(s) and key(s), prepare statistical programs used to create randomization list(s) and key(s)

· Develop statistical programming specifications (clinical data) and other statistical programs used to produce the tables, listings, and figures for studies, all versions used for the Data Monitoring Committee, safety surveillance plans, FDA annual report, interim analyses (if applicable), and any ad hoc analyses

· Produce data-populated tables, listing, and figures for studies, the Data Monitoring Committee, safety surveillance plans, FDA annual reports, interim analyses (if applicable), and any ad hoc analyses

· Develop all versions of CDISC validation plans, and write and revise as necessary CDISC validation reports summarizing results from CDISC validation and including all output from the Pinnacle 21 Open CDISC validation software (or latest version of Open CDISC)

· Develop and revise as required statistical programming specifications used to create CDISC-compliant datasets, SDTM, Analysis Data Model (ADaM) datasets, and Standard for Exchange of Nonclinical Data (SEND) (for non-clinical data); Develop define.xml and define.pdf to include coding conventions used in the statistical programs (all versions) for CDISC datasets; Develop SEND datasets conforming to CDISC standards (non-clinical data); Develop SDTM datasets conforming to CDISC standards; Develop ADaM datasets conforming to CDISC standards as required

· Develop and update as required CDISC reviewer’s guides

· Provide responses to sponsor and FDA requests/queries regarding statistical products

Subtask 5.2.7 Pharmacovigilance:

The Contractor shall provide medical regulatory support for activities relating to the detection, evaluation, understanding, and prevention of adverse reactions to investigational products. Pharmacovigilance support includes but is not limited to the following

· Develop pre-market and post market safety surveillance plan(s) specific to products/protocols that include signal detection tools and templates necessary to implement the safety surveillance

· Develop and maintain safety management plan(s) that delineate the roles, responsibilities, processes, and timelines for safety activities) and drives the execution of the safety related activities during a trial

· Establish Data Safety Monitoring Boards/Committees, which includes identifying members, developing, reviewing and finalizing the initial Charter and any revisions

· Schedule and coordinate Data Safety Monitoring Board/Committee Meetings (organizational, in-process, executive, and ad hoc), including a face to face initial data safety monitoring board/committee organizational meeting at a central location within the continental United States, and provide an agenda

· Develop and prepare written Data and Safety Monitoring Board meeting minutes for each meeting per ORA Standard Operating Procedures (SOP).

· Provide the Data Safety Monitoring Board/Committee Chair Recommendation(s) form, completed and signed by the Data Safety Monitoring Board/Committee Chair within 24 hours of the meeting conclusion, documenting the Data Safety Monitoring Board/Committee decisions and recommendations to the ORA Safety Office

· Provide pharmacovigilance support that includes but is not limited to reviewing clinical protocols and associated documents, conducting literature searches, providing risk-benefit analyses, developing comprehensive risk mitigation plans, and writing white papers

· Provide pharmacovigilance guidance and subject matter expertise

· Receive, process, evaluate, and manage reported safety cases through electronic systems, such as Argus, which may include but are not limited to data entry and preparation of serious adverse event narratives, generating analyses of similar events, data element coding of event terms in the safety database utilizing the Medical Dictionary for Regulatory Activities and preforming quality control reviews of the entered data

· Monitor the safety mailbox at a minimum twice a day 7 days a week, to include weekends and holidays, for new incoming unexpected and related serious adverse events

· Triage safety reports, interpret clinical data, and perform regulatory evaluation for regulatory reporting purposes

· Track follow-up information /correspondence through to case closure

· Report serious adverse events to the FDA and other applicable regulatory authorities in accordance with 21 CFR 312.32 and 312.33, and ICH Guidelines

· Identify database cases eligible for archiving and assist with archiving all documents in compliance with government internal standards and regulatory guidelines

· Provide strategic input or oversight for regulatory documents including, but not limited to, IND application safety reports (MedWatch), annual reports, final clinical study reports

· Notify the investigator(s) of safety information, including expedited serious adverse events, according to Government procedures and in accordance with 21 CFR 312.32 and 312.33 and ICH Guidelines

· Manage and process reported pregnancy cases through electronic systems, which may include but is not limited to data entry and preparation of narratives, generating and sending follow-up queries as appropriate until term, generating analyses of similar events, data element coding of event terms in the safety database utilizing the Medical Dictionary for Regulatory Activities dictionary and performing quality reviews of data entered into the electronic data management system and other systems as applicable

· Reconcile data and documentation in the Safety Database and the Clinical Database at a minimum annually before the annual report and before study database lock

· Develop and/or review protocol specific documents and clinical safety documents including but not limited to clinical protocols, informed consent forms, investigator brochures, data monitoring committee charters, safety management plans, safety surveillance plans, safety-related source document and other associated clinical safety documents

· Develop a protocol/product specific unblinding plan prior to the start of a clinical trial

Subtask 5.2.8 Investigational Product and Chemistry, Manufacturing, and Controls:

The Contractor shall provide regulatory support for the development of manufacturing strategies and execution of investigational product activities throughout all phases of the product development to ensure compliance with the applicable regulations, guidance documents, policies, and standards. Investigational product and chemistry, manufacturing, and control support includes but is not limited to the following

· Provide investigational product and chemistry, manufacturing, and control support to integrated product teams or working groups, which includes working with the team members, advising the team of investigational product and chemistry, manufacturing, and control activities and issues, and attending meetings with the team and any industry partners; Develop strategies for and execute investigational product activities, including investigational product storage, shipment, and destruction, throughout all phases of the product development; Review and document investigational product accountability, which includes maintaining adequate product receipt, shipment, inventory, and distribution records including temperature logs; Provide input for the final formulation of the investigational product, which may require specific subject matter expertise (e.g. Small molecule formulations); Assist in developing product specifications (list of tests, references to analytical procedures, and appropriate acceptance criteria) for drug, biologic, devices, and combination products; Review product labels for compliance with applicable regulations and requirements; update ORA leadership and the sponsor’s representative through routine reports

· Write, review, and revise regulatory submission documents relevant to the investigational product, such as sections of the protocol relevant to investigational product, investigational brochures, and electronic Common Technical Document (eCTD) Module 2 and Module 3

· Release and document investigational product to clinical and nonclinical sites; Interact with the manufacturing and quality units conducting lot release functions and provide current Good Manufacturing Practices documentation for the investigational product; Review and document that the lot release documentation is adequate for the phase of development; Review the investigational product certificates of analysis and test data for product compliance with the pre-established specifications and to ensure test data are adequate for IND application submission and the phase of development; Update the sponsor’s product accountability system ; Maintain the product accountability log

· Write, review, and/or revise investigational product specific storage and handling instructions, which may be written in the investigational brochure, protocol, pharmacy manual or other document

· Assist in development of and review Design History Files

· Review product data to ensure they meet all established specifications and document and investigate any discrepancies (failures, Out of Specifications, Out of Trends, etc.) found in the testing records and including managing deviations, test anomaly reports and corrective and preventative action plans; communicate discrepancies through periodic reports to ORA leadership and sponsor’s representative as necessary

· Obtain and review investigational product shipment records to track product batch, review shipping conditions, and ensure product accountability and cold chain management; Facilitate import and export of investigational product and ensure compliance with all the applicable regulations and requirements; Manage Investigational Product requests and respond to investigational product requests/order forms by keeping the product accountability system up to date

· Add and maintain appropriate records in the Trial Master File (TMF)

· Review, maintain and store in the TMF the Trial Prescription Template and Template Order/Transfer Form

· Review investigational product temperature logs, document this review, and investigate any temperature excursions until resolution is achieved with a final report generated

· Document investigational product destruction using the Government provided process and form

· Evaluate and develop reports for candidate manufacturing sites by performing pre-award assessment visits, site qualification visits for various contract manufacturing organization, due-diligence visits, person-in-plant visits, sponsor audits, and or for-cause inspections

· Review master batch production records and document that the records are acceptable and in compliance with current Good Manufacturing Practices; Review batch production records, which are the executed master batch production records, and document that the records are adequate and in compliance with current Good Manufacturing Practices

· Review and revise stability protocols and reports and document that the protocols and reports are adequate for the product and the level of development and are in compliance with applicable regulations and requirements

· Develop, review, and/or revise bioanalytical/analytical method qualification and validation protocols and reports and ensure they are adequate for the phase of development and in compliance with the appropriate regulations and requirements

· Perform current Good Manufacturing Practices and…