FDA-RFP-19-1208111_61719.pdf

FDA-RFP-19-1208111

Clinical and Laboratory Applied Regulatory Science

PART I

SECTION A

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued.

This solicitation is a Request for Proposals (RFP). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2019-02. The applicable North American Industry Classification System (NAICS) code assigned to this procurement is 541714 -- Research and Development in Biotechnology (except Nanobiotechnology). Its associated Small Business Size Standard is 1,000 employees.

This requirement is for full and open competition. All responsible offerors are permitted to submit a proposal as a result of this combined synopsis/solicitation.

SECTION B - SUPPLIES OR SERVICES AND PRICES

B.1 SOLICITATION DESCRIPTION

The Contractor shall furnish all necessary facilities, materials, and personnel, and shall perform all non-personal services and program support necessary in a requirement titled, “Clinical and Laboratory Applied Regulatory Science.”

B.2 CONTRACT TYPE

In accordance with FAR 52.216-27, the government intends to make a single Indefinite- Delivery, Indefinite-Quantity (IDIQ) Contract award with the issuance of Time and Material, Labor Hour and Firm-Fixed (or hybrid) price individual orders. The structure of the contract shall be a five (5) year period.

B.3 CONTRACT CEILING

The IDIQ guaranteed minimum amount will be $5,000.00 over five (5) years. The contract maximum ceiling amount will be $30,000,000.00 over five (5) years.

B.4 PRICING

The pricing chart attached outlines the procedure and labor categories that are anticipated throughout the life of the contract. Minimum requirements for these categories are described in greater detail in Attachment 2. The Contractor shall provide services in accordance with the Statement of Work with fully loaded, fixed hourly rates. Task/procedure category pricing will be all inclusive (labor, materials, etc.). Only requirements not captured by the task/procedure menu/categories can be billed as Labor Hours or Time and Material. It is anticipated that Orders will have Material “pass through” pricing such as drug prices and study subject stipends that are standard for the phase 1 clinical research industry.

See Attachment 1 for the Estimated Overall Task/Procedure Priced Categories - menu items are all inclusive (labor, materials, etc.)

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

C.1 BACKGROUND

The United States Food and Drug Administration (FDA) has the need for Phase I-type clinical trial operations. In addition, the Agency needs execution of supportive laboratory studies related to bioanalytical/biomarker work, either as part of clinical trial execution or standalone. Overall, this would support a full range of services from Phase I protocol development through clinical trial executing, conducting supportive laboratory studies, and bioanalytical/biomarker services, where required.

The FDA has a mission to protect public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. In addition, FDA is responsible for facilitating innovations that make medicines more effective, safer, and more affordable. To accomplish these goals, FDA has stimulated advancement of regulatory science, which is defined as “the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA regulated products.” FDAs vision is to facilitate the integration of new science into the process of evaluating the safety and efficacy of proposed and marketed products and to close the gap between scientific innovation and this process of drug review. To achieve this vision, we perform mission-critical research to develop and evaluate tools, standards, and approaches to assess the safety, efficacy, quality, and performance of drugs.

Depending on the project, the Phase I clinical trials under this contract may include assessment of many types of biomarkers in different settings (e.g. target populations may be healthy volunteers, demographic subsets of healthy volunteers, or subjects with conditions of interest) as well as single or multiple dose administration of different drug or biologic products (e.g. small molecules, peptides, proteins or oligonucleotides). In addition, other supportive laboratory studies and bioanalytical support may be needed for assessment of the biomarkers within these clinical trials or could be required as a standalone option for mission-critical needs. The results of studies and other performed work under this contract will be used to advance regulatory science.

C.2 OBJECTIVE

The FDA requires the scope of the activities to be performed by the contractor shall include the provision of a Phase I clinical research unit, the conduct of Phase I clinical trials and the provision of a full range of services to support the clinical trials and reporting of the results. All clinical trials shall be carried out in a timely fashion, as will be specified in individual orders, and in compliance with all FDA regulations and International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice

(GCP) guidelines.

The contractor shall provide laboratory studies including bioanalytical/biomarker support that includes determination of drug concentration, anti-drug antibodies, and multiple pharmacodynamic biomarkers. Any bioanalytical/biomarker work shall be carried out in a timely fashion, as will be specified in individual orders, and in compliance with FDA regulations and adhere to Good Laboratory Practice (GLP) guidelines when requested.

C.3 SCOPE OF WORK

The Contractor shall ensure requested contracting support is provided to the FDA. This Statement of Work (SOW) has been divided into 2 performance areas: A) Overall Clinical Operations Support and Clinical Trial Execution in Healthy Subjects or Patients and B) Bioanalytical/Biomarker Analysis and Laboratory Support.

C.4 ASSIGNMENTS

Tasks may require the contractor to perform the following assignments and require all deliverables to be submitted electronically, as approved by the FDA Contracting Officer Representative (COR). Specific deliverables and dates shall be specified at the respective order level.

Assignment 1: Performance Area A: Overall Clinical Operations Support and Clinical Trial Execution in Healthy Subjects or Patients

Under this performance area, the contractor shall perform activities related to overall administration and implementation of the clinical operation services including but not limited to the setup for project management, technical preparedness and support, communications and submission of deliverables and the ongoing archive of completed trial data and reports. In addition, the contractor shall perform all activities associated with the conduct of Phase I clinical trials as specified below. Specifically, for overall administration and implementation of the clinical operation services, the contractor shall:

Provide a Principal Investigator (PI) and support staff to effectively complete the required tasks who will be responsible for overall project management including the development, implementation and maintenance of a project management plan to ensure effective management of the contract infrastructure including clinical and support services, the tracking of progress, communication and preparation of deliverables and the archival activities. The PI shall be a licensed physician (M.D. or equivalent) or shall possess a PhD or a PharmD degree and have multiple years of experience with Phase I clinical trials. If the PI is not a licensed physician, then a licensed physician shall be part of the study leadership team.

Prepare and deliver a Project Management Plan (PMP) within 30 days after an award. The PMP shall address and include, at a minimum, the following (if needed, alterations to this requirement will be made in specific Orders):

o Standard operating procedures (SOPs) for the conduct of Phase I-type clinical trials and for all other integrated and collaborating services;

o Personnel listing including their roles and responsibilities;

o If any work is subcontracted, your subcontracting plan.

o Human subject considerations (e.g., federal wide assurance (FWA), initial and continuing human subject training/education for personnel, data and safety monitoring plan, consenting procedures, procedures for managing medical emergencies on-site, reporting of adverse events (AEs), serious adverse events (SAEs), unexpected adverse events, hospitalizations and procedures for prompt reporting of SAEs in compliance with FDA regulations);

o Training program for clinicians, clinical site staff, data management staff and other support staff in the protocol procedures with every order protocol to ensure reliability of evaluation, treatment and assessment procedures;

o Data management procedures and systems planning that comply as specified with the contract terms and conditions including but not limited to development of database and case report forms (CRFs) using specified common data element where applicable, data collection, data monitoring, data safety review;

o Pharmacy management procedures for receiving, storing and dispensing agents, including scheduled and nonscheduled substances; also, to be included a procedure for randomization and, if specified in an Order, stratification of eligible subjects (unless provided by the Government);

o Procedures for blinding, including during pharmacy, clinical and data management activities, where specified in Orders;

o Clinical and laboratory quality monitoring procedures, where specified in Orders;

o Procedures for preventing, identifying, handling, reporting and resolving protocol deviations;

o Quality control plans and procedures;

o Establishment and demonstration for independence of oversight including quality assurance procedures;

o Recruitment planning and timelines and procedures for identification and resolution of deficient recruitment and enrollment;

o Procedures for ensuring adequate follow-up of study subjects with clinically significant adverse events or treatment-emergent laboratory abnormalities;

o Archival plans for securing completed trial data per regulatory requirements;

o Contingency planning; and o Close-out plan

Conduct teleconferences and meetings for:

o Pre-RTOPs meetings if required: to review the order requirements, timelines, milestones and deliverables; discuss order plans and approaches and identify any anticipated difficulties in completing the order requirements;

o Standing and/or ad hoc teleconferences/webinars: as requested by the Contracting Officer Representative (COR), Contracting Officer (CO) or study team, participate in teleconferences or webinars to review progress and performance, discuss modifications to procedures, and/or discuss other issues related to project management or infrastructure of the overall contract or individual clinical trials;

o Site Visits: Host site visits as requested by COR, CO or FDA study team, as needed;

o Prepare minutes of all site visits and teleconferences/webinars and submit to the COR, CO, or FDA study team for review and approval within 2 business days of the meetings.

Archive the final locked dataset with de-identified data for each clinical trial conducted under each order in Performance Area A in an agreed upon format (e.g., R, SAS, SPSS, ASCII) that is readily usable by FDA or FDA designee.

Specifically, for performing all activities associated with the conduct of Phase I clinical trials, the general requirements are as described below.

Protocol Development and Finalization:

1. Finalize a full protocol based on protocol synopsis and/or draft protocol provided by the FDA study team and submit to FDA for scientific review and approval in compliance to the timelines specified within the Order. Prepare the informed consent form (ICF) which contains reference to the Privacy Act system germane to data collection for awarded orders and all other protocol specific supporting documents (e.g., subject recruitment advertisements), and submit the final protocol, ICF and other documents to the institutional review board (IRB) for review and approval. FDA’s IRB (Research in Human Subjects Committee [RIHSC]) would also need to approve these documents unless an IRB authorization agreement (IAA) between FDA and the contractor or contractor’s IRB is in place. The contractor shall prepare all the necessary documents (including, but not limited to, IAA memos and forms) for such an IAA request to FDA’s RIHSC.

2. Throughout the process, essential regulatory documents as specified in ICH guideline should be generated and stored in files/folders and be available for monitors and for use in the subsequent quantity option when executed. Essential regulatory documents may include but are not limited to: signed IRB approved protocol, informed consent form and advertisement for subject recruitment; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, conflict of interest declaration, indemnification/insurance documents, Form FDA 1571, Form FDA 1572.

Trial Execution:

The contractor shall provide most of the services at its own institution, but exceptions can be made on a case by case basis after prior approval by the Government. Any subcontracted work or facilities will be included in the submitted subcontracting plan or specified in the order. All clinical trials to be conducted under this contract must be completed as per finalized protocol requirement. The time duration for a clinical trial from protocol writing to study completion can be variable based on specific needs and will be specified in respective Orders. The Government will be responsible for providing a detailed clinical trial synopsis or draft protocol for each clinical trial.

A. Protocol Implementation: Compliance and Oversight

1. Activities required prior to clinical trial initiation

a) Register the clinical trial in the National Library of Medicine’s Clinical Trials registry (http://www.clinicaltrials.gov) (FDA may take responsibility for this as needed; this would be specified in the Order)

b) Ensure all requisite regulatory approvals are in place (e.g., IRB and FDA submissions) including that the investigational agent has appropriate FDA clearance confirming the agent’s suitability for testing in humans prior to initiating recruitment

c) Obtain any necessary Material Transfer Agreement (MTA) from contributor if required

d) Prepare and deliver the Manual of Operations to include at a minimum:

Data Safety and Monitoring (DSM) plan (this may be with the participation of FDA as needed)

Recruitment and retention plan (e.g., enrollment of a diverse subject pool, including women and minorities per the constraints of the inclusion/exclusion criteria, rate of subject accrual, subject retention, plans for deficient enrollment)

Data management plan CRFs using specified common data element where applicable and the corresponding data dictionary and any other supporting documents Statistical analysis plan (this may be handled by the FDA as needed) Pharmacy management plan including a system for random treatment assignment and, if specified in Orders, stratification of eligible subjects Plan to monitor and track AEs and SAEs, including prompt reporting of SAEs, which may include with coding in the most recent (at time of study start) version of MedDRA (to be specified in order)

Blinding plan, including during pharmacy, clinical/pharmacokinetic and data management activities, as specified in Orders

Plan for quality control and quality assurance e.g. monitoring plans, data quality plans and audits.

e) Conduct a clinical trial initiation meeting that includes external contractors (e.g., central readers or raters, laboratory analysis providers) as specified in Orders.

2. Regulatory Compliance

a) Throughout the studies essential regulatory documents should be generated and stored in files/folders and be available for monitors and at the end of the studies all essential regulatory documents at the clinical research unit should be placed in the master regulatory file for archiving. Regulatory documents may include but are not limited to:

IRB approved protocol, ICF and advertising; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, indemnification/insurance documents, Form FDA 1572, shipment receipts, etc. During the conduct of the clinical trial, all new relevant information/data must be appended to the essential documents as it becomes available.

b) Ensure that the conduct of the clinical trials performed complies with all FDA and ICH GCP regulations and guidelines.

c) Ensure the confidentiality of all clinical records and information about subjects enrolled in the clinical trial conforms to all Privacy Act requirements.

3. Clinical Trial Initiation The contractor’s clinical trial team and support staff shall participate in a clinical trial initiation meeting at the Contractor’s clinical research facility or through teleconference, as specified in Orders. Prepare and deliver a summary report of the initiation meeting to include but not be limited to the agenda and the list of participants.

4. Protocol Amendments Prepare all protocol amendments and modifications, as needed.

a) Upon FDA approval, the contractor will submit the amended protocol and ICF to the IRB for review and approval. Amending the protocol will include an updated version of the protocol (‘clean version’), a version of the protocol with tracked changes, and a summary document of changes.

b) Upon IRB approval, the amended protocol and revised ICF shall be archived in the master regulatory file.

c) The Manual of Operations, case reports forms and other supporting documents will be modified to reflect the protocol amendments.

d) If necessary, the PI or designee will conduct a training session describing the protocol amendment and its impact on clinical trial procedures and assessments.

5. Protocol Oversight Oversee all clinical activities conducted at the clinical research facility and all collaborating sites including research pharmacy, clinical laboratory, data management center and subcontracting sites.

Ensure that each participant: meets protocol entry criteria; has given informed consent and has undergone all the screening and baseline assessments as specified in the protocol.

For each Order protocol:

1. Track subject enrollment and adherence to defined recruitment goals.

2. Review and assess participant data as specified within the data management plan, protocol requirements and/or quality assurance requirements; for example:

Monitor continuously for the validity and integrity of the accumulating data Monitor continuously (i) protocol adherence and (ii) compliance with current ICH

GCP guidelines, DHHS Protection of Human Subjects regulations (45 CFR Part 46) and FDA regulations and report all protocol deviations

Report of any serious adverse events and/or unexpected adverse events and discontinuations to FDA, IRB and COR

Report all performance-related issues and proposed resolutions or corrective actions taken

Database summary tables for monitoring and tracking purposes throughout the course of the clinical trial including subject enrollment updates

6. Data Management and Quality Control

a) Modify the database to support any protocol amendments that are implemented during the conduct of the clinical trial, as required.

b) Provide quality control to ensure initial data entry within 24 hours and to correct or issue a data query within 48 hours and inform promptly the clinical research staff of any missing, incomplete and erroneous data.

7. Audit Compliance The FDA at their discretion may undertake an audit of the contractor’s facility including all collaborating sites. The contractor shall make available all facilities, records and files as related to the contract. The contractor will submit a report describing the implementation of any corrective actions.

B. Study Agents and Clinical Specimens

1. Study Agents

a) Maintain inventory records of study agent(s) in accordance to the pharmacy SOPs.

b) Maintain documentation that the study agent(s) will be stored and quarantined under appropriate conditions, or as specified in Orders, in the research pharmacy per the sponsor and regulatory requirements.

c) Mechanism for the return and/or destruction of study material.

2. Clinical Specimens

a) Ensure collection, processing, labeling, temporary storage under conditions and management of all collected biological specimens as specified in Orders.

b) Ensure shipping of biological specimens for testing and/or repository deposition, as specified in the protocol, in compliance with current Good Laboratory Practice (cGLP), cGCP and domestic laws and regulations.

C. Clinical Trial Analysis, Close-Out and Final Clinical Trial

Reporting

1. Close-Out and Analysis Following the last subject’s completion of clinical trial procedures including any outpatient follow-up visits, the contractor shall (in discussion with the FDA study team):

a) Continue to monitor any residual safety concerns (i.e., AEs & SAEs) until complete resolution or until no clinical changes or sequelae are expected

b) Complete data editing/cleanup; Review the unlocked database with FDA for potential data clarifications and resolve the data clarifications to the satisfaction of FDA

c) Finalize and lock the database

d) Conduct the statistical analysis as described in the manual of operations if specified for a Order (this may be handled by FDA as needed)

e) Deliver the locked de-identified database in agreed upon format (e.g., R, SAS, SPSS, ASCII) and schedule as requested by the COR, CO, or FDA study team

2. Completion In discussion with the FDA study team:

a) Prepare for archiving the final dataset and all associated clinical trial records. Clinical trial records are considered case report forms and detailed documentation necessary to assess the final dataset with specific codes for all variables including all transformation that have been created (i.e., data dictionary), as needed.

b) Prepare and deliver draft and final clinical study report, if needed and as specified in an Order.

D. Facilities, Equipment and Other Resources

The Contractor shall be responsible for the adequacy and availability of all facilities, equipment, and other resources necessary for the conduct of a clinical trial which may include, but is not limited to, the following.

Provide Inpatient Clinical Research Facility:

a) Accreditation with a national or state accreditation board for the conduct of clinical trials, if required.

b) Areas to allow for waiting, check-in and discharge.

c) Examination rooms to allow for protocol-related assessments.

d) Standard clinical support services for inpatient care, twenty-four hours/day, seven days/week.

e) Capability to recruit healthy volunteers and/or target populations with the condition of interest.

f) Adequate and secure computing resources for communication and data management (e.g., entry editing, quality control).

g) Adequate and secure electronic access to the data management center.

h) Emergency care and a definitive plan for management of life-threatening adverse events, including on-site resuscitation equipment and hospitalization procedures in the event a participant requires these services.

i) Adequate equipment, staff and services for performing routine safety evaluations (e.g., vital signs, ECG), precisely timed phlebotomy, urine and other bodily fluids for PK/PD trials and processing of PK and PD samples, as needed.

j) Staff with expertise in the conduct of Phase I clinical trials including but not limited to physicians, pharmacologists, clinical specialists, registered research nurses, study coordinators, clinical research associates, research assistants, Independent Safety Monitor(s) (ISM) and research pharmacists.

k) Pharmacovigilance capabilities for composition of serious adverse event reports and narratives.

Provide Clinical/Research Laboratory Facility:

a) Adequate space for the processing and temporary storage of biological specimens.

b) On-site sample storage facilities at room temperature, 4, -20 and -70 degrees Celsius.

c) Clinical laboratory support services with provisions of 24 hours/day processing/testing if required by the protocol.

d) Adequate and secure electronic access to the data management center.

Provide Research Pharmacy Facility:

a) Research pharmacist with expertise in the preparation, distribution and storage of study agents for Phase I clinical trials.

b) Limited cGMP capability for compounding and manipulations such as over-encapsulation.

c) Adequate space for processing, storing and dispensing study agents under conditions as specified in Orders.

d) Adequate and secure electronic access to the data management center.

e) Have current license, accreditation and/or certification for the performance of pharmacy services.

Provide Data Management Center:

a) Adequate computing resources to support data collection activities.

b) Personnel knowledgeable about data management activities and operations including but not limited to data management planning and reporting, performance reporting, quality assurance and administrative support.

c) Clinical data warehousing capabilities/facilities to provide a centralized, integrated system for data storage, analysis, reporting and ad hoc query of clinical data.

d) Data management capabilities necessary to support the conduct of Phase I clinical trials, such as case report form (CRF) design, data dictionary development, database programming, database design and development in compliance with Good Clinical Practice (GCP) guidelines and Clinical Data Interchange Standards Consortium (CDISC), as needed.

Provide other facilities and equipment, as may be specified by the Order protocols.

E. Insurance

The contractor and all collaborating sites participating in the conduct of approved protocols shall provide sufficient malpractice insurance and indemnification for trial related injuries to volunteers as typical for phase 1 clinical pharmacology studies. The Government will not provide third party liability insurance.

NOTE: The Government will not provide medical care or financial compensation for research-related injuries to clinical trial volunteers. The Government will also not provide financial compensation to contractors.

1. Technical Performance Reports

Performance Area A

The Contractor shall be required to prepare and deliver the following reports for Performance Area A:

a) Progress Report

Progress report requirements will be outlined in specific Orders, as needed.

b) Project Management Plan (PMP)

The PMP report shall address and include all elements as listed in the SOW requirements for this report as set forth under Performance Area A or per the PMP requirements in specific Orders.

Reporting requirements may be amended or updated with each Order award.

The Contractor shall also prepare and deliver the following reports for each Order awarded under Performance Area A:

SOW Deliverable Delivery Schedule Protocol Development and Finalization

Final protocol and any related amendments/modifications, to include all required regulatory forms for contributor to obtain open IND for proposed trial (e.g.

FDA Form 1571 and 1572).

3 weeks after receiving protocol synopsis from the Government unless otherwise specified in the Order

Clinical Trial Execution

Summary Report for each clinical trial meeting

2 business days after meeting

Locked database to be specified by the terms of each study protocol

Will be determined by terms of each trial Order

Reporting requirements may be amended or updated with each Order award.

Assignment 2: Performance Area B: Bioanalytical/Biomarker Analysis and Laboratory Support

Under this performance area, the contractor shall perform activities related to development of laboratory work that may include sensitive bioanalytical methods and validation per current FDA guidance followed by quantitative analyses of drug and/or metabolite concentrations, biomarkers in plasma/serum, urine, tissue homogenates, and other biological fluids found in animal species and humans, as applicable for small and large molecules for study samples.

These analyses can include but are not limited to flow cytometry and cell-based assays, ligand binding assays, immunohistochemistry, liquid chromatography-tandem mass spectrometry and molecular assays and genomics. Contractor will be responsible for final bioanalytical reports and for shipping samples to designated facility if needed. Any subcontracted work or facilities will be included in the submitted subcontracting plan or added as an amendment if approved by the Government.

The general requirements for the different components under performance area B are as described below.

A. Administrative Provide a Principal Investigator (PI) or other managerial designate and support staff to effectively complete task requirements who will be responsible for overall project management including the development, implementation and maintenance of a project management plan to ensure effective management of the contract infrastructure including support services, the tracking of progress, communication and preparation of deliverables and the archival activities.

Prepare and deliver a Project Management Plan (PMP) within 30 days after the base/initial Order award. The PMP shall address and include, at a minimum, the following (if needed, alterations to this requirement will be made in specific Orders):

o If any work is subcontracted, your subcontracting plan.

o Standard operating procedures (SOPs) for the conduct of bioanalytical/biomarker or laboratory support work as specified in the Order and for all other integrated and collaborating services;

o Data management procedures and systems planning that complies as specified with the contract terms and conditions including but not limited to development of databases using specified common data element where applicable, data collection and data monitoring;

o Laboratory quality monitoring procedures, as specified in Orders;

o Procedures for preventing, identifying, handling, reporting and resolving protocol deviations;

o Quality control plans and procedures;

o Establishment and demonstration for independence of oversight including quality assurance procedures;

o Archival plans for securing completed data per regulatory requirements;

o Contingency planning; and o Close-out plan

Conduct teleconferences and meetings for:

o Pre-TORFP meetings if needed: to review the order requirements, timelines, milestones and deliverables; discuss order plans and approaches and identify any anticipated difficulties in completing the order requirements;

o Standing and/or ad hoc teleconferences/webinars: as requested by the Contracting

Officer Representative (COR), Contracting Officer (CO) or study team, participate in teleconferences or webinars to review progress and performance, discuss modifications to procedures, and/or discuss other issues related to project management or infrastructure of the overall contract or Order work;

o Site Visits: Host site visits for the COR, CO and other FDA staff, as needed;

o Prepare minutes of all site visits and teleconferences/webinars and submit to the

COR, CO, or FDA study team for review and approval within 2 business days of the meetings.

Archive the final locked dataset conducted under each order in Performance Area B in an agreed upon format (e.g., R, SAS, SPSS, ASCII) that is readily usable by FDA or FDA designee.

Within 45 days of an Order expiration, the contractor shall provide the COR, CO, or FDA study team with a proposed Transition Plan for an orderly and complete transition/relocation of the order resources to a successor Contractor or to the Government.

The plan shall include details on the relocation/disposition of: unused materials and supplies; manuals and directories developed by the contractor; and all other government property not listed. Upon written direction by the Government, the contractor shall transfer all Government property as directed, and fully cooperate with any successor contractor and the Government to ensure an efficient transfer.

Audit(s): The FDA at their discretion may undertake an audit of the contractor’s facility including all collaborating sites. The contractor shall make available all facilities, records and files as related to any activity under performance area B. The contractor will submit a report describing the implementation of any corrective actions.

B. Study Agents and Biological Specimens

1. Study Agents

a) Maintain inventory records of study agent(s) in accordance to the SOPs.

b) Maintain documentation that the study agent(s) will be stored and quarantined under appropriate conditions per the sponsor and regulatory requirements and as specified in Orders.

c) Mechanism for the return and/or destruction of study material.

2. Biological Specimens

a) Ensure collection, processing, labeling, temporary storage under appropriate conditions and management of all collected biological specimens and as specified in Orders.

b) Ensure shipping of biological specimens for testing and/or repository deposition, as specified in the protocol, in compliance with current Good Laboratory Practice (cGLP), cGCP and domestic laws and regulations as applicable.

c) Each agent will be considered potentially hazardous. Therefore, all necessary precautions must be taken to protect personnel and the environment against possible exposure to the agents being tested.

The contractor shall perform all work associated with this contract in accordance with all applicable Federal, State and local regulations including transportation and disposal of hazardous waste.

C. Analysis, Close-Out and Final Reporting

1. Close-Out and Analysis Following completion of Order work, the contractor shall (in discussion with the FDA study team):

a) Complete data editing/cleanup

b) Finalize and lock the database

c) Deliver the locked database in agreed upon format (e.g., R, SAS, SPSS, ASCII) and schedule as requested by the COR, CO, or FDA study team

2. Completion In discussion with the FDA study team:

a) Prepare for archiving the final dataset and all associated records. Records are considered detailed documentation necessary to assess the final dataset with specific codes for all variables including all transformation that have been created (i.e., data dictionary), as needed.

b) Prepare and deliver draft and final report, as specified in Orders.

D. Facilities, Equipment and Other Resources

The Contractor shall be responsible for the adequacy and availability of all facilities, equipment, and other resources necessary for the conduct of bioanalytical work, which may include, but is not limited to, the following.

Provide Clinical/Research Laboratory Facility:

a) Adequate space for the processing and storage of biological specimens.

b) Adequate facilities and equipment for conducting protocol-required tests and assays such as PK and specialty PD assays on blood, plasma, other body fluids and tissues found in both animal species and humans, as applicable and as needed.

c) On-site sample storage facilities at room temperature, 4, -20 and -70 degrees Celsius.

d) Clinical laboratory support services with provisions of 24 hours/day testing if required by the protocol.

Provide Information Technology System:

a) Securely submitting, compiling, storing, collating, analyzing, tracking and retrieving data, structures, results, specimens, reagents, biological agents, drug product produced and released, documents generated in product development, and data received from other compound screening activities performed by third parties. This database will contain confidential/ proprietary information that shall not be used for data-mining purposes by the contractor or any potential subcontractors.

b) Ensuring secure electronic communications, including email, word processing and transmission of data files, between the contractor, FDA staff, subcontractors and consultants.

c) Organizing, maintaining, and transferring information on protocols and test results and provide electronic copies of all reports to the COR, CO, or FDA study team. All electronic deliverables shall comply with Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d).

d) Maintaining the confidentiality of data received from FDA or third parties and data generated within the scope of the contract. [Note: The Government reserves the right to have complete access to those files relevant to FDA studies in databases, provide access to third parties, and to transfer all rights and custody to a successor contractor.]

Provide other facilities and equipment, as may be specified by the Order protocols.

Technical Performance Reports

The Contractor shall prepare and deliver the following reports for each Order awarded under Performance Area B:

a) Project Management Plan (PMP)

The PMP report shall address and include all elements as listed in the SOW requirements for this report as set forth under Performance Area B or per the PMP requirements in specific Orders.

Reporting requirements may be amended or updated with each Order award.

5. Inspection and Acceptance Criteria

The Contracting Officer or the duly authorized representative will perform inspection and acceptance of materials and services to be provided. Inspection and acceptance shall be stated at the respective order levels.

For this SECTION, the FDA COR is the authorized representative of the Contracting Officer (CO) as specified by the CO. Otherwise, only the CO has authority to act on behalf of the

FDA.

Inspection and acceptance will be performed at either the contractor’s facility or at the FDA.

Acceptance of work, materials, services, and reports may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized representative within 30 days of receipt.

This contract incorporates the following clause by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available.

C.5 ANTICIPATED LABOR/KEY PERSONNEL

The following Labor Categories are anticipated as being necessary to support the requirements of this contract:

Principal Investigator * Investigator Project Manager * Pharmacist * Clinical Technician Lab Technician Statistician Technical Writer Data Manger Analyst

Additional information regarding the labor category descriptions are set forth in Attachment 2.

* The contract Principal Investigator, Pharmacist and Project Manager are considered Key Personnel.

Minimal qualifications for key personnel are as follows:

Principal Investigator – as written in section C.4; shall be a licensed physician (M.D. or equivalent) or shall possess a PhD or a PharmD degree and have multiple years of experience with Phase I clinical trials. If the PI is not a licensed physician, then a licensed physician shall be part of the study leadership team.

Pharmacist - shall be a licensed pharmacist and have experience with Phase I clinical trials.

Project Manager - shall have experience managing Phase I clinical trials, prefer at a sponsor or CRO company; should have two or more years of clinical operations experience in project plans and timeline management, quality standards and risk mitigation; read, write and speak fluent English; excellent verbal and written communication skills.

SECTION D - PACKAGING AND MARKING

All deliverables required under this contract shall be packaged, marked and shipped/submitted in accordance with the Government specifications below. At a minimum, all deliverables shall be marked with the contract number and contractor name.

1. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

2. The Contractor shall scan all deliverables for viruses before submitting to the FDA.

3. Deliverables under this contract shall be prepared and packaged for shipment using standard shipping practices to ensure safe and timely delivery.

Electronic delivery is the preferred method of delivery and all deliverables shall assume to be submitted electronically, unless otherwise specified by the COR.

SECTION E - INSPECTION AND ACCEPTANCE

The FDA COR will inspect and make acceptance decisions for all materials, documents, and services provided under this contract. For the purpose of this Section, the FDA COR is the authorized representative of the Contracting Officer.

SECTION F - DELIVERIES OR PERFORMANCE

F.1 ANTICIPATED DELIVERABLES

Note: Actual deliverables, deliverable schedules, Progress Reports and Status meetings shall be established in the issuance of each individual Order. Additional Reporting Requirements may be included in each Order.

Progress Reports - The Contractor shall submit one (1) electronic copy of the Progress Report to the COR and Contracts Specialist. The report shall include a status update on each task worked on and deliverables submitted, any problems encountered, and suggestions for addressing problems each period. If the tasks are cost reimbursable in nature, an accounting of applicable staff who worked on the tasks as well as any deviations from the original projection of hours planned vs. actually incurred will be required.

Monthly reports shall be submitted electronically as a “PDF” attachment emailed to the COR.

Program Status Review meetings (PSRs) - The Contractor shall facilitate and participate in PSR meetings as needed. PSRs shall be held in person at the Contractor’s facility or remotely via teleconference, at FDA’s discretion. PSRs shall encompass review of Contractor’s overall performance under the applicable order, quality and quantity of services (including review of inspection services, results, and all facets of performance), quality and timeliness of deliverables, and any other issues pertaining to performance of the order under this contract. If requested by FDA, the Contractor shall provide advance copies of all relevant performance and QA data requested by FDA prior to a scheduled PSR.

F.2 ORDERING PERIOD/ PERIOD OF PERFORMANCE

The period of performance for the base period of the contract shall be five (5) years from the effective date of the contract. Orders may be issued up to the final day of this contract, and the contract shall remain in force to allow for the completion of all orders issued (See FAR 52.216- 22 for more information). However, the Government shall not issue, and the Contractor shall not accept any new orders issued subsequent to the performance period of this contract.

F.3 PLACE OF PERFORMANCE

The place of performance will be specified at the Order level. Orders may be issued for performance in any of the United States or its territories.

SECTION G - CONTRACT ADMINISTRATION DATA

G.1 ORDERING PROCEDURES

Orders for individual clinical trials will be completed through a Request for Proposal (RFP) process. Individual Orders may be only in Part A, only in Part B, or integrated between Part A and Part B. In a firm, fixed price order, the government will provide a study schedule of events (see sample schedule of events) and order items from the price schedule fixed in the base contract. Certain items cannot be specified in advance without the details of the study design in the Order, such as Materials pass through costs (e.g. subject stipends, drug price). If additional services are needed within the scope of this contract outside of the Task/procedure cost categories, a labor hour component may be added. It is anticipated that these Orders will be cost-reimbursement, completion-type Orders and will have variable periods of performance.

The actual number of RFPs issued will depend upon programmatic needs and funding availability and may vary from year to year. The contractor shall initiate work only when authorized by issuance of an approved Order.

NOTE: FDA will issue RTOPs for individual clinical trials under Performance area A activities and for individual bioanalytical/biomarker and laboratory support work under performance area B.

Performance areas are outlined above and are to be considered general requirements that will be executed following issuance of individual Order awards. Each individual (or combination) performance area Order award will also define specific and additional requirements as specific for that Order Statement of Work.

Ordering services under this contract shall be accomplished by the issuance of written orders specifying the inspection services required by State. All orders issued under this contract shall conform to the provisions of the contract clauses in Part II, Section I entitled “Contract Clauses” (See FAR 52.216-18 and 52.216-19). The only office authorized to process orders through the Office of Acquisitions & Grants Services is the Food and Drug Administration (FDA) Contracting Officer.

ORDER PROCESSING

All orders issued hereunder are subject to the terms and conditions of this contract.

This contract shall control in the event of conflict with any order. Orders shall be “issued” for purposes of this contract upon the effective date of the order.

The general process for individual orders is as follows:

a) The FDA will prepare a statement of work. The SOW will include, at a minimum, the following elements:

1. Description of work in terms of the purpose or objectives of the work and location to be performed.

2. Description of how the work performance is assessed relative to objectives, goals, and outcomes.

3. Period and place of performance

4. Reporting requirements and deliverables

5. Whether the order will be fixed price, labor hour, time and material or a hybrid type order.

b) Requests for Order Proposals (RFPs) shall only be issued by the Contracting Officer.

c) The Contractor shall prepare and submit a task proposal addressing all areas of the requirement. The Contractor shall submit the task proposal within the time period specified in the RTOP and adhere to the ceiling rates established in the contract. No separate payment will be made to the contractor for the price to prepare, submit and/or negotiate an order proposal.

The Government shall evaluate order proposals for technical acceptability and price reasonableness.

G.2 CONTRACTING OFFICERS REPRESENTATIVE (COR)

The following COR will represent the Government for the purpose of this contract: (To Be Determined Upon Contract Award)

The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the Statement of Work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

G.3 CONTRACTING OFFICER (CO)

The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in an order; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract.

The contact information for the Contracting Officer is:

Matthew J. Bucher Email: Matthew.Bucher@fda.hhs.gov Tel: (240) 402-7566

The contact information for the Contract Specialist is:

Robert Maydwell Email: Robert.Maydwell@fda.hhs.gov Tel: (301) 348-1814

G.4 INVOICE SUBMISSION

A. The contractor shall submit all invoices to:

U.S. FOOD AND DRUG ADMINISTRATION

Attn: Vendor Payments Division of Payment Services 10903 New Hampshire Ave WO32 - Second Floor

MAIL HUB 2145

Silver Spring, MD 20993-0002 301-827-3742 FDAVendorPaymentsTeam@fda.hhs.gov

*** Acceptable methods of delivery include: E-mail (preferred) and Standard Mail. Provide a copy marked courtesy to the COR or Technical Point of Contact (TPOC). The COR/TPOC is (insert name and email address.)

B. Invoices submitted under this contract must comply with the requirements set forth in FAR Clauses 52.232-25 (Prompt Payment) and 52.232-33 (Payment by Electronic Funds Transfer - System for Award Management) and/or other applicable FAR clauses specified herein. To constitute a proper invoice, the invoice must be submitted on company letterhead and include each of the following:

(i) Name and address of the contractor;

(ii) Invoice date and invoice number;

(iii) Contract/Order number (including a reference to any base award for Indefinite- Delivery/Indefinite-Quantity Contracts or Blanket Purchase Agreements);

(iv) Description, quantity, unit of measure, unit price, and extended price supplies delivered, or services performed, including:

(a) period of performance for which costs are claimed;

(b) itemized travel costs, including origin and destination;

(c) any other supporting information necessary to clarify questionable expenditures;

(d) the contractor shall include the award item number for each description, quantity, unit of measure, unit price, and extended price supplies delivered, or services performed;

(v) Shipping number and date of shipment, including the bill of lading number and…