Sol_Doc - RFP - BODY (Pages 3-145) - CDER IDIQ - 75F4012R00064 - FINAL.pdf

FDA SYNOPSIS/SOLICITATION #:

75F40124R00064

Food and Drug Administration (FDA)

Solicitation No: 75F40124R00064

Single Award Indefinite Delivery, Indefinite Quantity (IDIQ) Contract

Center for Drug and Evaluation Research (CDER)

OFFICE OF CLINICAL PHARMACOLOGY

CLINICAL STUDIES AND LABORATORY SUPPORT

NOTICE OF COMBINED SYNOPSIS/SOLICITATION

This is a synopsis/solicitation for the acquisition of a single award commercial services FDA IDIQ set aside 100% for Small Business and prepared in accordance with the format in Federal Acquisition Regulation (FAR) Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a separate written solicitation will not be issued. This is a request for proposal (RFP) for commercial items IAW the procedures of FAR part 12 – Acquisition of Commercial Items, in conjunction with FAR part 15 – Contracting by Negotiation.

CONTRACT TYPE

This is a single-award Indefinite Delivery-Indefinite Quantity (IDIQ) type contract, per FAR subpart 16.5. The Authorized Task Order (TO) type under this IDIQ contract is Firm-Fixed- Price (FFP).

MINIMUM AND MAXIMUM CONTRACT VALUE

IDIQ Minimum: The minimum guarantee for this IDIQ contract is $2,500, which will be obligated at the time of IDIQ award.

IDIQ Maximum: The maximum aggregate dollar value of all task orders awarded over the 5-year ordering period of this IDIQ shall not exceed the IDIQ ceiling amount of $50,000,000.

See FAR Clause 52.216-19 (Oct 1995) for individual task order limitations.

The resultant base contract ordering period will be 5-years with no options. The amount of individual task orders will be based on need and availability of funding.

NOTICE OF SET-ASIDE/ NAICS CODE/ SAM REGISTRATION

This requirement is being solicited as a 100% Small Business Set-Aside. The associated North American Industry Classification System (NAICS) code is 541714 – Research and Development in Biotechnology (except Nanobiotechnology) and 541715 - Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology), each with a small business size standard of 1000 employees.

Offerors must have an active registration in SAM.gov (https://sam.gov/), with completed representations and certifications, by the close date of the solicitation. Proposals submitted by Offerors not registered in SAM.gov will not be considered. This requirement will be competed in the open market.

https://sam.gov/

REQUIREMENT

The scope of activities FDA may require of the contractor shall include the capability to conduct multiple Phase I clinical trials within a year and at times in parallel, 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 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 should also be able to provide laboratory studies including bioanalytical/biomarker/omics 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. Unless otherwise specified, method validation shall be performed in compliance with FDA’s Bioanalytical Method Validation Guidance (https://www.fda.gov/media/70858/download). Sample analysis does not need to be performed under complete Good Laboratory Practice (GLP) guidelines.

The Contractor shall ensure adequate 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/’Omics’ Analysis and Laboratory Support. To qualify for award, organizations must have in-house capabilities in Performance Area A, which will represent the majority of the work. Organizations may either have in-house or sub- contracting capability for Performance Area B.

See the Section C Statement of Work (SOW) for the full requirement.

NOTICE OF FEDERAL ACQUISITION CIRCULAR (FAC)

This solicitation document incorporates provisions and clauses in effect through Federal Acquisition Circular FAC 2024-05, effective May 22, 2024.

FAR provisions and clauses referenced in this solicitation can be found on the following website:

www.acquisition.gov

Health and Human Services Acquisition Regulation (HHSAR) provisions and clauses referenced in this solicitation can be found on the following website:

https://www.hhs.gov/grants/contracts/contract-policies- regulations/hhsar/index.html

PRICES AND PROPOSAL SUBMISSION

Using the Uniform Contract Format (UCF), Section L provides Proposal Instructions, Conditions, and Notices to Offerors or Respondents, and Section M provides https://www.fda.gov/media/70858/download http://www.acquisition.gov/ https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html

Evaluation Factors for Award for award of this single award FDA IDIQ set aside 100% for small business.

Please see Attachment 1, Pricing Worksheet, for completion to be included in submission of proposals. The Contractor’s pricing schedules for labor categories shall contain fully burdened hourly rates. The fully burdened hourly rates for each labor category shall include wages, indirect costs, fringe benefits, overhead, general and administrative costs, and profit. Hourly rates shall apply to services at both Government and non-Government sites.

Table of Contents Table of Contents

Section C – Description/Specifications/Statement of Work

BACKGROUND

OBJECTIVES/SCOPE

CONTRACT TYPE AND ORDERING MECHANISM

DELIVERABLES/SPECIFIC TASKS

4.1 TASK 1 - Program/Project Management

4.2 TASK 2 - Trial Execution

4.2.1 Protocol Implementation: Compliance and Oversight

4.2.2 Study Agents and Clinical Specimens

4.3 Clinical Trial Analysis, Close-Out and Final Clinical Trial Reporting

4.3.1 Facilities, Equipment and Other Resources

4.4 Insurance

4.5 Technical Performance Reports

Performance Area B: Bioanalytical/Biomarker/Omics Analysis and Laboratory Support

5.1 TASK 1 - Program/Project Management

5.2 TASK 2 – Study Agents and Biological Specimens

5.3 TASK 3 – Sample Analysis, Close-Out and Final Reporting

5.4 TASK 4 – Facilities, Equipment and Other Resources

Other Deliverables:

GOVERNMENT FURNISHED EQUIPMENT (GFE)/ GOVERNMENT FURNISHED

INFORMATION (GFI)

PERIOD OF PERFORMANCE

PLACE OF PERFORMANCE

STAFFING/KEY PERSONNEL

INSPECTION AND ACCEPTANCE CRITERIA

IT ARCHITECTURE AND TECHNICAL STANDARDS

11.1 Architecture Standards

11.2 Technical Standards

11.3 EPLC Compliance

SECURITY STANDARDS

SECURITY AND PRIVACY REQUIREMENTS

CONFORMANCE WITH APPLICABLE LAWS, REGULATIONS, POLICIES, AND

STANDARDS

14.1 Contractor Compliance

14.2 Section 508 Standard Requirements

Additional Deliverables

Section D - Packaging and Marking

Section E – Inspection and Acceptance Terms

Section F - Deliveries or Performance

Section G - Contract Administration Data

Section H - Special Contract Requirements

Section I - Contract Clauses

Section J – List of Documents, Exhibits and Other Attachments

SECTION K – Representations, certifications, and other statements of offerors or respondents

Section L – Instructions, Conditions, and Notices to Offerors or Respondents

Section M – Evaluation Factors for Award

Section C – Description/Specifications/Statement of Work

STATEMENT OF WORK

Office of Clinical Pharmacology Clinical Studies and Laboratory Support

BACKGROUND

The United States Food and Drug Administration (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.” FDA’s 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.

The FDA has the need for Phase I-type clinical trial operations. Depending on the project, the clinical trials under this contract may include assessment of different drug and metabolite concentrations, biomarkers levels, or include novel experimental methodologies.

The clinical trials may require enrollment of different subjects depending on the research topic (e.g., target populations may be healthy volunteers, demographic subsets of healthy volunteers, or subjects with conditions of interest) as well as allow for single or multiple dose administration of different drug or biologic products (e.g., small molecules, peptides, proteins, or oligonucleotides). The clinical trials may also require multiple sites to ensure timely enrollment and study completion. All clinical trials shall be carried out 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 FDA also requires execution of supportive laboratory studies related to bioanalytical/biomarker/omics (omics refers to range of techniques for characterization and quantification of biologic molecules). These assessments may be needed for samples collected from within the clinical trial 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.

Overall, the efforts would support a full range of services from clinical trial protocol development, clinical trial execution, conducting supportive laboratory studies, and bioanalytical/biomarker/omics services, where required.

OBJECTIVES/SCOPE

The scope of activities FDA may require of the contractor shall include the capability to conduct multiple Phase I clinical trials within a year and at times in parallel, 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 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 should also be able to provide laboratory studies including bioanalytical/biomarker/omics 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. Unless otherwise specified, method validation shall be performed in compliance with FDA’s Bioanalytical Method Validation Guidance (https://www.fda.gov/media/70858/download). Sample analysis does not need to be performed under complete Good Laboratory Practice (GLP) guidelines.

The Contractor shall ensure adequate contracting support is provided to the FDA. This Statement of Work (SOW) has been divided into two (2) Performance Areas: A) Overall Clinical Operations Support and Clinical Trial Execution in Healthy Subjects or Patients and B) Bioanalytical/Biomarker/’Omics’ Analysis and Laboratory Support. To qualify for award, organizations must have in-house capabilities in Performance Area A, which will represent the majority of the work. Organizations may either have in-house or sub- contracting capability for Performance Area B.

CONTRACT TYPE AND ORDERING MECHANISM

The Government intends to make a single award indefinite delivery, indefinite quantity (IDIQ) type contract award resulting from this solicitation. There is a 5-year base contract ordering period with no options. The amount of individual task orders will be based on need and availability of funding. See FAR Clause 52.216-19 (Oct 1995) for individual task order limitations. Allowable task order types under this contract includes only Firm-Fixed-Price (FFP).

The IDIQ Minimum and Maximum amounts are as follows:

IDIQ Minimum: The minimum guarantee for this IDIQ contract is $2,500, which will be obligated at the time of IDIQ award.

IDIQ Maximum: The maximum aggregate dollar value of all task orders awarded over the 5-year ordering period of this IDIQ shall not exceed the IDIQ ceiling amount of $49,544,491.88.

https://www.fda.gov/media/70858/download

DELIVERABLES/SPECIFIC TASKS

Tasks may require the contractor to perform the following requirements, and require all deliverables to be submitted electronically, as approved by the FDA Contracting Officer Representative (COR). Task orders will be completed through a Task Order Request for Proposal (TORFP) process. Individual task orders may be applicable to Performance Area A only, Performance Area B only, or a combination of Performance Areas A and B. The actual number of TORFPs 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 task order.

NOTE: The FDA will issue TORFPs for individual clinical trials under Performance Area A and for individual bioanalytical/biomarker/omics and laboratory support work under Performance Area B. The activities outlined below are to be considered general requirements that will be executed following issuance of individual task order awards.

Each individual task order award will also define specific and additional requirements as appropriate for that task order Statement of Work. Cost/Price for individual task orders will be evaluated at the time an order is placed to determine fair and reasonable pricing, since rates have not been established under the base IDIQ contract.

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:

4.1 TASK 1 - Program/Project Management

a. Prepare responses to TORFPs issued under Performance Area A

b. Provide a Principal Investigator (PI) and appropriate support staff 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.

o The PI shall be a licensed physician (M.D. or equivalent) or shall possess a PhD or a PharmD degree and have significant experience (i.e., at least 5 years of experience) with Phase I clinical trials.

o If the PI is not a licensed physician, then a licensed physician shall be part of the study leadership team.

c. Prepare and deliver a Project Management Plan (PMP) within 30 days after a task order award. The PMP shall address and include, at a minimum, the following (if needed, alterations to this requirement will be made in specific task 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 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 task 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 appropriate stratification of eligible subjects (unless provided by the Government);

o Procedures for blinding, including during pharmacy, clinical and data management activities, as appropriate;

o Clinical and laboratory quality monitoring procedures, as appropriate;

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 for operational delays and interruptions; and o Close-out plan

d. Conduct teleconferences and meetings and coordinate site visits:

o Pre-TORFP meetings (if required): Review the task order requirements, timelines, milestones and deliverables; discuss task order plans and approaches and identify any anticipated difficulties in completing the task order requirements;

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

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.

4.2 TASK 2 - Trial Execution

The FDA expects the contractor to have adequate facilities for completing task orders applicable under Performance Area A at its own institution. All clinical trials to be conducted under this contract must be completed as per the most recent version of the protocol provided by the FDA.

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 task orders. The requirements below are grouped into five categories: Protocol Implementation: Compliance and Oversight; Study Agents and Clinical Specimens; Clinical Trial Analysis, Close-Out, and Reporting; Facilities, Equipment, and Resources; and Insurance.

4.2.1 Protocol Implementation: Compliance and Oversight

1. Activities required prior to clinical trial initiation:

a) 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 task order.

b) Prepare the informed consent form (ICF) which contains appropriate reference to the Privacy Act system germane to data collection for awarded task orders and all other protocol specific supporting documents (e.g., subject recruitment advertisements), and submit the final protocol, ICF and other documents to the designated institutional review board (IRB) for review and approval.

• FDA’s IRB would also need to review and approve these documents and either establish an approved IRB authorization agreement (IAA) if FDA is engaged in the research or determine that FDA is not engaged in the research.

• In case an IAA is required, the contractor shall prepare and provide all the necessary documents required for the IAA request to the FDA and the FDA will submit these materials to the FDA IRB for review and approval of the IAA.

c) Register the clinical trial in the National Library of Medicine’s Clinical Trials registry (http://www.clinicaltrials.gov). Alternatively, FDA may take responsibility for this as needed; this would be specified in the task order. If the FDA is registering the clinical trial, the contractor is responsible for ensuring such steps have been completed before the clinical trial begins enrollment.

d) 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.

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

f) 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

• Case report forms (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 necessary, appropriate 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 task order)

• Blinding plan, including during pharmacy, clinical/pharmacokinetic and data management activities, as appropriate

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

2. Regulatory Compliance

a) 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 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 http://www.clinicaltrials.gov/ 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.

• At the end of each study, the contractor is responsible for delivering the master regulatory file to FDA for archiving (both hard copy and digital records).

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

a) Conduct a clinical trial initiation meeting that includes external contractors (e.g., central readers or raters, laboratory analysis providers) as appropriate. The clinical trial initiation meeting can be at the Contractor’s clinical research facility or through teleconference, as appropriate.

b) 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

a) Coordinate with the FDA study team to update the study protocol and/or ICF in preparation for the study or as needed during conduct of the study.

b) The contractor is responsible for processing all study protocol and ICF updates with the contractor’s IRB. Upon COR, CO or FDA study team 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.

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

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

e) 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

a) Oversee all clinical activities conducted at the clinical research facility and all collaborating sites including research pharmacy, clinical laboratory, data management center, imaging center and subcontracting sites.

b) 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.

c) For each task order protocol:

• Track subject enrollment and adherence to defined recruitment goals.

• 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

a) 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.

4.2.2 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 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 appropriate conditions and management of all collected biological specimens. All sample handling will be as outlined by the FDA in the protocol or other specific sample handling documents.

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.

4.3 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 task 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) Within 45 days of task 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 task order resources to a successor Contractor or to the Government. The plan shall include details on the relocation/disposition of unused materials and supplies; manuals and directories developed by the 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.

c) Prepare and deliver draft and final clinical study report, if needed and as specified in a task order.

4.3.1 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 (other facilities and equipment may be needed and will be specified in individual task orders):

1. 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) Capability to enroll and achieve target enrollment timelines for multiple clinical studies within a year, at times running more than one study in parallel.

g) Adequate and secure computing resources for communication and data management

(e.g., entry editing, quality control).

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

i) 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.

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

k) 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.

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

2. Provide Clinical/Research Laboratory Facility:

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

b) On-site sample storage facilities at room temperature, 4, -20 and down to -80 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.

3. 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 appropriate conditions.

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

e) Have current accreditation and certification for the performance of pharmacy services.

4. 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. Access should be obtainable for a subset of FDA clinical study team members for review while study is ongoing.

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 data standards supported on the FDA Data Standards Catalog, as needed.

4.4 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. The FDA will not provide third party liability insurance.

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

4.5 Technical Performance Reports

Performance Area A

Reporting requirements may be amended or updated with each task order award.

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

Deliverables Estimated

Quantity/Frequency Review or Delivery

Date

5.1 Task 1 - Program/Project Management

Copies of all relevant contractor SOPs and/or manuals for studies in the Task Order; relevant documents for study personnel including CVs and signed non- disclosure agreements

Within 3 months after award or before any study initiation dates (whichever is earliest)

Project Management Plan TBD at the Task Order Level

Within 3 months after award or before any study initiation dates (whichever is earliest)

Progress reports of clinical trial meetings and activities (weekly or biweekly), status updates (weekly or biweekly), and trial timelines (provided at least monthly)

2 business days after weekly or biweekly meeting

5.2 Task 2 - Trial Execution

Final protocol and any related amendments/modifications for submission to either the Office of the Chief Scientist (OCS) Human Subject Protection Officer (HSP) or all required regulatory forms for contributor to obtain open IND for proposed trial (e.g., FDA Form 1571 and 1572) [Note: May vary depending on study in Task Order].

TBD at the Task

Draft documents 3 weeks after receiving protocol synopsis from the FDA unless otherwise specified in Task Order

Approval/Determination from FDA IRB and approval from local IRB

3 months after award

Summary Report, enrollment updates, and adverse event reports for each clinical trial meeting (clinical trial meetings will be either weekly or biweekly)

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 Task Order

Shipment of study biological specimens to FDA for storage or disposal as outlined in the Task Order

Will be determined by terms of each trial Task Order

Copy of master regulatory file and any other essential regulatory documents

Will be determined by terms of each trial Task Order

Reporting requirements may be amended or updated with each task order award. Deliverables (both in draft and final versions) shall be provided as Microsoft Office products. Weekly, interim, informal, and working-copy products may be provided by e-mail to the COR.

Performance Area B: Bioanalytical/Biomarker/Omics 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.

The general requirements for the different components under Performance Area B are as described below. Activities for Performance Area B can be combined with or may be maintained separately from Performance Area A depending on the activity.

5.1 TASK 1 - Program/Project Management

a. Prepare responses to TORFPs issued solely under Performance Area B (or, if applicable, in combination with Performance Area A)

b. Provide a Principal Investigator (PI) or other managerial designate and appropriate support staff 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.

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

o Standard operating procedures (SOPs) for the conduct of bioanalytical/biomarker or laboratory support work as specified in the task 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 appropriate;

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 for operational delays and interruptions; and o Close-out plan

d. Conduct teleconferences and meetings for:

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

o Standing and/or ad hoc teleconferences/webinars: as requested by the COR, 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 task 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.

5.2 TASK 2 – Study Agents and Biological Specimens

1. Study Agents

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

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

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.

b) Ensure shipping of biological specimens for testing and/or repository deposition, as specified in the protocol, in compliance with 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.

5.3 TASK 3 – Sample Analysis, Close-Out and Final Reporting

1. Sample Analysis and Close-Out– Following completion of the kickoff meeting, the contractor shall (in discussion with the FDA study team):

a) Obtain necessary materials such as reference standards, internal standards, blank matrix and plate for specific assays and sample analyses when instructed by the FDA COR to begin.

b) Initiate method development/validation of specific assays, only after instructed by

FDA COR, to quantitate the concentration of specified drugs, metabolites, and/or biomarkers, in line with the FDA Bioanalytical Method Validation Guidance (https://www.fda.gov/media/70858/download).

c) Issue a Method Validation electronic Common Technical Document (eCTD) Report for each method upon completion of method validation.

d) Perform non-GLP primary sample analysis and incurred sample reanalysis (ISR) on 10% of primary samples handling samples according to the study protocol.

e) Issue an eCTD Compliant Bioanalytical Report associated with each study.

f) Store samples at least until issuing the Bioanalytical Report and then shall ship samples to FDA unless instructed to destroy the samples by FDA COR.

g) Complete data editing/cleanup.

h) Finalize and lock the database.

i) 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.

• Within 45 days of task 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 task order resources to a successor Contractor or to the Government. The plan shall include details on the relocation/disposition of: unused materials and supplies; manuals and directories developed by the 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.

b) 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.

5.4 TASK 4 – 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.

1. Provide Clinical/Research Laboratory Facility:

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

https://www.fda.gov/media/70858/download

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 down to -80 degrees Celsius.

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

2. 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 task order protocols.

Technical Performance Reports

The Contractor shall also prepare and deliver the following reports and materials for each task order awarded under Performance Area B:

Deliverables Estimated

Quantity/Frequency Review or Delivery Date

Task 1 - Program/Project Management Copies of all relevant contractor SOPs and/or manuals for studies in the Task Order;

relevant documents for study personnel including CVs and signed non- disclosure agreements

Within 3 months after or award or before any study initiation dates (whichever is earliest)

Project Management Plan 2 business days after meeting

Task 3 - Sample Analysis, Close-Out, and Reporting Initiate method development/validation.

Method development/validation for specific assay(s) is initiated only after instruction from FDA COR; Task 2 will be repeated for additional assays upon FDA COR instruction

Within 2 weeks of request by FDA COR

Method validation and eCTD report.

Completion of method validation will be delivery of report and will repeated for additional assays upon FDA COR instruction

Within 8 weeks of initiating method development/validation for single analyte and 10 weeks for multiple analytes

Sample analysis completed for primary sample analysis or incurred sample reanalysis. Data transferred with QC if requested.

As samples are received for specific study(ies)/assay(s).

Within 7 weeks of all samples being received for a specific assay for a specific study. Data transfer, as requested, available within 1-2 weeks of completing sample analysis.

eCTD compliant bioanalytical report completed for each study or study part and repeated for subsequent studies or parts upon FDA COR instruction

Draft report within 5 weeks and final report within 9 weeks of completing sample analysis for a specific assay for a specific study

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

Will be determined by terms of each trial Task Order

Shipment of study biological specimens to FDA for storage or disposal as outlined in the Task Order

Will be determined by terms of each trial Task Order

Reporting requirements may be amended or updated with each task order award.

Other Deliverables:

Note: Actual…