Sol_Doc_FDA-22-RFP-1249967 Final.pdf

FDA-22-SOL-1249967 – Multi-phase / Multi-site Clinical Studies and Laboratory Support

PART A – SOLICITATION INFORMATION

A.1 Purpose

This Request for Proposal (RFP) is to acquire Clinical Study Laboratory Support Services for FDA Office of Clinical Pharmacology (OCP).

A.2 Notice of Combined Synopsis/Solicitation

This is a combined synopsis/solicitation for commercial items prepared in accordance with (IAW) the format in 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 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.

A.3 Notice of NAICS

This requirement is being solicited as a competitive Full and Open opportunity. The associated North American Industry Classification System (NAICS) code is 541380 (Testing Laboratories). Offerors must have an active registration in SAM.gov (https://beta.sam.gov/), with completed representations and certifications, by the close date of the solicitation. Proposals submitted by offerors without an active registration in SAM.gov will not be considered.

https://beta.sam.gov/

PART B – PRICE SCHEDULE

B.1 Overview of Pricing Schedule

The Contractor’s pricing schedules for all 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, and profit. Hourly rates shall apply to services at both Government and non-Government sites.

By mutual agreement of the parties, additional labor categories may be added to this IDIQ to support the tasks of this contract.

The awarded labor categories and rates will be used throughout the period of performance of this IDIQ contract. The contractor shall use these rates, as applicable, for all Task Orders issued under the contract.

B.2 Pricing Terms

The Contractor shall comply with FAR 52.232-7, Payments under Time-and-Materials and Labor-Hour Contracts (Aug 2012), with regard to the ceiling price for any labor-hour (LH) or time-and-material (T&M) type task orders issued.

The total amount specified in firm fixed-price (FFP) task orders shall be fixed for the task order period of performance and shall not be subject to adjustment; except, as a result of a direct action or inaction by the Government which delays the Contractor from completing the task order within the time specified in the order. The Contractor shall comply with FAR Clause 52.232-1 Payments (APR 1984) in regard to the firm-fixed-prices for individual task orders.

B.3 Contract Type

It is anticipated that a single-award Indefinite Delivery-Indefinite Quantity (IDIQ) type Contract will be awarded as a result of this solicitation. The quantities of services ordered under this contract shall be accomplished by the issuance of task orders that will describe the contract type, objectives, scope, period of performance, and deliverables. All task orders are subject to the terms and conditions in the IDIQ base contract. The following contract types are authorized for task orders issued under this IDIQ contract: Labor-Hour (LH), Time and Materials (T&M), and Firm-Fixed-Price (FFP). Ordering periods may be included in task order awards.

B.4 Minimum and Maximum Contract Value

IDIQ Minimum: The minimum guarantee for this IDIQ contract is $450,000.00, which will be met with the award of the first task order.

IDIQ Maximum: The maximum aggregate dollar value of all task orders awarded over the 5-year Performance Period of this IDIQ contract shall not exceed the IDIQ ceiling amount of $45,000,000.00.

See FAR Clause 52.216-19 for individual order limitations.

The Contractor shall provide all resources, including supervision, labor, materials, tools, parts and equipment necessary to provide the required services in accordance with the Statement of Work (SOW) Part C.

In the event the contractor exceeds the total ceiling amount it shall be at the contractor’s own risk. The ceiling amount shall only be exceeded with prior approval and modification issued by the contracting officer in accordance with FAR 52.232-7.

The Government is not obligated to issue work orders for any specific minimum or maximum number of services from any one labor category or combination of labor categories.

B.5 Ordering

A request for task order proposal (RFTOP) will be issued for individual task orders. Task orders against the IDIQ contract will be issued via email and will be in accordance with FAR 16.505 and FAR clause 52.216-18.

Ordering Procedures Any Contracting Officer (CO) of the Food and Drug Administration (FDA) is authorized and may place orders under this IDIQ contract. Each individual task order will describe the specific performance requirements for data volume and timeliness and may include required reporting processes and/or document handling procedures. When a need for services within the scope of this IDIQ contract arises, the process for issuing task orders is as follows:

1. The FDA CO will issue a RFTOP via email. The RFTOP will include the following information:

a. SOW

b. Period of performance

c. Anticipated contract type

d. Specific reporting requirements and deliverables

e. Any Key Personnel

f. Any special terms and conditions specifically applicable to the task order

2. The Contractor will typically have a minimum of five (5) business days, unless otherwise specified, to provide a proposal in response to the RFTOP. The proposal shall include:

a. Brief description of the technical approach to the task order requirements

b. Price buildup (including labor categories, hours for each labor category, extended pricing, total task order pricing, and concurrence with the anticipated contract type)

c. Resumes of any key personnel identified in the RFTOP

3. The FDA will evaluate the task order proposal for technical acceptability and price reasonableness. If the FDA has questions or concerns, the Contracting Officer will contact the Contractor and may request a revised proposal.

4. If the task order proposal is determined acceptable, the Contracting Officer will issue a task order. All task orders will, at a minimum, include the following:

a. Task Order number

b. Date of Task Order

c. Funding for the Task Order

d. Task order SOW and specific deliverables and due dates

e. Task order pricing

f. Period of performance of the task order

g. Any terms, conditions and instructions specific to the task order

Any work that the Contractor undertakes prior to receiving a fully executed task order that has been signed by the Contracting Officer (or the Contractor has received prior authorization to proceed from the Contracting Officer) shall be at the Contractor’s risk.

Pricing of Orders

a. Proposals submitted in response to a RFTOP must be in accordance with the Ordering Period rates in the IDIQ Price Schedule based on the performance start date of the task order, and that rate must be used for the duration of the task order performance period. The Contractor may propose lower rates in response to a RFTOP.

b. RFTOPs may include ordering periods in accordance with FAR clause 52.217-9. However, ordering periods must utilize the ordering period rates listed in the IDIQ Price Schedule, based on the performance start date of the option period.

c. Labor-Hour (LH) and Time-and-Materials (T&M) type task orders will include a ceiling price.

d. If a task order’s stated period of performance must be extended as a result of Government delay, the Contractor may request that the most current labor rates be used to price the work effort during the extended period for LH and/or T&M task orders.

These Ordering Pricing terms and conditions apply to all task orders issued against this IDIQ contract.

B.6 Labor Categories/Key Personnel

The Government anticipates the following labor categories:

Labor Category Minimum Qualifications

Project Manager* • Leads and performs program area work. Proposes and implements creative methods to complete work effectively and efficiently. Meets with client regularly, if not daily, to ensure work meets/exceeds client objectives.

• Bachelor’s degree in Business administration

• 8 years of experience

Principal Investigator* • Supervises clinical research trials by effectively managing investigational sites, developing study protocols, preparing CRFs and IRB submissions, and ensuring compliance with study protocols, FDA regulations, IRB requirements and clinical strategy. Supervises research team, providing direction and guidance to clinical research associate.

• Bachelor’s degree in applied statistics, computer science, data mining, machine learning or related quantitative field that is relevant to the contract and 2 years of progressive experience (or equivalent combination of education and experience) for Data Scientist, 5 years of experience for Senior Data Scientist, 10 years of experience for Principal Data Scientist.

Pharmacist • Compounds and dispenses prescribed drugs.

• Minimum education: Graduation from an accredited school of pharmacy and in possession of a valid unrestricted pharmacy and controlled substance license in the state of employment

• Experience in specialty: 2+ years of experience in past 36 months.

• Certification: State License, controlled substance license if required

Investigator • Assist in the design, planning and execution of clinical research trials by effectively managing investigational sites, assisting with development of study protocols, preparing CRFs and IRB submissions, and ensuring compliance with study protocols, FDA regulations, IRB requirements and company clinical strategy. Control drugs under investigation.

• Bachelor’s degree in Business administration or related field

• 3 Years of experience

Clinical Technician • Performs research activities and other tasks. Has knowledge of commonly-used concepts, practices, and procedures within a particular field. Relies on instructions and pre-established guidelines to perform the functions of the job. Works under immediate supervision.

• Minimum education: Graduation from an approved program in Pharmacy Technician. Must obtain CPHT certification and state licensure as required.

• Experience in specialty: 1+ years of experience in past 24 months.

• Certification: CPHT certification, state licensure if required, BLS/ACLS

Lab Technician • Performs research activities and other tasks. Has knowledge of commonly-used concepts, practices, and procedures within a particular field. Relies on instructions and pre-established guidelines to perform the functions of the job

• Education: Bachelor’s Degree in related field.

• Licensure: Not required

• Certifications: American Society of Clinical Pathology (ASCP) Certification, preferred. Basic Life Support (BLS)

• Certification, as required by using agency’s inclusion in the Statement of

Work/Performance Work Statement.

• Experience: Minimum twelve months experience in respective specialty, preferred

Statistician • Identifies methodologies and measures for assessment and summarization of findings. Selects appropriate statistical and epidemiologic techniques and databases. Assists in developing and managing databases for analysis.

Ensure reliability and consistency of the data. Provide technical assistance on the use of complex statistical and epidemiologic techniques. Serves as technical expert in all phases of statistical interpretation. Disseminate results of research projects in a wide

• Bachelor’s degree in Business administration or related field

• 3 Years of experience

Technical Writer • Writes a variety of technical articles, reports, brochures, and/or manuals for documentation for a wide range of uses. May be responsible for coordinating the display of graphics and the production of the document.

• Bachelor’s degree in English, business, technical writing or other related discipline that is relevant to the contract and 2 years of progressive experience (or equivalent combination of education and experience).

Data Manger • Assist with the design and produce tools and materials to support data collections and surveys, including survey instruments and data entry tools.

Develop, clean, and maintain databases.

• Bachelor’s degree in related Field, computer science, databases, IT, technical or other related discipline that is relevant to the contract and 5 years of progressive experience (or equivalent combination of education and experience)

Analyst • Participates in research and development activities.

• Bachelor’s degree in computer engineering, computer science, databases, IT, technical or other related discipline that is relevant to the contract and 3 years of progressive experience (or equivalent combination of education and experience)

*Key Personnel

The contract Principal Investigator, Pharmacist and Project Manager are considered Key Personnel for Performance Area A.

#The contract Lab Technician and Project Manager are considered Key Personnel for Performance Area B.

Additional requirements regarding Key Personnel are subject to the terms pursuant to the following clause:

352.237-75 – Key Personnel (DEC 2015)

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to the contractor voluntarily diverting any of the specified individuals to other programs or contracts the Contractor shall notify the Contracting Officer and shall submit a justification for the diversion or replacement and a request to replace the individual. The request shall identify the proposed replacement and provide an explanation of how the replacement's skills, experience, and credentials meet or exceed the requirements of the contract (including, when applicable, Human Subjects Testing requirements). If the employee of the contractor is terminated for cause or separates from the contractor voluntarily with less than 30 days notice, the Contractor shall provide the maximum notice practicable under the circumstances. The Contractor shall not divert, replace, or announce any such change to key personnel without the written consent of the Contracting Officer. The contract will be modified to add or delete key personnel as necessary to reflect the agreement of the parties

Project Management and Administration

The Contractor shall ensure the Project Manager possesses the skills, knowledge, training, and clearances to perform laboratory support services required by the contract. The Contractor’s Project Manager shall ensure that personnel maintain any generally required certifications related to their area of expertise. The Contractor’s project manager must establish and maintain a documented quality management (control) system capable of assuring successful performance of this Contract.

At the end of each WOA the Project Manager shall provide a report including a description of the work performed, material purchased, and any issues noted or needing resolution.

PART C - PERFORMANCE WORK STATEMENT

C.1 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.

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.

C.2 Objectives

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. A contractor with multiple Phase I clinical research sites is preferred, however not required, to meet the scope of activities FDA may require. All clinical trials shall be carried out in a timely fashion and in compliance with all FDA regulations and International

Council for Harmonisation 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.

C.3 Scope of Services

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 areas A, which will represent the majority of the work. Organizations may either have in-house or sub-contracting capability for Performance Area B.

C.4 Tasks

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). Task Orders will be completed through a Request for Task Order Proposal (RFTOP) process. Individual Task Orders may be only in Part A, only in Part B, or a combination of Part A and Part B. In a firm, fixed price task order, the government will provide a study schedule of events (see sample studies – Attachment 6) 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 Task Order, such as Materials pass through costs (e.g. subject stipends, drug cost). 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 Task Orders will be cost-reimbursement, completion-type Task Orders and will have variable periods of performance. The actual number of RFTOPs 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.

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.

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

Specifically, for overall administration and implementation of the clinical operation services, the contractor shall:

A. 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 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 Contracting Officer Representative (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;

B. Trial Execution The FDA expects the contractor to provide most of the services at its own institution, but exceptions can be made on a case by case basis after prior approval by FDA. All clinical trials to be conducted under this contract must be completed as per the most recent version of the protocol. 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.

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). 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.

b) 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.

c) 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 http://www.clinicaltrials.gov/ approval.

• FDA’s IRB would also need to review and approve these documents unless there is an IRB authorization agreement (IAA) documenting FDA’s agreement to rely on the contractor’s designated IRB for IRB review and continuing oversight of nonexempt human subjects research in which FDA is engaged.

• 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.

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 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 in cases involving an IAA. 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.

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.

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.

• 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) Prepare and deliver draft and final clinical study report, if needed and as specified in a Task Order.

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 PK/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.

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.

1. 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:

SOW Deliverable Delivery Schedule

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 Within 3 months after or 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

Trial Execution – Protocol Implementation:

Compliance and Oversight

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].

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

Approval from FDA IRB or local IRB (if under an IAA)

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

Trial Execution – Clinical Trial Analysis, Close-Out and Final Clinical Trial Reporting

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 as specified below. 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.

A. Program/Project Management

a. Prepare responses to RFTOPs 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-RFTOP 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 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 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.

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.

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.

C. 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…