RFP_15-01_Attachments_1_through_24_-_one_document.pdf

ATTACHMENT #1

PACKAGING AND DELIVERY OF PROPOSALS

Your proposal shall be prepared and organized in accordance with SECTION L.- Instructions, Conditions, and Notices to Offerors,” of the RFP. Marking, copies, shipment and delivery of proposals shall be as indicated below.

Proposals for furnishing the supplies and/or services in the SCHEDULE will be accepted at the location specified below, and in the number of copies specified until 4:30 pm (EST), September 4, 2015.

EXTERNAL PACKAGE MARKING

In addition to the address cited below, the outside of each package should be marked with the following information:

“RFP NO. NIH-NINDS-15-01”

“TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY”

NUMBER OF PROPOSAL COPIES:

TECHNICAL PROPOSAL: ORIGINAL AND 5 COPIES (Hard Copy)

BUSINESS PROPOSAL: ORIGINAL AND 3 COPIES (Hard Copy)

In addition to the number of hard copy versions mentioned above, offerors must deliver ten (10) CD copies of the complete technical proposal and five (5) CD copies of the complete business proposal. It is preferred that the CD proposals, including any and all attachments to the proposals, be submitted in either a Microsoft or a searchable PDF format, except for the budget spreadsheets which must be submitted in Microsoft Excel© format.

DELIVERY ADDRESS

If hand-delivered or delivery service If using U.S. Postal Service

Contracting Officer Contracting Officer Office of Acquisitions, Neurosciences Office of Acquisitions, Neurosciences

NINDS R&D CMB, NIDA, NIH NINDS R&D CMB, NIDA, NIH

6001 Executive Blvd., Suite 3287 6001 Executive Blvd., Suite 3287, MSC 9531 Rockville, MD 20852 Bethesda, MD 20892-9531

NOTE: Please be aware that the U.S. Postal Service’s “Express Mail” DOES NOT deliver to the Rockville, Maryland address AND delivery to the Bethesda, Maryland address will result in a delayed delivery to our office in Rockville, MD (up to 3 – 5 days). If a proposal is not received by the RFP receipt date and time, it will be considered a “late proposal.”

ATTACHMENT #2

PROPOSAL INTENT RESPONSE SHEET

RFP No. NIH-NINDS-15-01

PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL. FURNISH THE

INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY THE EARLIEST

PRACTICABLE DATE. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL

GREATLY ASSIST US IN PLANNING FOR PROPOSAL EVALUATION.

[ ] DO INTEND TO SUBMIT A PROPOSAL

[ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING

REASONS:

COMPANY/INSTITUTION NAME:

AUTHORIZED SIGNATURE:

TYPED NAME AND TITLE:

DATE:

RETURN TO:

Contracting Officer Office of Acquisitions, Neurosciences NINDS R&D Contracts Management Branch 6001 Executive Boulevard, Suite 3287 Bethesda, Maryland 20892-9531

ATTACHMENT No. 3

Phase I Clinical Trials for Development of Neurotherapeutics Statement of Work

1. Introduction/Background The National Institute on Neurological Disorders and Stroke (NINDS) has the need for a full service, turn-key Phase I clinical trials operations and facility for the development of novel neurotherapeutics. This full service facility would support a full range of services from protocol development through submitting a clinical study report.

The term neurotherapeutics shall include novel agents developed by the National Institutes of Health (NIH) and its grantees (henceforth known as the “Contributor (s)”) and provided to the NINDS for collaborative development as well as investigational agents supported by and through the NINDS including the Blueprint Neurotherapeutics Network http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm. The Phase I clinical trial investigational agents to be assessed may include small molecules, peptides, proteins or oligonucleotides. The data generated from the Phase I clinical trials will be used by NINDS, contributors or sponsored investigators in support of IND applications. The results of these Phase I clinical trials will be the basis to advance candidate compounds for further clinical development (i.e., additional Phase I, Phase II/III clinical trials), and submitted ultimately to the FDA in support of a New Drug Application (NDA) submission.

The emphasis of this contract shall be on Phase I first in human clinical trials to determine the tolerated dose range, the dosing regimen, the safety profile and pharmacokinetic (PK) parameters and may include pharmacodynamics (PD), and evaluation of biological effects and early signs of efficacy.

Pharmacodynamics is used here to encompass measures to assess target engagement, modulation of biological processes subsequent to target engagement, and modulated processes relevant to disease pathogenesis. Depending on the project, target populations may be healthy volunteers, demographic subsets of healthy volunteers, or subjects with conditions of interest, typically mild forms of the proposed disease indication.

The Contractor is expected to be capable of performing both Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) type Phase I clinical trials. It is anticipated that the majority of Phase 1 trials to be conducted under this program will be Single Ascending Dose trials. However, should the need arise, the NINDS may require performance of either a Multiple Ascending Dose trial or a combination of a SAD/MAD trial. The NINDS anticipates conducting 1-2 clinical trials per year over the next ten years.

2. Scope The scope of activities to be performed by the Contractor shall include the provision of a Phase I clinical research unit, the conduct of Phase I clinical trials of neurotherapeutics and the provision of a full range of services to support the clinical trials and reporting of the results to regulatory agencies.

These trials shall be designed to develop or assess tolerated dose range, the dosing regimen, safety profile and PK parameters. At the request of the Government the trials may include PD measures, and evaluation of biological effects and early signs of efficacy. All clinical trials shall be carried out in a timely fashion and in compliance with all FDA regulations and International Conference on Harmonization (ICH) Good Clinical Practices (GCP) guidelines.

3. Contract Type and Ordering Mechanism

The Government intends to make multiple indefinite delivery/indefinite quantity (ID/IQ) type contract awards under this solicitation. The successful contractors shall then compete for future Phase I clinical trials as requirements become available. The Contractor shall perform work as directed in awarded task orders. Task Order awards will cover the following:

i) Performance Area A: Administrative and Overall Clinical Operations Support. The Task Order for Performance Area A will be a fixed-price order with a term of one year. The base Task http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm

Order for this performance area requirement will also contain nine annual one-year term options.

The additional nine term options would provide for continuation of work under this Performance Area for each successive year of the IDIQ order period at the election of the Government.

ii) Performance Area B: Clinical Trial Execution. Task orders for individual clinical trials of investigational agents will be competed through a Task Order Request for Proposal (TORFP) process under Performance Area B. It is anticipated that these task orders will be cost-reimbursement, completion-type task orders and will have variable periods of performance.

NINDS anticipates issuing 1-2 TORFPs under Performance Area B during each year of the contract. The actual number of TORFPs issued will depend upon programmatic needs and funding availability, and may vary from year to year. Due to changes in priorities within NINDS, the projected workload cannot be precisely described for each year. The Contractor shall initiate work only when authorized by issuance of an approved task order.

4. Specific Technical Requirements

The Contractor shall provide a Principal Investigator (PI) who is primarily responsible and accountable for the overall implementation of the awarded contract, who serves as the central contact for scientific and technical aspects of the contract and has significant experience in the conduct of Phase I clinical trials.

The PI shall be a licensed physician or shall possess a PhD or a PharmD degree. If the PI is not a licensed physician, then a licensed physician shall be part of the leadership team.

The Contractor shall assemble an investigative team with all the required core expertise including but not limited to clinicians, research nurses, study coordinator, research associates, data manager, data management support staff, research pharmacists, regulatory associates and other personnel with Phase I clinical trial expertise. The Government expects the Contractor to provide the majority of the services at its own institution. The Contractor shall have established facilities and the clinical research infrastructure, with the appropriate number and mix of clinical, laboratory and support personnel to conduct these clinical trials

All clinical trials to be conducted under this contract must be completed as per finalized protocol requirement. Ideally, the time duration for a clinical trial from recruitment initiation to the last subject’s protocol exit is estimated to be 6 months for SAD clinical trial and 8 months for MAD clinical trial (timelines may be longer for neurotherapeutics with a long half-life, e.g. some biological agents).

The Government will be responsible for providing the following for each clinical trial:

• A detailed clinical trial outline, synopsis or draft protocol;

• IND for the project (held by Contributor/sponsor);

• cGMP manufactured investigational agent as the active pharmaceutical ingredient (API) or in the final dosage form for the clinical trial;

• Access to reports of PK and PD assays used in preclinical development;

• Scientific information on the investigational agent and the indication under study

The Contractor shall carry out the scope of work and activities defined in each Task Order awarded under the following two performance areas:

Performance Area A: Administrative and Overall Clinical Operations Support

Under this performance area, the Contractor shall perform activities related with 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 archival of completed trial data and reports.

More specifically, the Contractor shall:

i) Prepare responses to TORFPs issued under Performance Area B.

ii) Provide a PI and appropriate support staff who will be responsible for overall project management including the development, implementation and maintenance of a Project Management Plan (PMP) 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.

iii) Prepare and deliver a Project Management Plan (PMP) within two (2) months after the base/initial task order award. After delivery of the initial PMP, subsequent updates/revisions to this report, shall be addressed in and included as an appendix to future quarterly progress reports. The PMP shall address and include, at a minimum, the following:

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

b) Personnel listing including their roles and responsibilities to include an organizational chart;

c) Human subject considerations (e.g., federalwide 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 and NIH policies);

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

e) Information Technology preparedness, security and compliance with contract requirements e.g. FISMA and 508 of the Rehabilitation Act of 1973, as amended by the Workforce Investment Act of 1998;

f) Data management procedures and systems planning that is in compliance as specified with the contract terms and conditions including but not limited to development of database and case report forms (CRFs) using NINDS common data element where applicable http://www.ninds.nih.gov/research/clinical_research/toolkit/common_data_elements.htm, data collection, data monitoring, data safety review;

g) Pharmacy management procedures for receiving, storing and dispensing investigational agents; also to be included a procedure for randomization and if appropriate stratification of eligible subjects;

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

i) Clinical and laboratory quality monitoring procedures;

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

k) Quality control plans and procedures;

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

m) Protection of Contributors intellectual property and data procedures;

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

o) Archival plans for securing completed trial data according to regulatory requirements;

p) Contingency planning; and

q) Close-out plan

iv) Conduct Teleconferences and Meetings for:

a) Pre-TORFP Meetings: to review the task order requirements, timelines, milestones and deliverables; discuss task order plans and approaches and identify any anticipated difficulties http://www.ninds.nih.gov/research/clinical_research/toolkit/common_data_elements.htm in completing the task order requirements;

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

c) Annual Site Visits: Host an annual site visit (one day) for the COR, the Contracting Officer (CO) and other NINDS staff;

d) Ad hoc Site Visits: Host a one day meeting as requested by COR and/or CO;

e) Prepare minutes of all site visits and teleconferences/webinars and submit to the COR for review and approval within 2 business days of the meetings.

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

Performance Area B: Clinical Trial Execution

NOTE: NINDS will issue TORFPs for individual clinical trials of investigational agents under Performance Area B. Performance Area B activities are defined below and are to be considered general Technical Requirements that will be executed following issuance of individual Performance Area B Task Order awards. Each individual Performance Area B Task Order award will also define specific and additional technical requirements as appropriate for that Task Order Statement of Work.

Under Performance Area B, the Contractor shall perform all activities associated with the conduct of Phase I clinical trials as specified below. Task Orders issued under Performance Area B, “Clinical Trial Execution,” will consist of a base requirement for protocol development and finalization and include a quantity type option for actual conduct of the trial called “trial execution.”

The technical requirements for the base and quantity option components are as described below.

Base Requirement: “Protocol Development and Finalization”

1. Finalize a protocol and submit to NINDS for scientific review and approval in compliance to the timelines specified within the task order. Provide all necessary documentation for the proposed clinical trial to the contributor required to secure the IND approval (e.g. Form FDA 1571, Form FDA 1572) and work with Contributors to submit documents for all requisite regulatory approvals (e.g., IRB and FDA submissions). Prepare the informed consent form (ICF) which contains appropriate reference to the NINDS 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 institutional review board (IRB) for review and approval.

2. Throughout the process essential regulatory documents as specified in ICH guideline should be generated and stored in files/folders and be available for monitors and for use in the subsequent quantity option when executed. Essential regulatory documents may include but are not limited to:

signed IRB approved protocol, informed consent form and advertisement for subject recruitment; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, conflict of interest declaration, indemnification/insurance documents, Form FDA 1571, Form FDA 1572.

Quantity Option: “Trial Execution”

A) Protocol Implementation: Compliance and Oversight

1. Activities required prior to clinical trial initiation:

a) Register the clinical trial in the National Library of Medicine’s Clinical Trials registry

(http://www.clinicaltrials.gov)

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

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

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

• the Data Safety and Monitoring (DSM) plan including an Independent Safety Monitor in accordance with NIH guidelines and policies for DSM for review and approval by the IRB (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm;

http://www.ninds.nih.gov/funding/ninds_patient_safety_guidelines.htm)

• the recruitment and retention plan (e.g., enrollment of a diverse subject pool, including women and minorities, rate of subject accrual, subject retention, plans for deficient enrollment)

• the data management plan

• the CRFs using NINDS common data element where applicable

(http://www.ninds.nih.gov/research/clinical_research/toolkit/common_data_elements.htm) and the corresponding data dictionary and any other supporting documents

• the statistical analysis plan

• the pharmacy management plan including a system for random treatment assignment and, if necessary, appropriate stratification of eligible subjects

• the plan to monitor and track AEs and SAEs, including prompt reporting of SAEs

• the blinding plan, including during pharmacy, clinical and data management activities, as appropriate

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

e) Conduct a clinical trial initiation meeting

2. Regulatory Compliance

a) Throughout the studies essential regulatory documents should be generated and stored in files/folders and be available for monitors and at the end of the studies all essential regulatory documents at the clinical research unit should be placed in the master regulatory file for archiving. Regulatory documents may include but are not limited to: IRB approved protocol, ICF and advertising; IRB approval letter; IRB membership list; PI and sub-investigators curriculum vitae; licenses for PI and sub-investigators; investigator’s brochure, normal laboratory ranges, laboratory certification, financial disclosure documents, indemnification/insurance documents, Form FDA 1572, investigational agent shipment receipts, etc. During the conduct of the clinical trial, all new relevant information/data must be appended to the essential documents as it becomes available.

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

c) Prepare a complete clinical study report in submission ready format for FDA unless otherwise specified. Additionally, the IND report for annual filing requirements to the IND application, as needed.

d) Ensure the confidentiality of all clinical records and information about subjects enrolled in the clinical trial conforms to all Privacy Act requirements (http://www.justice.gov/opcl/privacy-act-http://www.clinicaltrials.gov/ http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm http://www.ninds.nih.gov/funding/ninds_patient_safety_guidelines.htm http://www.ninds.nih.gov/research/clinical_research/toolkit/common_data_elements.htm http://www.justice.gov/opcl/privacy-act-1974

1974 and http://www.hhs.gov/ocr/privacy). This acquisition will require the Contractor to do one or more of the following: design, develop or operate a system of records on individuals to accomplish an agency function. Therefore, the Contractor shall comply with the Privacy Act of 1974 as amended at 5 U.S.C. 552a, FAR Clause 52.224-2, applicable agency regulations, and provisions of the NIH Privacy Act System of Record Notice (SORN) applicable to work under this contract. The Privacy Act SORN applicable to this contract is System No. 09-25- 0200, Clinical, Basic and Population-based Research Studies of the NIH, HHS/NIH/OD. The SORN is attached and made a part of this contract. Violation of the Act may involve the imposition of criminal penalties.

Information and records obtained from subject volunteers who have consented to participate in performance of work under this contract will be subject to the provisions of the Privacy Act.

The Contractor shall explain to participants exactly how information is to be collected, the purpose and use for which the information is being collected and how the information will be protected pursuant to the Privacy Act of 1974 (P.L. 93-579) and accompanying Privacy Act System Notice made a part of this contract, both of which are applicable to the performance of work under this contract. All participants must be made to understand, through use of the informed consent form and careful education, that the extent of their participation is entirely voluntary and that they may provide all, some or none of the information which the Contractor is intending to collect. Upon completion of each clinical trial, the system of records generated in performance of that study shall be disposed of in accordance with instructions to be furnished by the COR.

3. Clinical Trial Initiation

The Contractor’s clinical trial team and support staff shall participate in a clinical trial initiation meeting at the Contractor’s clinical research facility. Prepare and deliver a summary report of the initiation meeting to include but not be limited to the agenda and the list of participants.

4. Protocol Amendments

Prepare all protocol amendments and modifications.

a) Upon COR approval, the Contractor will submit the amended protocol and ICF to the lRB for review and approval.

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

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

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

5. Protocol Oversight

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

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

For each Task Order protocol:

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

2. Review and assess participant data as specified within the data management plan, protocol http://www.justice.gov/opcl/privacy-act-1974 http://www.hhs.gov/ocr/privacy requirements and/or quality assurance requirements; for example:

• Promptly provide all data reports for monitor review prior to start of dose escalation decisions

• 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 to FDA, IRB and

COR

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

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

6. Data Management and Quality Control

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

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

7. Audit Compliance

The NINDS 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 the corrective actions.

B) Investigational Agents and Clinical Specimens

1. Investigational Agent

a) Maintain inventory records of investigational agent in accordance to the pharmacy SOPs.

b) Maintain documentation that the investigational agent will be stored and quarantined under appropriate conditions in the research pharmacy according to the sponsor and regulatory requirements.

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

2. Clinical 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 current Good Laboratory Practice (cGLP), cGCP and domestic laws and regulations.

C) Clinical Trial Analysis, Close-out and Final Clinical Trial Reporting

1. Close-out and Analysis

Following the last subject’s completion of clinical trial procedures including any outpatient follow-up visits, the Contractor shall:

a) Continue to monitor any residual safety concerns (i.e., AEs & SAEs) until complete resolution.

b) Complete data editing/cleanup.

c) Finalize and lock the database.

d) Conduct the statistical analysis as described in the manual of operations.

e) Deliver the locked DE identified database in agreed upon format (e.g., R, SAS, SPSS, ASCII) and schedule as requested by the COR.

2. Completion

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).

b) Prepare and deliver draft and final clinical study report; the study report must be in a format suitable for submission to the FDA.

D) Facilities, Equipment and Other Resources

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

Provide Inpatient Clinical Research Facility:

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

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 target populations.

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

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

h) Emergency care and a definitive plan for management of life-threatening adverse events.

including on-site resuscitation equipment and hospitalization procedures in the event a participant requires these services.

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

j) Capabilities for the collection of cerebrospinal fluid (CSF) via lumbar puncture or with a temporary in-dwelling catheter.

k) Ability to provide experienced research staff to perform cognitive testing, using paper or computer based systems.

l) 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.

m) Access to clinical specialists in the therapeutic areas covered by NINDS and the Blueprint Neurotherapeutics Network for additional safety assessments that may be required in select clinical trials, such as ophthalmology exam or detailed neurologic examination.

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

Provide Clinical Laboratory Facility:

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

b) Adequate facilities and equipment for conducting protocol-required tests and assays such as PK and specialty PD assays on blood, plasma, CSF or other body fluids and tissues.

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

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

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

f) Have current certification and licensure for the performance of biological specimen assays and analyses.

Provide Research Laboratory Facility:

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

b) Adequate facilities and equipment for conducting protocol-required tests and assays such as PK and specialty PD assays on blood, plasma, CSF or other body fluids and tissues.

c) Capabilities to design and validate PK and PD assays.

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

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

f) Have current certification and licensure for the performance of biological specimen assays and analyses.

Provide Clinical Imaging Facility:

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

b) Adequate facilities and equipment for conducting protocol-required imaging procedures for diagnosis or special safety evaluations, including computerized tomography (CT), magnetic resonance imaging (MRI), proton emission tomography (PET), electromyography (EMG), and electroencephalography (EEG).

c) Electroretinography (ERG).

d) Have current certifications and licensures for the performance of imaging procedures.

Provide Research Pharmacy Facility:

a) Research pharmacist with expertise in the preparation, distribution and storage of investigational 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 investigational 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.

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 in order to provide a centralized, integrated system for data storage, analysis, reporting and ad hoc query of clinical data.

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

Provide other facilities and equipment, as may be specified by the task order protocols (e.g., biosafety laboratory facilities in compliance with Federal and state regulations).

E) Insurance

The Contractor and all collaborating sites participating in the conduct of approved protocols shall provide sufficient malpractice insurance and indemnification for trial related injuries to volunteers. The Government will not provide third party liability insurance.

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

F) Reporting Requirements and Deliverables

1) Technical Performance Reports

Performance Area A

The Contractor shall be required to prepare and deliver the following reports during the base year of the initial task order award for Performance Area A:

a) Quarterly Progress Report

These reports are due five (5) calendar days after the end of month 3, month 6, month 9 and month 12 after the base (initial) task order (TO) award. These reports shall address, but are not limited to, all performance activities related to FISMA requirements; staff training and updates;

human subject training; copies of minutes from meetings, teleconferences, webinars and site visits occurring during the reporting period; summary of all activities conducted for each active and completed trial (to be reported individually for each trial); list of all final archived locked data sets for all trials performed under the contract.

b) Project Management Plan (PMP)

The PMP report shall address and include all elements as listed in the SOW requirements for this report as set forth in Section (iii) under Performance Area A. The PMP shall be delivered by the end of month 2 following the base/initial TO award. The Contractor may submit a draft of this report, for review and comment by the NINDS COR, with 45 days after award of the base TO.

After delivery of the initial PMP, subsequent updates/revisions to this report, shall be addressed in and included as an appendix to future quarterly progress reports.

The Contractor shall be required to prepare and deliver the following report for each subsequent option year if exercised under Performance Area A:

a) Quarterly Progress Report

These reports are due five (5) calendar days after the end of month 3, month 6, month 9 and month 12 after award of the option extending the term of the task order period for out years 2 through 10. These reports shall address, but are not limited to, all performance activities related to FISMA requirements and security plan updates; IND requirements and submissions; PMP updates; staff training and updates; human subject training; copies of minutes from meetings, teleconferences, webinars and site visits; summary of all activities conducted for each active and completed trial (to be reported individually for each trial); list of all final archived locked data sets for all trials performed under the contract.

Performance Area B

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

SOW Deliverable Delivery Schedule

Base Requirement – Protocol Development and Finalization

Final protocol and any related amendments/modifications, to include all required regulatory forms for contributor to obtain open IND for proposed trial (e.g. FDA Form 1571 and 1572).

3 weeks after award of task order.

Quantity Option – Clinical Trial Execution

Manual of Operations (for each study)

10 days after exercise of option

Summary Report for each Clinical Trial Initiation meeting

2 business days after meeting

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

Will be determined by terms of each trial Task Order

Draft clinical study report Within 45 days after locking database

Final clinical study report Within 15 days of receiving comments from the NINDS COR/CO

Annual report for each IND application

Within 30 days of request of COR

2) Other Report Requirements

The Contractor shall prepare and deliver the reports specified below as part of their work effort under Performance Area A. These reports, which are in addition to the “Technical Performance Reports” specified above, are required FAR clauses that are applicable to and must be included and made a part of any resultant contract.

All reports shall be submitted in electronic format. All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d), as amended by the Worforce Investment Act of 1998 and the "Electronic and Information Technology Accessibility Provisions" set forth by the Architectural and Transportation Barriers Compliance Board (also referred to as the "Access Board") in 36 CFR part 1194.

Any paper/hardcopy documents/reports submitted under this contract shall be printed or copied, double-sided, on at least 30 percent post consumer fiber paper, whenever practicable, in accordance with FAR 4.302(b).

a) Information Security and Physical Access Reports

The Contractor shall submit the following reports as required by the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

i. Roster of Employees Requiring Suitability Investigations (Monthly IT Roster)

The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a Federal information system(s). The initial roster shall be submitted to the Contracting Officer's Representative (COR), with a copy to the Contracting Officer, within 14 calendar days after contract award. Monthly IT Roster reports shall be submitted thereafter. The monthly IT roster reports are due 5 calendar days after the end of each montly reporting period. (Reference subparagraph a.4. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

ii. IT Security Plan (IT-SP)

In accordance with HHSAR Clause 352.239-72, Security Requirements For Federal Information Technology Resources, the contractor shall submit the IT-SP within thirty

(30) days after contract award. (Reference subparagraph d.3.a). of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

iii. IT Risk Assessment (IT-RA)

Information Technology Resources, the contractor shall submit the IT-RA within thirty

(30) days after contract award. (Reference subparagraph d.3.b). of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

iv. FIPS 199 Assessment

Information Technology Resources, the Contractor shall submit a FIPS 199 Assessment within thirty (30) days after contract award. (Reference subparagraph d.3.c). of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECITON H of this contract.

v. IT Security Certification and Accreditation (IT-SC&A)

In accordance with HHSAR Clause 352.239-72, Security Requirements for Federal Information Technology Resources, the Contractor shall submit written proof to the Contracting Officer that an IT-SC&A was performed within three (3) months after contract award. (Reference subparagraph d.3.d). of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

vi. Contractor - Employee Non-Disclosure Agreement(s) The contractor shall complete and submit a signed and witnessed "Commitment to Protect Non-Public Information - Contractor Agreement" form for each contractor and subcontractor employee who may have access to non-public Department information under this contract. (Reference subparagraph E.3.d. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

vii. Vulnerability Scanning Reports: The contractor shall report results of monthly vulnerability scans within 10 calendar days following the end of each monthly report period. The first report shall cover the first full month of contract performance and is due 40 days after contract award. (Reference subparagraph E.5. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

b. Section 508 Annual Report

The contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION H of this contract.

c. Invention Reporting Requirement

All reports and documentation required by FAR Clause 52.227-11, Patent Rights-Ownership by the Contractor, including, but not limited to, the invention disclosure report, the confirmatory license, and the government support certification, shall be directed to the Division of Extramural Inventions and Technology Resources, OPERA, NIH, 6705 Rockledge Drive, Suite 310, MSC 7980, Bethesda, Maryland 20892-7980 (Telephone: 301-435-1986). One copy of each annual utilization report shall be submitted as an e-copy to the Contracting Officer on or before each anniversary date of the contract. The final invention statement (see FAR 27.303(b)(2)(ii)) shall be submitted as an e-copy to the Contracting Officer on or before the expiration date of the contract, listing all subject inventions or stating that there were none.

If no invention is disclosed or no activity has occurred on a previously disclosed invention during the applicable reporting period, a negative report shall be submitted to the Contracting Officer.

To assist Contractors in complying with invention reporting requirements of the clause, the NIH has developed "Interagency Edison," an electronic invention reporting system. Use of Interagency Edison is encouraged as it streamlines the reporting process and greatly reduces paperwork. Access to the system is through a secure interactive Web site to ensure that all information submitted is protected. Interagency Edison and information relating to the capabilities of the system can be obtained from the Web (http://www.iedison.gov), or by contacting the Division of Extramural Inventions and Technology Resources, OPERA, NIH.

d. Subcontracting reports

The Contractor shall submit the individual and summary subcontract reports as required and as set forth in Article H.16 in Section H. These reports shall be submitted via the "electronic Subcontracting Reporting System (eSRS) at http://www.esrs.gov .

http://www.esrs.gov/

Base/Initial Task Order Requirement

Performance Area A - Administrative and Overall Clinical Operations Support

NOTE:

The NINDS anticipates awarding a Task Order under Performance Area A with any resultant IDIQ award. That task order will cover the first year of the contract as outlined and described in the Statement of Work. Therefore, offerors are to include as a part of their proposal, a full and complete technical response that addresses all aspects of their approach, methods, resources and capabilities as to how they will carry out, perform and meet all aspects of Performance Area A requirements as set forth in the Statement of Work. The Statement of Work and Reporting Requirement/Deliverables for the Performance Area A task order will be as stated in Articles C.1. and C.2. of Section C – Description/Specifications/Work Statement of the RFP.

It is anticipated that award of this task order will be made on a fixed-price basis.

Sample Task Order B-1

Protocol Development for: A Phase I Single Ascending Dose Clinical Trial of a Novel Neurotherapeutic Agent

NOTE: The following sample Task Orders indicated in this attachment are provided to assess the offeror’s capabilities to conduct and fulfill the requirements of the Statement of Work for clinical trials of similar scope and size to be issued under Task Orders awarded in response to this solicitation. These sample Task Orders will NOT be executed nor will awards be issued for the sample work. Offerors are to include in their proposals a response that specifies the methods by which each sample Task Order will be fulfilled with associated costs.

(In Addition to the General Technical Requirements Associated with

Performance Area B)

1. Scope

The scope of activities includes all tasks and activities associated with the execution of the requested Phase I trial described herein. The development and finalization for the clinical protocol entitled: An Open- Label Single Ascending Dose Study of Safety and Pharmacokinetics of an investigational agent (i.e., BPN-XXXXX) in Healthy Adult Volunteers including but not limited to the development and finalization of study design elements, safety assessments, PK assessments and other protocol requirements performed by the Contractor.

Note: The offerors are to provide a technical proposal including timelines and cost estimate for the execution of above referenced protocol. For the purposes of proposal preparations, assume that the Contractor is tasked with designing a Phase I single ascending dose clinical trial to evaluate the safety profile and PK of BPN-XXXXX, a novel neurotherapeutic in healthy adult volunteers. Objectives of the protocol are: a) characterize the systemic safety profile of BPN-XXXXX in a single ascending dose trial and b) characterize the PK of BPN-XXXXX across the range of doses. The design is open label first-in-human clinical trial. All appropriate non-clinical studies, including the Investigational New Drug (IND)-enabling repeat-dose, Good Laboratory Practice (GLP) toxicology studies have been conducted.

Significant safety issues were identified at doses 10-fold above the No-Observed-Adverse-Effect Level (NOAEL) in each of these studies. BPN-XXXXX has a NOAEL of 1000 mg/kg/day in the most sensitive animal species tested (rats). Following multiple doses, changes in hematology were revealed. BPN- XXXXX is well absorbed orally and has an elimination half-life of approximately 8 hours in the rat.

2. Technical Requirements

Independently and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified personnel, materials, equipment and facilities not otherwise provided by the Government as needed to conduct the clinical trials as described in the Statement of Work.

In addition to the specific technical requirements specified below, the Contractor shall fulfill the general technical requirements defined in the Parent Statement of Work, Performance Area B Activities, which shall be considered general technical requirements for all task orders issued under Performance Area B.

Task orders issued under Performance Area B will consist of two components; a Base Requirement (Protocol Development) and a Quantity Option (Clinical Trial Execution).

Note: Please reference Sample Task Order B-1 Draft Protocol Synopsis for the purposes of preparing the technical proposal. A separate cost proposal will be provided for the Base Requirement and the Quantity Option.

Specifically, the Contractor shall perform all activities as outlined below:

A. Base Requirement: Protocol Development and Finalization This includes all items and activities described in Performance Area B that were listed under Specific Technical Requirements for Protocol Development and Finalization

B. Quantity Option: Trial Execution

This includes all items and activities described in Performance Area B in A-F under Trial Execution that were listed in Specific Technical Requirements

TASK ORDER B-1 DRAFT PROTOCOL SYNOPSIS

Study Title An Open-Label Single Ascending Dose Study of Safety and

Pharmacokinetics of BPN-XXXXX in Healthy Adult Volunteers

Study Number TBD

Study Phase Phase I, First in Human

Subject

Population Healthy Volunteers

Objectives 1. Characterize the systemic and ocular safety of single ascending multiple doses of BPN-XXXXX

2. Characterize the pharmacokinetics (PK) of single ascending doses of

BPN-XXXXX

Study Design and

Duration

This is an open label single ascending dose study. There will be 5 dose levels, each administered to a cohort of 6 subjects. Consistent with NINDS policies, 2-4 subjects in each cohort should be female and efforts should be made to include diverse races and ethnicity.

All subjects will participate in a Screening period lasting up to 28 days, during which they will be assessed for eligibility.

All cohorts will reside in the research unit from Day -1 through Day 3. On Day -1 baseline safety data will be obtained. Subjects will receive a single oral dose on the morning of Day 1.