SOW-Deliverables.GTRP.CCC.Renewal.Feb.22.2011.pdf

Gene Therapy Resource Program, Renewal Clinical Coordinating Center (CCC)

NHLBI-HV-12-05

February 22, 2011

STATEMENT OF WORK

I. BACKGROUND AND HISTORY

a. Background:

Over the years since the inception of gene transfer, a better understanding of the immunology and structural biology of vectors has emerged. Delivery systems with viral vector systems and non-viral vector systems continue to evolve, and in recent years a series of novel vectors and new viral serotypes have shown promise in preclinical studies. Many diseases may benefit from gene transfer, including monogenic genetic diseases and acquired conditions, such as cystic fibrosis, hemophilia, alpha-1 antitrypsin deficiency, certain malignancies and immunodeficiencies, peripheral and cardiovascular diseases, and others.

Given the advances in the development of new gene delivery mechanisms, understanding of disease biology, and increase in the number of clinical trials conducted over the past several years, continued research in vector system development and clinical applications is critical to advancing the gene transfer field into the realm of medical practice. Gene transfer still holds promise for providing treatment options for millions of patients who are affected by challenging diseases.

Though great strides have been made in the field of gene transfer, the translation of gene transfer research from the bench to the clinic remains an arduous task requiring diverse areas of expertise. Expertise is needed in virology, vectorology, immunology, pharmacology, toxicology, animal model development and testing, regulatory science, clinical trials science, and medical expertise in specific disease areas, ranging from very common to very rare diseases.

b. History: In June 2005 the NHLBI convened an expert Working Group to better understand the impediments to clinical progress in gene therapy and to advise the NHLBI how to best direct its limited resources to facilitate translational research in the field of gene therapy. The NHLBI responded to these recommendations by establishing the NHLBI Gene Therapy Resource Program (GTRP) in March 2007. The GTRP consists of a Clinical Coordinating Center (CCC) and four Core Laboratories. The CCC is the linchpin of the GTRP and it is the only component of the GTRP whose work spans across all of the Cores and the NHLBI. The CCC works very closely with Investigators who request services from the GTRP, the Core Laboratories, and the NHLBI to ensure that all aspects of the GTRP run smoothly and that the work performed is within with the scope of the GTRP and the Mission of the NHBLI. Fulfilling the various service requests requires extensive interactions with all parties involved and the process can take months to years, particularly those aspects related to human clinical trials. Therefore, it is critical that the CCC have demonstrated experience in the management of complex research programs and human clinical trials.

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II. OBJECTIVES

The objective of the NHLBI Gene Therapy Resource Program (GTRP) renewal is to continue supporting the translation of basic research in gene therapy to clinical application in the areas of heart, lung, and blood diseases. The GTRP renewal will continue to provide resources in the areas of preclinical and clinical-grade vector production in accordance with Good Manufacturing Practices (GMP), and in the conduct of pharmacology/toxicology studies. In addition, the GTRP renewal will provide funds and regulatory assistance to investigators wishing to conduct gene therapy clinical trials. The GTRP renewal will consist of the following five components: 1) a clinical coordinating center that will oversee and coordinate the logistics of the core laboratories and provide regulatory and funding assistance for clinical trials; 2) a preclinical-grade vector production core laboratory; 3) a clinical-grade vector production core laboratory for adeno-associated virus (AAV); 4) a clinical-grade vector production core laboratory for lentivirus; and 5) a pharmacology/toxicology core laboratory.

The primary objective of the CCC is to serve as the focal point for the coordination of the various components of the GTRP. Specific responsibilities of the CCC include, but are not limited to, the coordination of Program meetings, conference calls, and site visits; assisting the Core Laboratories in fulfilling the requests for their services; providing Regulatory Support services for GTRP investigators;

and dispersing the funds for those NHLBI-approved clinical trials receiving funding assistance from the

GTRP.

III. SCOPE

The Clinical Coordinating Center (CCC) for the existing Gene Therapy Resource Program (GTRP) facilitates the translation of basic research in gene therapy to clinical application in the areas of heart, lung, and blood diseases. The GTRP renewal allows the program to continue providing resources in the areas of preclinical and clinical-grade vector production in accordance with Good Manufacturing Practices (GMP), and in the conduct of pharmacology/toxicology studies. In addition, the GTRP will continue to provide funds and regulatory assistance to investigators wishing to conduct gene therapy clinical trials. The GTRP consist of a clinical coordinating center that oversees and coordinates the logistics of the core laboratories and provides regulatory assistance for clinical trials; a preclinical-grade vector production core laboratory; a clinical-grade vector production core laboratory for adeno-associated virus (AAV); a clinical-grade vector production core laboratory for lentivirus; and a pharmacology/toxicology core laboratory.

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February 22, 2011

IV. SPECIFIC REQUIREMENTS AND TASKS

a. Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to perform the Statement of Work set forth herein.

b. The Contractor shall deliver the items specified in the Statement of Work and in ARTICLE C.2 to the destinations indicated in ARTICLE F.1.

c. Specifically, the Contractor shall:

1. Within the first 21 calendar days, develop, finalize, and implement a transition plan with a timetable of costs to smoothly transition the operations of the GTRP CCC, should the existing GTRP Clinical Coordinating Center be replaced. This may include, but is not limited to the following: obtaining the GTRP database and all information therein; acquiring and maintaining the Manual of Operations (and/or Manual of Procedures) and Bylaws for the GTRP; acquiring any program-related materials that have been developed for Outreach efforts for the GTRP; obtaining from the incumbent any materials or information related to the administration and funding of clinical trials by the GTRP; and acquiring from the incumbent any other information or materials necessary to perform the duties of the GTRP CCC. The transition plan shall be initiated upon contract award, with completion within 90 calendar days of contract award.

2. The Principal Investigator (PI) shall participate as a member of the GTRP Steering Committee (SC), and subcommittees as necessary, which will provide overall guidance for the GTRP. The PI shall also attend SC meetings and participate in teleconferences as needed.

3. Schedule and coordinate the logistics of SC meetings, teleconferences, site visits, and other face-to-face meetings between the NHLBI, the Core Laboratories, and/or the CCC as needed. This includes preparation of the meeting materials and the recording and distribution of minutes of these meetings and teleconferences.

4. In collaboration with the NHLBI and the SC, review and refine the Request for Services Application

(RSA) forms for each of the GTRP Core Laboratories and the online application process used by Investigators to request services from the CCC or any of the Core Laboratories.

5. In collaboration with the NHLBI and the SC, review and refine the Feasibility Assessment (FA) form and process that is performed by the respective Core Laboratories and the CCC for fulfillment of an

RSA.

6. Assist Investigators in their efforts to register online with the GTRP and present their information to the NHLBI for review and approval of the requested registration.

7. Serve as a liaison between the Core Laboratories and Investigators requesting GTRP services to facilitate completion of the RSA and FA. This involves receiving and processing RSAs from Investigators requesting any of the services offered by the GTRP and assisting the Core Laboratories with the completion of the FA for presentation to the NHLBI for review and approval. This may also include working on RSAs and FAs for services requested by NIH investigators approved to receive

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GTRP. Additionally, selected RSAs may require a secondary review by the Scientific Review Board (SRB) and subsequent approval by the SC. The CCC will prepare the materials necessary for SRB and SC review of these selected RSAs. The GTRP services offered via an RSA include, but may not necessarily be limited to: preclinical-grade vector production; GMP-grade adeno-associated virus (AAV) or lentiviral vector production; pharmacological/toxicological studies; immunological testing;

regulatory assistance; and clinical trials funding assistance. Each RSA and associated FA should be assigned a unique tracking code number and be entered into a secure electronic database.

8. Ensure that at the time of submission of an RSA for GMP-grade vector production, the requesting

Investigator has had contact with the FDA regarding the proposed clinical trial and that there has been a review of the clinical protocol by the Recombinant DNA Advisory Committee (RAC).

9. Ensure that prior to the actual production of any GMP-grade vector there is approval from the FDA for the investigational new drug (IND) to proceed to a clinical trial, that there is final Institutional Biosafety Committee (IBC) approval of the clinical protocol, and that there is final or provisional Institutional Review Board (IRB) approval of the clinical protocol.

10. In collaboration with the NHLBI, identify potential ad hoc or standing members for the SRB and coordinate all logistics involved in the review of those RSAs that the NHLBI designates as needing secondary review by the SRB and the SC.

11. In collaboration with the NHLBI and each of the Core Laboratories, review and refine the customer satisfaction survey that includes requesting the Investigator’s assessment of the timeliness of service, the quality and acceptability of products produced or tested by the respective Core Laboratory, and the Investigator’s satisfaction with the services provided by the Core Laboratories and the CCC.

Collect all completed customer satisfaction surveys and submit collated results to the NHLBI Program Officer on a quarterly basis as detailed in ARTICLE C.2.

12. In collaboration with the NHLBI and the SC, update and maintain, in a secure and confidential manner, the electronic database that is used to capture information conveyed to and from the requesting Investigators, the NLHBI, and the various Core Laboratories regarding Request for Service Applications, FAs, results of any secondary review(s) of the RSA, customer satisfaction surveys, and all information about the assignment of approved RSAs.

13. Gather the information from Investigators and maintain a database of information regarding publications, presentations, or other achievements that have resulted from GTRP-funded research efforts.

14. Update and maintain the public Internet web site with pages for each Core Laboratory and the CCC.

Ensure that each Core Laboratory and the NHLBI has provided updated information to the CCC for posting on the web site. At a minimum, these updates should be on a yearly basis, but more frequent updates may be required. The site shall contain a link to the NHLBI public web site. Accepted industry tools and applications shall be used to develop the web site. The site must comply with all applicable Federal regulations, including Section 508 of the Rehabilitation Act of 1973 (29 USC 794d). See http://www.nih.gov/od/ocpl/wag/resources/pubs/develop.html and http://section508.gov.

http://www.nih.gov/od/ocpl/wag/resources/pubs/develop.html� http://section508.gov./�

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February 22, 2011

15. Ensure that each Core Laboratory has up-to-date versions of all required certifications, inspections, and assurances, and ensure that these are available for review during any site visit by the NHLBI or any other oversight authorities. At a minimum, these updates should be on a yearly basis, but more frequent updates may be required.

16. Ensure that any site approved to receive Clinical Trials Support funding from the GTRP has all of the required certifications and approvals necessary for human subjects research in gene transfer trials in place prior to the distribution of any funds to the site. Ensure that during the course of the conduct of the clinical trial these various certifications and approvals are updated and remain valid. At a minimum, these updates should be on a yearly basis, but more frequent updates may be required.

17. Update and maintain the Manual of Procedures /Operations (MOP) describing the operating procedures of the GTRP including, but not necessarily limited to: actions to be taken when processing and fulfilling RSAs for Core Laboratory services or Regulatory Support or Clinical Trials Funding assistance; the composition, role, and functioning of the SC; handling logistics for meetings and teleconferences; identifying potential ad hoc or standing members for, and supporting the functions of, the Scientific Review Board (SRB) and the Data and Safety Monitoring Board ( DSMB); and the preparation and submission to the NHLBI of all required reports.

18. Work with the NHLBI on outreach efforts including, but not limited to: developing informational materials about the GTRP for display and distribution; securing exhibitor space and staffing an NHLBI GTRP booth at relevant scientific meetings; identifying and developing opportunities for translational research in the field of gene transfer; working with other NIH Institutes, Centers, or Offices on collaborative efforts with the NHLBI GTRP; assisting with the preparation of materials for presentation by NHLBI staff at various meetings; and assisting the NHLBI in planning and executing the logistics of meetings, seminars, or symposia related to the NHLBI GTRP or field of gene transfer.

19. Manage travel-related expense reimbursements (airfare, and the standard government per diem and honoraria payments as applicable) for SC members, SRB members attending meetings, site visits, or participating in meetings held by teleconference.

20. Manage and coordinate travel-related logistics and reimbursements (airfare and the standard government per diem and honoraria payments as applicable) for NHLBI-appointed DSMB members attending meetings, site visits, or participating in meetings held by teleconference.

21. Schedule and coordinate the logistics of meetings and teleconferences for the NHLBI-appointed

DSMB which oversees gene therapy clinical trials. This includes preparation of the meeting materials and the recording and distribution of minutes of these meetings and teleconferences.

22. Collaborate with the SC and the NHLBI to arrange the logistics for site visits to each of the Core

Laboratories. These site visits may be conducted in conjunction with the twice annual in-person SC meetings. Over the 5-year course of the GTRP, each of the Core Laboratories and the CCC must have hosted at least one site visit for the SC and the NHBLI. The PI of the CCC and other key personnel should attend these site visits.

23. The CCC will not only coordinate the logistics of the GTRP and the services of the Core

Laboratories, but will also fulfill approved RSAs for Regulatory Support services and Clinical Trials

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Funding assistance. Work that may be involved in the fulfillment of RSAs for Regulatory Support services or Clinical Trials Funding assistance may include, but is not limited to the following:

a. Assisting the Investigator in the preparation and submission of materials to the FDA, IBC, IRB, NHLBI, and/or the NIH Office of Biotechnology Activities (OBA)

b. Assisting the Investigator in arranging and preparing for pre-pre IND or pre-IND meetings with the FDA. If requested by the Investigator, the CCC can arrange for expert scientific advice in study design (preclinical or clinical), even if this requires the CCC to sub-contract this service.

However, if this service is to be sub-contracted, the NHLBI must give approval prior to the execution of the sub-contract.

c. Preparation of the IND in compliance with 21CRF312

d. Compilation of the clinical protocol and other relevant documents required for review by the local

IBC(s) and IRB(s), including relevant communications from the FDA, NHLBI, and the NIH-

OBA

e. Assisting the clinical research site with the preparation or management of materials for the conduct of the clinical trial such as, but not limited to: a Manual of Procedures/Operations (MOP); other site management materials; submission of copies of the final approved clinical protocol to the IRB, IBC, FDA, NIH-OBA, and NHLBI; and ensuring submission of required reports to oversight bodies

f. Assist with regulatory support at sites receiving GTRP clinical trials funding assistance such as pre-initiation site visits, study monitoring, site-initiation and periodic site visits by the CCC and the NHLBI, close-out visits, or other technical regulatory support, even if this requires the CCC to sub-contract these services

g. Assist the research investigator in preparing materials for meetings of oversight bodies such as the FDA, IRB, IBC, NIH-OBA, and the DSMB

h. Assist, as needed, in securing an IBC for oversight of a protocol at an institution without a standing IBC

i. Assist in the preparation of NHLBI-required study reports, to the extent requested by the Investigator, for clinical trials receiving funding assistance from the GTRP

j. Ensure that all appropriate approvals, such as FDA, IBC, and IRB are in place prior to the enrollment of the first clinical trial participant and ensure that the study is being conducted in accordance with the NIH Guidelines for Research Involving Recombinant DNA Molecules

k. Register all applicable clinical trials being conducted in the GTRP on the ClinicalTrials.gov web site

l. Prepare a detailed budget and contract for the distribution of funds to the research organization receiving Clinical Trials Funding assistance from the GTRP

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m. Work with the Investigator and the NHLBI to establish a plan for the reporting of serious adverse events that occur in the course of the GTRP-supported gene transfer clinical trial. This may include receipt of de-identified SAE reports and the subsequent submission of these reports to the NHLBI, DSMB, IRB, and/or FDA.

Gene Therapy Resource Program Clinical Coordinating Center – Renewal

RFP NHLBI-HV-12-05

Reporting Requirements and Deliveries

V. REPORTING REQUIREMENTS AND DELIVERIES

In addition to those reports required by other terms of the contract, the contractor shall prepare and submit the following reports in the manner stated below and in accordance with the Statement of Work.

1.

Within the first 21 calendar days, develop, finalize, and implement a transition plan with a timetable of costs to smoothly transition the operations of the GTRP CCC, should the existing GTRP Clinical Coordinating Center be replaced. This may include, but is not limited to the following: obtaining the GTRP database and all information therein; acquiring and maintaining the Manual of Operations (and/or Manual of Procedures) and Bylaws for the GTRP; acquiring any program-related materials that have been developed for Outreach efforts for the GTRP; obtaining from the incumbent any materials or information related to the administration and funding of clinical trials by the GTRP; and acquiring from the incumbent any other information or materials necessary to perform the duties of the GTRP CCC. The transition plan shall be initiated upon contract award, with completion within 90 calendar days of contract award.

Transition Plan

2.

Within the first 45 calendar days, the Contractor shall be responsible for developing and submitting a master spreadsheet and Gantt chart summarizing the key proposed activities and deliverables (including but not limited to those enumerated below) with timelines for the entire program using a separate chart for each year funded.

Comprehensive Program Summary and Timetable

3.

The Contractor shall be responsible for augmenting and maintaining the existing manual of procedures containing all SOPs and policies governing the GTRP. This includes providing a description of all operations of the CCC, as well as any additions or revisions of procedures as necessary.

Manual of Procedures (MOP)

4.

Within 12 months of the contract’s expiration date, the Contractor shall begin working with the NHLBI COTR to develop a transition plan for either the phase out of the GTRP at the end of the contract period or for transition of the contract’s activities to another contractor should the GTRP be renewed. A draft of this transition plan is due to the NHLBI COTR within six (6) months of the contract’s expiration date and the final transition plan shall be submitted upon the contract’s expiration date. The transition plan is considered a contract deliverable and its due date(s) are set forth in Section F of this contract.

Technical and Business Transition Plan

5.

Within the first 60 calendar days, the CCC Contractor shall develop and submit a plan to improve utility and access to the GTRP’s public and private website. The updated website shall include a secure environment for necessary data management system(s) and informatics support to acquire, store, catalogue, query, and distribute documents and materials required for GTRP investigators and a public environment that would provide for any interested patient, provider, or researcher current information about the GTRP.

Website

6. Monthly Technical Narrative

This narrative shall document and summarize all work results for the period covered on the monthly invoice. This narrative shall be attached to the copy of the monthly invoice sent to the Contracting Officer. Specifically, the report shall include the contract number, title, period of performance being reported, Contractor’s name and address, telephone and facsimile numbers, and date of submission.

In addition, it shall include

a. A description of the work performed during the reporting.

b. A brief overview of any problems that occurred during the current reporting period and their resolution or status.

c. A summary of activities planned for the next reporting period.

d. A list of projects approved and initiated. A description of dissemination accomplished (e.g., abstracts submitted or approved, presentations by GTRP investigators) and a list of the manuscripts in preparation or submitted and publications resulting from the work of the Registry.

7.

The semi-annual technical reports, in a narrative form, shall be concise and informational. They shall include but not be limited to: a cover page which includes the contractor’s name and address, the contract number, the name of the Principal Investigator; a description of overall progress, current problems which may impede performance, and proposed corrective actions; and activities planned for the next reporting period. Specific vector production information shall be in tabular format and include the following: the name of the requesting investigator, the grant number (if applicable), the name of the project and the vector provided, the procedures adopted for vector production, information on quality control and quality assurance methods, vector lot numbers, and date of vector release. The report shall also address administrative matters and staffing changes. A semi-annual technical report will not be due when the final report is due.

Semi-Annual Technical Progress Report

8.

Copies of manuscripts (published or unpublished) derived from research under the contract and copies of all abstracts, manuscripts, preprints, and publications that resulted from work conducted or any protocol or method developed specifically under this contract during the performance period.

Abstracts and Manuscripts

9.

This report shall include a summation of the work performed and results achieved for the entire contract period of performance. The report shall be prepared in the format described for “Monthly Technical Progress Reports” and be in sufficient detail to describe comprehensively the results achieved. The report shall also include a plan for future long-term support of the GTRP preclinical vector core laboratory through additional funding sources other than the Government. A draft Final Report is due within ten (10) months of the contract’s expiration date for Contracting Officer and Contracting Officer’s Technical Representative’s review and approval to proceed with the Final Report. The Final Report shall be submitted on or before the last day of the contract performance period and shall be in sufficient detail to serve as a reference document.

Final Technical Report

10.

The contractor shall submit security information reports required by other terms of the contract.

Information System Security and Physical Access Reporting Requirements:

11.

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. The Section 508 Report Template and Instructions for completing the report are available at:

Section 508 Annual Report http://www.hhs.gov/od under "Vendor Information and Documents."

12. Multiple Principal Investigators Leadership Plan

The Contractor shall submit a revised/updated Leadership Plan in the event of a change in any of the Principal Investigators named in the Key Personnel Article in SECTION G of this contract. The revised plan is subject to review and approval by the Contracting Officer.

13.

The Contractor shall submit an Annual Invention Report as required by FAR CLAUSE 52.227-11 including, but not limited to, the invention disclosure report, the confirmatory license, and the government support certification. The annual utilization report shall be submitted in accordance with Articles in SECTION F and H of the contract.

Invention Reporting Requirement and Annual Invention Report

14.

The Contractor will be required to prepare and submit, with the final report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract.

Summary of Salient Results

15.

Contractor shall submit monthly invoices as detailed in SECTION G of the contract.

Monthly Invoices

16.

The Contract shall submit Individual Subcontract Reports (ISR) and a Summary Subcontract Report (SSR) in accordance with Articles in SECTION F and H.

Subcontracting Reports http://www.hhs.gov/od�