Attachment 3 Metabolomics SOW 4.25.12.docx

Attachment 3- Statement of Work Metabolomics Standards Synthesis Facility

RFP#: HHS-NIH-NHLBI-CSB-HV-2013-13-RSF

Background Information:

The Metabolomics Standard Synthesis Facility is a component of the National Institutes of Health (NIH) Common Fund Metabolomics Program. The NIH Common Fund supports cross-cutting programs that are expected to have exceptionally high impact and Metabolomics was identified as one such program. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress. Despite early promise, challenges remain before the full potential of metabolomics can be realized for translational research. One of the challenges identified was the lack of authentic standards to help in identification, coverage as well as quantitative and qualitative validation of metabolomic findings and this requirement is an effort to help overcome this challenge.

Statement of Work:

The NIH Common Fund has identified Metabolomics as one of the cross-cutting research areas that can potentially have wide ranging impact on our understanding of disease mechanisms and identifying novel therapeutic targets. In order to increase metabolomics research capacity in the United States, the NIH Common Fund has developed a multi-component Program to help overcome current challenges. This requirement is aimed at addressing one of the challenges, namely the lack of high quality and authentic standards for identification, characterization and quantitation of metabolites visualized through currently available analytical techniques. The goal is to increase the repertoire of chemically identifiable metabolites to achieve greater coverage of the metabolome.

The contractor shall support the NIH Common Fund Metabolomics Program for the production of candidate metabolomic standards, isotopically-labeled and unlabeled, from key mammalian metabolic pathways including but not limited to such pathways as the glycolytic pathway, tricarboxylic acid cycle pathway, sterol, lipid and aminoacid metabolism pathways. The Metabolomics Standards Synthesis Facility (SF) shall support the activities of the NIH Common Fund Metabolomics Program and provide services as a US FDA-defined current good manufacturing practice (cGMP) production facility for candidate metabolomic standards (http://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/questionsandanswersoncurrentgoodmanufacturingpracticescgmpfordrugs/ucm071836). The Metabolomics Standards Synthesis Facility shall perform synthesis as directed by the Contracting Officer’s Representative (COR) in consultation with the Common Fund Metabolomics Program Executive Committee.

Detailed Description of Duties for the Metabolomics Standards Synthesis Facility

The Contractor shall serve as a Metabolomics Standards Synthesis Facility for the NIH Metabolomics Common Fund Program. The Synthesis Facility (SF) shall perform the following specific tasks and activities which will be coordinated by the NIH in conjunction with the Common Fund Metabolomics Program Executive Committee.

1. Within the first 45 calendar days, develop and deliver a Comprehensive Program Summary and Timetable (i.e. Gantt chart) that summarizes the key activities and deliverables, with milestones, for the entire program. Use a separate chart for each contract year.

2. Participate as a member of the Metabolomics Program committees and subcommittees as necessary, which will provide overall guidance to achieve program objectives. Attend the annual Common Fund Metabolomics Program meetings and participate in monthly teleconferences with the Common Fund Metabolomics Data Repository and Coordinating Center. Further, participate in a monthly teleconference with the COR to discuss synthesis specific issues.

For Solicitation Purposes: Assume two key members of the synthesis facility shall travel to attend one annual two day Metabolomics Program Meeting.

3. Develop a manual of procedures (MOP) to describe the methodologies to be employed and amendments for the synthesis of requested metabolite standards. The MOP shall conform to US FDA cGMP guidelines as well as Good Laboratory Practices (GLP) guidelines and include procedures for production of candidate metabolomic standards. Provide the Metabolomics Program with updates to metabolomics standard molecules SF portion of the MOP.

4. Collaborate with the COR to document and record all requests for metabolomics standard synthesis and their current status in production.

5. Assist in developing Material Transfer Agreements (MTA) in collaboration with the COR and other components of the Program, for use between the SF and the research investigator’s institution that are part of the Metabolomics Program.

6. Provide services as a US FDA-defined current good manufacturing practice (cGMP) production facility for candidate metabolomic standards.

7. Synthesize metabolomic standards to ≥ 95% purity, process, analyze, store, and ship products synthesized.

8. Evaluate and report to the COR the feasibility of, and approximate time required to fulfill each request for synthesis received from the COR.

9. Collaborate with the COR and Metabolomics Program to contribute synthesized product data to its electronic databases and web sites. Submit data as defined and called for in the MOP.

10. Implement and maintain quality control and quality assurance plans to ensure at least 95% or greater purity for all candidate metabolomic standards requested. Perform analysis of chemical purity and propose a plan to monitor stability of the standards, detailing a recommended method and frequency of analysis. Synthesis shall be repeated as needed until the yield, procedures and purity are well established. Analytical protocols shall be developed to ensure metabolomic standards of uniform high quality are synthesized and shipped as requested by the COR.

11. Ensure that sufficient quantities of all metabolomic standards synthesized are available to meet the needs of the Metabolomics Program.

12. Design and implement monitoring plans for standards, including production and compliance with regulatory requirements. Maintain and make available for review, as necessary, records of monitoring activities.

13. Develop a tracking tool, accessible to the COR, of all requests received and corresponding estimated costs for synthesis and distribution.

14. Provide reports as described in Article C.2. Make available, for site visits, documents and data to support these reports, as requested by the Metabolomics Program.

15. Participate in site visits to the SF to be conducted by the Metabolomics Program.

16. Cooperate fully with the COR to resolve quality control and quality assurance issues related to the synethesis, purity, storage, or handling of compounds. If repeating of one or more steps in the synthesis protocol or re-purifying of compound is necessary, no costs shall be incurred to the contract. If a compound quality control or assurance issues cannot be resolved between the Contractor and COR, a scientific advisory group chosen by the COR and the Metabolomics Program shall be asked to review the synthesis, analysis, purification, storage, and handling protocols of the compound(s) in question and make recommendations to resolve the issues.

17. Maintain a laboratory that meets all requirements for the production of research grade and clinical grade reagents.

18. Provide complete protocol information, including quality control and quality assurance procedures, in accordance with the MOP to the COR for each synthesized product and also track amount of product remaining.

19. Establish and implement a plan to work with institutional technical transfer offices to facilitate the completion of material transfer agreements and contracts required to ship materials from one institution to another.

20. Outline transition and closeout activities in collaboration with the Metabolomics Program staff.