High Density Resequencing Microarray for Dectection of Pathogens in Blood

PART 1 - THE SCHEDULE 1.1 This is a combined synopsis/solicitation for commercial services prepared in accordance with the format in FAR 12.6, streamlined procedures for evaluation and solicitation for commercial items-as supplemented with additional information included in this notice. This solicitation is an RFP for a High Density Resequencing Microarray for Detection of Pathogens in Blood. The solicitation document and incorporated provisions and clauses in effect through the Federal Acquisition Circular 05-44. The associated North American Industrial Classification System (NAICS) code for this procurement is 334516. SECTIONS B-SUPPLIES OR SERVICES AND PRICES/COSTS B.1. TYPE OF CONTRACT The Government intends to award a firm fixed price contract. B.1.1 DESCRIPTION OF SERVICES CLIN QUANTITY UNIT TOTAL AMOUNT 0001 High Density Resequencing Microarray for Detection of Pathogens in Blood 1 LT $ B.3. GOVERNMENT FURNISHED PROPERTY The FDA investigators shall provide nucleic acid samples extracted from the various pathogens as well as nucleic acid extracted from blood samples that have been spiked with pathogens. B.4. PLACE OF PERFORMANCE AND TRAVEL. The Contractor will be working at the contractors' facility. B.4.1. ANTICIPATED TRAVEL Out-of-town travel will not be required. Local travel required between FDA facilities and contractor site is not reimbursable. Should travel become necessary, the Contracting Officer will modify the order prior to occurrence? SECTIONS C-DESCRIPTION/SPECIFICATIONS/WORK STATEMENT C.1. BACKGROUND: The Laboratory of Molecular Virology (LMV) is responsible for the development of diagnostic assays and tools against pathogenic threats to public health, particularly HIV, HTLV, and XMRV, in pursuit of FDA's mission of bringing more rapid, sensitive, and multiplex diagnostic tests to practical use. The LMV will provide the necessary samples, reagents, sequence information, and target information, and other necessary intellectual while the contractor in turn would provide numerous services, including Custom Design Services for turnkey design of array and assay for the detection of user-defined pathogens on a 100-format (117 kb) retrovirus array. Additional services include array design; mask fee (Affymetrix), primer selection, primer validation, multiplex primer formulation, laboratory validation of arrays with type strains and/or artificial templates, sequence analysis algorithm optimization, and data (results) report formatting. Collectively these contributions by LMV and services by the contractor will generate a research push toward the proof-of-concept development of a microarray chip capable of accurate, rapid, and multiplexed detection of pathogens. C.2 PURPOSE: The purpose of this contract is to develop and test a platform that can perform PCR on a nucleic acid sample extracted from blood testing for the presence of 10 or more pathogens simultaneously, and be capable of detecting new sequence variants of those pathogens and identifying the new sequences. The platform must be optimized to achieve the greatest degree of sensitivity possible while achieving the highest possible level of multiplicity and flexibility. C.3. OBJECTIVES HIV is a highly diverse virus with ongoing virus evolution resulting in new emerging variants that can escape detection by diagnostic and blood screening assays in addition to posing a major challenge for vaccine and drug efficacy. Our lab is conducting studies on HIV genetic diversity in Cameroon in West Central Africa where all known strains have been identified and new variants continue to emerge. Currently we perform full genome and single genome amplification to study viral diversity. We are interested in using the re-sequencing microarray technology to more efficiently identify new HIV or HIV-related new human retroviral strains as well as use it to determine genotype. We are currently investigating the presence of XMRV in blood samples from donors and other populations to provide more data on the public health significance of XMRV. The discordant test results observed in studies performed on patients with chronic fatigue syndrome and blood donors have been attributed to assay differences as well as the potential genetic diversity of this virus. We are interested in using the contractors' platform to study the viral genomes at the genetic level to determine the extent of viral diversity with this new retrovirus. The assay targets we would be interested are the following: HIV, XMRV and retroviruses 1. HIV subtypes A-G, CRF02_AG and CRF01_AE., HIV-1 group O, N, P, HIV-2 subtypes A-E and HTLV-I and HTLV-II. We would like to obtain subtype level information, also recombinant information for the major recombinants identified to date. Therefore differentiation of the subtypes is important. 2. It would be useful for the assay to be informative about the presence or absence of specific gene groups eg gags gene deletions in a given strain. 3. It would be useful to have information about major drug resistance mutations eg, protease, NNRTI etc. 4. Assay should have the potential to identify new retroviral sequences 5. Assay should have ability to determine presence or absence of retroviral genes of XMRV or Murine Leukemia virus genes in samples C.4 SCOPE OF WORK: If the microarray is shown to be effective for the detection of multiple pathogens in a single application, this will open up the doors for the production of many more such arrays that can be deployed to both resource-rich and resource-poor settings (such as Africa), which would universally benefit from this improved approach toward diagnostic testing. The current project aims to generate an array that can detect the following pathogens: HIV-1 group M (with differentiation of subtypes A1, A2, B, C, D, F1, F2 and G based on a small set of determinant site subtile sequences) HIV-1 group M CRF prototypes (CRF01-AE and CRF02-AG) HIV-1 group O HIV-1 group N HIV-1 group P HIV-2 subtypes A and B (most prevalent) and C, D, E, F (less prevalent) HTLV-I and HTLV-II XMRV and two murine leukemia viruses (Rauscher-Friend and Moloney) To highlight other significant aspects of this work, it should be noted that LMV will be providing samples obtained through collaborators (highly diverse Cameroonian HIV strains, well-studied XMRV samples, etc.) and there will be a concerted effort to develop oligonucleotides (oligos) that target the different conserved regions of genes of the pathogens of interest. Scientifically, the combined use of real-world clinical samples to develop an oligo tiling array gives this collaboration a high probability of success, and this approach allows us to detect and distinguish between similar or drug-resistant viral strains. NAT assays targeted to specific blood borne pathogens are comprised of oligonucleotide primer pairs and a set of reaction conditions that have been optimized to give the most efficient amplification of the target. Such NAT assays have been developed by scientists in the LMV of Division of Emerging and Transfusion Transmitted Diseases. The contractor will take these primer pairs and associated reaction conditions and combine them into a combination of amplification reactions and detection platform that screens for retroviral sequences in samples simultaneously. The platform will also incorporate internal standards to provide quantitative and QA/QC for each test. The FDA investigators will provide nucleic acid samples extracted from the various strains as well as nucleic acid extracted from blood samples that have been spiked with retroviral strains. The contractor will use these samples to evaluate and optimize the performance of the high density resequencing pathogen microarray platform. The contractor will report the data on limits of detection of each pathogen when assayed on the high density resequencing pathogen microarray platform. Task 1.0 Meet with the project officer and develop study design. Subtask 1.1 The Contractor's Project Manager shall meet with the Government Project Officer (PO) or designee within two weeks after the date of award to discuss the study design and requirements. The study design described in the proposal will be reviewed at this meeting. Subtask 1.2 The contractor shall prepare and submit a summary report of the meeting not later than seven (7) days after the meeting. Task 2.0 Receive oligonucleotide primers, probes, amplicon sequences and reaction conditions for individual pathogen detection NAT assays. Subtask 2.1 Accept delivery of primers, probe and amplicon sequences, notify sender of receipt, store properly. Task 3.0 Assemble high density resequencing retroviral microarray devices for detection of blood pathogen target sequences. Subtask 3.1 Design tiled probe sequences for hybridization with retroviral target sequences. Subtask 3.2 Arrange for manufacture of microarray chips containing the probes designed. Subtask 3.3 Store arrays for subsequent sample processing. Task 4.0 Receive and store nucleic acid samples from cultured strains. Task 5.0 Optimize detection with retroviral nucleic acid. Subtask 5.1 Demonstrate detection is possible. Subtask 5.2 Determine lower limit of analytical sensitivity for retroviruses Subtask 6.0 Report results to Project Officer or designee and plan subsequent experiments. Task 7.0 Optimize detection with nucleic acid from virus spiked blood. Subtask 7.1 Receive and store nucleic acid samples from virus-spiked blood. Subtask 7.2 Demonstrate detection is possible. Subtask 7.3 Report interim results to Project Officer or designee (telephone and email is sufficient). Subtask 7.3 Determine lower limit of sensitivity for virus spiked blood sample nucleic acid. Task 8.0 Finalize results. Subtask 8.1 Prepare results in publication-ready format. Subtask 8.2 Communicate results to Project Officer or designee. SECTIONS D-PACKAGING AND MARKING The contractor shall perform the following tasks or deliver the items in the quantities and during the time periods indicated below to the Project Officer, DETTD/OBRR, NIH Bldg. 29. Rm. 225, 29 Lincoln Dr., Bethesda, MD 20892. SECTIONS E-INSPECTION AND ACCEPTANCE Inspection and acceptance of all services called for by the contract shall be made by the FDA Project Officer or designee in conjunction with the Office of Acquisitions & Grants Services (OAGS) Contracting Officer. 4.1 The Contracting Officer's Representative (COTR) will perform inspection and acceptance of materials and services to be provided at location in Paragraph D. This contract incorporates the following clause, 52.246-4 Inspection of Services-Fixed Price (Aug 1996) by reference, with the same force and effect as if it was given in full text. Upon request, the Contracting Officer will make its full text available. SECTIONS F - DELIVERIES AND PERFORMANCE F.1 DELIVERY SCHEDULE: Item Description Due Date after award 1 Meet with project officer 2 weeks 1.1 Summary report of meeting 3 weeks 2 Accept delivery of retroviral primers, probes, amplicon sequences and reaction conditions, notify sender of receipt, store properly 1 month 3 Assemble high density resequencing pathogen microarray devices for detection of retroviral pathogen target sequences 3 months 4 Receive and store nucleic acid samples from cultured viruses 3 months 5 Optimize detection with viral nucleic acid 6 months 6 Meet with project officer or representative to evaluate the initial results and set agreed upon target viruses for validation in high density resequencing retroviral microarray assay 7 months 7 Interim report to Project Officer on progress 9 months 8 Optimize detection with nucleic acid from virus spiked blood 11 months 9 Submit final report to project officer with publication-ready data validating the limit of detection of the agreed upon strains assayed in high density resequencing retroviral microarray platform 12 months F.2. PERIOD OF PERFORMANCE/BASIS. The total performance period is one year. Phase 1 will consist of optimizing detailed experimental plan in consultation with scientists at CBER and transfer of NAT assay reagents to the contractor (3 months). Phase 2 will consist of high density resequencing microarray platform assembled and tested with reference samples (6 months). Phase 3 will consist of blood pathogen high density resequencing microarray platform evaluated for limit of detection in a blood sample for the major subtypes (1 year) or other combination of strains mutually agreed upon between the contractor and the Project Officer or his designee. Further details included in the Statement of Work (attachment A). F.3. REPORTING REQUIREMENTS AND DELIVERABLES. Contractor's Project Manager shall report to the FDA Project Officer or his designee by email with weekly program progress reports. At the end of each phase (approximately 3 months, 6 months and 1 year) the contractor's Project Manager will email a report to the FDA Project Officer or his designee that includes tables of quantitative results and protocols that clearly explain how the results were obtained. Two face-to-face meetings will be conducted during the contract period of performance between the contractor scientists and the FDA CBER personnel. One meeting will he held at the FDA CBER location and one at the contractor's facility. The purpose of these meetings is for planning and final discussion of the research performed. SECTIONS G - CONTRACT ADMINISTRATION DATA G.1. CONTRACTING OFFICERS TECHNICAL REPRESENTATIVE (COTR) The following COTR will represent the Government for the purpose of this contract: (To Be Determined at the Time of Award) The COTR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the Statement of Work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance. The Government may unilaterally change its COTR designation. The contact information for the Contracting Specialist is: Tawana Parker 5630 Fishers Lane Rockville, MD 20857 Tawana.Parker@fda.hhs.gov (301) 827-9691 Fax: (301) 827-7101 The contact information for the Contracting Officer is: Department of Health and Human Services Food & Drug Administration, OAGS Attn: Jose Bumbray, Room 2108 5630 Fishers Lane Rockville, MD 20857 Phone: (301) 827-9215 Jose.Bumbray@fda.hhs.gov G.2. INVOICE SUBMISSION All COs/CSs shall insert the following language into each new FDA award entered into PRISM as a three-way match: The contractor shall submit one (1) original copy of each invoice to the address specified below: FDA/OC/OA/OFO/OFS ATTN: DIVISION OF PAYMENT SERVICES 12345 PARKLAWN DRIVE, HFA-720 301.827.3742 OR 866.807.3742 fdavendorpaymentsteam@fda.gov ROCKVILLE, MARYLAND 20857 Invoices submitted under this contract must comply with the requirements set forth in FAR Clauses 52.232-25 (Prompt Payment) and 52.232-33 (Payment by Electronic Funds Transfer - Central Contractor Registration) and/or applicable Far Clauses specified herein. To constitute a proper invoice, the invoice must be submitted on company letterhead and include each of the following: (I) Name and address of the contractor; (II) Invoice Date and Invoice Number; (III) Purchase order/Award Number; (IV) Description, Quantity, Unit of Measure, Unit Price, and Extended Price Supplies Delivered or Services Performed, including: (a) Period of Performance for which costs are claimed; (b) Itemized travel costs, including origin and destination; and (c) Any other supporting information necessary to clarify questionable expenditures; (V) Shipping number and date of shipping, including the bill of lading number and weight of shipment if shipped on government bill of lading; (VI) Terms of any discount for prompt payment offered; (VII) Name and address of official to whom payment is to be sent (must be the same as that in the purchase order/award, or in a proper notice of assignment) (VIII) Name, title and phone number of person to notify in event of defective invoice; (IX) Taxpayer Identification Number (TIN); (X) Electronic Funds Transfer (EFT) banking information, including routing transit number of the financial institution receiving payment and the number of the account into which funds are to be deposited; (XI) Name and telephone number of the FDA Contracting Officer Technical Representative (COTR) or other program center/office point of contact, as referenced on the purchase order; and, (XII) Any other information or documentation required by the purchase order/award. An electronic invoice is acceptable if submitted in Adobe Acrobat (PDF) Format. All items listed in (I) through (XII) of this clause must be included in the electronic invoice. Electronic invoices must be on company letterhead and must contain no ink changes and be legible for printing. Questions regarding invoice payment should be directed to the FDA payment office at the telephone number provided above. G.3. INVOICE SCHEDULE The contractor will submit invoices for payment of completed tasks and deliverables, as identified in Paragraph F.2., above. SECTIONS H-SPECIAL CONTRACT REQUIRMENTS H.1. STAFFING The Contractor is responsible for providing personnel with the management, technical and subject matter expertise required to accomplish the activities and prepare the deliverables identified in this Statement of Work. The contractor shall submit in writing all proposed staff (name, resume, title, category, hourly rate, and FDA clearance status) to FDA. The contractor shall identify all key personnel proposed throughout the performance of this order. NOTE: Personnel may not be removed from the task without express approval of the Contracting Officer (CO) or the Contracting Officer Technical Representative (COTR). The Government reserves the right to reject or accept the resume of any employee. All staff proposed as KEY for this project must be full-time. In addition to the Contractor selection(s), the Government requires the Contractor Project Manager be designated as key personnel. The contractor shall provide personnel/staff that is adequately trained and who have attained knowledge necessary for the performance of the client's requirements. It is anticipated that contractor employees may have to attend conferences and symposiums to provide customer interface opportunities and attain knowledge necessary for the performance of client requirements. Funding for such experiences shall be at the discretion and direction of the FDA COTR. H.2. Contractor personnel performing work under this contract shall satisfy all requirements for appropriate security eligibility in dealing with access to sensitive information and information systems. H.3. The Contractor shall (1) develop, (2) have the ability to access, or (3) host and/or maintain a Federal information system(s). Pursuant to Federal and DHHS Information Security Program policies, the contractor and any subcontractor performing under this contract shall comply with the following requirements. - Federal Information Security Management Act of 2002 (FISMA), Title III, E-Government Act of 2002, Pub. L. No. 107-347 (Dec. 17, 2002); http://csrc.nist.gov/drivers/documents/FISMA-final.pdf Information Type [x] Administrative, Management and Support Information: Information Management Lifecycle/Change Management Record Retention Budget and Finance Reporting and Information [x] Mission Based Information: Consumer Health and Safety H.4. The Contractor shall use Security Content Automation Protocol (SCAP) - validated tools with FDCC Scanner capability to ensure its products operate correctly with FDCC configurations and do not alter FDCC settings. The Contractor shall test applicable product versions with all relevant and current updates and patches installed. H.5. As applicable, prior to any scanning of systems, the contractor shall coordinate with and get approval of the respective CISO if those systems reside on HHS or OPDIV networks at the time they are scanned. This will help ensure that unauthorized scanning doesn't occur, activities that could be construed as malicious are appropriately identified, or systems on the Department/OPDIV networks, beyond the scope of the contractor responsibilities, do not lose availability as a result of accidental scanning. H.6. Because of the sensitivity of much of the FDA data, contractor staff shall also be required to undergo a Level 5 Public Trust security clearance, including finger printing, performed under the auspices of the FDA. H.7. The contractor agrees that contractor personnel will not divulge or release data or information developed or obtained in connection with the performance of the resulting contract, unless made public by FDA or upon written approval of the Government. H.8. Except as may otherwise be permitted by a data owner, the contractor personnel agrees not to use, disclose or reproduce proprietary data, other than as required in performance of the contact; provided, however, that nothing herein shall be construed as precluding the use of any data independently acquired by the contractor without such limitation. H.9. When applicable, if information of a sensitive nature is involved, all contractor personnel will be required to sign a non-disclosure agreement before data and information otherwise exempt from public disclosure (e.g. Privacy Act or Data Collected Under an assurance of Confidentiality) may be disclosed to them. The CCA 8 does not contain any sensitive information. H.10. The contractor shall submit a roster, by name, position and responsibility, of all staff (including subcontractor staff) working under the task order that will develop, have the ability to access, or host and/or maintain a Federal information system(s). The roster shall be submitted to the COTR, no later than 1 day prior to starting work on site. Any revisions to the roster as a result of staffing changes shall be submitted within 7 calendar days of the change. H.11 HHS policy requires contractors/subcontractors receive security training commensurate with their responsibilities for performing work under the terms and conditions of their contractual agreements. The contractor shall ensure that each contractor/subcontractor employee has completed the FDA Computer Security Awareness Training course prior to performing any task order work and thereafter annually during the period of performance of the task order. HHS may change, add or modify Computer Security Awareness training requirements to enhance the HHS computer security program. H.12 Each contractor/subcontractor employee who may have access to non-public Department information under this task order shall complete and submit the FDA Form 3398: Contractor's Commitment to Protect Non-Public Information (NPI) Agreement available upon request from the FDA Intranet site. A copy of each signed and witnessed Non-Disclosure agreement shall be submitted to the COTR prior to performing any work under the contract. The COTR will inform the contractor of any additional forms and training that are required. H.13. STANDARDS OF CONDUCT. The contracting company shall be responsible for disciplinary action with respect to its participants' violations of any FDA laws, policies, and procedures. Additionally, FDA reserves the right to remove any contracted personnel for misconduct or violations of FDA or other Government policies, regulations, or laws. H. 14. COMFORMANCE WITH ALL APPLICABLE LAWS, REGULATIONS, POLICIES, AND STANDARDS H.15.1. CONTRACTOR COMPLIANCE The Contractor shall be responsible for knowledge of and compliance with all applicable federal information technology and information management laws, regulations, policies, and standards at the government-wide, HHS, and FDA levels. At the government-wide level, these include Office of Management and Budget (OMB), National Institute of Standards and Technology (NIST), and General Accounting Office (GAO). These can be primarily found at or through the Federal CIO Council website at: http://www.cio.gov/. HHS documents are found at http://www.hhs.gov/oirm/. H.15.2. 508 STANDARD REQUIREMENTS Pursuant to Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d) as amended by Public Law 105-220 under Title IV (Rehabilitation Act Amendments of 1998), all Electronic and Information Technology (EIT) developed, procured, maintained, and/or used under this contract shall be in compliance with the Electronic and Information Technology Accessibility Standards'' set forth by the Architectural and Transportation Barriers Compliance Board (also referred to as the Access Board'') in 36 CFR part 1194. The complete text of Section 508 Final Standards can be accessed at http://www.access-board.gov/sec508/standards.htm. H.15.3. DATA RIGHTS FAR Clause 52.227-14 (Alternate II, IV, and V), incorporated into Section I of the underlying ICT21 contract, governs the parties' rights in data created in the performance of this contract. H.15.4. FEDERAL INFORMATION SECURITY MANAGEMENT ACT (FISMA) COMPLIANCE The E-Government Act of 2002 recognized the importance of information security to the economic and national security interests of the United States. Title III of the E-Government Act, known as FISMA, states that effective information security programs include: ? Periodic assessments of risk; ? Policies and procedures that are based on Risk Assessments (RA), cost-effectively reduce information security risks to an acceptable level, and address information security throughout the EPLC; ? Plans for providing adequate information security for networks, facilities, Information Systems, or groups of Information Systems, as appropriate; ? Security awareness training to inform personnel; ? Periodic testing and evaluation of the effectiveness of information security policies, procedures, practices, and security controls to be performed with a frequency depending on risk, but no less than annually; ? A process for planning, implementing, evaluating, and documenting remedial actions to address any deficiencies in the information security policies, procedures, and practices of the organization; ? Procedures for detecting, reporting, and responding to security incidents; ? Plans and procedures for continuity of operations for Information Systems that support the operations and assets of the organization. H.16. QUALITY ASSURANCE The Contractor shall be responsible for the quality of products and services provided under the terms of this contract, to include those provided by subcontractors. The Contractor shall develop and implement a Quality Assurance Plan (QAP) for measuring and attaining quality of performance under this contract. The plan shall also include mitigation strategy to address any performance issues that require immediate response from the Contractor. The plan should include recommendations for process improvement. The Contractor shall update this plan on an annual basis. Government surveillance of the Contractor's performance shall include: (1) monthly government inspections at the performance locations; (2) customer surveys; (3) review of customer service requests and resolutions; and (4) review of all Contractor's deliverables for compliance to requirements and delivery schedules H.17. KEY PERSONNEL Pursuant to HHSAR Clause 352.270-5 Key Personnel, incorporated in section 15.0 of this order, the following individual(s) is/are considered to be key personnel and thus essential to the work being performed under this order: Personnel Name Personnel Title Project Manager SECTIONS I-CONTRACT CLAUSES I.1 52.252-2 CLAUSES INCORPORATED BY REFERENCE (FEB 1998) This contract incorporates one or more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at: www.acquisition.gov/far/index.html I.2. 52.212-4 CONTRACT TERMS AND CONDITIONS-COMMERCIAL ITEMS (MAR 2009) I.3. 52.245-1 GOVERNMENT FURNISHED PROPERTY (JUNE 2007) FAR CLAUSES BY FULL TEXT I.4. 52.212-3 OFFEROR REPRESENTATIONS AND CERTIFICATIONS-COMMERCIAL ITEMS. (Aug 2009) An offeror shall complete only paragraph (b) of this provision if the offeror has completed the annual representations and certifications electronically at http://orca.bpn.gov. If an offeror has not completed the annual representations and certifications electronically at the ORCA website, the offeror shall complete only paragraphs (c) through (m) of this provision. (a) Definitions. As used in this provision- "Emerging small business" means a small business concern whose size is no greater than 50 percent of the numerical size standard for the NAICS code designated. "Forced or indentured child labor" means all work or service- (1) Exacted from any person under the age of 18 under the menace of any penalty for its nonperformance and for which the worker does not offer himself voluntarily; or (2) Performed by any person under the age of 18 pursuant to a contract the enforcement of which can be accomplished by process or penalties. "Inverted domestic corporation" means a foreign incorporated entity which is treated as an inverted domestic corporation under 6 U.S.C. 395(b), i.e., a corporation that used to be incorporated in the United States, or used to be a partnership in the United States, but now is incorporated in a foreign country, or is a subsidiary whose parent corporation is incorporated in a foreign country, that meets the criteria specified in 6 U.S.C. 395(b), applied in accordance with the rules and definitions of 6 U.S.C. 395(c). "Manufactured end product" means any end product in Federal Supply Classes (FSC) 1000-9999, except- (1) FSC 5510, Lumber and Related Basic Wood Materials; (2) Federal Supply Group (FSG) 87, Agricultural Supplies; (3) FSG 88, Live Animals; (4) FSG 89, Food and Related Consumables; (5) FSC 9410, Crude Grades of Plant Materials; (6) FSC 9430, Miscellaneous Crude Animal Products, Inedible; (7) FSC 9440, Miscellaneous Crude Agricultural and Forestry Products; (8) FSC 9610, Ores; (9) FSC 9620, Minerals, Natural and Synthetic; and (10) FSC 9630, Additive Metal Materials. "Place of manufacture" means the place where an end product is assembled out of components, or otherwise made or processed from raw materials into the finished product that is to be provided to the Government. If a product is disassembled and reassembled, the place of reassembly is not the place of manufacture. "Restricted business operations" means business operations in Sudan that include power production activities, mineral extraction activities, oil-related activities, or the production of military equipment, as those terms are defined in the Sudan Accountability and Divestment Act of 2007 (Pub. L. 110-174). Restricted business operations do not include business operations that the person (as that term is defined in Section 2 of the Sudan Accountability and Divestment Act of 2007) conducting the business can demonstrate- (1) Are conducted under contract directly and exclusively with the regional government of southern Sudan; (2) Are conducted pursuant to specific authorization from the Office of Foreign Assets Control in the Department of the Treasury, or are expressly exempted under Federal law from the requirement to be conducted under such authorization; (3) Consist of providing goods or services to marginalized populations of Sudan; (4) Consist of providing goods or services to an internationally recognized peacekeeping force or humanitarian organization; (5) Consist of providing goods or services that are used only to promote health or education; or...