The procurement of services to complete metabolomic profiling in human serum samples.

1.0 DESCRIPTION The Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics/Clinical Genetics Branch (CGB), plans to procure, on a sole source basis, services to complete metabolomic profiling in human serum samples from Metabolon, Inc., 617 Davis Drive, Suite 400, Morrisville, NC 27650. The response close date of the notice for this requirement is in accordance with FAR 5.203(b). This acquisition will be processed under FAR Part 12 - Acquisition for Commercial Items and will be made pursuant to the authority in FAR Part 13.106-1(b)(1)(i); and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 541380 and the small business size standard is $19 million. It has been determined there are no opportunities to acquire green products or services for this procurement. 2.0 BACKGROUND The U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG) /Clinical Genetics Branch (CGB) has collected longitudinal cohort biospecimens, including blood and serum, from individuals with telomere biology disorders. Dyskeratosis congenita related telomere biology disorders (DC/TBDs) are highly cancer-prone syndromes characterized by very short telomeres due to pathogenic germline variants in telomere biology genes. Patients with DC/TBDs are at significantly elevated risk of multiple, life-threatening medical conditions including bone marrow failure, pulmonary fibrosis, and cancer. CGB's 15-year cohort study found the risk of cancer in DC/TBDs to be ~4-fold higher than that of the general population. Notably, the risks of tongue squamous cell carcinoma and myelodysplastic syndrome were >200-fold and >500-fold greater than the general population, respectively. CGB has previously reported that critically short telomeres drive the activities of deoxyribonucleic acid (DNA) repair enzymes known to consume the metabolite, nicotinamide adenine dinucleotide (NAD). Primary fibroblasts from DC/TBD patients and late generation telomerase knockout mice display lower NAD levels and an imbalance in the NAD metabolome. This includes an elevated cluster of differentiated 38 (CD38), and reduced poly (adenosine diphosphate-ribose) polymerase and silent mating type information regulation 2 homolog 1 (Sirtuin 1) activities. Supplementation with the NAD precursor, nicotinamide riboside (NR), or decreased NADase activity through CD38 inhibition, improved NAD homeostasis and alleviated telomere damage, defective mitochondrial biosynthesis and clearance, growth retardation, and cellular senescence of DC/TBD fibroblasts. Overall, CGB's data support restoration of NAD metabolism ameliorates the biologic consequences of very short telomeres in patients with DC/TBDs. However, the true frequency at which NAD pools are altered in DC/TBD patients, how dynamic cellular bioenergetic programs impact NAD levels in DC/TBD patients, and what cellular consequences result from NAD dysregulation, remain unknown. 2.1 OBJECTIVE The objective is to obtain the metabolomic profile on individuals with, and controls without, telomere biology disorders based on laboratory data that shortened telomeres are intimately linked to metabolic programs, specifically within the mitochondria. 3.0 SCOPE The contractor shall complete the metabolomic analyses of 285 samples using a global, unbiased platform. This platform shall have the capability to detect the maximum number of metabolites. Data from these samples shall be returned to CGB via Excel or other electronic, fully editable and searchable format. 4.0 CONTRACT REQUIREMENTS/ AND PERSONNEL QUALIFICATIONS The contractor shall perform the following tasks: Send tubes to CGB for sample preparation and shipping, if required by the contractor. If no specific tubes are required, CGB shall provide samples in screw-cap cryovials with barcoded labels. No personally identifiable information shall be included with these samples. Note: Samples shall be delivered to the contractor on dry ice via overnight delivery. Note, samples shall be provided to the contractor via de-identified labeled tubes. No Personally Identifiable Information (PII) or Personal Health Information (PHI) shall be provided under this contract. Once samples are received, the contractor shall run samples on an unbiased metabolomic platform per standard operating procedures as follows: All samples provided by CGB shall be run on the same metabolomic platform following all technical industry standards. While all metabolomic data obtained by the contractor shall be returned to CGB, CGB has a specific list of metabolites of interest. These include, but are not limited to, N-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4- pyridone-3-carboxamide, nicotinic acid adenine dinucleotide, quinolinic acid, L-kynurenine, tryptophan, homocysteine, methionine sulfoxide, nicotinuric acid, glutathione, thiamine, riboflavin (metabolites related to NAD metabolism). The contractor shall perform any and all required internal controls to ensure data integrity. Note: Samples shall be prepared, aliquoted, and provided by NCI to the contractor using the minimum required volume to complete the analysis. Any residual volume remaining shall be discarded. Send CGB final metabolomic datasets to NCI once sample analyses are completed. 5.0 TYPE OF ORDER The purchase order is firm fixed price. 6.0 PERIOD OF PERFORMANCE The proposed period of performance shall be March 15, 2023 to August 14, 2023. 7.0 PLACE OF PERFORMANCE Services shall be performed onsite at the contractor's facility. 8.0 REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE The TPOC shall review the contents of all draft deliverables. If no comments or requests for revisions are provided to the Contractor within 30 business days, the deliverables shall be considered acceptable. If revisions are required, NCI shall respond to the Contractor within five (5) business days of receiving the deliverable, specifying the required changes/revisions. Final copies of approved drafts shall be delivered to the NCI TPOC within five (5) business days after receipt of the Government's comments. All deliverables shall be provided electronically (Microsoft Word or Excel compatible format, unless approved by the NCI Technical Point of Contact (TPOC) per the following deliverable schedule: DELIVERABLE - Metabolomic Dataset DELIVERABLE DESCRIPTION / FORMAT REQUIREMENTS -Dataset in electronic copy easily editable and searchable (ie, Excel). DUE DATE - 30 business days prior to the purchase order expiration date. 9.0 UNIQUE QUALIFICATIONS OF THE CONTRACTOR It is critical to the project outcome to replicate the data quality based on previous studies completed by Metabolon on Contract HHSN261201700009I. The same techniques will be used to the current requested assays. It is critically important to use the same laboratory for the current requirement to ensure scientific comparability of the new results with previous results from the studies previously conducted. Procuring the services through another source would result in substantial inter-laboratory variation. Metabolon's experience in metabolomic analyses will allow us to capitalize on the assays they have developed that are critical to address these research questions. 10.0 SUBMISSION INSTRUCTIONS This notice is not a request for competitive quotations. However, if any interested party believes it can meet the above requirements, it may submit a proposal or quote for the Government to consider. The response and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. All responses and questions must be sent via email to the Contract Specialist, Holly Knott, at holly.knott@nih.gov by no later than 5:00 PM EST on March 8, 2023. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. In order to receive an award, Contractors must be registered and have valid certification through SAM.gov. Reference: 75N91023Q00043 on all correspondence.