SRM_1955a.doc

STATEMENT OF WORK

SRM 1955a Homocysteine in Frozen Human Serum

I. BACKGROUND INFORMATION

The National Institute of Standards and Technology (NIST) began selling SRM 1955 Homocysteine and Folate in Human Serum in 2005. This material sold out recently and a new material, SRM 3949 Folate Vitamers in Frozen Human Serum, is planned to replace the material for folates. However, based on customer feedback, there is still need for a multi-level homocysteine material which is not supported by the new SRM 3949. To address this need, NIST is creating a new lot of SRM 1955 that will focus on providing three levels of homocysteine. In order to create this three-level material, NIST will require pooled human serum material that contains a normal level of homocysteine. Portions of this material will be diluted with buffer to create a low-level homocysteine material or spiked with pure homocysteine to create a high-level homocysteine material.

II. SPECIFIC TASKS

The Contractor shall produce 1,500 vials each of three serum materials at the concentrations specified below, with each vial containing 1.0 mL of serum. The contractor shall acquire a minimum total of 4,500 mL of pooled serum. The lower level material (Level 1) can be diluted with phosphate buffered saline (PBS) to achieve the desired homocysteine target level. The normal level (Level 2) must consist of only pooled serum to achieve the target level. The high-level material (Level 3) can be attained by the addition of pure homocysteine to achieve the target homocysteine concentration. The homocysteine target value ranges for the materials are as follows:

Level 1: Pooled human serum, which can be diluted with PBS, containing homocysteine 3.7 µmol/L to 5.9 µmol/L

Level 2: Pooled human serum containing homocysteine 8 µmol/L to 11 µmol/L

Level 3: Pooled human serum, spiked with pure homocysteine, containing homocysteine 13 µmol/L to 18 µmol/L

For the Level 1 material, PBS must be used to dilute the base serum to obtain the target level.

For the Level 3 material, a solution of 20 mmol/L homocysteine must be prepared first in base serum and then spiked into the pooled serum to obtain the target level.

The contractor shall be responsible for the screening analysis of homocysteine values, but the analysis can be subcontracted out. The results of these analyses must be submitted to the Technical Point of Contact (TPOC) before or at the time of serum delivery. Measured values for homocysteine shall be reported in units of µmol/L.

The contractor shall test the serum units for biosafety. All sera shall be demonstrated to be non-reactive when tested for hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus, and human immunodeficiency virus antigen 1 by tests licensed by the U.S. Food and Drug Administration. The contractor shall provide written documentation stating the negative results of all donor units utilized for SRM 1955a preparation. Donor units testing positive for any of the stated infectious agents will not be included in the serum pools.

After the donor serum units are selected, they shall be pooled. The contractor shall thoroughly blend and filter the pools (0.22 µm PVDF). The contractor shall dispense the serum into labeled amber glass serum vials capable of withstanding ultracold temperatures (-80 °C), each containing nominally 1 mL of serum (1.1 mL dispensed with an accuracy better than 0.1 mL), and seal under nitrogen with a butyl rubber stopper and an aluminum crimp cap. The vials must be 3 mL amber serum vials, 17 x 37 mm, 13 mm crimp finish. The vials are available from Voigt Global Distribution (catalogue # 62413PV-3). The contractor must stress test the lot of serum vials prior to filling by picking 10 vials randomly from the lot and subjecting them to five (5) freeze and thaw cycles at -80 °C to ensure that there is no breakage.

Prior to filling, the contractor shall label vials with labels that are appropriate for use at low temperature; these labels will be provided to the contractor by the TPOC within 60 days after award. The contractor shall use three different color aluminum crimp caps to differentiate among the three specified serum levels for easy identification. Vials shall be transferred, in fill order, from the bottling equipment to a box in a "Z" pattern, filling each row left to right. The location of the first vial in each box shall be noted on each side of the outside corner of the box, and boxes will be numbered sequentially. Boxes shall be labeled to indicate their contents. The Materials shall be stored frozen (-80 °C) prior to overnight shipment on dry ice to NIST. Overnight shipments must not be sent on Friday/Saturday or before a Monday Federal Holiday. Delivery is expected within 180 days after award.

The Contractor shall provide the TPOC with details of the steps involved in material preparation not later than 180 days after award of this requirement to ensure documentation of any deviations as well as to provide information that shall be utilized in the NIST material acquisition Report of Analysis.

III.

DELIVERABLES AND DELIVERABLE DUE DATES

The contractor shall deliver the vials and Biosafety report to NIST, using FOB Destination shipping terms not later than 180 days after award.

At the time of shipment, the contractor shall notify the TPOC and the Contracting Officers Representative (COR) by e-mail, providing the date the deliverables are shipped, shipping method, tracking number, method of delivery and the anticipated delivery date it will arrive at NIST.

IV.

PROTECTION OF HUMAN SUBJECTS

(a) Research involving human subjects is not permitted under this award unless expressly authorized in writing by the Contracting Officer. Such authorization will specify the details of the approved research involving human subjects and will be incorporated by reference into this contract.

(b) The Federal Policy for the Protection of Human Subjects (the “Common Rule”), adopted by the Department of Commerce at 15 CFR part 27, requires contractors to maintain appropriate policies and procedures for the protection of human subjects in research. The Common Rule defines a “human subject” as a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual, or identifiable private information. The term “research” means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. The Common Rule also sets forth categories of research that may be considered exempt from 15 CFR part 27. These categories may be found at 15 CFR 27.101(b).

(c) In the event that human subjects research involves pregnant women, prisoners, or children, the contractor is also required to follow the guidelines set forth at 45 CFR part 46 subpart B, C and D, as appropriate, for the protection of members of a protected class.

(d) Should research involving human subjects be included in the proposal, prior to issuance of an award, the contractor shall submit the following documentation to the Contracting Officer:

(1) Documentation to verify that contractor has established a relationship with an appropriate Institutional Review Board (“cognizant IRB”). An appropriate IRB is one that is located within the United States and within the community in which the human subjects research will be conducted;

(2) Documentation to verify that the cognizant IRB possesses a valid registration with the United States Department of Health and Human Services' Office for Human Research Protections (“OHRP”);

(3) Documentation to verify that contractor has a valid Federal-wide Assurance (FWA) issued by OHRP.

(e) Prior to starting any research involving human subjects, the contractor shall submit appropriate documentation to the Contracting Officer for institutional review and approval. This documentation may include:

(1) Copies of the human subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms approved by the cognizant IRB;

(2) Documentation of approval for the human subjects research protocol, questionnaires, surveys, advertisements, and informed consent forms by the cognizant IRB;

(3) Documentation of continuing IRB approval by the cognizant IRB at appropriate intervals as designated by the IRB, but not less than annually; and/or

(4) Documentation to support an exemption for the project from the Common Rule [Note: this option is not available for activities that fall under 45 CFR part 46 subpart C].

(f) In addition, if the contractor modifies a human subjects research protocol, questionnaire, survey, advertisement, or informed consent form approved by the cognizant IRB, the contractor shall submit a copy of all modified material along with documentation of approval for said modification by the cognizant IRB to the Contracting Officer for institutional review and approval. The contractor shall not implement any IRB approved-modification without written approval by the Contracting Officer.

(g) No work involving human subjects may be undertaken, conducted, or costs incurred and/or charged to the project, until the Contracting Officer approves the required appropriate documentation in writing.

V.

Acceptable Quality Level The vials of all pooled serum with the associated physical and chemical properties specified in section III of this Statement of Work shall be suitable for use as reference materials. If deficiencies or inconsistencies between the material and the documentation (defined in sections II and III) are found, or if less than the stated number of vials are received intact, the contractor has 30 days to correct the deficiency at no additional cost to the Government.

VI.

Monitoring Method The TPOC and COR will verify that the materials were successfully prepared and acceptable. Acceptance will be based upon the delivery of 1,500 vials of each pooled serum material (4,500 vials total) intact and unbroken, accompanied by screening results for homocysteine levels in each of the three pooled materials. This will be completed no later than 30 days after receipt and acceptance of the vials.

VII.

PERIOD OF PERFORMANCE

The period of performance shall be 180 after award.

VIII.

MINIMUM CONTRACTOR CERTIFICATIONS

The Contractor shall provide documentation showing current certification for ISO 13485:2003, “Medical devices -- Quality Management Systems -- Requirements for Regulatory Purposes” and experience in analyzing the compounds in section III of this SOW in human serum. Documentation may be a certificate from ISO or from a certification organization or a letter authorizing the Contractor to use the ISO logo.

Alternatively, if the Contractor is not ISO 13485:2003 certified, they must provide not less than three (3) each of the following records for each of the analytes (i.e., 25(OH)D2 and 25(OH)D3) in section III of this SOW for a total of 30 records:

· Calibration records

· Quality control (QC) blank results

· QC spike amounts

· QC spike recovery

· Minimum detection limit determination data

The records shall be no older than three (3) years from the date of the solicitation. The Offerors shall provide the above records in hardcopy or as a pdf file.

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