SRM_967b.doc

STATEMENT OF WORK

SRM 967b Creatinine in Frozen Human Serum (Low and High Level)

I. BACKGROUND INFORMATION

The National Institute of Standards and Technology (NIST) has provided batches of SRM 967 Creatinine in Frozen Human Serum since 2007. This material supports the measurements of in vitro diagnostics manufacturers, reference laboratories, and clinical laboratories in the United States and globally. The current batch of SRM 967a Creatinine in Frozen Serum is expected to be out of stock in less than three years and the procurement of SRM 967b is required to provide continuous availability of this important SRM. The creatinine measurement community has also requested that the lower level of SRM 967b possess a target value of ≈0.4 mg/dL, which addresses the critical measurement of creatinine in pediatric serum samples. The low level will be based on a serum pool without dilution and the high level will be based on a normal serum pool that is spiked with creatinine.

II. SCOPE OF WORK

The Contractor shall produce 4,000 vials each of two serum materials at the creatinine concentrations specified below, with each vial containing (1.1 ± 0.1) mL of serum. The Contractor shall acquire a minimum of 4,000 mL of serum pooled at each level according to the CLSI C37-A Guideline https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/ for a total of approximately 8 L of serum. The pool of serum for the low level must not be diluted or stripped to achieve the target (0.4 ± 0.05) mg/dL creatinine. The low-level serum pool should be discreet from the high-level pool. A separate, normal human serum pool shall be spiked with crystalline creatinine to achieve an elevated level of creatinine (4.0 mg/dL ± 0.2 mg/dL). The serum shall be aliquoted into vials that are capable of withstanding long-term storage at -80 °C. (See below section for vial specifications.)

III.

SPECIFIC TASKS

Low Level: The Contractor shall provide 4,000 vials containing (1.1 ± 0.1) mL pooled human serum containing (0.4 ± 0.05) mg/dL creatinine High Level: The Contractor shall provide 4,000 vials containing (1.1 ± 0.1) mL pooled human serum containing (4.0 ± 0.2) mg/dL creatinine The High Level shall be prepared by spiking a normal serum pool with crystalline creatinine. The contractor is responsible for obtaining the creatinine used to spike the High Level.

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 967b preparation. Donor units testing positive for any of the stated infectious agents will not be included in the serum pools.

After the donor 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 bottles 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 Technical Point of Contact (TPOC) within 60 days after award. The Contractor shall use two different color aluminum crimp caps to differentiate between the two specified serums 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 box must provide separation between each vial to prevent breakage. 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. Materials shall be stored frozen (-80 °C) prior to overnight shipment on dry ice to NIST. Overnight shipments shall not be sent on Friday/Saturday or before a Monday Federal Holiday. Delivery is expected within 180 days after award.

The Contractor shall provide NIST 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.

Homogeneity: The Contractor shall assess homogeneity as defined in CLSI C37-A (Appendix A on page 9 of this document), measuring creatinine with an enzymatic-based assay instead of cholesterol. The method used to assay creatinine will have a within-run coefficient of variation (CV) < 2 % for creatinine values of 0.8 mg/dL and higher. The CLSI document includes statistics and acceptance criteria.

1.

DESCRIPTION OF SERUM AND CREATININE CONCENTRATION LEVEL

The Contractor shall follow the guidelines set forth for base pool specifications as detailed in CLSI C37-A Guideline for the preparation of this two-level creatinine in serum material. The target creatinine concentration levels are given in the Specific Tasks above. The low-level material must be based only on pooling of serum and not be diluted or stripped to obtain the target creatinine level. The high-level material shall be prepared by spiking a normal serum pool with crystalline creatinine. The serum shall be filled into pre-labeled vials (labels will be provided to the Contractor by the TPOC) flushed and sealed under an inert gas, and frozen according to the specifications given in CLSI Document C37-A.

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.

ANALYTES USED IN SPIKING

The contractor shall specify the source of added creatinine at the time of serum delivery.

2.

PILOT/VALIDATION RUN

The Contractor shall perform a pilot/validation run. The Contractor shall provide the TPOC with a Certificate of Analysis indicating creatinine concentrations by an enzymatic clinical method from randomly selected vials from each level to be shipped to NIST for inspection and analysis at the time of serum delivery.

3.

PACKING/SHIPPING SPECIFICATIONS

The material shall be packaged in trays or containers in an upright fashion. The packaging shall be of a nature to prevent breakage and keep the two levels separate and identifiable. The material shall be transported overnight on dry ice to NIST.

IV.

DELIVERABLES AND DELIVERABLE DUE DATES

The contractor shall deliver the vials, Certificate of Analysis for the creatinine concentration levels, 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 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.

V.

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.

VI.

ACCEPTABLE QUALITY LEVEL

The vials of all pooled serum with the associated physical and chemical properties specified in this Statement of Work shall be suitable for use as reference materials. If deficiencies or inconsistencies between the material and the documentation 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.

VII.

MONITORING METHOD

The TPOC will verify that the materials were successfully prepared and acceptable. Acceptance will be based upon the delivery of 4,000 vials of each pooled serum material (8,000 vials total) intact and unbroken, accompanied by screening results for creatinine. This will be completed no later than 30 days after receipt and acceptance of the vials.

VIII.

PERIOD OF PERFORMANCE

The period of performance shall be 180 days after award

IX.

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 creatinine for a total of 15 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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