Statment of Work (SRM 1955a).pdf

STATEMENT OF WORK

TITLE: SRM 1955a Homocysteine in Frozen Human Serum

LAB REQUESTING SERVICE: Material Measurement Laboratory, Chemical

Sciences Division

I. BACKGROUND INFORMATION

The National Institute of Standards and Technology (NIST) began selling Standard

Reference Material (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. SCOPE OF WORK

The contractor shall produce 1,500 vials of each of the three serum materials, at the concentrations specified below, with each vial containing (1.1 ± 0.1) mL of serum.

The contractor shall acquire a minimum of 4,500 mL of pooled serum according to the

CLSI C37-A Guideline (https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/; Clin Chem Lab Med. 2020 Feb 25;58(3):368-374. doi:

10.1515/cclm-2019-0732). The lower level material (Level 1) can be diluted with phosphate buffered saline (PBS) to achieve the required 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 listed in Section III:

III. SPECIFIC TASKS AND REQUIREMENTS

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

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

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

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

LINE ITEM 0003

RFQ# 1333ND21QNB640187

https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/

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 obtaining the homocysteine used to augment Level 3.

Task 4: Vial stress test results in accordance with the following and the requirements herein.

The Contractor shall provide the NIST Technical Point of Contact (TPOC) with vial stress test results prior to filling and the Certificate of Analysis, including pilot/validation results, prior to shipping of the vials to NIST.

Task 5: Certificate of Analysis, including pilot/validation study results in accordance with the requirements herein.

Task 6: Material Preparation Detail Report

The Contractor shall provide the TPOC with the material preparation report, including the source of the added homocysteine (brand, catalog number, and lot) and any deviations from the specified standard, and the Biosafety Report not later than 180 days after award, to ensure documentation of any deviations as well as to provide information that shall be utilized in the NIST material acquisition Report of Analysis.

This information must be provided to the TPOC as a pdf file, via email.

The NIST Report of Analysis is an internal NIST report. NIST is starting a new process whereby information is compiled from these internal reports and edited for eventual presentation as an external NIST Special Publication.

NIST intends to publish the Contractor’s responses to the solicitation and any Certificates of Analysis provided by the Contractor. NIST does not intend to publish proprietary information and will work with the Contractor to further redact information from internal

NIST reports to assemble the related external Special Publication.

Task 7: Biosafety Report in accordance with the requirements herein.

TASK REQUIREMENTS

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

(https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm).

The contractor shall provide a written Biosafety Report stating the negative results of all single-donor serum units utilized for SRM 1955a preparation. Donor units testing positive for any of the stated infectious agents must not be included in the serum pools.

Personal identifiers of donors must not be disclosed to NIST.

https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm

For the purpose of this statement of work, “Donor units” are serum volumes collected from individual human donors. The Contractor shall draw samples or obtain samples from a secondary blood collection site that follows the stated guidelines.

After the donor serum units are selected, they shall be pooled. The contractor shall thoroughly blend and filter the pools (0.22 µm PVDF) as defined in CLSI C37-A

(https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/;

Clin Chem Lab Med. 2020 Feb 25;58(3):368-374. doi: 10.1515/cclm-2019-0732). 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, USP Type 1 borosilicate glass, 13 mm crimp finish, available from

Voigt Global Distribution (catalogue # 62413PV-3) or equivalent.

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 5 freeze and thaw cycles at -80 °C to ensure that there is no breakage including small cracks or fissures. The Contractor must provide the results of the stress test via email to the TPOC prior to moving forward with vial filling.

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 NIST 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 with vial dividers 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.

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. In addition, the Contractor must notify the COR, at least 48 hours in advance of the shipment, to be sure that NIST staff are available to receive the shipment. Delivery must be completed not later than 180 days after award. The contractor shall notify the

NIST TPOC, 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.

The vials shall be shipped to:

National Institute of Standards and Technology

ATTN: Technical Point of Contact (To be identified at the time of award)

100 Bureau Drive

Bldg. 301/Shipping and Receiving

Gaithersburg, MD 20899

The Contractor shall assess homogeneity after vial filling and prior to shipment of vials to

NIST, as defined in CLSI C37-A (Appendix A, page 9)

(https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/;

Clin Chem Lab Med. 2020 Feb 25;58(3):368-374. doi: 10.1515/cclm-2019-0732), measuring homocysteine, instead of cholesterol. The CLSI document includes statistics and acceptance criteria.

Contractor shall follow the guidelines set forth for base pool specifications as detailed in

CLSI C37-A Guideline for the preparation of this three-level homocysteine in serum material. The target homocysteine concentration levels are given in the Specific

Tasks above.

For the Level 1 material, PBS must be used to dilute the base serum to obtain the target level. The Level 2 material must consist only of pooled base serum. 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 serum shall be filled into pre-labeled vials (labels will be provided to the Contractor by NIST) flushed and sealed under an inert gas, and frozen according to the specifications given in CLSI

Document C37-A (https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/; Clin Chem Lab Med. 2020 Feb 25;58(3):368-374. doi:

10.1515/cclm-2019-0732).

A pilot/validation run shall be performed by the Contractor, after vial filling and prior to shipment of the vials to NIST. The Contractor shall provide NIST with a Certificate of

Analysis indicating homocysteine concentrations of individual vials selected by the

Contractor according to CLSI C37-A (https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/; Clin Chem Lab Med. 2020 Feb 25;58(3):368-

374. doi: 10.1515/cclm-2019-0732) from each level of material. This data must be provided by NIST as a pdf via email to the TPOC before shipment of the entire production lot.

IV. DELIVERABLES AND DELIVERABLE DUE DATES

Biosafety Report

Due Date: 48 hours prior to shipment

Vial Stress Test Results

Due Date: Prior to vial filling https://clsi.org/standards/products/clinical-chemistry-and-toxicology/documents/c37/

Material Preparation Detail Report

Notification of Shipment

Certificate of Analysis

Level 1 SRM – 1500 vials

Due Date: 180 days from the date of award

Level 2 SRM – 1500 vials

Level 3 SRM – 1500 vials

V. PROTECTION OF HUMAN SUBJECTS

The contractor is required to draw the serum specimens or obtain serum specimens from an appropriate source. Human Subjects Clearance may be required. The contractor shall be responsible to satisfy all human subjects requirements prior to performing work relevant to this clearance. Reference the following requirements.

1352.235-70 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, must be suitable for use as reference materials. If deficiencies or inconsistencies between the material and the documentation listed in

Section III are found, or if less than the stated number of vials are received intact, the contractor shall have 30 days from notification by the TPOC, to correct the deficiency, at no additional cost to the Government.

VII. MONITORING METHOD

The NIST TPOC 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 which indicate that the three levels of material possess homocysteine levels within the specified target ranges. Verification and acceptance will be completed no later than 30 days after receipt of the vials at NIST.

VIII. MINIMUM CONTRACTOR QUALIFICATIONS

-Documented compliance with ISO 13485:2016 “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 a certificate from a certification organization.

VIII. RIGHTS IN DATA

The Government shall retain unlimited data rights to all required deliverables in accordance with the data rights clause, incorporated by reference, herein.