SOW_TroponinComplex.pdf

STATEMENT OF WORK

Acquisition of Human Cardiac Troponin Complex for SRM 2921a

I. BACKGROUND

To improve the quality of the clinical measurement of human cardiac troponin I (cTnI), a protein biomarker for heart attack and other forms of myocardial damage, NIST issued

SRM 2921 in 2004. SRM 2921 is widely used by manufacturers of clinical cTnI assays to assess the accuracy of their assays and to establish measurement equivalence between different commercial assay. SRM 2921 is a frozen aqueous solution of the human troponin complex which consists of the three proteins: human cardiac troponin T (cTnT), human cardiac troponin I, and human cardiac troponin C (cTnC). The troponin complex used to prepare SRM 2921 was extracted and purified from human heart tissue. The efficacy of

SRM 2921 in the standardization of clinical cTnI assays has been evaluated through studies involving commercial cTnI assays. Therefore, in order to maintain continuity and support efficacy, the material acquired to prepare SRM 2921a must be closely matched to the troponin complex present in SRM 2921.

To prepare SRM 2921a, the renewal batch of SRM 2921, the Bioanalytical Science group of the Biomolecular Measurement Division wishes to purchase human cardiac troponin complex which has been extracted and purified from human heart tissue.

II. SCOPE OF WORK

NIST intends to acquire approximately 60 mg (± 2 mg) of purified human cardiac troponin complex. The quality specifications of the required human cardiac troponin complex are outlined below.

Extraction and Purification:

The Contractor shall perform extraction and purification of the troponin complex from human heart tissue in mild conditions which will preserve the complex structure between the cTnT, cTnI, and cTnC protein subunits; denaturing detergents, organic solvents, and/or extremes in pH shall not be used during the sample processing.

The contractor shall test a blood sample from the human heart tissue donors and to ensure negative (non-reactive) results for hepatitis B surface antigen (HbsAg), human immunodeficiency (HIV) 1 and 2 antibodies, and hepatitis C virus (HCV).

Molecular Structure:

The human cardiac troponin complex submitted must contain all three protein subunits:

human cTnT, human cTnI, and human cTnC. The molar ratios of all subunit proteins must be equal to or close to 1 (± 20 %).

Purity:

Protein purity of the final human cardiac troponin complex submitted must be ≥ 80 % assessed using an appropriate analytical technique such as: gel permeation chromatography using UV detection, reversed-phase chromatography using UV detection, or electrophoresis using specific or non-specific protein staining.

Human Cardiac Troponin Complex Amount:

The Contractor shall deliver sixty milligrams (± 2 mg) of purified human cardiac troponin complex to NIST as a lyophilized powder or in a frozen aqueous solution.

Storage:

The Contractor shall store the human cardiac troponin complex at a temperature of ≤ -70

°C. The Contractor shall ship the human cardiac troponin complex overnight to NIST on dry ice. To ensure timely receipt of the package(s) by the end user and minimize the risk of environmental damage incurred during transit, the Contractor shall ensure the package is not delivered to NIST on a Friday, Saturday, Sunday, or on a Federal Holiday.

III. SPECIFIC TASKS

The Contractor shall prepare the requested human cardiac troponin complex through recombinant expression and then purification to a protein content of ≥ 80 %. The protein purity of the final human cardiac troponin complex preparation shall be ≥ 80 %, which the contractor shall verify using a chromatographic or electrophoretic method appropriate to assess purity.

The contractor shall provide documentation of protein purity and the method of preparation (such as in the form of a materials certificate of analysis).

The Contractor shall deliver Sixty milligrams (± 2 mg) of purified recombinant human cardiac troponin complex to NIST as either a lyophilized powder or a frozen aqueous solution.

Materials shall be stored in the freezer (≤ -70 °C) prior to overnight shipment to NIST on dry ice. To ensure timely receipt of the package(s) by the end user and minimize the risk of environmental damage incurred during transit, the Contractor shall ensure the package is not delivered to NIST on a Friday, Saturday, Sunday, or on a Federal Holiday.

IV. DELIVERABLES AND DELIVERABLE DUE DATES

Not later than 120 days after award of this order, the Contractor shall deliver to NIST:

60 mg (± 2 mg) of purified human cardiac troponin complex in the form of a lyophilized powder or frozen aqueous solution.

documentation describing the type(s) of analytical procedure(s) used and brief description of the experimental conditions used to assess the purity and the analytical characterization of the materials and the experimental results of the purity assessment and analytical characterization.

V. PROTECTION OF HUMAN SUBJECTS

(a) Research involving live 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 live 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 live 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 live 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 live 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 live 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 live 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.

VII. GOVERNMENT ACCEPTANCE

Required Service

Delivery of 60 mg (± 2 mg) of purified human cardiac troponin complex in the form of a lyophilized powder or frozen aqueous solution.

Delivery Standard

Materials must be prepared and packaged as described in the SOW and meet all specifications set forth in the SOW.

Acceptable Quality Level

The material will be deemed suitable when it meets all the specifications listed in the

Scope of Work above. The Government shall have 45 days to inspect all deliverables.

50 % partial payment will be made upon delivery and 50 % payment upon Government acceptance.

If deficiencies or inconsistencies between the material and the documentation are found, the Contractor has 60 days from the date the deficiencies or inconsistencies were identified to correct the deficiency.

Inspection

The NIST Technical Point of Contact (TPOC) will know that the human cardiac troponin complex has been successfully produced after reviewing the documentation provided by the vendor and when it is analyzed at NIST.

IX. DELIVERY

Delivery shall be FOB DESTINATION, and be completed in accordance with the due date stated in Section IV, Deliverables, above.

Delivery Address:

National Institute of Standards and Technology

Building 227, Room B248

100 Bureau Drive

Gaithersburg, MD 20899-8314

At the time of shipment, the Contractor shall notify the TIC by email, providing the date the deliverables are shipped, shipping method, tracking number, method of delivery, and the anticipated delivery date of arrival at NIST.

X. SHIPPING

Boxes shall be labeled to indicate their contents. Materials shall be stored at ≤ -70 ⁰C prior to overnight shipment on dry ice to NIST. The Contractor shall ship the deliverable to arrive during normal duty hours, which are 8:30 am and 5:00 pm Eastern Time, Monday through Friday, except Federal Holidays. Delivery is expected within 120 days after receipt of order to the delivery address above.

XI. MINIMUM CONTRACTOR QUALIFICATIONS

The Contractor shall have a minimum of three (3) years professional experience in the collection, preparation and storage of human proteins.