RFQ_Attachment_1_-_SOW_Urine_Acquisition.pdf

STATEMENT OF WORK

TITLE: ACQUISITION OF SINGLE DONOR HUMAN URINE MATERIAL FOR SRM

3666 DEVELOPMENT

I. BACKGROUND

The National Institute of Standards and Technology (NIST) Biomolecular Measurement Division of the Material Measurement Laboratory (MML) provides measurement science and reference materials to promote innovation and confidence in measurements needed to advance bioscience research and precision medicine. To support the accuracy and comparability of routine clinical urine albumin measurements for kidney function, NIST is partnering with the National Kidney Disease Education Program (NKDEP) and the International Federation of Clinical Chemistry (IFCC) Working Group for the Standardization of Albumin Assays in Urine (WG-SAU) to develop a reference measurement system for urine albumin. To support these efforts, NIST is seeking production of a multi-level (Level 1-4) pooled human urine standard reference material (SRM) for urinary albumin, based on specifications developed from the collaboration with the NKDEP and the IFCC, to be used as a quality assessment tool for clinical laboratories and assay manufacturers. This Statement of Work (SOW) describes the requirements for the collection of fresh, non-frozen single donor human urine specimens with endogenous urine albumin levels within the following target ranges: Level 1 ≈ 5 mg/L to 10 mg/L;

Level 2 ≈ 20 mg/L to 50 mg/L; Level 3 ≈ 60 mg/L to 180 mg/L; and Level 4 ≈ 275 mg/L to 375 mg/L. Candidate SRM 3666 (Albumin and Creatinine in Frozen Human Urine) is a four (4)-component material (Level 1, Level 2, Level 3 and Level 4) with concentration values certified by NIST for albumin and creatinine and the material will be labeled as SRM 3666 Level 1, SRM 3666 Level 2, SRM 3666 Level 3 and SRM 3666 Level 4 (in this document the levels are referred to as “Level 1”, “Level 2”, “Level 3” and “Level 4”).

II. SCOPE OF WORK

The Contractor shall collect fresh, non-frozen single donor human urine specimens with the following endogenous urine albumin concentrations: Level 1 ≈ 5 mg/L to 10 mg/L;

Level 2 ≈ 20 mg/L to 50 mg/L; Level 3 ≈ 60 mg/L to 180 mg/L; and Level 4 ≈ 275 mg/L to 375 mg/L, in accord with the specifications outlined in this SOW. The fresh, non-frozen and individually-packaged single donor human urine specimens shall be stored at ≤ -70 ºC and the frozen specimens (in batches, with a maximum of five shipments) shall be shipped overnight on dry-ice to a NIST-specified institution for further processing.

III. SPECIFIC TASKS

The Contractor shall at all times handle the single donor human urine specimens in accordance with standard practice for Biosafety Level 2 materials as defined in: CDC/NIH;

Biosafety in Microbiological and Biomedical Laboratories, 5th ed.; Richardson, J.;

Barkley, W.E.; Richmond, J.; McKinney, R.W., Eds.; U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention and National Institutes of Health; US Government Printing Office: Washington, DC (2007);

available at http://www.cdc.gov/biosafety/publications/bmbl5/.

The urine must be handled hygienically at all times, never exposed to temperatures above 25 °C (room temperature), and the Contractor shall take reasonable measures to prevent cross contamination between the individually-packaged urine specimens.

A. Donor Specifications

There shall be no restrictions on donors regarding age, gender, ethnicity, body mass index (BMI), or health status. Individuals with a known urinary tract infection or who are currently taking antibiotics are excluded from donation based on donor self-reporting.

All single donor urine specimens must test negative for: urine nitrites, leukocyte esterase, and the presence of blood in the urine using an FDA-approved urinalysis dipstick diagnostic assay. Through visual inspection, urine specimens with a color other than pale yellow, yellow, or amber will be excluded. The results of the urine nitrates, leukocyte esterase, blood in urine testing and visual urine inspection shall be provided to the NIST Technical Point of Contact (TPOC) in written form for each urine specimen prior to shipping to the NIST-specified institution.

B. Specifications of Equipment and Materials

The Contractor shall acquire the specified materials and submit the specifications (product name, product manufacturer, product number, manufacturer assay instructions, lot number, expiration date) to the NIST TPOC prior to collection of the urine specimens:

1. Urine Collection, Processing, Storage and Shipping Containers

a. Sterile 50-mL polypropylene collection, processing, storage and shipping containers

b. Storage and shipping containers shall be stable at ≤ -70 ºC for long-term storage

2. Urine Container Labels

a. Labels compatible with the collection, processing, storage and shipping containers and compatible with long-term storage at ≤ -70 ºC without peeling or fading.

b. Labels shall contain the following information for each single donor specimen: a donor code (code specified by Contractor that does not include subject’s name) and container number (if multiple containers per donor); the measured endogenous urine albumin concentration (in mg/L); the type of collection (random or overnight collection); the date of collection; and the total collection volume.

3. Centrifugation instrumentation

4. Clinical Assays (FDA-Approved) shall include the following specifications for each clinical assay: assay name, assay manufacturer, product number, manufacturer assay instructions, and the measurand.

a. Urine albumin [established, routine clinical assay]

b. Blood in urine [rapid response 10 parameter (10SG) urinalysis reagent test strips]

c. Urinary nitrites [rapid response 10 parameter (10SG) urinalysis reagent test strips]

d. Urinary leucocytes esterase [rapid response 10 parameter (10SG) urinalysis reagent test strips]

C. Human Urine Collection and Processing

The Contractor shall provide the donor with a sterile polypropylene collection container prior to collection with instructions for use. Acceptable donors must be able to supply 50 mL of urine for a random collection and store the specimen in a sterile urine collection container. Urine collection in excess of 50 mL for a single donor shall be processed and stored, as stated in this SOW, and shipped to the NIST-specified institution. The Contractor shall store the fresh urine in the original sterile collection container at room (ambient) temperature (20-25 ºC) for no more than six (6) hours after collection. Following collection, the Contractor shall transfer the urine from the sterile collection container to a 50-mL sterile polypropylene and store the specimens at low temperature (2-8 ºC) for no more than five (5) days prior to processing and freezing.

The Contractor shall label (supplied by the Contractor) each single donor specimen with the following information: a donor code (code specified by Contractor that does not include subject’s name) and container number (if multiple containers per donor);

the measured endogenous urine albumin concentration (in mg/L); the type of collection (random or overnight collection); the date of collection; and the total collection volume.

The labels should be compatible with long-term storage at ≤ -70 ºC without peeling or fading.

The Contractor shall maintain a written record of the following: specimen code, number of containers (if multiple containers per donor), date of collection, total volume of urine for each donor, total volume of urine per container, clinical results (urine albumin, urine nitrates, leukocyte esterase, and blood in urine testing), visual inspection results (urine color and absence of particulates in centrifugation supernatant) and provide the NIST TPOC the report for each batch prior to shipment to the NIST-specified institution for pooling and vialing of the single donor specimens.

Upon receipt of the fresh, non-frozen urine collection from the donor, the Contractor shall use the following protocol:

1. Label each collection container with a code (generated by the Contractor) and store the specimen in the original sterile collection container at room temperature (20-25 ºC) for no more than six (6) hours after collection.

2. Transfer the urine specimen from the sterile collection container to a 50-mL sterile polypropylene container(s) and store the specimen at low temperature (2-8 ºC) for no more than five (5) days prior to processing and freezing.

3. Allow each specimen to equilibrate to room temperature (20-25 ºC) for 45 min.

prior to processing.

4. Invert each specimen container 10 times to mix the urine material. Do not vortex.

5. Assay each urine specimen by a FDA-approved assay for the following analytes:

a. Urine albumin [established, routine clinical assay]

b. Blood in urine [rapid response 10 parameter (10SG) urinalysis reagent test strips]

c. Urinary nitrites [rapid response 10 parameter (10SG) urinalysis reagent test strips]

d. Urinary leucocytes esterase [rapid response 10 parameter (10SG) urinalysis reagent test strips]

The Contractor shall follow the instructions as specified by the assay manufacturer for the above clinical assays (including quality control material and result interpretation).

Acceptable single donor urine specimens must test negative for: urine nitrites, leukocyte esterase, and the presence of blood in the urine using an FDA-approved urinary test strip assay. The Contractor shall discard any specimens that test positive for blood, urinary nitrites or leucocyte esterase.

6. Visually inspect the color of each urine specimen and discard any specimen with a color other than pale yellow, yellow or amber.

7. Transfer the acceptable urine specimen (visual color inspection of pale yellow, yellow or amber; test negative for urine nitrites, leukocyte esterase, and the presence of blood in urine using an FDA-approved urinary test strip assay) to a sterile polypropylene container (labeled) suitable for centrifugation.

8. Centrifuge the urine specimen at 2000 x g for 10 min. at temperature between 2-5 ⁰C.

9. Perform a visual inspection of the supernatant, without disturbing the sediment, for the presence of particulate matter and record the results. Discard any samples that contain visible particulate matter in the supernatant after centrifugation.

10. Transfer the urine supernatant (without transferring any sediment) to one (1) or more 50-mL sterile polypropylene containers (labeled, provided by Contractor) suitable for long-term storage at ≤ -70 ºC.

11. Immediately freeze the centrifuged urine at ≤ -70 ⁰C and store at ≤ -70 ⁰C upon shipping to the NIST-specified institution for further processing.

12. The Contractor shall provide the NIST TPOC a written record containing the following information for each urine specimen:

a. The Contractor-generated specimen code

b. Donor age and gender

c. Container number, if multiple containers per donor

d. Collection date and time, total urine volume per donor, total number of specimen containers per donor, and the approximate urine volume of each container

e. Clinical results: urine albumin, urine nitrates, leukocyte esterase, and blood in urine testing

f. Visual inspection results: urine color and particulate matter following centrifugation

g. Shipment batch number, shipment date, expected delivery date, shipping method and shipment tracking information

D. Urine Material Requirements

The Contractor shall collect 50 mL of urine per donor for a total of 2700 mL (2.7 liters) of urine per Urine Albumin Level (Level 1-4), this represents a total of 54 donors per urine albumin level (total of 256 donors) for a total urine volume per Urine Albumin Level (Level 1-4) of 2700 mL (2.7 liters), as stated in the table below.

All individual donors intended for use in each Urine Albumin Level (Level 1-4) shall possess an endogenous urine albumin concentration within the target intervals listed in the table below. The Contractor shall not spike-in albumin or dilute high endogenous urine albumin levels to achieve the target urine albumin concentrations.

The Contractor shall use an established clinical assay (specify assay name, assay manufacturer, product number and manufacturer’s instructions) to measure endogenous urine albumin in the human urine material and provide the NIST TPOC with the urine albumin measurements in written form for each urine specimen. The Contractor must use the same method for all urine measurements.

The Contractor shall meet the following requirements for each Urine Albumin Level (Level 1-4) :

Level Volume of Total

Urine (mL) Volume of Urine per

Donor (mL) Number of Donors

Endogenous Urine Albumin Concentration (mg/L)

Level 1 2700 mL 50 mL 54 5 mg/L – 10 mg/L

Level 2 2700 mL 50 mL 54 20 mg/L – 50 mg/L

Level 3 2700 mL 50 mL 54 60 mg/L – 180 mg/L

Level 4 2700 mL 50 mL 54 275 mg/L – 375 mg/L

E. Shipment of Urine Material

Once the urine specimens (as noted in above table) have been collected in each Urine Albumin Level (Level 1-4), the Contractor shall submit a written report to the NIST TPOC and consult with the NIST TPOC on the selection of the single donor specimens to ship to the NIST-specified institution for further processing. The Contractor shall ship the selected specimens (selection conducted by NIST) directly to the processing NIST-specified institution, frozen and on dry ice (sufficient dry ice to maintain frozen conditions during shipment) at the expense of the Contractor. The number of shipment batches should not exceed five (5) batches and the Contractor shall notify NIST no later than two (2) weeks prior to shipping the material and provide the following shipping information: batch number, specimen code, shipment date, expected delivery date, shipment tracking information (upon shipping material), specimen identification, endogenous urine albumin content, total number of specimens and total volume per container for each specimen. The Contractor shall be available to ship the maximum of five batches during regular business hours, which shall be Monday to Friday from 8am-5pm, except Federal Holidays, between September 30, 2017 and March 30, 2018.

F. Progress Reports

The Contractor shall supply NIST with monthly progress reports, supplied by e-mail, describing the status of all tasks accomplished within that month, any issue(s) encountered while carrying out tasks, and the planned tasks for the next month.

IV. DELIVERABLES AND DELIVERABLE DUE DATES

Deliverable 1. The Contractor shall provide progress reports via e-mail on a monthly basis. The due date is by the fifth day of the next month. The reports shall summarize tasks accomplished the previous month, any issues, and planned work for the next month.

Deliverable 2. The Contractor shall deliver to the NIST TPOC (between September 29, 2017 and March 30, 2018):

1) The Contractor shall provide the following documentation to the NIST TPOC for each clinical assay used: manufacturer name; assay name; measurand;

instrument name (if applicable); assay lot number and expiration date;

instrument model number and serial number; quality control material information; and manufacturer’s assay instructions.

2) The Contractor shall provide the NIST TPOC a written record containing the following information for each urine specimen:

i. The Contractor-generated specimen code

ii. Donor age and gender

iii. Container number, if multiple containers per donor

iv. Collection date and time, total urine volume per donor, total number of specimen containers per donor, and the approximate urine volume of each container

v. Clinical results for the following assays: urine albumin, urine nitrates, leukocyte esterase, and blood in urine testing

vi. Visual inspection results: urine color and particulate matter following centrifugation

vii. Shipment batch number, shipment date, expected delivery date, shipping method and shipment tracking information

Deliverable 3. The Contractor shall deliver the labeled urine material (frozen, on dry ice) to the NIST-specified institution for further processing (to arrive at the NIST-specified institution between September 29, 2017 and March 30, 2018 during regular business hours, which shall be Monday to Friday from 8am-5pm, except Federal Holidays):

1) Single donor urine specimens shipped to the NIST-specified institution for further processing, see the urine specifications in Section III.

2) Urine collection in excess of 50 mL for a single donor shall be processed, stored and documented, as stated in this SOW, and shipped to the NIST-specified institution.

V. PROTECTION OF HUMAN SUBJECTS

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.

Research Activities Involving Human Subjects, Human Tissue, Data or Recordings Involving Human Subjects Including Software Testing. Any tasks that includes research activities involving human subjects, human tissue/cells, or data or recordings from or about human subjects, must satisfy the requirements of the Common Rule for the Protection of Human Subjects (“Common Rule”), codified for the Department of Commerce at 15 C.F.R. Part 27. Research activities involving human subjects who fall within one or more of the classes of vulnerable subjects found in 45 C.F.R. Part 46, Subparts B, C and D must satisfy the requirements of the applicable subpart(s). In addition, any such application that includes research activities on these subjects must be in compliance with all applicable statutory requirements imposed upon the Department of Health and Human Services (DHHS) and other Federal agencies, all regulations, policies and guidance adopted by DHHS, the Food and Drug Administration (FDA), and other

Federal agencies on these topics, and all Executive Orders and Presidential statements of policy on applicable topics.

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). In the event 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.

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 Contractor shall submit the following documentation to the NIST TPOC prior to issuance of the award: verification of a relationship with an Institutional Review Board (cognizant IRB), located within the United States and within the community in which the human subjects research will be conducted; valid registration of IRB with United States Department of Health and Human Services' Office for Human Research Protections (OHRP); and valid Federal-wide Assurance (FWA) issued by OHRP of the Contractor.

A. Determination of Not Research: If a task involves human subjects as defined in the

Common Rule, but the Contractor indicates to NIST that the task is not research as determined by the cognizant IRB, the following information shall be submitted to NIST prior starting the research:

(1) Justification, including the rationale for the determination and such additional documentation as deemed necessary by NIST to review and/or support a determination that the task is not research as defined in the Common Rule.

(2) If the Contractor used a cognizant IRB that provided a determination that the task is not research, a copy of that determination documentation must be provided to

NIST.

NIST will review the information submitted and may coordinate further with the Contractor before determining whether the task will be defined as research under the Common Rule in the applicable NIST project.

B. Determination of Research Not Involving Human Subjects: If a task is determined to be research and involves human subjects, but the Contractor indicates to NIST that the task was determined to be not human subjects research (or research not involving human subjects) by the cognizant IRB, the Contractor shall submit the following documentation to NIST prior starting the research:

(1) Justification, including the rationale for the determination and such additional documentation as may be deemed necessary by NIST to review and/or support a determination that the task is not research as defined in the Common Rule.

(2) If the Contractor used a cognizant IRB that provided a determination that the task is research not involving human subjects, a copy of that determination documentation must be provided to NIST.

C. Determination of Research Involving Human Subjects: If the task is determined to be research that involves human subjects by the cognizant IRB, the Contractor shall submit the following documentation to NIST prior starting the research:

(1) The name(s) of the institution(s) where the research will be conducted.

(2) The name(s) and institution(s) of the cognizant IRB(s), and the IRB registration number(s) with OHRP.

(3) The FWA number of the Contractor linked to the cognizant IRB(s);

(4) If the IRB review(s) is pending, the estimated start date for research involving human subjects.

(5) The IRB approval date and the final IRB-approved protocol.

a. This includes the human subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms approved by the cognizant IRB

(7) A signed and dated approval letter from the cognizant IRB(s) that includes the name of the institution housing each applicable IRB, provides the start and end dates for the approval of the research activities, and any IRB-required interim reporting or continuing review requirements.

(8) A brief description of what portions of the IRB submitted protocol are specifically associated with the task outlined in this SOW NIST

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

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.

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. PERFORMANCE REQUIREMENT SUMMARY

Required Service:

Production of 2700 mL (2.7 liters) of collected single donor urine per Urine Albumin Level (Level 1-4) (see Section III for detailed description of urine level requirements) shall be shipped to a NIST-specified institution.

Performance Standard:

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

2. A total of 2700 mL (2.7 liters) of collected single donor urine per urine albumin level (see Section III for detailed description of urine levels requirements) shall arrive intact, frozen, and unbroken. Urine collection in excess of 50 mL for a single donor shall be processed, stored and documented, as stated in this SOW, and shipped to the NIST-specified institution intact, frozen, and unbroken.

Acceptable Quality Level:

The material must be suitable for use as a certified reference material (CRM). If deficiencies or inconsistencies between the material and the documentation (defined in section IV) are found, or if less than the stated number of donors or urine volume is received, the Contractor has 30 days to correct the deficiency. The Contractor shall correct all deficiencies at no additional cost to the Government.

Monitoring Method:

Acceptance will be based upon the delivery of 10.8 liters of single donor urine specimens [2700 mL (2.7 liters) per Urine Albumin Level (Level 1-4) ; see Section III) at each of the four Urine Albumin Level (Level 1,2,3,4) frozen, intact and unbroken. This will be completed no later than 30 days after receipt and acceptance of the vials. The NIST TPOC will confirm that the single donor urine specimens were successfully collected when the final pooled material is analyzed as part of the certification process. The certification process will be completed no later than 365 days after receipt and acceptance of the requested materials.

VII. DELIVERY

Delivery shall be FOB DESTINATION, and be completed in accordance with the due date stated in Section IV, above. (NIST-specified Institution)

At the time of shipment, the Contractor shall notify the NIST TPOC by email, providing the date the deliverables are shipped, shipping method, tracking number, method of delivery, and the anticipated delivery date of arrival to the NIST-specified institution.

VIII. PAYMENT

One payment shall be made for the final deliverables in CLIN 0001 which is the total value of the contract. NIST will test and accept the final deliverables no later than 30 days from receipt of the total quantity of line item 0001. The Contractor shall invoice for the total price of the contract upon written acceptance from the NIST TIC that all deliverables were accepted by the Government. Partial payments are not authorized.