SOW_FOR_RFQ.pdf

Request for Quotation Number SB1341-15-RQ-0950

Statement of Work

BACKGROUND

The National Institute of Standards and Technology (NIST), Organic Chemical Measurement

Science Group within the Chemical Sciences Division is responsible for chemical measurements in a broad range of areas, including the development of reference materials to support accuracy and comparability of clinical laboratory assays for health status markers. Total bilirubin and direct bilirubin are commonly-measured species in blood samples by routine medical testing laboratories. Members of the clinical measurement community have relied on SRM 916a bilirubin to ensure their bilirubin measurement accuracy.

Total bilirubin refers to both its unconjugated form as well as its compositional isomeric forms (predominately III, IXand XIII) within the solid bilirubin material. The profile of the major bilirubin isomers (III, IXand XIII) is not critical to the determination of the overall purity of the bilirubin material but has been observed to range significantly between the 916a and candidate 916b materials upon dissolution and analysis via LC-UV (5 to 3%, 83 to 90% and 12 to 6%, respectively for 916a and candidate 916b).

Since the depletion of SRM 916a stock (2010), a replacement material (candidate SRM 916b) has been under evaluation to provide a certified value of a high-purity content of bilirubin (> 98% mass fraction). It has been recently determined by NIST evaluations that this material is of considerably lower purity ( 95%) and may not be suitable to support routine clinical measurements. Thus, given this material’s unsuitability for measurement calibration and standardization purposes, it may not be released as a SRM with certified values for bilirubin. NIST requires a high purity chemical standard for bilirubin to develop a suitable, high purity replacement for SRM 916a. Prior to acquisition of the bulk material, purification capabilities must be demonstrated through production of a small batch of the material (10 g).

An exemplary source of bilirubin material was that obtained for SRM 916a. The material was originally isolated from porcine bile and crystallized as the acid. It was purified by reflux in chloroform, fractioned over a sodium sulfate column and distilled, followed by recrystallization from diethyl ether and chloroform.2

The above referenced method is provided as historical information. NIST does not warranty, endorse or otherwise guarantee that the above referenced process would be successful in the performance of this required work.

SPECIFICATIONS

The Contractor shall provide bilirubin that meets all of the following minimum specifications:

a. Chemical purity shall be ≥ 98.5% (total bilirubin mass fraction of 0.985 g/g or greater);

b. Moisture content loss upon drying shall be ≤ 0.1% mass fraction (16 hrs at 90 oC under vacuum);

c. The molar absorptivity shall be ≥75,000 L/ molcm @ 598 nm in alkaline azopigment solution (uncorrected value).1,3

d. The ash content shall be ≤ 0.2 % mass fraction.

e. The iron (Fe) content shall be ≤ 0.1 % mass fraction.

f. Documentation indicating the identity and purity of the lot provided and method(s) used to determine this purity must be included with the reagent. This documentation must show that the purity specification of 98.5% mass fraction is met or exceeded.

Documentation must also include manufacturing and purification process. All documentation must be delivered with the candidate batch.

g. The bilirubin material must be provided from a single manufacturing lot for which the identity and purity have been demonstrated.

TASKS:

1. The Contractor shall manufacture the material (micro-scale) and perform bulk characterization to include, at a minimum, determination of oven volatiles, purity determination by UV spectrophotometric, elemental analysis, and ash content. UV measurements must be performed in accordance with the reference (Fog, J. Bilirubin –

Purification – Purity. Scandinav. J. Clin. Lab. Investigation (1964) 49-54.)

The Contractor must utilize the method described in their quotation to manufacture the

10g of material.

The Contractor shall provide NIST with 10 g of material and documentation indicating the identity and purity of the lot provided as well as the method(s) used to determine this purity. This documentation must show that the purity specification of 98.5% mass fraction is met or exceeded.

NIST will assess the purity by UV spectrophotometry, possible NMR screening, and oven volatile analysis. NIST will provide the screening results to the Contractor. If the lot meets all required specifications, the Contractor shall be paid in accordance with the line item schedule.

If NIST determines that that the batch does not meet all required specifications, no payment will be made. The Contractor must revise their method(s) accordingly, contact the

NIST Technical Point of Contact (TPOC), via phone, to discuss changes made to the method(s), and re-purify a second 10 grams of bilirubin. Revisions to the method(s) must be discussed with the TPOC prior to the second 10 grams of bilirubin being purified.

2. The Contractor shall deliver the second purified 10g of bilirubin and documentation indicating the identity and purity of the lot provided to NIST. NIST will assess the purity and provide screening results to the Contractor in accordance with paragraph 1. If the lot meets all required specifications, no further work is required and the Contractor shall be paid in accordance with the line item schedule.

If the lot does not meet all required specifications, the Contractor must provide additional revisions to their method(s), discuss revisions with the TPOC in accordance with paragraph 1, and proceed to purify a third and final lot of 10 grams of bilirubin.

The third and final lot must be delivered to the TPOC with documentation indicating the identity and purity of the lot provided. The lot will be assessed by NIST in accordance with paragraph 1.

If the third and final lot of bilirubin does not meet all required specifications, the contract will end and no payment shall be made to the Contractor. If the third and final lot is successful, the Contractor shall be paid in accordance with the line item schedule.

3. OPTION LINE ITEM – Line item 0002 is an option line item for a lot of 200 g of bilirubin. The Government may exercise this option line item, at its discretion, subject to the availability of funds, if any of the 10g batches of bilirubin are determined to meet all required specifications. Pricing for this line item shall remain in effect for a period of one year from the date of award.

The Contractor must purify the lot of 200 g of bilirubin in accordance with the methods identified within the documentation of the successful 10 g lot of bilirubin. Any changes to the methods must be discussed with the TPOC and approved prior to implementation and execution of the change.

NIST will assess the purity by UV spectrophotometry, possible NMR screening, and oven volatile analysis. NIST will provide the screening results to the Contractor. If the lot meets all required specifications, the Contractor shall be paid in accordance with the line item schedule. If the lot does not meet all required specifications, the lot will be returned to the Contractor and no payment shall be made.

PERIOD OF PERFORMANCE

The period of performance shall be nine months from the date of award.

If the option line item is exercised, delivery shall be completed not later than nine months from the date the option is exercised.

DELIVERABLES

Bilirubin – Initial Batch 10 g including required documentation

DUE DATE: 30 days from the date of award

Subsequent 10g batches

DUE DATE: To be determined by the Contractor - not later than nine months from the date of award

PLACE OF PERFORMANCE

All work shall be accomplished at the Contractor’s facility. The material shall be delivered to NIST.

GOVERNMENT FURNISHED PROPERTY

None

ACCEPTANCE TESTING

Upon receipt of the material, the Government will conduct inspection/acceptance testing on the bilirubin by using the follow methods to confirm that the purity is 98.5 mass fraction was met or exceeded:

American Association for Clinical Chemistry Committee on Standards, Working Group on Bilirubin. “Protocol for measurement of bilirubin molar absorptivity values”

January 1998 Revision.

Cohen, A., et. al. “Certification of bilirubin SRM 916a”, Fresenius J Anal Chem, (1990) 338 426-429 (1990).

The results of the evaluation and acceptance testing shall be sent to the vendor via email.

ATTACHMENTS

None

PERFORMANCE REQUIREMENT SUMMARY

Desired Output

Performance

Standard Monitoring Method

On time delivery of

Bilirubin material that meets the performance specifications

Refer to section II in the statement of work

The Government will verify that the container(s) are unopened/undamaged and supplied with a certificate of analysis listing the identity and purity of the lot provided, and the method(s) used to determine this purity. NIST will assess

Desired Output

Performance

Standard Monitoring Method this documentation and will confirm the purity by analysis. The purity must meet or exceed the specifications (i.e., ≥ 98.5% mass fraction).

REFERENCES

1 Certificate of Analysis of Standard Reference Material 916a Bilirubin; Report of

Analysis 639.02-02-11-065 describing an LC evaluation of candidate material 916b

Bilirubin.

2 Fog, J. Bilirubin – Purificaiton – Purity. Scandinav. J. Clin. Lab. Investigation (1964)

49-54.

3Doumas, B.T., Perry, B.W., McComb, R.B., Kessner, A., Vader, H.L., Vink, K.L.J., Koedam, J.C., Paule, R.C. Molar Absorptivities of Bilirubin (NIST SRM 916a) and its Neutral and

Alkaline Azopigments. Clin. Chem. (1990) 1698-1701.