SOW_For_RFQ.pdf

Request for Quotation Number SB1341-15-RQ-0230

Statement of Work

I. BACKGROUND

The National Institute of Standards and Technology (NIST)/Biomanufacturing Initiative includes development of a suite of fundamental measurement science, standards, and reference data to enable more accurate and confident characterization of key attributes of protein drugs. As part of that project, NIST has acquired a large quantity of IgG1k monoclonal antibody intended for development into a NIST Reference Material. This material will be released with physicochemical data as well as quantitative data traceable to fundamental units of measurement, and is expected to be utilized as a system suitability tool in the biopharmaceutical industry.

Definitions

Homogenized Bulk (HB)= Bulk: Original material (multiple lots) transferred from NIST to

Contractor.

Dilution 1 to 3 = Reference Material (RM): Diluted version of small portion of

Homogenized Bulk. Labeled as Lot 14HB-D-001, 14HB-D-002, and 14HB-D-003. To be prepared by Contractor as part of this solicitation.

II. SCOPE OF WORK

NOTE: The protocol outlined in this section is a general outline of work to be performed.

The Contractor shall be responsible for the proposed equipment, process, and material handling as indicated in their quotation.

Pre-Fill Development

Not later than five days from the date of award, approximately 20 mL of NIST IgG1k monoclonal antibody (10 mg/mL) will be delivered to Contractor in accordance with the details provided in the section entitled “Transfer of Homogenized Bulk to Contractor”.

The Contractor shall perform a pre-fill study with the NIST IgG1k monoclonal antibody to demonstrate compatibility of the container closure system. The pre-fill study shall include testing and selection of contact/closure systems through a small scale fill and freeze/thaw study. Each vial for the test shall be filled and labeled in the same manner as described for the large scale fill, however this portion of the requirement may be performed manually. Automated fill instrumentation is not required for the pre-fill development, however, is required for 14HB-D-001, 14HB-D-002, and 14HB-D-003 as described in the sections herein. The pre-fill product must be tested and meet specifications as outlined below:

1. No more than 5% sample loss as determined via concentration measurement (for ten vials) as determined by UV-Vis (triplicate measurement on each vial) absorption using an extinction coefficient of 1.42 at A280. The vial to vial reproducibility shall be reported by performing UV-Vis. The vial to vial precision shall be no more than 5% coefficient of variation. Absorbance readings along with standard deviation for concentration determination shall be reported.

2. Pictures of the labeled vials shall be taken pre-and post-fill. No indication of stress marks or damage to the vial shall be noted due to freeze/thaw. Pictures shall be sent to the Contracting Officer’s Representative (COR) prior to the final fill as discussed below.

Data from the Pre-fill development must be sent to the COR not later than 30 days following award. This data will be evaluated by the COR for consistency with specifications. The Contractor must receive acceptance from the COR prior to beginning final material fill. During pre-fill development, transfer of the remaining material for final fill shall be planned and executed.

In the event that pre-fill development reveals one or more of the specifications cannot be met, NIST reserves the right to pay the Contractor for the pre-fill development only and then terminate the contract for the convenience of the Government.

NIST reserves the right to discuss potential solutions with the Contractor and re-evaluate with additional pre-fill development studies. Line Items 0002 and 0003 are option line items. These option line items are for two additional pre-fill development studies. If exercised, the Contractor must repeat the pre-fill development in an effort to successfully complete the pre-fill development. If subsequent attempts to successfully complete the pre-fill development are not successful, the Government will pay the

Contractor for the subsequent pre-fill development studies and terminate the contract for the convenience of the Government.

Transfer of Homogenized Bulk to Contractor

The Contractor shall contact the COR upon award for delivery of the Homogenized Bulk

Material and to plan the date for shipment. Three one liter containers of Homogenized

Bulk will be transferred to the Contractor for preparation of the reference material.

The material to be sent to the Contractor is a purified monoclonal antibody Homogenized

Bulk (NOT INTENDED FOR HUMAN OR ANIMAL USE) in 12.5 mM L-His, 12.5 mM L-His HCl (pH 6.0) at 100 mg/mL. The material will be shipped overnight on dry ice from NIST to the

Contractor. The Contractor must verify, via email to the COR, that the material was received frozen, and immediately transfer the material to -80oC storage until beginning the production method for each lot.

Production Method Lot 14HB-D-001

The techniques and handling utilized throughout must maintain sterility. For the purpose of this statement of work, sterility means that the work must be performed in a cleanroom or biosafety cabinet. A maximum of one thaw/freeze cycle shall be used for the Reference

Material Preparation. Undue mechanical stress such as stirring and/or agitation must be minimized in order to reduce the risk of aggregation such that monomeric purity is maintained, but such that vial to vial concentration homogeneity is achieved as described below. The material shall not exceed a temperature above 30 degrees C at any time.

The Contractor shall thaw an individual one Liter container of Bulk and dilute this material to 1/10 of its original concentration with the buffer specified in Section IV, Buffer Composition, and prepare Lot 14HB-D-001 of the Reference Material.

The individual diluted bulk must be aliquotted into 10,000 (±300) units of 800 µL (±20) each using an automated platform. Screw top cryovials compatible with -80 degree C storage shall be used. Thermo Matrix #3741, or equivalent, container and closure meeting all of the salient characteristics identified in Section III.

Each individual vial shall be labeled with human readable text as described in Section

III. Any secondary containers (e.g. rack, box, etc.) containing multiple vials must also be labeled as described in Section III.

The filled, capped, and labeled vials must be flash frozen within two hours of filling at

-80 degrees C. A total of one thaw/freeze cycle shall be used in going from bulk to final reference material. The final lot reference material must meet the specifications outlined in sections III, IV, and IX.

The final concentration shall be +/-0.5mg/mL of the 10 mg/mL target concentration as determined by the UV-Vis absorption. Vial to vial reproducibility of both homogeneity and volume are of critical importance to this procurement.

The time from thaw to refreeze in final vial shall be less than 48 hours, and no additional freeze/thaw may be performed. The material shall not exceed a temperature of

30 degrees C; Minus 80 degrees C shall be the final storage temperature.

The container closure for this lot shall contain a lid of a different color than the other lots.

The Contractor must notify the COR immediately if, at any time during the production process for any production lot, the Contractor identifies that the production method has developed problems, may not or does not meet specifications or may not or will not be successful.

Production Method Lot 14HB-D-002

The process described for Lot 14HB-D-001 shall be repeated in its entirety on a new one liter container of bulk. This lot must be appropriately labeled as Lot 14HB-D-002 as described in section III. The container closure for this lot shall contain a lid of a different color than the other lots.

Production Method Lot 14HB-D-003

The process described for Lot 14HB-D-001 shall be repeated in its entirety on a new one liter container of bulk. This lot must be appropriately labeled as Lot 14HB-D-003 as described in section III. This container closure for this lot shall contain a lid of a different color than the other lots.

Concentration:

The protein concentration of each RM lot shall be ± 0.5 mg/mL of the 10 mg/mL target concentration as determined by UV-Vis absorption using an extinction coefficient of 1.42 at A280. The vial to vial reproducibility shall be reported by performing UV-Vis as described above on ten vials (triplicate measurement on each vial) of each RM lot chosen at random to cover the entire production run. The vial to vial precision shall be no more than 5% coefficient of variation. Absorbance readings along with standard deviation for concentration determination shall be reported.

Return of product to NIST

A total of 30000 (± 1000) 800 µL containers shall be returned to NIST on dry ice.

Material shall remain frozen and packed with sufficient dry ice to maintain a frozen state throughout shipment. NIST must receive the material frozen.

III. Packaging and Labels

Primary Packaging:

The reference material shall be packaged, using methods to maintain homogeneity, into semitransparent plastic vials; Thermo Matrix vials and rack system, Thermo Scientific product number 3741, or equivalent. Containers must be approved by the COR prior to beginning the fill. Each vial must contain a volume of 800 (±30) µL of material per vial.

The vials must meet or exceed the following criteria. This criterion also represents the salient characteristics of the Thermo Scientific product 3741:

1. Vials shall be sterile;

2. The vials must be compatible with long term storage at -80 degrees C;

3. The filled and labeled containers shall not show any signs of stress or damage upon one freeze (-80 degrees C)and thaw;

4. The containers shall be screw top. The tops of each lot shall be a different color;

5. The containers shall be composed of Class VI medical grade polypropylene;

6. Each individual vial shall be labeled as discussed below.

Primary Package Labeling

The Contractor shall provide labels for, and label each individual vial with human readable text as described below. Vialing may occur prior to or after filling, but must occur before freezing of the vials and must ensure sterility of the Reference Material is maintained. Individual vial labels may be placed either horizontally or vertically, however the proposed placement must:

1. Be stable to withstand -80 degree C without peeling or fading;

2. Be demonstrated (using filled vials) that the label does not induce stress such as striations in the container or damage due to freeze/thaw as discussed in the pre-fill development;

3. Labeled vials shall fit into the original secondary containment device without damage to the label or vial itself;

4. Contain lot appropriate, human readable text. The design for each label will be provided by NIST and will contain the text:

a. RM 8670 NISTmAb, Humanized IgG1κ, Lot 14HB-D-001, NOT FOR USE IN HUMANS, NIST 301-975-2200

b. RM 8670 NISTmAb, Humanized IgG1κ, Lot 14HB-D-002, NOT FOR USE IN HUMANS, NIST 301-975-2200

c. SRM 3650 NISTmAb, Humanized IgG1κ, Lot 14HB-D-003, NOT FOR USE IN HUMANS, NIST 301-975-2200

Secondary Packaging and labeling

The secondary containment boxes, 96 place racks, shall require an appropriate label that will be provided by NIST. Each secondary container shall be labeled with NIST provided label prior to freezing.

IV. TECHNICAL REQUIREMENTS OF DELIVERED PRODUCT

Concentration:

RM: The protein concentration of each RM lot shall be ± 0.5 mg/mL of the 10 mg/mL target concentration as determined by UV-Vis absorption using an extinction coefficient of 1.42 at A280.

The vial to vial reproducibility shall be reported by performing UV-Vis as described above on ten vials (triplicate measurement on each vial) of each RM lot chosen at random to cover the entire production run. The vial to vial precision shall be no more than 5 % coefficient of variation. Absorbance readings along with standard deviation for concentration determination shall be reported to the COR.

Quantity:

RM: Three individual lots of 10,000 vials, for a total of 30,000 vials (± 1000 vials)

Buffer composition:

USP Grade L-Histidine-HCl 12.5 mmol• L-1

USP Grade L-Histidine 12.5 mmol• L-1 pH 6.0

Water shall be sterile, endotoxin free, protease free.

Homogeneity:

All vials shall be delivered as frozen protein solution. When thawed, the solution shall be in the form of a clear, colorless liquid. No precipitates or turbidity shall be present.

Storage: Temp at -80 degrees C.

V. PROTECTION OF HUMAN SUBJECTS

All material IS NOT INTENDED FOR HUMAN USE and must be labeled as such. This project does not involve human subjects.

VI. DELIVERABLES

1) The Contractor shall provide a progress report every two weeks. The report shall be delivered via e-mail. The Contractor shall provide the reports no later than the following Tuesday for a given 2-week reporting period. Reports shall include a summary of all work completed during the reporting period, any problems or issues and steps taken to resolve them, and the completion date for all required work.

2) Results of Pre-Fill Study and associated data.

Due Date: Not later than 30 days after award

3) The Contractor shall deliver to NIST 30,000 (±1000) vials containing of 800 µL each of the RM (+/-0.5 mg/mL of the 10 mg/mL target concentration).

Due Date: Not later than 60 days after award of contract.

4) The Contractor shall provide a final report with a detailed explanation of the steps involved in material preparation. The explanation shall include all of the following, at a minimum:

-Receipt and Transportation of material to and from NIST.

-Estimated time of each step including estimated temperature of each step;

-Methodology for preparation of dilution buffer.

-Methodology and instrumentation used for dilution, fill, freeze, and storage of RM;

-Containers used for storage of RM including composition, closure system, etc. Specific manufacturer and product number of containers must be provided;

-Methodology and Instrumentation to satisfy analytical testing requirements as outlined in Concentration, section II.

Due Date: Not later than 90 days after award of the contract.

The Government will maintain unlimited data rights to all deliverables in accordance with the clause at 52.227-14, Rights in Data.

VII. PERIOD OF PERFORMANCE

The period of performance shall be 90 days after receipt of 3 X 1L containers of Bulk material.

VIII. GOVERNMENT-FURNISHED PROPERTY, DATA, AND/OR

INFORMATION

NIST will provide a total of three (3) liters of bulk monoclonal antibody. Loss, damage, or vialing of this material in a manner which does not meet or exceed specifications listed herein will have a significant and negative impact on the NIST Biomanufacturing

Program, NIST Healthcare Initiative, and the Quality System of NIST stakeholders.

It is the responsibility of the Contractor to handle this material in a manner that meets or exceeds the specifications stated herein.

NIST will provide the Contractor with labels for secondary containment boxes, if necessary, appropriate for use at the temperature at which NIST will store the material upon receipt.

IX. PERFORMANCE REQUIREMENT SUMMARY

Performance Standard

1) All materials shall be prepared and packaged as described herein and meet all specifications identified herein;

2) All materials must arrive intact and unbroken;

3) All materials must be received frozen;

4) Vials shall be free of stress marks and/or damage;

5) RM shall not undergo more than one thaw/freeze cycles from Bulk container to final container.

Acceptable Quality Level

The material must be suitable for use as a standard. 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 shall correct all deficiencies at no additional cost to the Government.

Monitoring Method

Acceptance analysis of Concentration, Purity and Identity as described below will be performed at NIST using NIST methodology upon delivery of the material. Material delivered to NIST must pass acceptance criteria as stated below.

Identity: An identity test shall be used to verify the identity of the protein is unchanged pre- and post-processing. Intact mass spectrometry will be used to verify the product identity.

Concentration of each RM lot: The protein concentration of each RM lot shall be ± 0.5 mg/mL of the 10 mg/mL target concentration as determined by UV-Vis absorption using an extinction coefficient of 1.42 at A280.

The COR shall analyze the materials upon receipt.