NB645030-25-01699 Statement of Work.pdf

STATEMENT OF WORK

NB645030-25-01699

TITLE: Contract Vialing of Monoclonal Antibody Reference Material

LAB REQUESTING SERVICE: Material Measurement Laboratory, Biomolecular Measurement Division, Biomolecular Structure and Function Group

I. BACKGROUND INFORMATION

The Biomolecular Structure and Function (BSF) group in the Biomolecular Measurement Division of the Materials Measurement Laboratory at the National Institute of Standards and Technology (NIST) (1) advances novel measurement methods and models for the determination and analysis of the structure and function of biological macromolecules, including lipids, DNA, RNA, and proteins and macromolecular complexes and assemblies formed by these molecules; (2) advances methods to determine the physical and chemical factors which determine the specific interactions of macromolecules with cofactors and ligands;

(3) studies the relationships between biomolecule structure, dynamics, function, and energetics using computational, biophysical and biochemical techniques; (4) develops reference databases for these properties; and (5) advances measurement methods for engineering complex biological systems.

The BSF group has an IgG1k monoclonal antibody that was developed into a reference material (NISTmAb, RM 8671) and released in 2016. It also has an associated in-house IgG1k monoclonal antibody (NISTmAb, PS 8670). NISTmAb, RM 8671was released with physicochemical and quantitative data and utilized by the biopharmaceutical community as a system suitability and analytical method development tool. Additionally, NIST is developing a monoclonal antibody expressed from the NISTCHO reference cell line as a NIST Reference Material (NIST RM). The material is intended to be highly representative of CHO-expressed monoclonal antibodies used as biopharmaceuticals. This NIST RM is planned to be a companion molecule to both the NISTmAb (RM 8671) monoclonal antibody reference material (reference product) and the NISTCHO (RM 8675) cell line reference material (non-originator expressing cell line). As such, the BSF group intends to contract vialing each of these monoclonal antibody RMs to produce several lots of both NISTmAb RM 8671 and cNISTmAb RM 8672.

These RM lots will be released with quantitative data traceable to fundamental units of measurement and are expected to be utilized as a system suitability tools in the biopharmaceutical industry.

II. SCOPE OF WORK

NOTE: The protocol outlined in this section is a general outline of work to be performed. Specific details as to proposed equipment, process, and material handling shall be outlined in the Contractors bid.

General Qualifications of the Manufacturer

Contractor shall have experience handling and processing protein therapeutics. The techniques and handling utilized throughout must maintain the sterility of the final product at a level equal to that of the stock material.

Potential contractors shall provide details of the content of a standard data package informing on the vialing process in the proposal.

Potential contactors shall provide details of production timelines and delivery of final product.

Kick-off Meeting

The contractor shall attend a kick-off meeting, via phone or video conference, no later than 14 days after the award of the contract. The NIST subject matter expert (SME), contract officer’s representative (COR) and other authorized NIST personnel shall be in attendance. The contractor’s team must be present, and the meeting will be utilized to review all contract requirements and deliverables.

Status Meetings

The contractor shall participate in status meetings on a reoccurring basis (minimum monthly but to be decided between contractor and SME and COR) to obtain an update on the intended delivery data of the Government furnished product.

During these meetings, the contractor shall advise the SME and COR of any anticipated problems or issues that may have arisen or may further delay work upon receipt of the product. Status meetings shall be conducted via conference call. The contractor and NIST SME and COR shall establish a meeting schedule.

Part A. Monoclonal Antibody A Vialing (NISTmAb RM 8670/8671)

1. One 1L container labeled as PS 8670 Humanized Monoclonal Antibody and Three 1L containers labeled as RM 8671 Humanized Monoclonal Antibody homogenized bulk will be transferred to the contractor under frozen (dry ice) conditions, not to exceed -20 degrees C and must be stored at -80 degrees C upon arrival and until thaw.

2. Each individual 1L bulk container shall be thawed at no greater than 25 degrees C (room temperature) and the material shall not exceed a temperature above 30 degrees C at any time. A maximum of one freeze/thaw cycle shall be used for generation of vialed material.

3. Each 1L container shall be individually diluted to 10 mg/mL in 12.5 mM L-histidine, 12.5mM L-histidine hydrochloride pH 6.0. Both materials must be USP grade.

4. Each individual diluted homogenized bulk container will be aliquoted into 10,000 (±300) units of 800 µL each, for a total of 40,000 (±1000) units of 800 µL (± 25 µL) each.

5. Containers shall be immediately frozen at -80 degrees C.

6. The time from thaw to refreeze in final vial should be less than 48 hours, and no additional freeze/thaw may be performed. The material shall not exceed a temperature of 30 degrees C.

7. The container used should be compatible with -80°C storage, have a sealed lid (not a vial intended for clinical use). The closure shall be screw-top containing 800 (±50) μL of material per vial. Thermo matrix vial and rack system (Product number 3741) must be used.

8. The protein concentration should 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 mL · mg−1 · cm−1 at A280. The vial to vial reproducibility should be reported by performing UV-Vis on ten vials of the vialed material chosen at random. 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.

9. The purity of the monomeric molecule shall be ≥95% and demonstrated through high-performance size exclusion chromatography. Contractor must provide testing on at least one sample of each lot of 10,000 vials.

10. Documentation will be recorded to trace vials originating from each specific 1L container. Vial to vial reproducibility of both homogeneity and volume are of critical importance

11. Each container shall be labeled with a label provided by NIST. Each box of 96 containers shall be labeled with a label provided by NIST.

12. All vials shall be delivered as frozen protein solution. When thawed, the solution should be in the form of a clear, colorless liquid. No precipitates or turbidity shall be present. Vials shall be free of damage including striations, cracks, or visible leakage.

13. 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:

-Transportation of material to and from NIST.

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

-Methodology and instrumentation used for dilution, fill, freeze, and storage -Methodology and instrumentation used for analytical testing and product specifications

Deliverable 1: 30,000 labeled vials of 10 mg/mL NISTmAb RM 8671 monoclonal antibody separated into 3 lots of 10,000 vials each.

Deliverable 2: 10,000 labeled vials of 10 mg/mL NISTmAb PS 8670 monoclonal antibody in one lot of 10,000 vials each.

Deliverable 3: Copies of reports and documentation for all steps of material preparation as outlined in step 13 above.

Part B. Monoclonal Antibody B Vialing (cNISTmAb RM 8672)

1. Three 1L containers labeled as RM 8672 cNISTmAb, Monoclonal Antibody homogenized bulk will be transferred to the contractor under frozen (dry ice) conditions, not to exceed -20 degrees C and must be stored at -80 degrees C upon arrival and until thaw.

2. Each individual 1L homogenized bulk container shall be thawed at no greater than 25 degrees C (room temperature) and the material shall not exceed a temperature above 30 degrees C at any time. A maximum of one freeze/thaw cycle shall be used for generation of vialed material.

3. Each 1L container shall be individually diluted to 10 mg/mL in 12.5 mM L-histidine, 12.5mM L-histidine hydrochloride pH 6.0. Both materials must be USP grade.

4. Each individual diluted homogenized bulk container will be aliquoted into 10,000 (±300) units of 800 µL each, for a total of 30,000 (±1000) units of 800 µL (± 25 µL) each.

5. Containers shall be immediately frozen at -80 degrees C.

6. The time from thaw to refreeze in final vial should be less than 48 hours, and no additional freeze/thaw may be performed. The material shall not exceed a temperature of 30 degrees C.

7. The container used should be compatible with -80°C storage, have a sealed lid (not a vial intended for clinical use). The closure shall be screw-top containing 800 (±50) μL of material per vial. Thermo matrix vial and rack system (Product number 3741) must be used.

8. The protein concentration should 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 mL · mg−1 · cm−1 at A280. The vial to vial reproducibility should be reported by performing UV-Vis on ten vials of the vialed material chosen at random. 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.

9. The purity of the monomeric molecule shall be ≥95% and demonstrated through high-performance size exclusion chromatography. Contractor must provide testing on at least one sample of each lot of 10,000 vials.

10. Documentation will be recorded to trace vials originating from each specific homogenized bulk container. Vial to vial reproducibility of both homogeneity and volume are of critical importance

11. Each container shall be labeled with a label provided by NIST. Each box of 96 containers shall be labeled with a label provided by NIST.

12. All vials shall be delivered as frozen protein solution. When thawed, the solution should be in the form of a clear, colorless liquid. No precipitates or turbidity shall be present. Vials shall be free of damage including striations, cracks, or visible leakage.

13. 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:

-Transportation of material to and from NIST.

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

-Methodology and instrumentation used for dilution, fill, freeze, and storage -Methodology and instrumentation used for analytical testing and product specifications

Deliverable 1: 30,000 labeled vials of 10 mg/mL monoclonal antibody separated into 3 lots of 10,000 vials each.

Deliverable 2: Copies of reports and documentation for all steps of material preparation as outlined in step 13 above.

NIST SME and NIST authorized personnel shall visit the contractor’s site after award of contract and prior or at the start of production to ensure product/process conformance.

III. Final Product SPECIFICATIONS

Requirements for the Performance of the Scope of Work

1. The Contractor shall deliver an electronic PDF document to the COR/SME a compiled report of material preparation

Acceptance by NIST of the monoclonal antibody vialed lots

2. Material shall remain and arrive frozen (≤ -80 °C)

3. The protein concentration should be ± 0.5 mg/mL of the 10 mg/mL target concentration as demonstrated by UV-Vis absorption.

4. The purity of the monomeric molecule shall be ≥95% and demonstrated through high-performance size exclusion chromatography.

Transfer of Materials and Documentation from the Contractor to NIST

5. The Contractor shall arrange for appropriate transportation and/or shipping of the labeled monoclonal antibody containers, which maintains the units under appropriate dry ice storage conditions (≤ -80 °C), to the NIST Office of Reference Materials (ORM) or other NIST provided location. The Contractor will maintain responsibility for the quality of the monoclonal antibody units until they are officially received by NIST ORM.

6. The Contractor shall deliver, as (an) electronic PDF document(s), to the COR a compiled report of analysis of the monoclonal antibody containers.

IV. PERIOD OF PERFORMANCE

The period of performance shall be 18 months from award of this requirement.

V. PLACE OF PERFORMANCE

All work shall be completed at the Contractor’s facility. All homogenized bulk monoclonal antibody deliverable units will be transferred to the NIST Office of Reference Materials storage facility with mailing/delivery address of Office of Research Materials, NIST, 100 Bureau Drive, Gaithersburg, MD

20899. Normal duty hours are Monday through Friday, 8:30 a.m. to 5:00 p.m. with the exception of Federal holidays.

VI. GOVERNMENT FURNISHED PROPERTY

The NIST Biomolecular Structure and Function Group will provide the contractor with the Homogenized bulk monoclonal antibody 1L units as described in the specifications. The COR will provide an electronic document, the design of the labels to be applied to the homogenized bulk units as described in the Specifications.

VII. DELIVERABLES

Description Quantity Due Date

Progress reports delivered every two (2) weeks. Per contract

Part A: 30,000 labeled vials of 10 mg/mL RM 8671 monoclonal antibody separated into three lots of 10,000 vials each.

30,000 Per contract and within 90 days after shipment of material to contractor.

Part A: 10,000 labeled vials of 10 mg/mL PS 8670 monoclonal antibody 10,000 Per contract and within 90 days after shipment of material to contractor.

Part A: Copies of reports and documentation for all steps of material preparation (electronic pdf document)

1 Per contract and within 90 days after shipment of material to contractor.

Part B: 30,000 labeled vials of 10 mg/mL RM 8672 monoclonal antibody separated into three lots of 10,000 vials each.

30,000 Per contract and within 90 days after shipment of material to contractor.

Part B: Copies of reports and documentation for all steps of material preparation (electronic pdf document)

1 Per contract and within 90 days after shipment of material to contractor.

VIII. ACCEPTANCE REQUIREMENT SUMMARY

1. Monoclonal antibody vialing report of analysis will be accepted once it has been received by the COR and/or SME and reviewed by NIST BSF group chemists to verify the findings listed. COR/SME agrees that this review shall be completed within 15 working days of receiving the monoclonal antibody vialing report of analysis. COR/SME reserves the right to address scientific or quality questions to appropriate and authorized quality and/or scientific Contractor representatives, as described in the Contractor’s Quality Manual, Quality Plan or Technical Procedures and to pause the 15 working day review period while awaiting Contractor response to such questions.

IX. RISK ASSESSMENT

The HSPD-12 Security Risk Level assigned to this Task Order is: None

X. GENERAL INFORMATION

Safety: The Contractor employee shall be responsible for knowing and complying with NIST installation safety prevention regulations (http://www-i.nist.gov/mml/safety/policies/index.htm.) Such regulations include, but are not limited to, general safety, fire prevention, and waste disposal.

Patent Rights: The Government retains a Government use license to all inventions arising from this work.

Security: NIST and the NIST/IBBR maintain restricted campuses. An identification badge is required for access for entry into buildings and may be obtained from the security desk upon arrival.

Identification Badges: Contractor employees shall comply with NIST identification and access requirements. The Contractor employee is responsible for absences due to expired identification and access documents. Each Contractor employee entering the NIST Campus shall wear a visible identification badge provided by the NIST Office of Security. The badge must show the full name, title, and if required by NIST, the words “Contractor” in front. The Contractor employee shall turn in the NIST identification badge to the SME, COR, or Contracting Officer (CO) upon termination of their services under this contract.

Media Inquiries: The Contractor employee shall not respond to any media inquiries. Any inquiries from the media shall be immediately relayed to the SME, COR, and/or CO. There shall be no interviews, comments, or any other response without the knowledge and approval of the NIST Director.

http://www-i.nist.gov/mml/safety/policies/index.htm