SOLICITATION NOTICE
A -- Humanized Monoclonal Antibody HB22.7 Cell Line Development - S09-162 RFP Cover Page
- Notice Date
- 6/3/2009
- Notice Type
- Combined Synopsis/Solicitation
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bldg 427, Room 12, Frederick, Maryland, 21702
- ZIP Code
- 21702
- Solicitation Number
- S09-162
- Archive Date
- 7/31/2009
- Point of Contact
- Howard Souder, Jr., Phone: 301-846-5096
- E-Mail Address
-
souderhr@mail.nih.gov
(souderhr@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- This is the Subcontract Agreement with the SOW contained in Attachment 1 of the document. This document must accompany the RFP Cover Page with any Offerors' submission. Cover Page to RFP with Offeror Instructions. This page must be signed and submitted by any/all Offerors' official who has the authority to obligate their company. Humanized Monoclonal Antibody HB22.7 Cell Line Development 1. Task Objectives 1.1. Develop a mammalian cell line expressing a therapeutic monoclonal antibody HB22.7 (anti-CD22 antibody) for clinical manufacturing. 1.2. Demonstrate a minimum cell line productivity of 10pg/cell/day using a batch, fed-batch, or perfusion process at 1L scale. 1.3. Demonstrate stability of the cell lines in cell growth and product expression for a minimum of 60 generations. 2. Work to be performed 2.1. Material 2.1.1 Product Gene and Product Expression Regulation 2.1.1.1. SAIC-F will provide a full length gene sequence of the construct containing the humanized monoclonal antibody HB22.7 and necessary components for transfection and expression. 2.1.1.2. SAIC-F will provide the construct containing the humanized monoclonal antibody HB22.7 and necessary components for transfection and expression. 2.1.1.3. The Subcontractor may provide recommendations towards optimum expression including expression strategy, transfection method, expression promoter, lead sequence, codon optimization, selection and screening method, and other expression regulation components. The Subcontractor may provide rationale for the modification of the vector. The construct designing will be finalized upon approval of SAIC-F. 2.1.2. Cell Line(s) and Cell Culture Medium 2.1.2.1. A mammalian cell line(s) such as Chinese Hamster Ovary (CHO) suspension cell, or dihydrofolate reductase-deficient (dhfr-) CHO DG44 or DUXB11 or mouse myeloma NS0 are the planned host cell lines for the project. The cell line(s) is suspension. SAIC-F may provide qualified CHOs and/or CHO DG44 cell line. If the Subcontractor prefers to use other cell line(s) such as NS0 or CHO DUXB11, Subcontractor will provide the cell line(s) with clear history and characterization. 2.1.2.2. A defined mammalian cell culture medium will be used to culture the cells. Either commercial sources or vendor developed medium can be used to culture the cell line. However, commercial sources medium with containing non-animal sources components and non-protein is preferred. 2.2. Milestones with Procedure and Activities 2.2.1. Milestone 1. Plasmid Construction 2.2.1.1. Using a selection system such as glutamine synthetase (GS) or dihydrofolate reductase-deficient (dhfr-) or other selection for high producers in the expression system is highly preferred. 2.2.1.2. Conduct the plasmid(s) designing and construction, if it is necessary. Modification of the construct is upon approval from SAIC-F. 2.2.1.3. Conduct preparation of the plasmid(s) provided by SAIC-F or modified and constructed by the vendor at sufficient quantity and high quality of low endotoxin for plasmid transfection to the cell line(s) such as NS0 or CHOs, or CHO DG 44 or CHO DUXB11. 2.2.1.4. Conduct full length sequencing of the plasmid. 2.2.2. Milestone 2. Plasmid Transfection and Stable Pool Selection 2.2.2.1. Conduct transfection of the plasmid to the cell line(s) such as NS0 or CHOs, or CHO DG 44 or CHO DUXB11. Conduct selection of stable transfection pool based on selection mechanism. 2.2.2.2. Reasonable transfection efficiency is expected through optimization of transfection methods, reagents, DNA/host cell ratio, ratio of plasmids coding light and heavy chains if it applicable. 2.2.2.3. Collect a stable transfected pool(s) of the cells for making stable pool frozen stock. 2.2.2.4. Stable sub-pools may be generated with a reasonable viable cell counts. 2.2.2.5. Supernatant from stable pool and stable sub-pools is measured for product titer through ELISA, and/or SDS-PAGE, and/or Western Blotting. 2.2.3. Milestone 3. Cloning and Cell Line Development 2.2.3.1. Conduct screening high producers from the stable pool or stable sub-pools and select at least 1000 clones from the pool(s) of cells through cloning and amplification procedures using ELISA method or other high throughput methods. 2.2.3.2. If CHO dhfr- expression system is used, conduct measurement of product HB22.7 expression in comparison to cell resistance to MTX concentration. If the product expression level is associated with MTX resistance level, selection of clones at high MTX concentration up to at least 0.5 uM of MTX in culture medium is preferred. Otherwise, use a MTX concentration at which productivity is maximized. 2.2.3.3. Five or more single clones are selected through cloning procedure to provide for further cell line characterization and process development. 2.2.3.4. Conduct initial cell growth study to demonstrate that the high producers will be able to reach cell density at 5 x 106 cells/ml with ~5 days batch culture procedure or 8 x 106 cells/ml with ~10 days fed-batch culture procedure. Productivity at least reaches at 10 pcd or 250mg/L for batch culture and 400mg/L for fed-batch culture. 2.2.4. Milestone 4. Cell Line Characterization 2.2.4.1. Perform cell line stability study for at least 20 passages or 60 generations with productivity variation not greater than 15% of the accession bank productivity without selection pressure. 2.2.4.2. It is preferred to characterize coding sequence integration site in chromosome of the cell line and copy number. 2.2.4.3. It is preferred to quantify message RNAs of the heavy and light chains with a time course to cover regular production duration. 2.2.4.4. If CHO dhfr- expression system is used, conduct a stability study of expression of the product in a medium without selection pressure MTX. 2.2.4.5. If glutamine synthetase (GS) selection system is used, characterization of integration of the coding sequence in chromosome would be preferred for the high producer(s). 2.2.5. Milestone 5. Production Process Development 2.2.5.1. Perform medium screening in shake flask to select a suitable medium determined by cell growth and product expression. 2.2.5.2. Perform cell culture development at 1-5L working volume to determine process parameters, basal medium metabolic profile, viable cell counts time course, and supplemental feeding strategy. 2.2.5.3. Perform three 5L pilot development runs from seed expansion, cell culture, expression, harvest and protein A chromatography isolation. The material recovered will be delivered to SAIC-F for process and product assessment as well as downstream process development. 2.3. Quality Control 2.3.1. Cell Line(s) 2.3.1.1. The proposed host cell line(s) are mammalian cell line(s) such as mouse myeloma NS0, suspension CHO, CHO DG44 or DUXB11 or others. SAIC-F will provide CHOs and/or CHO DG44 cell line(s). If the Subcontractor prefers to use other line(s), such as DUXB11, a clear cell line history and qualification data sheet should be available. 2.3.1.2. Critical components including antibody coding regions, promoter regions, expression regulation elements are required to be sequenced with the final cloned cell line(s). 2.3.1.3. Provide procedures for sequencing of the promoter and transgene coding region in the selected high producer. Messenger RNA sequence and information regarding the location of the transgene(s) in the host cell is preferred but not required. 2.3.1.4. Gene copy number information of the clone(s) is required. 2.3.1.5. Providing information on ratio of heavy and light chains at mRNA and protein levels is preferred. 2.4. Documentation and Technical Report 2.4.1. A traceable history of the host cell used in the study is required. 2.4.2. A clear history of the plasmid vector used in the study is required, if there will be a modification associated with the plasmid. 2.4.3. A cell culture medium that is GMP compatible is required. 2.4.4. Generation of a cell line expressing the product is well documented. 2.4.5. All the sequence information of the plasmid and cell line must be made available in standard electronic formats. 2.4.6. A complete technology transfer technical report is required. A sample table of contents for the standard technical report is to be included in the proposal response. 2.4.7. A description of any licenses that will be required and/or freedom of action to deliver the service to SAIC-F without encumbrances for SAIC-F and the NCI. 3. Requirement of Vendor 3.1. Materials 3.1.1. Complete growth cell culture media should be filter sterilized following formulation and used with twenty eight (28) days of sterilization in storage of 40C. All culture medium used will be sterile and traceable, which is documented. 3.1.2. Cell line-contact containers and supplies are purchased pre-sterilized and sterilized on-site. 3.1.3. Preparation of medium and other reagent in the project must be fully documented. Documentation including supplier, catalog number, lot number, and expiration date (if any) must be maintained for the raw material used. 3.1.4. The unnecessary use of animal-derived materials should be avoided. Raw materials of animal origin must not be sourced from a TSE-affected country (9 CFR 94.18) and must be tested by the supplier to be free of adventitious agents. Copies of Certificates of Analysis (COA) and Certificates of Origin (COO) any animal-derived materials used will be provided to SAIC-F. 3.2. Laboratory Space and Equipment 3.2.1. Laboratory areas must be clean. Measures will be taken to segregate and limit use of laboratory areas during the performance of laboratory activities for this project. Appropriately maintained equipment must be used. Shared equipment used must be cleaned prior to its use; documentation of the cleaning is required. 3.3. Record Keeping 3.3.1. Activities must be adequately documented in laboratory notebooks for all the activities. 3.4. SOPs and Reference 3.4.1. The following SOPs are the property of SAIC-F and are provided to Subcontractor solely as a guide to the US Food and Drug Administration's (FDA) Good Laboratory Practice (GLP) Regulations. Notwithstanding the FDA's GLP regulations, the Subcontractor shall perform the work to the standard described in the section headed "Requirements of Subcontractor" above. SOPs may not be distributed to any other parties without written consent of the SAIC-F Contracting Officer. a. BDP SOP 21408: Laboratory Notebook Control and Use b. BDP SOP 21409: Good Documentation Practices 3.5. Program Milestones 3.5.1. SAIC-F and Subcontractor will establish an expected period of performance for each milestone. Milestone 1. Plasmid Construction [Section 2.2.1]. Milestone 2. Plasmid Transfection and Stable Pool Selection [Section 2.2.2]. Milestone 3. Cloning and Cell Line Development [Section 2.2.3]. Milestone 4. Cell Line Characterization [Section 2.2.4]. Milestone 5. Production Process Development [Section 2.2.5]. Note: Subcontractor shall not proceed with the next Milestone until written authorization is provided by the SAIC-F Technical Representative. 4. Procedure Acceptance Criteria The procedure and activities in Section 2.2. will be considered acceptable if: 4.1. Cell culture is in a suspension condition. 4.2. Viable cell density to reach 5 x 106 cells/mL. 4.3. Cell doubling time in the range of 15-35 hours. 4.4. Viability of culture greater than 90% for 5 days for a batch culture greater than 50% for a fed-batch culture at harvest. 4.5. More than 5 days for batch process or more than 9 days for fed-batch process. 4.6. Productivity of greater than 10pg/cell/day is required. For a minimum 5 days culture with 5 x 106 cells/ml cell density in the peak, a production titer is expected to be 250mg/L or greater. For a 9 days fed-batch culture, a production titer is expected to be ~450mg/L (monomer). 4.7. The productivity and product quality are stable within 15% variation for at least 20 passages or 60 generations under no selection pressure. 4.8. Productivity and product quality are measured through analytical protein A chromatography followed by HPLC-SEC. 4.9. Antibody monomer is more than 80% purity in product monomer content after protein A column purification. 5. Meetings 5.1. It is anticipated that meetings with the Subcontractor will occur as needed to keep the SAIC-F Technical Representative informed regarding the progress of the project. In the absence of formal meetings, contact with the contractor will occur via phone, fax, or electronic mail. Any travel shall be subject to written approval prior to any arrangements being made, and are subject to the Federal Travel Regulations (FTR). ARTICLE 2. REPORTING REQUIREMENTS In addition to those reports required, the Subcontractor shall prepare and submit the following reports in the manner stated below: 1. Monthly Progress Reports 1.1. The Subcontractor will submit to SAIC-F monthly technical and business reports. The monthly technical report is to be provided by the fifth (5th) business day of each month and the monthly business report is to be included with the monthly invoice. These reports shall contain detailed information of the work performed during the calendar month or invoice period as appropriate. The reports may be combined into a single document assuming all pertinent information is included for both technical and business aspects. The monthly technical reports shall contain the following information: • Subcontractor name and address • Name of person submitting the report • SAIC-F Subcontract Agreement number • Summary of activities completed within the Statement of Work including procedures, results, conclusions and references, if applicable • Assessment of schedule status and risk statement pertaining to delay in progress; include an activity plan for the next 30 day period • Request for scope modification, if required • Key communications conducted during the reporting period The monthly business report shall contain the following information: • Subcontractor name and address • Name of person submitting the report • SAIC-F Subcontract Agreement number • Signature of Subcontractor's Authorized Representative indicating adherence to all compliance requirements • Total percentage of Funds expended to date, including total actual costs accumulated by category expended to date. • Total percentage of Work competed to date • If percentage of funds expended to date do not match percentage of work completed, provide explanation and what is needed to bring work and funding in balance. • Any pertinent notation pertaining to administrative procedures and activities Note: Delay in submission of monthly progress reports will delay payment of invoices. 2. Final Report 2.1. Subcontractor shall submit a Final Report within 60 days from the last day of the subcontract period containing the following: Title page to include the following information: a) Subcontract title and Subcontract Agreement number b) Period of performance being reported c) Subcontractor's name and address d) Date of submission Additionally, the final report shall include: 1) An introduction describing the purpose and scope of the subcontract effort 2) A summary of the milestone progression and completion including pertinent data to present significant results achieved and a scientific evaluation of the data. Note: Delay in submission of the Final Report will delay payment of invoices.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/FCRF/S09-162/listing.html)
- Place of Performance
- Address: Vendor's location, United States
- Record
- SN01834778-W 20090605/090603235219-37b04a5cccc2898f9ec0f8b9ad9aa0b7 (fbodaily.com)
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