MODIFICATION
A -- RECOVERY-Development of rhIL-15 (E. coli) cGMP Lyophilized Clinical Product
- Notice Date
- 3/23/2010
- Notice Type
- Modification/Amendment
- 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
- ST10-1033
- Archive Date
- 5/8/2010
- Point of Contact
- Howard R. Souder, Jr., Phone: 3018465096
- E-Mail Address
-
souderhr@mail.nih.gov
(souderhr@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- Please download the attached document for specific instructions and more details. Failure by any offeror to follow the instructions detailed will be interpreted as non-responsive, and will not be considered by SAIC-F. Project Title: RECOVERY - Development of rhIL-15 (E. coli) cGMP Lyophilized Clinical Product Introduction IL-15 is a 14 - 15 kDa member of the 4 -helix bundle family of cytokines. It shares a number of biological activities with IL-2, including stimulation of the proliferation of activated CD4+, CD8+ and gamma-delta subsets of T cells. Recombinant human IL-15 (rhIL-15) expressed in E. coli was manufactured by the BDP under cGMP to yield active rhIL-15 for cancer therapy adjuvant vaccines in human clinical trials. The purpose of this document is to describe the requirements for the development of a cGMP lyophilized product for future clinical studies. Background A previous study (data to be provided to the selected Subcontractor) demonstrated that rhIL-15 formulated in a Citrate, Mannitol, Sucrose, Tween-80 buffer was stable and retained its potency following lyophilization. Preliminary assessment of lyophilization parameters resulted in a uniform cake formation with minimal cracks. An ideal moisture value of < 1% was not attained and additional cycle development studies are needed before GMP activities are initiated. Project Management Plan The Subcontractor will be required to submit a Project Management Plan (PMP) describing the means of accomplishing the Project Tasks. The PMP will include milestones to meet the Project Deliverables. Milestones will include but are not limited to 1) completion of the R&D lyo studies and 2) completion of cGMP production. Risk Management Plan The PMP will include a risk management plan (RMP) to identify potential technical problems that might arise during the course of work. The Subcontractor shall suggest solutions or alternative back up plans to address these potential problems. Reports and Meetings 1. Project meetings will occur bi-weekly or as required by the SAIC-F Contracting Officer's Technical Representative (SAIC-F COTR). 2. Subcontractor will submit monthly technical and financial status reports to the SAIC-F COTR and SAIC-F Subcontract Specialist. 3. Reports will include lyophilization cycle profiles, technology transfer report, certificates of analysis and a manufacturing report for the GMP process that will support clinical use of the resulting GMP materials. Project Tasks: 1. Develop a lyophilization cycle based on the formulation previously evaluated by SAIC-F using the vendor's equipment that is translatable to cGMP production of 4000 vials with a fill concentration of 50ug rhIL-15/vial. 2. Recombinant human IL-15 will be formulated into the Citrate, Mannitol, Sucrose, Tween-80 buffer and provided to the vendor for Lyophilization-cycle development at a small scale of 10 - 20 mg; with an expected net yield of 200 - 400 vials 50ug/vial reconstituted to 1 ml). The components for container/closure are listed in Appendix A of this document. 3. The lyophilized vials will be evaluated for: a. Reconstitution time b. Acceptable cake appearance c. Osmolality and visual appearance upon reconstitution to be free of particulates 4. Upon satisfactory completion of Task 3, samples will be provided to SAIC-F for analysis by (i) Potency, (ii) RP-HPLC, (iii) HPLC-SEC/LS, (iv) Protein Assay (Coomassie), (v) Moisture Content (Karl Fischer), (vi) Opalescence, (vii) Sterility, (viii) Endotoxin content. 5. Task 2 will be repeated with 200 mg rhIL-15 lyophilized to reproduce the small scale study results with an expected net yield of 4000 vials at 50ug/vial. 6. Criteria for deliverables shall include a lyophilization cycle of rhIL-15 that results in maintenance of the characteristics of the original dosage form upon reconstitution, including a. Solution properties showing no particulates upon reconstitution b. Stability/potency of IL-15 as shown by BDP analyses, c. Structure or conformation of rhIL-15 as defined by item 4 above and d. Particle-size distribution of suspension, with an overall residual moisture content of ≤ 1%. 7. Preparation of cGMP batch production documentation. 8. Receipt and controlled storage of cGMP bulk rhIL-15 from the BDP. 9. Completion of aseptic vialing and lyophilization for rhIL-15 to net at least 4000 vials at 50 ug/vial. 10. Completion of all required CMC documentation of the lyophilized clinical product to enable an IND filing. This shall include regulatory documentation to cross-reference or submit the necessary Subcontractor facility, operation and quality system information for an initial IND filing. Deliverables and Acceptance Criteria Criteria for deliverables shall consist of a lyophilization cycle of rhIL-15 that results in maintenance of the characteristics of the original dosage form upon reconstitution, including but not limited to: a. Solution properties showing no particulates upon reconstitution b. Stability/potency of IL-15 as shown by BDP analysis, c. Structure or conformation of rhIL-15 and d. Particle-size distribution of suspension, with an overall residual moisture content of ≤ 1%. Final inspection and acceptance of all work performed, reports and other deliverables will be approved by the SAIC-F COTR. All cGMP deliverables are also subject to the final review of documentation and release by the SAIC-F Quality Assurance department. Period of Performance The period of performance is 12 months from the date of award of the Subcontract. Other Requirements 1. Facility audit for technical capability and cGMP compliance must be completed and found to be satisfactory to the SAIC-F Quality Assurance team prior to a Subcontract being awarded by the SAIC-F Contracting Officer. 2. Execution of a Quality Agreement prior to subcontract award must be made between the potential Subcontractor and SAIC-F. A template of the agreement is available at http://web.ncifcrf.gov/research/bdp/ (1- Click on the Request Documents button; 2 - search using key words "Quality Agreement" & click on the search button; 3 - then click on the box "Quality Systems -Auditing/Oversight of Manufacturing Operations & click the Add Documents button; 4 - fill out the remaining information & click the 508 Compliance box.). A copy of the Quality Agreement should be delivered within 2 business days of the request. 3. This effort is to be solely funded by the American Recovery and Reinvestment Act (ARRA) Funds. The Offeror(s) with the ARRA-funded projects will be subjected to all the ARRA-mandated activities and reporting requirements as applicable. Tasks for this effort must be performed in accordance with the ARRA rules and regulations.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/FCRF/ST10-1033/listing.html)
- Place of Performance
- Address: Potential Offeror's location - TBD, United States
- Record
- SN02100527-W 20100325/100324000140-b1c1f398c2022e412066f200af9f8539 (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's FBO Daily Index Page |