Biological Process Development Facility completes its first cGMP production run in newly commissioned facility
The University of Nebraska-Lincoln Biological Process Development Facility (BPDF) achieved a major milestone by producing its first cGMP batch of bulk drug substance in the recently commissioned facility. At the request of the Mintaka Foundation (Geneva, Switzerland), the BPDF developed and scaled-up a process for cGMP production and purification of 5P12-Rantes, a microbicide effective in preventing transmission of HIV in vitro and SIV in vivo in non-human primate studies. The cGMP product will be shipped to the Mintaka Foundation for formulation as a vaginal cream for use in Phase I clinical trials.
Completed in 2009, construction of this state-of-the-art expansion provides the BPDF with a second cGMP suite that makes an additional 1300 square feet of production and support space available. The newly commissioned space complements existing upstream and downstream development laboratories as well as a smaller scale cGMP production area. This new suite features clean staging, buffer preparation, fermentation, and product purification rooms, and a dirty staging area. A QC Microbiology laboratory adjoins the suite.
The heart of the Class 100,000 Fermentation laboratory is a 200 L Bioengineering fermentor with a working volume of ~150 L. A Westfalia CSC-20 Disk-Stack Centrifuge, a Niro NS3006H Homogenizer, a Microfluidics M110-EH Microfluidizer, two Model 50 TFF Membrane Systems, and a Sani-Matic CIP skid complete the inventory of major equipment available in the Fermentation laboratory.
The Purification laboratory is Class 10,000 and equipped with a walk-in cold room, an NC-SRT Chromatography skid, NC-SRT Model 10 and Model 5 TFF Skids, and a wide range of Chromatography columns.
Newly installed and qualified utilities enable the BPDF to be relatively self-contained. A continuous water deionization system coupled with a pure steam generator and condenser, an 1100 gallon storage tank, and hot and ambient distribution loops provide Water for Injection (WFI) throughout the facility. An oil-free dry air system, additional air handlers, a 170 ton chiller, an uninterruptable power supply, a diesel backup generator, and “kill” and neutralization tanks for outgoing waste complete the list of major utility improvements.
Successful scale-up and production of 5P12-Rantes, the first cGMP BDS produced in the new facility, caps a multi-year campaign comprised of development and qualification of analytical methods, optimization of fermentation, development of purification methods, process scale-up, production of cGMP product for Phase I clinical trials, and successful technology transfer to a large-scale manufacturing facility.
Key to the success of the GMP production run was rigorous Quality Assurance (QA) and Quality Control (QC) programs. The QA staff reviewed all cGMP activities, ensuring that all regulatory requirements for the production, handling, and storage of this Active Pharmaceutical Ingredient were met. The QC laboratory provided microbiological services, including environmental monitoring, as well as chemical characterization and analytical release testing.
Robin Offord, Mintaka’s executive director, said, "Properly validated GMP production is key to Mintaka’s plans to empower women and girls in developing countries with a means of protection from HIV/AIDS. We are happy with the robust nature of the process developed at the BPDF. Already, we have successfully transferred the technology to our collaborating institution in South Africa with excellent pilot scale results.”
Founded in 1990, the BPDF has developed processes and produced products for a range of private and public sector clients, including projects to produce vaccines against several bioterrorism agents.