Center for Biocatalysis and Bioprocessing, University of Iowa
The Center for Biocatalysis and Bioprocessing (CBB) at the University of Iowa operates a world-class microbial fermentation and bioprocessing facility. This facility specializes in the production of novel bio-based chemicals, with an emphasis on recombinant proteins of commercial value. Since its inception in 1995, this core facility has served as either a contract manufacturing organization (CMO) or contract research organization (CRO) for approximately 300 clients ranging in size from large multi-national corporations to early-stage startup companies. Other clients include universities, government agencies, and foundations. Geographically, our clients range from New Zealand to Germany; while most are located in the biotech belts on both the east and west coasts of the United States.
CBB’s biomanufacturing facility is operated by a dedicated professional staff with experience in upstream fermentation, downstream bioprocessing, process optimization, and scale-up for commercial manufacturing. A wide range of upstream and downstream services is available to clients, ranging from cloning to scale-up to product purification and analytical characterization. Five stage scale-up (ranging from shake flask to 1000-L) is commonly used to establish manufacturing conditions. Large-scale purification systems are available based on both chromatographic and non-chromatographic methods.
This CBB core facility operates two separate manufacturing suites – one for research process and development (RPD) and one for cGMP manufacturing. The RPD suite specializes in bench to pilot-scale process development. The cGMP suite is capable of manufacturing proteins, and other bio-based chemicals, under strict quality control conditions suitable for Phase I clinical testing of investigational new drug. In some cases, our RPD suite is used to scale-up and optimize both upstream and downstream bioprocess before moving seamlessly into the cGMP suite for final manufacturing.
Technology Transfer: Contract work performed within the CBB fermentation facility supports client specific objectives. Typically, all work is covered under a Master Service Agreement that details specifications for the scale-up, optimization, and manufacturing arrangements. In general, CMO operations make no claim on intellectual property for process development efforts and clients retain ownership of all processes.
Resources – RPD Suite: The RPD suite occupies 13,000-ft2 of laboratory space dedicated to upstream and downstream bioprocessing unit operations. The upstream laboratory consists of 16 fermentors with capacities of 2-, 10-, 15-, 30-, 75- 100- and 1,000-liters. Each fermentor is computer-controlled and continuously monitored to provide real-time process information. A complementary array of downstream bioprocessing equipment and instrumentation is available for state-of-the-art purification, analytical characterization, and formulation control of the final product. Novel purification methods are developed based on an array of possible chromatographic techniques, including affinity, size-exclusion, or ion exchange separations. Alternatively, selective biotransformation processes based on engineered cells or enzymes or protein conjugation reactions can be performed to meet client-specific needs.
Although process scale-up of both upstream and downstream processes is our specialty, many clients use our RPD suite to manufacture tens of kilograms of product per year for commerce. Others contract with us to produce lesser amounts of protein-reagents used in-house for proprietary manufacturing processes.
Resources – cGMP Suite: CBB’s cGMP biomanufacturing suite occupies XXXX square-feet of dedicated laboratory space for cGMP fermentations and an additional 7,000 square-feet of laboratory space dedicated to downstream unit operations. The fermentation suite houses three separate fermenters with volumes of 30, 100, and 300 liters. The downstream processing suite is built around two independent ISO 7 clean rooms and two cold room units. Both the upstream and downstream cGMP laboratories contain scalable processing equipment essentially identical to our RPD facilities, thereby facilitating seamless transfer of processes from RPD to cGMP manufacturing. Examples of redundant equipment between the RPD and cGMP suites include a continuous LAPX 404 centrifuge and high-capacity ÄKTA protein purification systems.
To date, our cGMP operations has successfully completed 70 cGMP manufacturing campaigns for the production of eight biologics, including 3 oral drugs, 5 vaccines, and 2 GMP-grade reagents.
cGMP Quality Assurance: A dedicated cGMP Quality Team works to establish and maintain cGMP manufacturing standards that follow the Guidance for Industry cGMP for Phase 1 Investigational Drugs issued by the FDA in July 2008. Under these guidelines, manufacturing protocols are created for investigational new drug applications and sufficient quantities of cGMP-quality material can be produced for Phase 1 clinical testing.
For each cGMP project, a Quality Service Agreement (QSA) is established with the objective of delivering a product that meets the highest standards of identity, strength, quality, and purity. The QSA defines responsibilities and communication paths for quality-related activities and specifies commitments between the parties regarding the procurement and release of raw materials, creation of operational batch records, and documentation of specifications for in-process samples and the final product. Release of goods and storage conditions are also defined. The rigorous specifications of such quality agreements are driven by practices outlined in our Quality System Manual (QSM) regarding: 1) raw material release specifications; 2) documentation systems; 3) custom procedures and methods; 4) staff training; 5) facility controls including Environmental and Water Monitoring; 6) manufacturing specifications; 7) out of specification processes; 8) analytical testing results; 9) product release documentation; and 10) change control notification.
RPD and cGMP Operations: Operations in both the RPD and cGMP suites are carried out by a full-time team of 18 scientific professionals. This group includes 11 staff dedicated to performing upstream and downstream operations, three who compose our Quality Assurance Team, a Technical Director, Research Lead, an Administrative Assistant, and a Center Director. The CBB staff is made up of highly trained individuals with bachelors, masters and doctorate degrees in a wide range of scientific disciplines, including bioorganic chemistry, physical chemistry, analytical chemistry, microbiology, biochemistry, biology, and biological engineering.
The Center for Biocatalysis and Bioprocessing at the University of Iowa offers the following advantages:
• A dedicated, full-time professional staff with expertise in fermentation, purification, and documentation;
• Immediate access to specialized university laboratories and centers;
• State-of-the-art equipment for :
o Fermentation optimization and scale-up,
o Downstream processing,
o Production capability to 1,000-liters,
o Analysis and evaluation;
• Established RPD and cGMP programs to generate quality results in a timely manner; and
• A dedicated Quality Assurance Team that ensures compliance with all cGMP standards and regulations.