OR WAIT 15 SECS
Extensive adoption of single-use technologies and unidirectional flow reduces cross-contamination risk in the company?s new biomanufacturing facility.
Expected growth in demand for biologic drugs is leading to investment in new production facilities. Part of the decision-making involved in expanding or building biomanufacturing facilities is to what extent to use single-use technologies in the equipment used for biopharmaceutical manufacturing. In April 2013, Catalent Pharma Solutions opened a new biomanufacturing center of excellence in Madison, Wisconsin. The facility was designed to extensively leverage single-use technologies. Michael Jenkins, general manager of Catalent’s new Madison facility, spoke with Cynthia Challener, editor of the Pharmaceutical Sciences, Manufacturing & Marketplace Report, about the drivers of growth in biologics and the application of single-use technologies in biopharmaceutical manufacturing.
Ensuring reliable productionPharmaceutical Sciences, Manufacturing and Marketplace Report: What were the leading market drivers and other reasons that led Catalent to invest in a completely new biologics manufacturing facility rather than expand its existing operations?
Jenkins (Catalent): Because of significant customer interest in our GPEx cell-line engineering technology for the rapid development of stable, high-yielding cell lines and the growing market demand, it became clear we needed a larger facility in view of capacity constraints at our 43,000-ft 2 facility in Middleton, Wisconsin. The new, state-of-the-art cGMP facility at Madison quadruples our clinical-scale biomanufacturing capacity. We wanted to ensure reliable production at our old site while we expanded and did not want to assume any risk to cGMP manufacturing during construction. At the same time, we made a strategic decision to transition from stainless-steel production vessels to single-use technologies, increasing our flexibility at the same time as reducing cross-contamination risk.
Designed for optimum efficiencyPharmaceutical Sciences, Manufacturing and Marketplace Report: Can you explain the facility design and how the operations are organized at the new facility?
Jenkins (Catalent): Moving to the new, larger facility allowed us to focus on some of the fundamental principles of good manufacturing practice, including unidirectional people and material flows to minimize the risk of cross-contamination and to make an investment in the building infrastructure and services, such as WFI (water for injection) production and a design in which softwalls were not required for production. Additionally, our new facility has full-purpose designed media and buffer kitchens.
We then looked at the efficiency of production and designed the ability to produce three different products in each suite. This approach dramatically increases the number of production runs we can complete each year and maximizes flexibility and scalability. Lastly, we incorporated the ability to move bioreactors so that we can reconfigure the suites to produce a variety of batch sizes and simultaneously maintain efficiencies. Such an arrangement is only possible with single-use reactors.
Our cell-line development area was also redesigned to optimize efficiency. The areas in Middleton were originally designed to work toward the production of transgenic cows, but our GPEx technology for engineering mammalian cells for use in production vessels is a far more evolved process. The Madison cell-line engineering laboratory is approximately 30% smaller than that at the Middleton facility, and yet has a greater capacity. It is also much more user-friendly for the cell-line development technicians.
Single-use for flexibility and reduced riskPharmaceutical Sciences, Manufacturing and Marketplace Report: With respect to the equipment, can you describe the different types of systems that were selected and why?
: We are using single-use bioreactors, and the typically associated advantages of avoiding product cross-contamination and fast suite turnover are real and very valuable, particularly at the Phase I/II clinical-trial stages. In addition, avoiding clean- and-place and steam-in-place processes, which are required for stainless reactors, is a big efficiency and safety advantage.
Furthermore, the ability to reconfigure the suites is key to increasing efficiency. Our process dictates that product spends from approximately 112 to 120 days in the terminal reactor, and we can reconfigure our suites to have any reactor size from 10 L up to 1000 L in the area where this production occurs. This ability to use reactors interchangeably fundamentally allows us to be more flexible than a traditional stainless facility.
We also took a single-use approach to mixing vessels and liquid management, including the use of disposable tubing for pumping protein between rooms in the suite and buffers from the clean corridor into the processing rooms. Our tangential flow filtration skids also use disposable flow paths.
In designing the operation, however, we did not assume that single-use systems will always be appropriate. For example, we chose traditional downstream processing skids because we found that they are more versatile, and the cost of the disposable flow paths for downstream skids was quite high. Similarly, in the process-development area, we continue to use traditional glass vessels. These systems are relatively easy to clean and sterilize, and using them avoids the cost of the single-use vessels.
Platform approachPharmaceutical Sciences, Manufacturing and Marketplace Report: What types of activities will be pursued at the new facility? Will special manufacturing techniques be implemented?
Jenkins (Catalent): We carry out mammalian-cell-line engineering, process development, analytical development, master cell bank production, manufacturing of the quantities required for toxicology, and Phase I/II manufacturing. We have a platform approach. The techniques employed vary from product to product, but revolve around bioreactor production, clarification, column purification, membrane absorption, and bulk filling of bulk drug substances. The manufacturing activities are also supported by integrated analytical, formulation development, and viral-clearance capabilities, small-scale and large-scale process development laboratories, and separate microbiology and quality-control functions.
With respect to special manufacturing capabilities, Catalent will be employing its proprietary GPEx cell-line engineering technology at the new Madison facility, as well as the SMARTag precision protein-chemical engineering technology from Redwood Bioscience for the development of advanced antibody drug conjugates (ADCs), which we recently licensed. Redwood’s novel, site-specific protein modification and linker technologies enable the generation of homogenous bioconjugates engineered to enhance potency, safety, and stability. The combination of these two advanced technologies and the broad range of analytical and fill-finish services at the Madison facility will enable Catalent to further expand our ability to help customers develop more and better biologic treatments.
Potential for expansionPharmaceutical Sciences, Manufacturing and Marketplace Report: Is there room for further expansion at the new facility? Does Catalent have any additional plans for the site?
Jenkins (Catalent): The ability to expand was, in fact, a major reason for our move to the Madison location; there were no good longer-term expansion options at our old site in Middleton. At the Madison site, we have the room to expand into a space equivalent to one GMP suite and would just need to build out. We also have the possibility of building out into the current parking lot. Short term, our focus is on considering whether we should scale up our current capabilities for commercial production. This decision will depend on client input.