You probably won’t find a lot of presidents of successful contract manufacturing organizations gleefully operating the forklift inside the manufacturing plant, but Barry Holtz is no ordinary leader — which is quite fitting because iBio is no ordinary biopharma facility.
“Anyone can build monuments,” says Dr. Holtz. “But the fun comes in seeing them in action — being the one to push that green button. Building systems that work is the greatest reward.”
The iBio facility is a testament to what can be accomplished when efficiency is built into the design from the start. Formerly operated by Caliber Biotherapeutics, the Bryan, Texas, facility was designed, constructed and fully functional in less than 18 months from groundbreaking. The facility boasts meticulous design considerations ranging from concepts as simplistic as locating parking lights across the street to avoid insect infestation to the sophistication of an automated, multilevel growing environment that uses proprietary LED lighting.
The 139,000-square-foot building, conveniently located in the “bio-corridor” abutting the campus of Texas A&M University, was developed with funding from the Defense Advanced Research Projects Agency (DARPA) as part of the Blue Angel project. The Blue Angel project focused on new ways to produce large amounts of high-quality, vaccine-grade protein in less than three months in response to emerging biological threats. iBio’s proprietary plant-made pharmaceutical technology was licensed to Caliber for the project, which demonstrated successful use of the technology on a commercial scale.
In January 2016, iBio, together with investors Eastern Capital Limited, purchased the Caliber facility and formed iBio CMO — a contract manufacturing organization for the development, scale-up and large-scale manufacturing of biologicals.
This summer, the U.S. FDA granted Orphan Drug Designation to iBio’s lead investigational biotherapeutic product, iBio-CFB03, for the treatment of systemic sclerosis. Additionally, iBio recently announced the successful application of its plant-based technologies to achieve the first milestone in its commercial development agreement with AzarGen Biotechnologies for the development and manufacture of an improved surfactant protein for the treatment of neonatal respiratory distress syndrome (RDS).
iBio’s primary research, development and manufacturing system employs vacuum-infiltrated Nicotiana benthamiana plants — tobacco relatives indigenous to Australia — grown in a fully contained, hydroponic system for transient expression of recombinant proteins. In plain English, once the plants have been infiltrated with agrobacteria, the bacteria hijacks the protein-making functions of the plant and the plant leaves replace a traditional bioreactor, becoming a “protein factory.” The plant biomass is then harvested and the resulting extract is purified through a downstream process similar to what you’d see in a typical biopharma facility. (See sidebar)
The iBio CDMO facility can grow over 4 million plants hydroponically as “in process inventory” and can deliver over 300 kilograms of finished therapeutic protein per year if run at full capacity. Technology transfer and scale-up is vastly simplified because the need to adapt cell lines to the scale of the bioreactor is eliminated in the plant-based process. Simplification also equates to customer cost-savings. As a CDMO using proprietary plant-made biopharmaceutical development and manufacturing technologies, iBio can take a potential protein into commercialization faster and more cost-effectively than traditional CDMOs. A recent, in-depth, technoeconomic peer-reviewed paper reported the cost of goods for a monoclonal antibody was estimated at $160 /gram at a yearly production rate of 300 kg per year. Economical production at this smaller scale is difficult in CHO. And yet, the great majority of mAbs coming forward have smaller total production requirements, between 10-120 kg.
The building was designed in a parametric building information management (BIM) and estimation model using advanced three-dimensional, computer-aided-design (CAD) systems. The BIM process involves creating digital representations of the physical and functional characteristics of the facility. Several sophisticated software systems, such as D-Profiler (a parametric 3D CAD-based estimating tool), Revit object-based 3D CAD design system, Navisworks for ‘in silico’ design conflict resolution and Synchro Design timeline planning were utilized. This “virtual construction” allowed the design team to work out design problems and inefficiencies prior to actual construction. The 3-D design software enabled the team to visualize concepts and simulate how the designs would perform.
The manufacturing facility project was design-build. Design-build, often seen as a faster, more cost-effective alternative to traditional design-bid-build methods, enables the design-build team to work under a single contract with the project owner to provide design and construction services. “One entity, one contract, one unified flow of work from initial concept through completion — thereby re-integrating the roles of designer and constructor,” explains the Design-Build Institute of America.