Vaccines for large populations typically take 10 to 17 years to move through the clinic to licensure. But for critical situations like pandemics and biological attacks, years must be collapsed into months or even weeks. Recognizing that the country had no such capabilities after the H1N1 pandemic, the Defense Advanced Research Projects Agency (DARPA), a division of the Department of Defense, awarded G-CON a grant that sought to address this major concern. Within 21 months of signing the contract, G-CON had to be able to produce a plant-produced recombinant protein for an influenza vaccine at a rate of 100 million doses per year.
G-CON had one year to design, build and commission this DARPA biotherapeutics facility — a delivery 1400 percent faster than normal.Using a plant-based protein source represented a change versus traditional vaccine production and would require a shift from the typical pharmaceutical manufacturing facility’s design. Because plants would serve as the upstream bioreactors, multiple purification systems needed to be “at the ready” to produce medical countermeasure proteins. DARPA selected G-CON’s cleanrooms, also known as PODs, for its downstream facilities to accomplish this goal.
Completing the project would be tough: G-CON had to develop a vaccine three times faster than conventional systems, scale the process to commercial capacity and design and construct the facility seven times faster, at 10% of the usual cost. All the while, the team had to ensure production occurred under stringent manufacturing guidelines.
COLLABORATION EQUALS SOLUTION
Traditionally, drug manufacturers will undergo years of drug development before building a commercial scale facility. Once a facility is needed, construction occurs in a sequential fashion with the cleanroom build-out occurring last. Instead of following this traditional and time-consuming path, G-CON sought a partner and chose the Global Solutions team at Rockwell Automation.
The two teams collaborated to develop a severely compressed schedule that demanded that many steps occur simultaneously. The POD concept was key to making this tight schedule a reality — while the shell of the facility was under construction, the downstream-process PODs were built and commissioned at G-CON’s neighboring manufacturing facility.
“We were excited to collaborate with G-CON to develop a truly innovative solution that raises the bar in autonomous cleanroom environmental control and process data management,” said Terry Gebert, vice president, Rockwell Automation. “Pushing the limits of our project management, control system design and implementation capabilities are what we do every day.
The two companies have been working together since the production of G-CON’s first prototype POD, designing an unequaled, automated modular solution that integrates the life-science expertise of G-CON and its manufacturing capabilities with the project management and control system design and implementation capabilities of Rockwell Automation. As a result, the two teams were ready to meet the aggressive deadline for development and commissioning required for the DARPA project.
Self-contained and autonomous, each POD cleanroom houses a particular process at the DARPA facility.
“PODs are autonomous, self-contained cleanrooms that provide as much as 768 square feet of cleanroom space each — complete with their own control, ventilation, fire suppression and data-management systems. The host facility need only provide chilled water, electricity and moderate air conditioning,” said Holtz. “Each POD houses particular unit processes; when combined, they yield an entire process system to purify and deliver biotherapeutics. Each zone operates independently, but is part of the greater structure.”
PODs are equipped with Allen-Bradley ControlLogix programmable automation controllers (PACs). The device controls the POD environment and is an integral part of the POD’s autonomous information management package. Data from PODs and upstream processes are managed by LAN based on FactoryTalk software. As technology evolves, the controller easily adapts — interfacing with new technology that is added, without having to re-validate the core firmware, saving time and money.
The PODs leverage EtherNet/IP industrial network to communicate between various process equipment within the POD. EtherNet/IP also enables “clustering” of multiple PODs to efficiently and securely meet the demands of a flexible manufacturing process. EtherNet/IP provides the industrial backbone for POD process control and data management as a single network environment, and allows for seamless integration for “clusters” of PODs. This network topology is essential to implementing a quality Manufacturing Execution System.
G-CON also specified FactoryTalk’s VantagePoint application to access data sources throughout the POD. The application collects and aggregates production data and compiles it into Web-based reports to give G-CON real-time data of the process operations. If the temperature is too high, if a fan fails or if there is an interruption in the purification process, FactoryTalk applications notify G-CON personnel so that the issue can be addressed immediately. But for G-CON, perhaps the most important aspect the software provides is data management. “Quality data is the currency of our business,” Holtz said. “FactoryTalk Historian software automatically collects and archives real-time process data to help us meet regulatory requirements.”
From the discovery of a newly created drug, a drug manufacturer has a limited amount of time to reap the rewards of its invention before its patent expires and generic products enter the market. For this reason, speed is of paramount importance. Traditionally, drug manufacturers have built monolithic, dedicated production facilities that take three to seven years to complete and likely even longer to validate for production. With the advent of single-use technologies and process improvements, a significant shift is occurring making such large scale facilities less viable operationally and financially. Instead, modular, scalable, flexible manufacturing solutions are the industry’s goal. G-CON, a builder of biotherapeutics-manufacturing facilities, created the POD platform to respond to this need. With its automation partner Rockwell Automation involved in its development, the POD’s concept became the comprehensive solution organization’s like DARPA and the biopharmaceutical community need to meet critical social and business goals.
“In our experience, PODs have proven to be the most comprehensive offering on the market today,” said Barry Holtz, chief science and technology officer of G-CON.
BACK UP THE TRUCKS
On March 22, 2011, upon substantial completion of construction of the new facility, POD-bearing trucks backed into the loading docks of G-CON’s 145,000-square-foot facility in Bryan, Texas. After unloading the PODs, a team of six workers slid them into place and connected them to the larger facility’s water and power system.
In less than one year, the facility was ready to produce vaccines at the rate that DARPA required — within the project’s $60 million budget and 21-month operational deadline. In an industry where similar facilities take years and cost hundreds of millions of dollars more to build, this accomplishment is unprecedented.