By Jim Montague, Executive Editor
Fast time to market doesn't usually mean saving lives by treating kids with rare genetic diseases—but sometimes it does. For instance, when another biopharma manufacturer's process broke down—threatening global supply of several vital lysosomal medicines—the U.S. Food and Drug Administration asked Shire Biopharmaceuticals and its Human Genetic Therapies (HGT) division if they could greatly accelerate the construction of a planned, single-use, biotech process and greenfield facility to make six of the drugs.
"We had to speed up our project schedule, shift basic process design, minimize costs, perform testing and complete certifications as soon as possible, and deliver a fully redundant system," says Lloyd Vallance, Shire HGT's senior process control engineer. "Above all, we had to help these patients. Our management even posted pictures of them around our facility as a reminder for everyone."
Vallance presented "Rapid Deployment of a Single-Use Biotech Facility" at Honeywell Users Group Americas Symposium 2011 on June 14 in Phoenix.
Thanks to its commitment, Shire HGT broke ground in spring 2008 and got its $210-million, three-story, 250,000-square-foot Atlas manufacturing plant up and running by June 2010—five months ahead of schedule. Located in Lexington, Mass., the plant is now the world's largest single-use bioreactor facility, and is operating in current good manufacturing practices (cGMP) operating mode.
In addition, Shire HGT's accelerated construction project and single-use bioreactor process uses Honeywell Process Solution's Experion Batch Manager system, C300 controllers, and some OneWirelesss networking. The bioreactors also use Profibus networking to control 170 peristaltic pumps and employ Foundation fieldbus networking to control temperature measurement and other devices.
"Experion Batch Manager enabled us to execute all procedure levels in the controller environment," says Vallance. "Its benefits for us included one platform and application for system training; recipe flexibility because we're not limited to a fixed number of levels; and appropriate levels of redundancy."
In addition, single-use means Shire HGT's bioreactors consist of two 200-liter and two 2000-liter plastic bags that serve as liners, which are filled and mixed while being supported in a steel box, and so require far less cleaning and testing time than conventional reactors. These bioreactors are fed by 3000-liter bags as part of a perfusion process that delivers nutrients and other raw materials. Vallance reported that, even though the single-use bags can cost up to $10,000, they allow Shire HGT's staff to changeover bioreactors in just six hours. Traditional vessels can take two weeks to be cleaned and recertified.
"To get this project done successfully we needed skillful project management, which focused on safety first, aggressive scope management, and used integrated, online scheduling and document tracking and approvals," explains Vallance. "Honeywell's global approach helped us coordinate tasks and perform integrated testing, qualification and commissioning, and also help our teams cooperate faster."
Vallance reported that Shire HGT's speedy bioreactor project also heavily used VMware's computer virtualization methods and technologies. "We employed a virtual system that mimicked our plant-floor system, and we ran on a single CPU to further reduce hardware and setup time," he said. "This was the first time anyone has used disposable bioreactor liners at this scale. However, the rapid prototyping we had to do was helped by our early process development and offline testing, which allowed us to find areas for process improvement, and our parallel design effort and integrated factory acceptance testing (FAT). We were even able to assemble much of the new bioreactor process and facility at a rented space while the new building was still under construction."