In late September, GE Healthcare’s “ReadyToRock” Tour 2012 made a pit stop at the company’s Piscataway, NJ, facility. ReadyToRock is a 1,000 square foot, adjustable-width truck equipped with GE’s ReadyToProcess manufacturing platform for vaccines and monoclonal antibodies. Attendees viewed several brief presentations in the truck’s meeting area, and walked through typical bioprocesses of up to 200 L scale.
ReadyToProcess consists of components and instruments for upstream and downstream processing. The platform includes bioreactors, filters, tubing, connectors, and pre-packed chromatography columns and systems. Also on exhibit were products from Xcellerex, which GE acquired in May.
One could argue, though, that the company’s singular accomplishment was winning and maintaining an advantage in the “size war” for disposable bioreactors with a 2,000 L bag—currently the industry’s largest. With those capabilities, GE now supplies the entire continuum of biopharmaceutical development with end-to-end capabilities, from small, early-stage protein or vaccine production through large-scale manufacturing.
With Xcellerex, GE also secures a set of manufacturing products, services, and technologies that complete the larger firm’s ability to provide production-related services. For example, Xcellerex’ turnkey FlexFactory® is a modular, portable, single-use production train based on process automation and compact cleanroom architecture. Through its BridgeSourcing™ services, Xcellerex manufactures a customer’s product while the customer prepares for commissioning of its own new FlexFactory.
The bottom line for single-use bioprocess equipment is, simply, the bottom line: cost savings from reduced time, material, and energy usage related to cleaning and cleaning validation, rapid ramp-up of production campaigns, and more flexible, comprehensive utilization of facilities and equipment.
Numerous authors, many not affiliated with single-use vendors, have confirmed the cost-effectiveness of disposable bioprocessing. Estimates on labor savings vary from a low of 3% to a high of 50% and everything in between.
Pushback from customers tends to occur at the early stages of adoption. End-users believed, for example, that GE’s pre-packed columns (part of ReadyToProcess) were not as cost-effective as single-use or single-campaign equipment. Every advance in single-use processing was met with similar skepticism.
Every process and situation is different. GE Healthcare uses a process economics calculator—actually an Excel spreadsheet—to determine if single-use is the correct strategy based on approximately 20 factors related to the process, frequency, time, type of alternative equipment, and others.
For example at small scale for a “typical” disposable flask-based culture, GE’s Wave bioreactor™ reportedly reduces cost per run by about $400, or $7,000 per year. Savings for stirred-tank vs. Wave are similar, but with the added intangible benefits of eliminating cross-contamination (which, in fact, may also be valuated economically).
It is for high-cost operations like chromatography that the calculations get really interesting. Despite roughly equivalent equipment costs per cycle, the ReadyToProcess column saved about 15 hours of labor in packing, testing, and cleaning, 30 hours in cleaning and cleaning validation per cycle, said Attridge.
According to GE, ReadyToProcess columns are targeted to customers, particularly CMOs, that generate pilot batches, toxicology runs, and small clinical batches.
Several case studies were available at the ReadyToRock event. One compared a 100 L mAb process in a single-use format and to the identical process in a stainless steel tank and with conventional downstream processing. The ReadyToProcess operation used a Wave bioreactor, ÄKTA ready™, ReadyToProcess columns, and ReadyCircuit™ and ReadyToProcess™ hollow fibers.
The product quality, purity, and yield were identical in both processes, but the ReadyToProcess run reduced processing time by approximately 22 hours, noted a GE official.
Another case study examined the benefits of single-use processing for influenza vaccine production in mammalian VERO cell culture. Single-use equipment will play prominently as more vaccines are produced in cells, by reducing development timelines and adding flexibility. In this study investigators grew attachment-dependent VERO cells on Cytodex™ microcarriers inside a Wave bioreactor. Vaccine production batches tend to be quite small. In this instance a 2 L bioreactor can grow enough virus for 50,000 doses.
The investigators concluded that the Wave system, even without optimization was “a suitable system” for producing influenza virus.