Vendors Meeting Diverse Needs
The uniqueness of filtration trains and specific products to individual processes becomes obvious from discussions with large bioprocess companies, particularly those who manufacture multiple products.
A large, diversified company like GlaxoSmithKline faces more challenges during the development of filtration unit operations than normal due to its unusual breadth of host organisms and molecule types. Still, Bruno Marques, Ph.D., an investigator at the company, notes that filter manufacturers have done a good job of addressing end-users’ needs. The evidence, he says, is in vendors’ responses to problems.
“Increasing titers made one thing crystal clear, that every unit operation along the purification process needs to achieve higher capacities and throughput.” As an example, Dr. Marques cites virus filtration. “Because of its relative high cost, improving virus filter capacity has been quite important to us. Top vendors have done a good job of addressing this issue, and of listening to our concerns.”
What could be improved? “Filter companies would do well to emulate chromatography resin companies and try to improve their scale-down models, eventually to achieve high-throughput methods for screening filter membranes.” Dr. Marques is referring to scalable, high-throughput methods that could be performed by robotic liquid-handling systems.
The problem with current filter scale-down models is that they are still in the 10–25 cm2 range for filter surface area. Each test consumes one gram or more of product, a price that Marques says is too high. “It would be great if at some point in the next few years biomanufacturers were able to plug scaled down versions of membranes into high-throughput systems.”
Sanofi-Pasteur, which manufactures influenza vaccine through an egg-based manufacturing process, relies primarily on ultrafiltration to remove lower molecular weight materials, and sterile filtration as a step important to antigen production and final product formulation. Success, says Joseph Frantz, Ph.D., director of pharmaceutical technology, depends on understanding and characterizing the material being filtered in light of available membrane types and materials that may be more or less compatible with the product.
Dr. Frantz calls filter product suppliers “excellent partners” for their willingness to conduct product compatibility studies. Other significant support areas include testing for integrity and Vmax, a parameter for estimating throughput and filter clogging.
Sanofi-Pasteur recently employed presterilized, plug-and-play particulate filters for processes ranging from less than 100 L up to about 1,000 L and is working with suppliers to extend this methodology to sterile filtration systems. Disposables have been game-changers for the manufacture of small protein batches as well as for vaccines. Their success has been based not only on disposability and all its attendant benefits, but on connectivity and configurability. “When you purchase these products you’re not just buying a filter,” Dr. Frantz explains. “It’s critical to have the right sterile connectors and tubing, and with them the ability to plug the cartridge, aseptically, directly into the process.”