Downstream Processing

"First, the maturation of Protein A chromatography—this resin has been the workhorse of antibody purifications. One starts with crude harvest, often colored materials with multiple components from the harvest and in one step produces highly purified IgG antibodies. This high selectivity of Protein A for the IgG antibodies allows for very selective capture of the antibody while almost all the other components the mixture pass through. In spite of these advantages, the early Protein A chromatographic resin leached high levels of Protein A with the antibody, resulting in a new in-process contaminant. This issue was addressed with better linkage chemistry, and newer supports have improved other aspects of this type of chromatography. Second, high speed and high capacity resins to streamline processes have emerged. No longer are we doing overnight steps in coldrooms. We're able to go into room-temperature conditions and rapidly isolate and purify protein therapeutics. Third, mixed-mode resins can now separate by two orthongonal methods in one step. In addition, high-throughput membranes now allow very rapid polishing steps to take place after the initial capture and purification of the IgG antibodies. We should adopt some advances taking place in other industries, such as continuous processing and simpler initial recovery steps."

Uwe Gottschalk

"The CMO sector has always been very innovative, and that is because we obtain a clear benefit from flexible concepts. We have seen some interesting developments, including also the appearance of single-use technologies which has had a big impact, especially in the sector of contract biomanufacturing.

"For the next 25 years, I personally want to see more disruptive type of changes, not just more of the same. Not only operational excellence but also concepts that go beyond the current physical limitations. In downstream processing, for example, which is my comfort zone, I want to see concepts that enable downstream processing to keep pace with fermentation and to deliver final products no matter what quantity and what location within a couple of days. We might also see closed systems so that we are meeting the requirements for the perfect conditions that we now have in fermentation."

Steve Walfish

Validation

"I think the biggest advantage that the biotech industry has—and is seeing—in the area of validation is the ability for us to move into what I call a consistent validation model—that is a validation model that is very similar to its counterparts in the pharmaceutical and the medical device arena. We're getting efficiencies across the board, and this is crucial for us as an industry because, as most people know, we're seeing more and more combination products. In the world of combination products, companies that historically have grown up as a medical device manufacturers are now taking raw materials that are biologics, putting them together into a single product, and having that product go forward and validated. Having a model for validation that's consistent with the other parts of the FDA regulated industry is a tremendous advantage for our industry.

"In addition, we now have the ability to be efficient in method validation and test methods. Through the ICH Q2 (analytical validation) document and similar guidance documents, we now have a scientific and technological advantage as an industry—that is, consistency of methods across the global landscape."