Downstream Processing

The Emerging Generation of Chromatography Tools for Virus Purification

Chromatography media and methods have evolved continuously since their introduction a half century ago. Traditional methods use columns packed with porous particles. They still dominate chromatography applications in the field of virus purification, but the past 20 years have witnessed the ascendance of alternative supports, namely membranes and monoliths. These newer media exploit the familiar surface chemistries — ion exchange, hydrophobic interaction, and affinity — but they use unique architectures that offer compelling performance features. The Architecture of Chromatography Media…

Multicolumn Chromatography

Downstream processing is a sequence of unit process operations that purify biopharmaceuticals and prepare them primarily for bulk formulation (Figure 1). Typically, a large volume (hundreds to thousands of liters containing kilograms of therapeutic protein) is delivered from an upstream fermentation or cell culture process — and this ends up as a small volume (a few liters) of purified concentrate product after processing. Figure 1: () For many years, biopharmaceutical manufacturers have been working to increase capacity, address upstream production…

Proactive Debottlenecking

It wasn’t so long ago that people in the biotherapeutics industry talked about a “capacity bottleneck” to describe the difficulty faced by bioprocessors as their many products moved forth through development to require production at larger and larger scales (1). Expression technologies at the time were making proteins at levels suggesting that huge amounts of manufacturing capacity would be needed soon. Just after the turn of the century, product titers (in terms of protein present per liter of culture broth/supernatant)…

Austria Welcomes BioProcessors

When it comes to agriculture, the people of Austria are among the most dead-set against so-called “genetically modified organisms” of any population in Europe (1). But as is so often the case elsewhere, their attitude toward biotechnology used in medicine is much more friendly. This may have to do with the country’s traditional strength in environmental biotech (ranging from wastewater treatment and organic waste composting to anaerobic digestion for biogas generation) and also food biotechnology. That is the suggestion of…

Anything But Chromatography?

In 2006 a new term was coined that is now all too familiar in the industry: downstream bottleneck. With observations of a slow cycle of downstream process improvements indicating potential solutions in the next five years, downstream processing is a very hot topic at conferences and in publications. Thus, the Recovery and Purification track will be highly focused on this pertinent and timely issue. Beyond discussing the bottleneck itself head-on in the opening sessions, the track will focus on alternatives…

Integrity Testing Low-Area Filters Using Air–Water Diffusion and an Automatic Integrity Tester

Both FDA and EMEA guidelines require integrity testing of filters used in processing sterile solutions such as large- and small-volume parenterals (LVPs and SVPs). The same regulatory agencies also require that corresponding test documentation be included with batch product records. PRODUCT FOCUS: PARENTERALSPROCESS FOCUS: DOWNSTREAM PROCESSING, SCALE-UPWHO SHOULD READ: QA/QC, PROCESS ENGINEERS, AND ANALYTICAL PERSONNELKEYWORDS: FILTRATION, INTEGRITY TESTING, VALIDATION, AUTOMATIONLEVEL: BASIC The function of integrity testing is to determine whether a particular filter is within or outside the validated specifications…