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Preparative chromatography has played a key role in the purification of fine chemicals and active pharmaceutical ingredients (APIs) for many years. Increasingly, however, chromatography also plays a key role in biotechnology, where it has become the workhorse in the downstream processing of biopharmaceuticals. The technology continues to evolve rapidly creating not only opportunities for new applications but also new scientific challenges that demand for a forum where scientists and engineers from industry and academia can get together with media and equipment suppliers to share the latest advances in the field. For many years the PREP Symposium has provided just that. The 24th PREP Symposium was held in Boston on July 10–13, 2011. The symposium was attended by more than 300 people from 25 different countries, with two-thirds from the US and one third from outside the US; 25% of the participants were from academia and 75% from industry. The Exhibit included 24 equipment and media suppliers. Three training Workshops were offered addressing preparative chromatography for biomolecules, preparative chromatography for APIs, and regulatory and marketing aspects of biopharmaceuticals. The Scientific Program included 66 oral papers and more than 90 posters.

A keynote session on Industrial Case Studies in Protein Chromatography included talks by MedImmune, Amgen, Shire, Genentech, and GSK who shared their hands-on experiences with quality by design, pH excursions in cation exchange columns, scale-down models, the complex elution behavior of an aglycosylated monoclonal antibody (mAb), and a sophisticated framework to characterize cation exchangers for intermediate mAb purification. All presenters emphasized the need for better process understanding. A plenary on Biomolecular and Process Modeling introduced new approaches to describe diffusion in dextran-grafted matrices, to obtain scale-up parameters from gradient elution experiments, and to predict the effects of pH and ionic strength on retention of mAb charge variants in ion exchange columns. The session also demonstrated the application of advanced molecular dynamics simulation tools to predict protein-ligand interaction in multimodal chromatography. High-throughput screening was shown to play a big role in process development. Mini-columns are now available for rapidly testing conditions and stationary phases.

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New stationary phases were also introduced, including new polyethylene glycol-modified capillary-channeled polymer fibers for high-performance chromatographic separations.

A second keynote session offered several Industrial Case Studies in Continuous Chromatography. Presenters from UCB and AMPAC discussed the application of continuous chromatography for API resolution providing comparisons with batch supercritical fluid chromatography (SFC) and crystallization, respectively. The study by UCB found that multi-column continuous chromatography (MCC) offered greater productivity than SFC, while AMPAC's study concluded that simulating moving bed (SMB), despite the higher unit operations cost, offered greater yields and significant overall cost benefits compared to crystallization. Papers by Xendo, Semba, and Tarpon addressed bio-applications of multicolumn systems for the purification of proteins, vaccines, and virus-like particles. The session suggested that chromatography is no longer limited to batch applications and that large-scale continuous processing is becoming a reality both for small molecules and biopharmaceuticals. New developments in continuous chromatography introduced at this Symposium, including a new system extending SMB to ternary separations, a two-column semicontinuous SMB process requiring simpler equipment, and a process integrating SMB separation coupled with racemization for high-yield production of amino acids, confirmed that the field is rapidly evolving.

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Several talks discussed approaches to speed process development and increase column lifetime in bioprocess applications. A surface neutralization step (SNS) using a specially selected buffer was shown to improve the lifetime of ceramic hydroxyapatite columns. Platform processes integrating multiple modalities (ion exchange chromatography, hydrophobic interaction chromatography, and monolith and membrane chromatography) received a lot of attention. In one study, conditions minimizing aggregates and charge variants were found through buffer matrix screening. Design of experiment was used to optimize the cation exchange chromatography step to remove more than 10 charge variants at various scales. Another study evaluated two commercial cation exchangers identified by high-throughput screening for capturing an Escherichia coli protein. Detailed studies were then done by examining dynamic binding capacity and linear gradient elution while varying load and elution pH. Finally, a multiple injection technique was introduced to improve the isolation of a target protein from mixtures.

Several papers demonstrated the value of theory for process optimization. A study on core-shell particles suggested that these materials offer distinct advantages when conditions are not globally optimized. However, the production rate and solvent consumption advantages of core-shell particles relative to totally porous particles were predicted to vanish for holistically optimized conditions. New experimental approaches were also introduced, including using positron emission particle tracking to determine the movement of tracer particles in expanded beds.

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Monolith and Membrane Chro-matography received special attention. A study presented by BIA demonstrated an approach based on pressure drop data to determine the thickness and configuration of grafted polymers and adsorbed plasmids in monoliths. Monoliths were also shown to be effective for the chromatography of large bio-particles, such as baculoviruses and influenza viruses. New tailored membranes incorporating finely ground cation and anion exchange particles were shown to be effective for the recovery of valuable proteins from cheese whey. A study on convective media compared membrane and monolith performance for affinity capture, ultimately concluding that both are ready for large-scale applications.

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The PREP2011 program concluded with two keynote sessions on SFC. These sessions addressed the complex behavior of supercritical CO2, with and without modifiers. Density was shown to be the most important variable affecting transport properties and retention factor. Proper choice of the injection strategies was shown to be critical in SFC. Papers by Genentech and Merck & Co. addressed the use of ammonium hydroxide as an additive, and the role of SFC in supporting pharmaceutical process chemistry. These sessions suggested that SFC is very promising as an environmentally friendlier and potentially more efficient alternative to high-performance liquid chromatography. However, it also presents substantial challenges due to operating complexities and current lack of reliable models. Advances are expected in the future as the technique is attracting increasing interest.

On behalf of the Organizing Committee and as PREP2011 Program Chair, I want to thank all sponsors, exhibitors, participants, contributors, and members of Scientific and Industrial Advisory Committees for making the Symposium a success. Date and venue of the next PREP Symposium will be posted in the near future at the conference website.

Giorgio Carta, Department of Chemical Engineering, University of Virginia, Charlottesville, VA, USA

Editor, Biotechnology Journal

PREP2011 Program Chair