36th International Symposium on Preparative and Process Chromatography
Philadelphia, PA, United States May 28-31, 2024
As in all PREP Symposia for an in-depth introduction to several topics of Preparative and Process Chromatography, 6 workshops are organized on Tuesday May 28 - 3 in parallel in the morning and 3 in parallel in the afternoon.
Registration for theses workshops is optional for symposium participants, with a fee of $475,00 per workshop. These workshops are also available without symposium registration.
Tuesday May 28 AM
Chaired by Olivier Dapremont and Geoffrey Cox
This workshop will focus on development of methods for the preparative purification of small molecules for the pharmaceutical industry. After an introduction to the theory of mass-overloaded chromatography, the course will discuss its application to the optimization and best practices of preparative chromatography in both batch (HPLC/SFC) and continuous (Simulated Moving Bed) for small molecule separations. The instructors will present practical approaches to the development of preparative separation through a series of both chiral and achiral examples. Attendees will learn valuable techniques to apply in the laboratory and at manufacturing scale to increase and optimize throughput and performance.
Tuesday May 28 AM
Chaired by Sharon Bola and Khaled Mriziq
Chromatography plays a critical role in purifying and producing biomolecules. Its use in bioprocessing operations allows for the purification of complex mixtures in bioproduction through the utilization of adsorbents (stationary phases) and a series of equipment and steps. This workshop will begin with an introductory level to chromatography, focusing on key factors for design and scale-up, and its application in downstream bioprocessing. The workshop will include a general introduction to chromatography principles, the chemistry and structure of chromatography adsorbents (resins) and columns, and equipment for small and large scales, along with operational modes. The second part of the workshop will feature case studies that cover downstream chromatography purification steps for various biomolecules. These case studies will address capture steps, intermediate and final polishing steps commonly used for purifying target biomolecules. Additionally, the workshop will cover process and product impurities and how chromatography is used to remove them to achieve the desired final biomolecule purity. The workshop is designed to provide attendees with a high level of familiarity with chromatography materials, equipment, and applications.
Tuesday May 28 AM
Chaired by Chiara De Luca and Mattia Sponchioni
This workshop is organized in two units, focused on oligonucleotides and peptides, respectively. During this course, a brief introduction on the 'tides features will be given, together with their main applications as pharmaceuticals. Due to the variety of their bioactivity and increasing number of approvals, their market is growing at fast pace. As such, an increase in the installed manufacturing capacity for these biomolecules is expected in the near future. This brings about considerations and issues related to the scalability and sustainability of the current manufacturing strategies. After an analysis of the available processes for the production of ‘tides, these issues will be mainly tackled with reference to their downstream processing. In fact, the main synthetic routes to produce 'tides at industrial level lead to the formation of unwanted impurities, which must be removed to ensure product safety and quality. Different purification techniques will be reviewed during this workshop, especially based on chromatography. A special emphasis will be given to process intensification, achievable through continuous chromatography processes, such as Multicolumn Countercurrent Solvent Gradient Purification.
Tuesday May 28 PM
Chaired by Urh Cernigoj, Alisa Strobel and Stefano Menegatti
Messenger RNA (mRNA) was discovered in the 1960s, but only the COVID pandemic brought the need for its large-scale production. Fulfilling those opportunities imposes significant challenges on process developers and column manufacturers to improve existing downstream processes. Focus of modern separations is the development and commercialization of a set of chromatographic columns and processes covering all areas from purification of raw plasmid DNA (pDNA), through monitoring the production up to final mRNA polishing. Among the new technologies presented in this workshop for mRNA purification are monolith chromatographic columns, especially suitable for separation of large biomolecules due to the convection-based mass transport of analytes to the active surface.
The second segment of this workshop will be a deep dive into the purification of plasmid DNA (pDNA), a crucial starting material for the production of mRNA and viral vectors. With the rising demand for vaccines and gene therapies, cost-effective downstream processes are becoming increasingly important. Current pDNA manufacturing challenges will be addressed, and strategies explored to overcome them. The focus will be on improving the chromatographic steps at several stages of the pDNA purification process to achieve a higher yield and purity, which involves, for example, selecting an appropriate chromatography matrix and optimizing loading and washing conditions.
The third and final segment will focus on the purification of viral vectors for gene and cell therapies, including AdenoAssociated Virus (AAV), LentiVirus (LVV), AdenoVirus (AdV), and Baculovirus (BeV). After a quick introduction on viral structure, mechanism of transduction, and therapeutic applications, we will dive into the Affinity adsorbents for viral capture and purification and Ion Exchange adsorbents for polishing and full-capsid enrichment. We will evaluate process operations in bind-and-elute as well as flow-through mode, current and upcoming platform process designs, and their integration with at-line analytical technologies. Finally, we will review quantitative metrics of success for the purification process and evaluate the goals that viral vector chromatography ought to meet to make gene therapies successful.
Tuesday May 28 PM
Chaired by Gerard Rosse
The basic principles and recent advances in Supercritical Fluid Chromatography (SFC) for the separation of small molecules, lipids, peptides and natural products will be presented. Carbon dioxide provides an eco-friendly mobile phase for chromatographic purification minimizing our impact on the environment and significantly reducing operational costs. Emphasis will be directed towards pharmaceuticals and nutraceuticals. Applications in these areas will illustrate the significant benefits of SFC in chiral and achiral separations. An overview of Supercritical Fluid Extraction (SFE) and its combination with SFC will also be discussed.
This workshop is aimed at anyone currently using GC, HPLC or other chromatographic techniques and interested in improving purification efficiency and reducing costs.
Tuesday May 28 PM
Chaired by Nick Vecchiarello and John Welsh
The objective of this course will be to introduce participants to concepts related to mechanistic chromatography modeling and high-throughput (HT) chromatography screening techniques as a precursor to presentations in the PREP Symposium focused on these topics. In addition to covering the fundamentals of modeling and HT screens, we will discuss how physical phenomena including thermodynamics, transport, and kinetics dictate separation quality and performance.
For modeling, adsorption isotherm formalisms relevant to bioseparations will be explained and different methods for measuring and fitting isotherm parameters will be covered. Experimental methods for determining transport, kinetic, and column parameters will also be explained and discussed in the context of calibrating models. Hybrid models with mechanistic and empirical or machine learning components will be briefly introduced. Finally, quantitative structure-property relationship (QSPR) modeling techniques based on biophysical protein structures will also be covered.
For topics in high-throughput chromatography screening, different formats will be introduced with benefits and trade-offs of each technique explained. These will include resin plates, micropipette tips, microfluidics, and RoboColumns. Examples of how these can effectively be used as part of separation development workflows will be shown.
Interactive case studies will be used to illustrate principles throughout the workshop and will include isotherm parameter fitting, transport parameter fitting, and linkage of high-throughput models to larger scales.