Two sessions of 2 workshops will be held during the afternoon of Sunday, October 7. Please register during the registration process. Each workshop is available at a fee of 85 euro.
||Chairman: P. Mota, O. Dapremont
Chairman: A. Butte
||Multicolumn Processes: From Historical SMB to the Latest Advances in the Purification of Biomolecules
From Development to Commercial Scale: How to Integrate QbD Tools and Data Analysis
Chairman: M. Schulte
|Chairman: A. Jungbauer, N. Andersson
Preparative HPLC of Peptides and Small Molecules: Phase Screening, Method Optimisation, Process Design
|Real Time Monitoring and Control of
Session 1: 14:00 - 15:30
Workshop 1 - Multicolumn Processes: From Historical SMB to the Latest Advances in the Purification of Biomolecules
P. Mota, O. Dapremont
Multi-column (MCC) processes have become the workhorse of chromatographic separations. They are able to overcome the limitations of low throughputs and excessive solvent consumption that characterize conventional single-column processes. Despite the higher complexity as compared to single column processes, the design and operation of a MCC separations is in fact rather simple. The workshop will trace the developments in MCC starting from the classical SMB mainly used for small molecule purification and slowly progress to more recent innovations related to large-molecule purifications. The workshop will be held in three parts.
The first part aims at providing the fundamentals of the SMB technology. We will cover the basics of SMB technology: modeling, design, and optimization of SMBs; engineering issues associated to the industrial use of SMBs.
The second part covers recent advancements in multi-column chromatography. The increasing use of the SMB as a multipurpose unit in the pharmaceutical and fine chemistry industries has led to the development of novel cyclic operating schemes, some of which are substantially different from the conventional process. Broadly speaking, the new operating schemes introduce periodic modulations of selected control parameters into the operating cycle. We shall discuss concepts such as asynchronous port switching, cyclic modulation of feed concentration, time-variable manipulation of the flow rates, and solvent-gradient operation. We shall end our presentation with a discussion of the pros and cons of using SMBs with very few columns.
The final part deals with the use of multi-column chromatography for the purification of biomolecules. In the downstream processing of valuable therapeutic proteins, achieving high purity and high yield simultaneously, is a key prerequisite for the production of safe biopharmaceuticals at low and competitive costs. On the chromatography side, the use of cost-effective, non-affinity stationary phases and gradient chromatography in combination with multicolumn continuous chromatographic processes (MCSGP) presents an option for biopurifications. Advantages over batch chromatography include the possibility of simultaneous achievement of high yield and purity, a higher throughput and lower buffer consumption. We will discuss the fundamentals of these operations and discuss academic/industrial case studies.
The workshop is designed in such a way to require only a basic understanding of chromatography as a prerequisite; no previous exposure to the SMB technology is required. It will be an in-depth primer for the newcomers to the field, and it will offer a structured presentation of the MCC fundamentals to those aiming at a better understanding of the technology. The workshop will put all participants in the position to be able to follow and profit from the scientific presentations about MCC during the conference.
Jose P. Mota is full professor of chemical and biochemical engineering at the department of chemistry of University Nova de Lisboa (Portugal). He has authored over one hundred papers in the areas of separation science and transport phenomena. He has received 8 international awards, is member of the Scientific Council of Sciences and Engineering (CCCE) of the Portuguese National Science Foundation (FCT/MCTES), and member of the Board of Directors of the International Adsorption Society (IAS).
Olivier Dapremont received his Ph.D. degree in Chemical Engineering and Applied Chemistry in Simulated Moving Bed technology (SMB) and chiral applications in 1997 from the University of Pierre and Marie Curie in Paris. He started his career, in 1992, developing SMB technology for Prochrom R&D then joined in 1997 Chiral Technologies Europe, as manager of the SMB kilo lab. Olivier joined Aerojet Fine Chemicals, now AMPAC Fine Chemicals (AFC) in Rancho Cordova, CA, at the beginning of 2001. At AFC, Dr Dapremont is in charge of the development of chromatographic processes as well as continuous chemistry for APIs and intermediates. To this day, he has developed and implemented more than 20 chiral and non-chiral separations using SMB from kilogram to multi ton scale.
Workshop 2 - From Development to Commercial Scale: How to Integrate QbD tools and data Analysis
In this workshop, the complex path that is connecting the choice of the appropriate purification method (process development) to the start of a production campaign (process validation and transfer) is discussed and it will be supported by study-cases. In this context, a significant part of the discussion will focus on the regulatory aspects connected to the development and validation of the process, like the definition of the critical process parameters, and on how concepts like Quality by Design (QbD) can help correctly framing the scale up process and dealing with the risks associated to it. Basic concepts of Design of Experiments (DoE) and Multi-Variate Data Analysis (MVDA) will be also introduced. It will be also discussed how development and validation can be supported by more complex tools, which are integrating process knowledge (and so-called deterministic models), data analysis and basic machine-learning tools, and online sensors (e.g., the use of Raman spectroscopy for the online detection of Mabs).
Alessandro Butté received his Ph.D. in Chemical Engineering in 2000 from ETH Zurich. After a two-year post-doc at the Georgia Institute of Technology, he join the group of Prof. Morbidelli at ETH Zurich and completed his habilitation in 2008. During this period, his research activities focused on polymer engineering, production of nano-materials for protein purification (monoliths by reactive-gelation) and chromatography purifications of peptides, proteins and Mabs. In 2008, he joined Lonza as responsible for downstream activities in the sectors small molecules and peptides and as project manager. He was also involved in the pilot program to introduce Quality by Design into R&D. In 2013, he joined back ETH as senior researcher and, in 2017, he co-founded DataHow, a spin-off company dealing with digitalization of production processes in pharma and chemical industry. He is author of more than 60 papers on international peer reviewed journals, several book chapters and patents.
Session 2: 16:00 - 17:30
Workshop 3 - Preparative HPLC of Peptides and Small Molecules: Phase Screening, Method Optimisation, Process Design
Michael Schulte, Jochen Strube, Ulrich Emde
Where to start in preparative HPLC when a peptide or a complex active pharmaceutical ingredient has to be isolated in large scale? For many of the substances to be purified by preparative HPLC a certain method development and process design is needed. Either a generic method has to be developed which is able to separate a large number of substances following a certain protocol or – for production purposes – a specialized, highly optimized and economic production route has to be developed. This workshop will try to help developing a good, robust and efficient preparative HPLC method using Liquid Chromatography (LC) as well as Supercritical Fluid Chromatography (SFC)
Using the example of a complex drug molecule you will learn about the importance of stationary and mobile phase as well as mode of operation selection. The workshop will demonstrate how methods developed at analytical column dimensions can be used to optimize a preparative method in different chromatographic regimes (LC,SFC, batch and continuous mode). Experiments to determine the physical properties needed for model based process design will be explained. Finally interactive simulation tutorials will be offered on batch and multi-column chromatography to optimize the process parameters.
Preparative HPLC, Supercritical Fluid Chromatography (SFC), phase screening, method development, stationary and mobile phase selection, process design, simulation tutorial
Michael Schulte is Director of Chromatography R&D at Merck KGaA. He did is Ph.D. work in the group of Professor Blaschke at the University of Münster, developing new chiral stationary phases. Since joining Merck in 1995 he has more than 20 years of experience in stationary phase design and process development in preparative chromatography.
Jochen Strube, is Univ.-Prof. Dr.-Ing. habil. at Clausthal University of Technology, Institute for Separation and Process Technology and director of that Institute since 6 years. Before that, Jochen has worked 7 years at Bayer Technology Services AG/Leverkusen in advance and education as chemical engineer at University of Dortmund with Diploma, Dr.-Ing and Habilitation.
Ulrich Emde studied chemistry at the Philipps University in Marburg. For his Ph.D. he moved to Berlin doing natural product synthesis and finished his thesis at Humboldt University in the year 2000. Subsequently he did a postdoc in the Williams group at Indiana University, Bloomington. In 2002 he joined Merck KGaA as medicinal chemist. For eleven years he worked there in different roles starting in the lead finding group, later as external synthesis manager and head of laboratory. Beside synthesis he concentrated on analytical and preparative liquid chromatography topics. In 2005 he introduced the first SFC at Merck KGaA. Early 2013 he was appointed head of the liquid chromatography laboratory in the central analytics department. With his team he performs analytical and preparative tasks in nearly all major liquid chromatography fields (UHPLC/HPLC, SFC, SEC/GPC, TLC, IC & CE). He is (co)-author of over 30 patent and patent applications and 10 scientific papers.
Workshop 4 - Real Time Monitoring and Control of Process Chromatography
Alois Jungbauer, Niklas Andersson
Online monitoring solutions are already state of the art in the chemical and food industries. The biopharmaceutical sector is currently attempting to also implement such technologies. Regulatory recommendations for quality by design instead of quality by testing raised increasing interest in monitoring and control of chromatography. The final goal is a real time release. The monitoring and control is a step towards this goal. In this workshop the state of the art of protein chromatography and monitoring and control concept will be shown. The different ways to monitory process chromatography by at-line in-line and on-line analysis will be shown. The chemometrical approaches for monitoring will be overviewed. An outlook will be given how to reach the state of real time release.
Process chromatography, protein, biopharmaceutical, monitoring, real time release.
Alois Jungbauer received his PhD in Food Technology and Biotechnology from the University of Natural Resources and Life Sciences Vienna, Austria 1986. He serves since then as a professor at the Department of Biotechnology. He teaches Protein Technology and Downstream Processing and Bioprocess Engineering. He also acts as area head and Dep. Director of Research in the Austrian Centre of Industrial Biotechnology. He is currently working in the field of bioengineering of proteins, plasmids and viruses with special focus on expression, downstream processing and characterization of large biomolecules.
As a proliferate researcher he has more than 320 publications on recombinant protein production and bioseparation, 15 patents and 12 book contributions and recently a monograph entitled “Protein Chromatography , Process Development and Scale Up”. He is executive editor and co-founder of Biotechnology Journal, and member of editorial boards from numerous journals in the area of biochemical engineering.
Niklas Andersson has a PhD in chemical engineering with focus on model-based engineering. He has previously worked with model-based simulation, calibration and optimization. His research has treated parameter estimation of large systems that arise when modelling process plants. The current research involves the integration of column sequences, real-time control and monitoring of chromatography steps.