Short Programs

Pharmaceutical Crystallization and Downstream Processing: Batch and Continuous Processing

This course is in development for 2013 or beyond. The below description should be taken as an example of content and is subject to change. If you are interested in this course, please
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Course Summary  |  Learning Objectives  |  Who Should Attend  |  Program Outline  | 
Participants' Comments  |  About the Lecturers  |  Location  |  Updates

Course Summary

Crystallization is a key component of almost all processes in the manufacturing of small molecule pharmaceuticals. Whether for purification of intermediates, formation of the product, or prevention of crystallization in amorphous products, crystallization is essential in both processing and development. In the new approach to pharmaceutical development and manufacturing, in which Process Analytical Technology (PAT), Quality by Design, and Continuous Processing play central roles, understanding not only the fundamentals of crystallization, but the connection of crystallization with downstream processing is essential.

The course will focus on the fundamentals of crystallization and downstream processing with an emphasis on problem solving. Control of critical quality attributes, such as crystal size distributions, polymorphs, impurity-crystal interactions, and morphology, is emphasized across key areas of downstream processing, with multiple approaches evaluated. The design of processes to yield optimal products will be a key aspect. In addition, cutting-edge technologies will be assessed. The entire course will emphasize enhancing both development and manufacturing efficiency via a systems and integration approach from crystallization to final dosage form.

Learning Objectives

The participants of this course will be able to:

1. Define the fundamentals of pharmaceutical crystallization and downstream processing.
2. Identify ways to enhance the efficiency of crystallization and downstream processing.
3. Apply state of the art systems, integration, and control strategies.
4. Analyze strategic approaches to crystallization and downstream processing.
5. Apply knowledge of cutting-edge pharmaceutical processing approaches and technologies.

Who Should Attend

This course is targeted for scientists and engineers in pharmaceutical development and manufacturing for whom crystallization or downstream processing more generally plays a role in their work. The course will be of particular benefit to those who wish to enhance their skill in efficiently and effectively solving technological problems that arise in pharmaceutical downstream processing. Those who should attend include:

• Chemists, pharmaceutical scientists, and engineers in pharmaceutical manufacturing
• Chemists, pharmaceutical scientists, and engineers in pharmaceutical development
• Managers responsible for pharmaceutical development, manufacturing, and regulatory affairs

Program Outline

Day One
Session 1--1.5 hours
Introduction: Quality by Design and “Continuous” Manufacturing applied to Crystallization and Downstream Processing, Strategic Approach and Business Case (Trout)

Break

Session 2--1.5 hours
Crystallization fundamentals: Solubility, Supersaturation, Polymorphism (Myerson)

Lunch (provided)

Session 3--1.5 hours
Crystals, crystal growth, and nucleation (Myerson)

Break

Session 4--1.5 hours
Modeling of Molecular Systems and Solubility Predications (Trout)

Day Two
Session 5--1.5 hours
Batch and Continuous Processing (Myerson)

Break

Session 6--1.5 hours
Polymorphism, PAT, Quality by Design, and Continuous Processing (Trout)

Lunch (provided)

Session 7--1.5 hours
Regulatory issues in Pharmaceutical Processing: Current State and Future (Raju)

Break

Session 8--1.5 hours
Powder Handling, Filtration, Drying, Granulation, and Tableting (Myerson)

Day Three
Session 9--1.5 hours
Integration of Crystallization, other Separations Techniques, and Downstream Processes (Trout)

Break

Session 10--1.5 hours
Control and Systems Approach to Crystallization and Downstream Processes (Braatz)

Lunch (provided)

Session 11--1.5 hours
Problems from Audience and Case Studies

Participants' Comments

Senior Regulatory Affairs Specialist, Infinity Pharmaceuticals
“I really benefited from learning the fundamentals of crystallization, polymorphs, crystal morphology, etc. As a non-chemist, I felt I took away a great background that I could apply to my job.”

Associate Scientist II, Gilead Alberta ULC
“The course I took was well explained and the outline was very easy to follow. The campus was beautiful and the state of the art technology was amazing.”

Fellow, Novartis Pharmaceuticals Corporation
“Comprehensive overview of science and engineering as applied to pharmaceuticals.”

About The Lecturers

Professor Richard D. Braatz
Richard D. Braatz is the Edwin R. Gilliland Professor of Chemical Engineering at MIT. He received his M.S. and Ph.D. degrees from the California Institute of Technology and held positions at Chevron, DuPont, and the University of Illinois before moving to MIT.

Professor Braatz’ research focuses on the engineering of manufacturing processes and products that arise in the pharmaceutical, chemical, and related industries. Much of his research has been in the development of models and systems technologies for the design of pharmaceutical crystallization processes to control molecular purity, polymorphic form, and size distribution. Braatz’ has consulted or collaborated with many pharmaceutical companies in the United States, Europe, and Asia including Merck, Bristol-Myers Squibb, Abbott Laboratories, Pfizer, and Eli Lilly. His contributions to crystallization process development in the pharmaceutical industry have been recognized by the AIChE Excellence in Process Development Research Award and the Collaboration Success Award from The Council for Chemical Research. He has coauthored 3 books and over 130 journal papers, and has one patent and one patent pending on process technologies.

Professor Allan S. Myerson
Allan S. Myerson is the Professor of the Practice in the Department of Chemical Engineering at MIT. Before joining MIT, he had a number of positions, including the Philip Danforth Amour Professor of Engineering at the Illinois Institute of Technology (IIT) in Chicago, the Provost and Senior Vice President at IIT (January 2003-June 2008), and Dean of Engineering and Science (January 2000-January 2003). Prior to his position at IIT Professor Myerson served on the faculty at Polytechnic University (NY), Georgia Institute of Technology, and the University of Dayton. Professor Myerson was educated at Columbia University (B.S.) and the University of Virginia (M.S. and Ph.D.).

Professor Myerson’s research focuses on separations processes in the chemical and pharmaceutical industry with an emphasis on crystallization from solution. He has published 5 books, including the Handbook of Industrial Crystallization 150 papers and is the inventor on 32 US patents. Professor Myerson serves as associate editor of Crystal Growth and Design, a journal published by the ACS. Professor Myerson has consulted for approximately 100 companies worldwide and was honored in 2008 with the American Chemical Society Award in Separations Science and Technology.

Dr. G.K. Raju
G.K. Raju is Executive Director for Manufacturing Initiatives at the Center for Biomedical Innovation (CBI) at MIT. He is also Distinguished Fellow and Chairman of the Biomanufacturing Steering Committee at the Center for Biomedical Innovation (CBI) at MIT. He is Chairman and CEO of Light Pharma Incorporated - a consulting and technology company that is focused on pharmaceutical and biotechnology manufacturing. He is also a Special Government Employee (SGE) of the U.S. Food and Drug Administration (FDA) and has served on a number of FDA Advisory Committees. Dr. Raju has also been Adjunct Professor of Industrial Pharmacy at Purdue University and Executive Director of the Consortium for the Advancement of Manufacturing of Pharmaceuticals (CAMP) for about ten years. He obtained his M.S. in Chemical Engineering from MIT in 1989, his M.B.A from the MIT Sloan School of Management in 1994, and Ph.D. in Chemical Engineering from MIT in 1998.

Dr. Raju has worked with or consulted for most of the top pharmaceutical and biotechnology companies. His expertise is in defining the strategic role of pharmaceutical development and manufacturing and enabling its performance with the pharmaceutical and biotechnology industry. He has benchmarked the pharmaceutical and biotechnology industry's manufacturing practices for a large number of years and has been involved in multiple organizational transformation efforts. His work focuses on pharmaceutical process innovation and addresses issues of manufacturing science, regulatory compliance, six sigma, operational excellence, systems dynamics, organizational learning, process analytical technology, on-line sensors, economic modeling, data analysis, pattern recognition, and knowledge based systems. Dr. Raju’s work makes extensive use of simulation. He is the author of several publications and book chapters.

Professor Bernhardt L. Trout
Bernhardt L. Trout is a Professor of Chemical Engineering at MIT. He is currently Director of the Novartis-MIT Center for Continuous Manufacturing and the Co-Chair of the Singapore-MIT Alliance Program on Chemical and Pharmaceutical Engineering. He received his S.B. and S.M. degrees from MIT and his Ph.D. from the University of California at Berkeley. In addition, he performed post-doctoral research at the Max-Planck Institute.

Professor Trout’s research focuses on molecular engineering, specifically the development and application of both computational and experimental molecular based methods to engineering chemical products and processes with unprecedented specificity. Since 2000, he has focused on molecular engineering for crystallization, formulation, and the development of pharmaceutical separation processes. In 2007, together with several colleagues from MIT, he set up the Novartis-MIT Center for Continuous Manufacturing, a $65 million partnership with the objective of transforming pharmaceutical manufacturing. In addition to Novartis, he has worked with many other pharmaceutical companies in research or consulting. He has published over 100 papers and currently has 6 patent applications submitted.

For more information on Prof. Trout and his research, please visit http://web.mit.edu/troutgroup/.

Location

This course takes place on the MIT campus in Cambridge, Massachusetts. We can also offer this course for groups of employees at your location. Please contact the Short Programs office for further details.

Updates

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