Cambridge Healthtech Training Seminars

August 6-7, 2015

DAY 1 2:00-5:30 pm • DAY 2 8:30 am - 4:30 pm

(TS6) Bulk API: Freeze-Thaw Operations

Instructor: Parviz A. Shamlou, Ph.D., George B. and Joy Rathmann Professor, and Director, Amgen Bioprocessing Center, Keck Graduate Institute

Freeze-thaw is a key unit operation in biomanufacturing, but despite its wide spread use, it is treated more as activity than a unit operation. In this seminar a new method of freeze–thaw is described using experimental data obtained from freezing of purified API solution including proteins and monoclonal antibodies. The method is based on freezing protein solutions in rectangular rather than cylindrical containers. It is hypothesized that the change in container geometry allows for linear scale-up of the freeze–thaw operation based on equivalency of temperature–time profile. The hypothesis is tested using freeze–thaw data from a miniature (30 ml) and a 2.4 litre container. Computational fluid dynamics techniques are used to simulate the freeze process and the simulations are compared with experimental results. Protein quality is assessed as a function of freeze conditions using dynamic light scattering, circular CD, size-exclusion and reverse-phase HPLC measurements. The results demonstrate the applicability of the new approach. Freezing of protein solution at concentrations of approx. 200 mg/ml is shown to be possible with no damage to the molecule for multiple cycles of freeze–thaw. The results are scaled-up and confirmed using data from full-scale operation in a biomanufacturing setting.

• Freeze operation of bulk API including proteins and monoclonal antibodies
• Design and use of a scale–down (10-20ml) freeze-thaw device
• Definition and characterization of commercial freeze unit operation
• First-principle modeling of freeze-thaw operation
• Predicting freeze rate and freeze time in commercial scale operation
• Impact of freeze-thaw operation on quality of API
• Impact of freeze- storage temperature on storage of API
• Container-closure for freeze operation
• Monitoring freeze-thaw operation
• Impact of freeze operation and protein concentration on sub-visible particles
• DOE and QBD issues in API freeze-thaw operation

Target audience:
Scientists and engineers working in different functional areas in API and Drug Product (DP) including Bioprocess Design and Development (BR&D), Analytical and Biophysical Characterization and Drug Product Formulation.

What students will gain from attending the seminar:
Students attending the seminar will learn how to combine and use basic knowledge of heat transfer, scale-down, first principle modeling, DOE and QBD to design unit operations for freezing and thawing of bulk API in a biomanufacturing setting.

Instructor biography: 

Dr. Shamlou is chemical engineer with over 30 years of academic and industry experience bioprocess design and development with emphasis on biopharmaceutical therapeutics. Dr. Shamlou received his first academic appointment in 1983 in the Department of Chemical and Biochemical Engineering at University College London (UCL). At UCL, Dr. Shamlou pioneered new areas of bioprocessing research at the interface with life science discoveries, with an emphasis on the creation of new scale-down methods and miniaturization to speed up the translation of discovery to outcome, and to allow prediction of full-scale bioprocessing of advanced biologics, including therapeutic genes, antibodies and cellular systems. This work included biophysical characterization of non-viral drug delivery systems, the design of miniaturized techniques for fermentation and cell-culturing operations and the bioprocess engineering issues related to manufacturing of advanced vaccines and tissue-engineered products. His research at UCL was supported by 20 different industry and government grants and 35 PhD and postdoctoral researchers.

In 2003 Dr. Shamlou joined Eli Lilly and Company's headquarters in Indianapolis, Indiana where he was responsible for innovation and technology evaluation for development and commercialization of biotherapeutics. At Eli Lilly and Company Dr. Shamlou extended his first principle approaches combined with scale-down techniques to improve manufacturing operations of registered products and speed up development of pipeline molecules from discovery to commercialization. Projects worked on included insulin, human growth hormone and several monoclonal antibody molecules currently in development for treatment of Alzheimer's, rheumatoid arthritis, cancers, diabetes and lupus.

During his 30 years of industry and academic work Dr. Shamlou also served on several scientific committees and boards including European Federation of Biotechnology and UK's Institution of Chemical Engineers (IChemE). Dr. Shamlou was the Editor-in-Chief of the peer-reviewed Journal of Biotechnology and Applied Biochemistry (2003-2012). He is a Fellow of the British Institution of Chemical Engineers. He is the co-author of over 200 publications in peer-reviewed journals, chapters in books and presentations at national and international conferences and reports.

In March 2014, Dr. Shamlou joined the Keck Graduate Institute of Applied Life Sciences (KGI). He was appointed George B. and Joy Rathmann Professor of Bioprocessing and Director of the Amgen Center for Bioprocessing following a nationwide search to replace the founding director.

Each CHI Training Seminar offers 1.5 Days of instruction with start and stop times for each day shown above and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment breaks, as applicable, and lunch is “on your own”.

Each person registered specifically for the training seminar will be provided with a hard copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend the seminar, but after these have been distributed no additional books will be available.

Those not attending a full training seminar, but who are registered for other tracks on those days of the conference, may participate in the training seminar sessions. We ask that those joining the seminars while they are in progress enter the room only during scheduled break periods to avoid disrupting the class in progress.