Scale-Up, Cycle Transfer, and Maximum Throughput Capability for Lyophilized Products

Why Should You Attend:

By far, one of the most difficult tasks in getting a lyophilized product from the laboratory bench to the commercial freeze-dryer is scale-up, or cycle transfer. Problems that typically arise from scale up issues include shattered vials, melt back, collapse, higher residual moisture levels, and decreased shelf life.

This webinar will help you identify the critical scale-up issues for your lyophilized product and understand equipment differences. You will learn how to use this knowledge to successfully produce a consistent, quality, product whether it is being dried in a development-scale dryer, a clinical-scale dryer, or a large commercial-scale dryer. The presenter will also discuss the phenomenon known as sonic water vapor flow or, “choked flow” in a freeze-dryer. This is a problem that typically manifests itself when scaling-up a lyophilization cycle or transferring that cycle to another freeze-dryer, and is characterized by a loss of control over the vacuum in the sample chamber. This webinar will cover the reasons for choked flow, how to recognize choked flow is occurring, and how to prevent this from happening in future cycles.

Areas Covered in the Webinar:

• Critical parameters in scale-up and cycle transfer
• Scale-up strategy
• Mapping studies
• Dryer configuration
• Determining and preventing choked flow conditions
• Understanding the differences between development, pilot, and productions dryers
• Proper information gathering (IQ, OQ, manufacturer specifications, operator knowledge, etc.)
• Design and execution of a well thought out scale up strategy
• Identifying choked flow conditions, and designing a cycle to prevent choked flow from occurring

Who Will Benefit:

This webinar will provide valuable assistance to those companies involved in the handling of powders, lyophilized products, solid pharmaceutical dosage forms, and dried foods. Personnel who will benefit include:

• Development scientists
• Product and process engineers
• QA/ QC
• Product managers
• Manufacturing
• Operations

Jeff Schwegman
Founder and CEO, AB BioTechnologies LLC

J. Jeff Schwegman, Ph.D. is currently the founder and chief executive officer of AB BioTechnologies (www.ab-biotech.com) where he develops formulations, lyophilization cycles, determines residual moisture by Karl Fischer, and provides thermal characterization studies including freeze-dry microscopy and DSC. Additionally, Dr. Schwegman specializes in speaking and consulting in parenteral pre-formulation, formulation, analytical, and lyophilization of both small molecules and large biomolecules. He also holds patents and develops new technologies within the lyophilization field.

Dr. Schwegman received his BS in Biochemistry from Indiana University in 1992 and began working at Cook Imaging in Bloomington Indiana, where he gained experience in analytical, formulation and process development. In 1999 he began graduate study in the Department of Industrial and Physical Pharmacy at Purdue University under the direction of Dr. Steve Nail, where his focus of research involved studying changes in the physical structure of biological molecules during lyophilization.

Dr. Schwegman received his PhD from Purdue University in 2003 and returned to Bloomington where he worked at Baxter Pharmaceutical Solutions as a Research Scientist in the Pharmaceutical Development group. In November 2005, he left Baxter and formed BioConvergence LLC with 3 other founders which specialized in developing new formulations and manufacturing processes for parenteral products. In February 2008, he left BioConvergence, which has become a successful company, to form AB BioTechnologies. He is currently the course Director for a 4-day course called “Lyophilization Technology, a Hands-On Approach”, which he teaches through SP Scientific. He routinely lectures around the world on formulation, stabilization and process development of lyophilized products.

Topic Background:

Lyophilization cycle scale-up and cycle transfer between dryers has traditionally been one of the most challenging issues in manufacturing. Cycles that have been designed on development-scale equipment, and are producing acceptable product, can suddenly start suffering from both physical and chemical instability when scaled-up to a larger freeze-dryer, or transferred between production freeze-dryers. Without understanding the scientific principles behind scale-up and cycle transfer, many companies will try tweaking the cycle parameters when problems are encountered during scale-up. While this approach may work occasionally, often, it will lead to additional problems such as excessively long cycle times, shattered vials, higher residual moisture content, etc.

Taking the time to design and execute a well thought out scale up study will ensure that cycles and products will transfer seamlessly from dryer to dryer without costly time delays and product rejection. One issue in particular that has been observed during scale-up is loss of vacuum control within the product chamber of the freeze-dryer. Common sense would dictate a vacuum pump failure or a vacuum leak as the source of failure; however, the phenomenon known as, “choked flow”, is something completely unrelated to vacuum pumps and vacuum leaks. Being able to identify the difference between vacuum system issues and choked flow makes correcting the problem much easier, saving both time and money in diagnosing and correcting the problem.

Many problems have arisen in the past when designing and scaling-up lyophilization cycles because this process was more of an art than a science, and cycles were designed and scaled-up based on a "trial and error" approach. Companies that do not understand the scientific principles behind their cycles run the risk of being delayed in getting their products approved and on the market, which can have a dramatic impact on their profit margin.

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