Process, changes scale

The influence of transport process in two-phase reaction systems depends on flow conditions, which change with the size of the equipment. This is the reason for the historic observation that performance changes as processes are scaled up and therefore scale-up should be done in several steps, each limited to a small increase in size. This is a slow and expensive method and still does not guarantee optimum design. 

During full scale production, particularly initially, chemical reaction hazards may be reevaluated. More tests may be necessary as a consequence of increased knowledge of the process, changed production requirements, or other process changes such as the use of different feed stocks. 

Kuo SW, Chan SC, Chang FC. Correlation of material and processing time scales with structure development in isotactic polypropylene crystallization. Macromolecules 2003 36 6653-6661. 

For purification, scale-up considerations are important even in the earliest phases of development. It is important to avoid the use of purification techniques of limited scale-up potential even for early clinical production because thorough justification of process changes and demonstration of biochemical comparability are necessary prior to product licensure. For successful scale-up, it is important to understand the critical parameters affecting the performance of each purification step at each scale. Conversely, it is important to verify that the scaled-down process is an accurate representation of the scaled-up process, so that process validation studies, such as viral clearance and column lifetime studies, can be performed at the laboratory scale. 

Irrespective of the type of coating process used, the potential process changes that commonly occur on scale-up include ... 

The process of scale-up in the pharmaceutical industry generally involves moving a product from research and development into production. Numerous pitfalls could be met on this path. It is a well-known fact that often the production process cannot achieve the same product quality as was envisioned in the development and pre-approval stages. Losses in terms of effort and money can be enormous, which is why scale-up and postapproval changes are so important and so strictly regulated. 

This short-term pilot-scale evaluation was accomplished by testing various filtration units under the same set of process conditions. Not only did this work result in a final equipment specification, but revealed significant wafer fabrication process changes. The conclusions of this process design project are listed below ... 

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