Scale-down changes

Study. Their location represents the range of the conditions that should be used in a statistically designed set of experiments for kinetic studies and not actual conditions at the particular location. This way, the same flow is again maintained on all three scales and the troublesome effect of changing flow conditions on scale-up can be eliminated. The proposed idea, for scale-up by scale-down from the view point of the catalyst, was proven to be effective in many industrial projects. 

Suffice it to say that almost all operations on scale are possible if money and time are not issues of course, money rarely flows freely, and time is one of the major issues for developing drugs. Operations are almost always changed in progressing from the discovery route to scale-up. The best approach for rapid, successful scale-up is to scale down operations to the lab, and then develop processes that can be scaled up by mimicking conditions that will subsequently be encountered on scale. 

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. 

This guidance provides recommendations to NDA and ANDA sponsors who intend to make changes to the product during the postapproval period. Changes include any change in components or composition of the product, the site of manufacture, the scale-up/scale-down of batch size, and/or the manufacturing process and/or equipment of an immediate-release oral formulation. 

Changes in Batch Size Postapproval changes in the size of a batch from the pilot scale used to manufacture product for clinical trials to larger or smaller commercial batch sizes require submission of additional information in the apphcation. Scale-down below 100,000 dosage units is not covered by this guidance. All scale-up changes should be properly validated and, where needed, inspected by appropriate FDA personnel. 

TABLE 6 Changes in Batch Size Scale-Up/Scale-Down... 

What would happen if the radii of the spheres were made smaller and smaller In general, changes in the magnitude of a parameter (size, temperature, time, velocity, field, etc.) ultimately lead to new phenomena Thus, the engineer knows well that scaling up or scaling down generally results in new modes of behavior. 

V. CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)... 

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