Scale-Up on Process Performance and Product Quality

IMPACT OF SCALE-UP ON PROCESS PERFORMANCE AND PRODUCT QUALITY 

One of the chief concerns when scaling up biological process is the effect of minor variations in the microenvironment at different scales that may affect process yields and product quality. 

Due to the complex nature of biologies, extensive biochemical characterization of physicochemical parameters is needed to demonstrate product comparability upon scale-up. If any differences are detected, there is the possibility of having to perform animal and/or human studies to further demonstrate product comparability upon scale-up. 

There is so much concern about this issue that in some instances in the past, it has been considered preferable to increase the number of units instead of the scale of each unit of production to avoid potential differences in product quality. In some other instances, an approved biologic, even thought manufactured using less than ideal methods, may not be deemed to be replaced by a more advanced manufacturing method due to differences in the protein structure or composition. The market value of biologies and their complexity justifies this ultra conservative approach. 

Nowadays, however, the analytical tools and the cummulative regulatory experience available make it possible to propose upgrades of production methods to either preapproved or to already approved products. In order for these changes to be implemented, the sponsor needs to demonstrate that the product is comparable before and after the changes. 

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