Process, changes optimization

Process Changes Optimization. In the original process, considerable quantities of acetylene and ammonia had to be disposed of as waste products. After the drastic reduction in the amount of resin produced, the consumption of these raw materials could be carefully scrutinized. Improvements can be achieved by ... 

It is beneficial to consider the optimal solution for this case study shown by Fig. 1.3, with the process changes marked in thick lines The solution features... 

Considerable attention should be paid to obtaining samples truly representative of the production process early in method development. Production processes generate mixtures that are far more complex and variable than may be generally realized therefore, a separation developed using an early production sample may prove to be inadequate for a later sample. Minor peaks observed in the chromatogram, whether known or unknown, serve as a record of the consistency of the process and can be used to monitor process changes. Sometimes a particular peak can be associated with a desirable or undesirable property of the product and used for controlled process optimization. 

Clearly, our effort toward understanding the course of the dehydrogenation reaction was key in achieving optimal performance for production. The understanding of this reaction, however, goes beyond the finasteride process changing the way that we think about quinone oxidations. 

The FDA guidance on IVIVC development and validation defines a number of circumstances where an IVIVC can be used to justify a biowaiver request in support of (1) level 3 process changes, (2) complete removal or replacement of non-release-controlling excipients, (3) level 3 changes in release-controlling excipients, (4) approval of lower strengths, and (5) approval of new strengths. Additionally, use of the IVIVC to justify biorelevant dissolution specifications is cited as the optimal approach. 

Standardizing the coefficients of the model entails modifying the calibration equation. This procedure is applicable when the original equipment is replaced (situation 1 above). Forina et al. developed a two-step calibration procedure by which a calibration model is constructed for the master (F-X), its spectral response correlated with that of the slave X-X) and, finally, a global model correlating variable Y with both X and X is obtained. The process is optimized in terms of SEP and SEC for both instruments as it allows the number of PLS factors used to be changed. Smith et al. propose a very simple procedure to match two different spectral responses. 

Brent Pollock (Biomira Inc.) presented a talk on the rational development of a second-generation production process for recombinant human interleukin-2 that incorporates recent advances in cell expression systems, fermentation optimization, protein extraction, refolding, and purification. A key concept of this talk was to know thy protein. The driving forces for process changes were regulatory concerns/robustness, economics, the ability to use standard equipment, and the elimination of bottlenecks in the process. 

This process may take several months. If initial specifications on product quality cannot be met, then changes may be made to mechanical equipment present, chemicals applied, rate of crude-oil charge, type of crude oil processed, or product quality specifications. The process of optimizing the desalting program then starts again. On particularly difficult crude oils this process may last many years, as is the case in refineries processing heavy crude oil. 

All these studies on the process are generally done after the optimization of the formulation. However, because the effects of formulation and process changes are not generally independent, it may become necessary to carry out some sort of process study at the same time as the formulation optimization. 

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