Scale, Development Stage

Figure 5.11 Mass indices and environmental factors E at different process development stages for the synthesis depicted in Scheme 5.7. The parameters have been determined using the software EATOS (L) laboratory (f 0.1 kg), (P) pilot (f 400 kg), and (O) operation (f 1 000 kg) scale.

Based on these positive results, a continuously operating Cytos Pilot Plant was constructed by CPC Systems GmbH and is used for fine chemical production. The results of the evaluation on production scale confirm those results obtained already during the process development stage, which have been discussed in detail elsewhere. ... 

A comparison of results for fire effluents from full scale and small scale fire tests has to be done in steps. A full scale fire is a developing event where temperature and major constitutions changes continously. A small scale fire test either take one instant of that developing stage and try model that or try to model the development in a smaller scale. On a priority one level rate of heat release, temperature, oxygen concentrations and the ratio of C02/C0 concentrations have to be similar for a comparison. The full scale fire experiments reaches a temperature of 900 C at the moment of flashover, while the small scale fire tests are reaching temperatures just above 400 °C for NT-FIRE 004 and the cone experiments. For the DIN 53436-method the temperature was set to 400 °C. 

Restrictions which may exist for the choice of a commercial reactor need not be imposed at the development stage. In some cases, a reactor of one type may be best for acquiring data in model characterisation, whereas a reactor of another type might be more suitable for full-scale production. (The cautions expressed in Sect. 4 must be taken into account.) Continuous flow back-mixed reactors can be very useful for kinetic studies because the absence of concentration gradients can reduce uncertainties in concentration measurements. When these reactors have attained a steady state, many of the problems associated with stiffness (see above) can be avoided. 

In JP monographs, the specification value and testing procedure are described as a comparative limit test for the quantity of heavy metals that exist in drug substances as inorganic impurities. The permissible limit on the ppm scale for heavy metals (as Pb) is prescribed as the specification value. From the development stage to the establishment of the limit test method for a monograph, the validation in place has to be done for both the quantitative method for actual measurement and the comparative limit method with the control solution. However, the quantitative procedure has not been stated in the section on the heavy metals limit test in the JP s General Tests and other Japanese official... 

The clinical development stage comprises three distinct components or phases (I, II, and III), and culminates in the filing of the NDA/MAA. Each phase involves process scale-up, pharmacokinetics, drug delivery, and drug safety activities. During phase I clinical development, the compound s safety and pharmacokinetic profile is defined. The determination of maximum concentration at steady state (Cmax), area under the plasma concentration time curve (AUC), elimination half-life, volume of distribution, clearance and excretion, and potential for drug accumulation is made in addition to studies that provide estimates of efficacious doses. Dose levels typically... 

Bioprocessing addresses the phases, developments, and process unit operations required to take a technology from the conceptual or bench-scale stages of development to the pilot, demonstration, and commercial development stages. These critical steps in technology development o ften stand between the invention and the ultimate goal of commercial success. 

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