Process development is a complex and diverse field because the targets of process development, its strategies, and approaches differ depending on the kind ofproduct and the production scale. These can range from millions of tons of basic chemicals, where an improvement in the reaction selectivity of less than 1% saves several million Euros, to sensitive pharmaceuticals, where world production varies between 100 kg and several tons per year under strict quality requirements (GMP). For any product in between these extremes, an adequate process needs to be developed, taking into account a number of specific basic conditions:
• Proportion of material costs
Any given product can be classified by the ratio of material costs to total production costs. For large-scale chemicals, material costs may exceed 70% of the total cost, whereas for fine chemicals the percentage may be well below 10%. The higher the percentage of the material costs in relation to total costs, and the higher the scale, the more will the process aim at ''selectivity'' rather than at ''space-time yield.''
• Available budget
The process development for the production of bulk chemicals requires a far larger budget than the process development for the production of fine chemicals. This factor influences the size and dedication of the combinatorial screening apparatus. For big projects, it is profitable to design dedicated, process-tailored workstations, whereas for small projects commercially available standard equipment is usually favored.
The development of a new process for a bulk chemical can take more than 5 years, whereas the first 10 kg of a new pharmaceutical development candidate usually has to be delivered within a few months. If only a limited number of experiments can be performed before the next milestone, the effort to be put into the development of specific parallelization methods has to be considered precisely.
• Constraints given by existing equipment/plants
Since new processes in the area of fine chemicals usually have to be developed in accordance with the existing production facilities, the chemist has to consider whether the reactor where the target process is to be realized is already fixed and known.
In general, when developing a process for a dedicated plant, custom-made or specially adapted equipment is recommended, whereas for multipurpose plants a standard (commercial) parallel screening apparatus seems adequate.
Tab. 30.1. Factors which influence the design of parallelized equipment.
Scale of the process Plant
Dedicated, tailored Often primary catalyst
0.01-1000 tons Batch
Multipurpose 10 days to 2 years Low Low
Multifunctional, standard Late-stage process screening
Ratio material costs per total costs Budget for process screening Screening apparatus Screening stage, where started screening
Given that in the fine chemical business dedicated plants will only be built for runaway successes, the production of most fine chemicals requires processes with a high degree of simplicity which fit a standard apparatus. • Topical stage of development
Improving an existing industrial process usually includes minimizing investments and changing as little as possible in the plant's equipment. Often, process parameters are optimized within narrow margins determined by the already existing plant reactors, which can be changed only at extraordinary costs. In this case, it is not necessary to set up a primary screening for a totally new synthesis. If the goal is to find a new, revolutionary route to a product using new feedstocks or totally different chemistry (''dream reactions''), the situation is reversed.
All of these factors have to be taken into account when discussing parallelization in process development more precisely. Table 30.1 gives a short summary of the key issues.
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