Optimal process development

TIPS To Efficiently Optimize Process Development in the Laboratory... 

In the new product development, many aspects of product performance, production, and regulations have to be defined. The most elaborate systems are used in pharmaceutical industry because of the very high cost of their research. It is estimated that entire process from research to implementation involves over 10,000 interdependent activities. These activities include five principles of optimal process development, such as ... 

CMP processes have been developed, though for Ge/SiGe the CMP process is already in an advanced level. Overall the implementation of Ge/SiGe as high mobility channel material is already more mature compared to the activities on III—V materials. As only limited experimental CMP data are currently available, it is clear that these high mobility material CMP processes could stiU be improved with optimized consumables and recipe parameters. Whether or not this optimized process development will be needed remains to be seen, as it is not 100% sure yet that these high mobility materials will indeed be introduced into the <10 nm CMOS technology nodes. 

The original hot carbonate process developed by the U.S. Bureau of Mines was found to be corrosive to carbon steel (55). Various additives have been used in order to improve the mass transfer rate as well as to inhibit corrosion. Vetrocoke, Carsol, Catacarb, Benfteld, and Lurgi processes are all activated carbonate processes. Improvements in additives and optimization of operation have made activated carbonate processes competitive with activated MDEA and nonaqueous solvent based systems. Typical energy requirements are given in Table 9. 

The first two categories, clarifying and crossflow filters, have been very well developed and optimized for use in biotechnology and standard wastewater treatment applications. Equipment is easily available for these applications, whether as small 0.2 micron sterilizing filter used to terminally sterilize 100 ml of product solution, or a small 500 ml crossflow filter used to concentrate a small amount of antibody solution. Many vendors of this equipment to wastewater treatment applications have their origins in the CPI (Chemical Process Industries), and have incorporated many of the scale-up and optimization properties developed in much larger units used in large scale chemical production. As a result, these two filtration unit operations are one of the most optimized and efficient used in wastewater treatment. 

The first component of the systems approach to error reduction is the optimization of human performance by designing the system to support human strengths and minimize the effects of human limitations. The hiunan factors engineering and ergonomics (HFE/E) approach described in Section 2.7 of Chapter 2 indicates some of the techniques available. Design data from the human factors literature for areas such as equipment, procedures, and the human-machine interface are available to support the designer in the optimization process. In addition the analytical techniques described in Chapter 4 (e.g., task analysis) can be used in the development of the design. 

In current practice the fluorescence assay is often followed by the use of hybridization techniques when more selectivity is required. We have for instance used the fluorescence techniques to obtain data on the nucleic acid content of malaria vaccine proteins produced in Escherichia coli. The rapid turnaround time of the fluorescence assay is particularly useful during the early stages of purification to determine the optimal process conditions. After the final process has been arrived at and a variety of methods used to assess the nucleic acid content (including the hybridization techniques), the fluorescence method can be developed for routine quality-control purposes. In certain cases, particularly at high protein concentrations, the dye may bind to the protein with... 

The SimuSolv optimize function can be used for minimization of a user defined cost expression. However, at this early stage of process development, no attempt was made to determine parameters for an economic optimum. Instead, many simulations were run to determine parameter sensitivities and malce comparisons of various possibilities which satisfied a necessary objective of reaching the desired low level of residual monomer. Attention was given to minimizing total finishing time, the amount of initiator required and residual initiator level at the end of the finishing step. Based on simulation results for... 

According to an older German study, the time-to-market of new chemical products, besides optimizing the internal research and development as outlined above, could profit from faster administrative approval by the public authorities [138]. For example, the phase of getting the concession has a share of about 20% of the overall time for process development, amounting on average to 7.5 years in Germany. Process development in other countries is faster, e.g. 5.0 and 5.7 years in Japan and the USA, respectively. 

Vor dem Sprung in die Produktion, Chemie Produktion, December 2002 Prognoses on speed of implementation PAMIRmarket study industry s demands numbering-up risks expert opinions Clariant pigment micro-reactor production smallness not an end in itself general advantages of micro flow industrial process development and optimization share of reactions suited for micro reactors hybrid approach standardized interfaces start of industrial mass production of micro reactors unit construction kit [208],... 

In another investigation, process development and optimization studies were undertaken [67]. In the framework of a study conducted as contract research for... 

Besides applications in serial screening, the process development and optimization studies mentioned above referred to the general advantages of micro flow processing in terms of enhanced heat and mass transfer [67] (see a more detailed description in [26]). 

In order to overcome the optimization process of the (hyper) polarizabilities calculations, we have been led to deeply study the perturbational and variational methods and in particular the variation-perturbation treatment introduced by Hylleras (20) since 1930. We will not develop here the theoretical framework of the recent study of N. El Bakali Kassimi (21). We propose criteria for generating adequate sets of polarization functions necessary to calculate (hyper) polarizabilities. 

In any catalyst selection procedure the first step will be the search for an active phase, be it a. solid or complexes in a. solution. For heterogeneous catalysis the. second step is also deeisive for the success of process development the choice of the optimal particle morphology. The choice of catalyst morphology (size, shape, porous texture, activity distribution, etc.) depends on intrinsic reaction kinetics as well as on diffusion rates of reactants and products. The catalyst cannot be cho.sen independently of the reactor type, because different reactor types place different demands on the catalyst. For instance, fixed-bed reactors require relatively large particles to minimize the pressure drop, while in fluidized-bed reactors relatively small particles must be used. However, an optimal choice is possible within the limits set by the reactor type. 

Evolutionary methods cannot guarantee the development of an optimal process. In the past, process optimization in fine chemicals manufacture was not that important because the vast majority of products were H(igh)-A(dded)-V(alue) products, and even non-optimal manufacture provided a sufficiently large profit. Today, the number of competitors in this field is growing fast, and this competition forces companies to optimize processes via better... 

Table 5.4-9 gives examples of the use of reaction calorimetry in process development and optimization. 

Kinetic models developed for reactor scale-up are also suitable for reactor optimization. The development of detailed kinetic models accounting for all factors influencing process rates is a time-consuming task. Therefore, more empirical simplified models are often used for simulation and optimization of existing reactors. 

B. Bjorkman, J. Eriksson, L. Nedar and C. Samuelsson, Waste Reduction through Process Optimization and Development, JOM, Vol. 48, No. 3, p. 45, March 1966. 

Validations fall into two types prospective and retrospective. In prospective validation (see flow chart in Figure 2) the validation is done in a sequential manner, involving installation qualification and operational qualification (IQ/OQ) of equipment (e.g., chromatography instrumentation or column hardware). Appropriate calibrations accompany the IQ/OQ. Process qualification, or PQ, involves formal review and approval of a PQ protocol, execution of this protocol, and issuance of a formal PQ report which includes data analysis and recommendations (i.e., approval/certification of the process). If the process is not approved, the report may recommend a redesign or redoing of the validation protocol and, in some cases, a return of the process to process development for further optimization. 

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