Process Optimisation Report

On completion of the work programme, a Process Optimisation Report should be written. This will summarise the results of the activities specified in the protocol and provide a rationale to define the operating limits for the process and the critical parameters affecting product quality or performance. The report should also conclude that the specifications for the raw active, excipients, components, in-process and product can be met. 

The Development Report should be concise and structured. Clearly, it cannot be finalised until development is complete, but the preparation is much easier if summary reports have been compiled during development, such as the product and process optimisation reports. The Development Report needs to be available to the FDA prior to the inspection, ideally, to give the FDA inspection team confidence that the product has been developed satisfactorily, perhaps resulting in a shorter inspection. 

After the process optimisation (Scheme 7), the final results gave similar yields to the ones reported in batch trials [19]. The overall conclusion was positive as the continuous reaction procedure afforded more constant yields, a safer handling of... 

However, as important as the Hu and Bentley Model is the stepwise approach to process optimisation that Hu and Bentley have reported [33]. The focus on quantitative analysis of protease degradation of the product over time, along with the similar approach followed by Cruz et al. [25], also indicate new directions to follow in mathematical modelling regarding product expression optimisation. 

Various models of SFE have been published, which aim at understanding the kinetics of the processes. For many dynamic extractions of compounds from solid matrices, e.g. for additives in polymers, the analytes are present in small amounts in the matrix and during extraction their concentration in the SCF is well below the solubility limit. The rate of extraction is then not determined principally by solubility, but by the rate of mass transfer out of the matrix. Supercritical gas extraction usually falls very clearly into the class of purely diffusional operations. Gere et al. [285] have reported the physico-chemical principles that are the foundation of theory and practice of SCF analytical techniques. The authors stress in particular the use of intrinsic solubility parameters (such as the Hildebrand solubility parameter 5), in relation to the solubility of analytes in SCFs and optimisation of SFE conditions. 

Reports of on-line SFE-FIPLC are rare, perhaps because the majority of analytes that have been extracted using SFE can be separated using either GC or SFC. On-line SFE-HPLC is often used to monitor extraction efficiencies. SFE-HPLC optimised for temperature (120 °C), pressure (384 bar), SCF flow and modifier (methanol) has been used for the quantification of Irganox 1010 and Irgafos 168 extracted from PP. In this case Thilen and Shishoo [12] varied three SFE parameters for optimisation of the extraction efficiency, and five parameters for the collection efficiency, see Figures 7.7 and 7.8. Despite these efforts, low recoveries were observed (Table 7.16). This was attributed to problems associated with the compounding process, and not to uncertainties in the extraction and analytical method. 

Does the organisation comply with the agreed requirements What problems and nonconformities have been revealed How can cost-effectiveness be optimised Are there any opportunities for improvement that can be realised Answers to these questions will be provided to the Chemical Leasing partners in a comprehensive report, which covers the certification process and documents not only results, but also opportunities for improvement, the keyword here being "Continuous Improvement Process". 

Recently, the evolutionary strategy (ES) has been successfully applied for the iterative optimisation of catalysts in a series of reactions [7, 10, 15, 27-30]. For all the case studies reported, the optimisation process was found to converge rapidly after typically four to six generations. 

In the mid-1990s few papers related the use ANN for catalysts development by predicting performances from their elemental compositions [35-38] but without clear efficiency due to limited data sets. Today, hundreds of catalysts can typically be screened in a week, which opens up the prospect of using ANNs as pre-screening tools for speeding up the optimisation process. This concept was recently reported for modeling quantitatively the performances of ODHE catalysts as a function of elemental composition [39]. 

Conducting polymers have already been well documented in conjunction with the classical ionophore-based solvent polymeric ion-selective membrane as an ion-to-electron transducer. This approach has been applied to both macro- and microelectrodes. However, with careful control of the optimisation process (i.e. ionic/electronic transport properties of the polymer), the doping of the polymer matrix with anion-recognition sites will ultimately allow selective anion recognition and ion-to-electron transduction to occur within the same molecule. This is obviously ideal and would allow for the production of durable microsensors, as conducting polymer-based electrodes, and due to the nature of their manufacture these are suited to miniaturisation. There are various examples of anion-selective sensors formed using this technique reported in the literature, some of which are listed below. 

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