Robust process

M. Morari and E. Zafiriou, Robust Process Control, Prentice-HaH, Inc., Englewood Chffs, N.J., 1989. 

Inherently safer design is a fundamentally different way of thinking about the design of chemical processes and plants. It focuses on the elimination or reduction of the hazards, rather than on management and control. This approach should result in safer and more robust processes, and it is likely that these inherently safer processes will also be more economical in the long run (Kletz, 1984, 1991b). 

It is inherently safer to develop processes with wide safe operating limits that are less sensitive to variations in critical safety operating parameters, as shown in Figure 4.3. Sometimes this type of process is referred to as a forgiving or robust process. If a process must be controlled within a very small temperature band in order to avoid... 

The main difference between robustness and controllability is that a capable or controlled process will stay within the desired parameters. A robust process can exhibit exclusions outside the control parameters, but the critical attributes wiU not be significantly affected by the excursion beyond specifications. 

The solution developed (see Figure 5.5) considers simultaneously, and in an optimal way, the most important aspects affecting the copper production. In order to cover the process itself and the necessary information and decision flow, the solution builds on a valid and robust process model that captures the main chemical reactions and is able to link the variable material amounts with predicted processing times. The main input data comprises ... 

Development of robust processes based on new catalytic reactor engineering solutions to improve energy and process efficiency and economics, and which combine reaction and separation. Special attention needs to be paid to cope with the natural variability in the quality of raw materials. 

If the uncertainty has a known structure, structured singular values are used. In the book by Morari and Zafiriou (Robust Process Control, 1989, Prentice-Hall) this topic is discussed in detail. 

Technical and business rationales (increase process robustness, process efficiency, improved quality, cost reduction, etc.)... 

In some manufacturing process analysis applications the analyte requires sample preparation (dilution, derivatization, etc.) to afford a suitable analytical method. Derivatization, emission enhancement, and other extrinsic fluorescent approaches described previously are examples of such methods. On-line methods, in particular those requiring chemical reaction, are often reserved for unique cases where other PAT techniques (e.g., UV-vis, NIR, etc.) are insufficient (e.g., very low concentrations) and real-time process control is imperative. That is, there are several complexities to address with these types of on-line solutions to realize a robust process analysis method such as post reaction cleanup, filtering of reaction byproducts, etc. Nevertheless, real-time sample preparation is achieved via an on-line sample conditioning system. These systems can also address harsh process stream conditions (flow, pressure, temperature, etc.) that are either not appropriate for the desired measurement accuracy or precision or the mechanical limitations of the inline insertion probe or flow cell. This section summarizes some of the common LIF monitoring applications across various sectors. 

Despite these caveats, IR is an excellent tool for API process monitoring because of its chemical information content. This is particularly valuable in early-stage development when it can yield crucial information about unexpected reaction intermediates and side reactions and therefore lead directly to a more robust process. Commercial instrumentation is widely available for this purpose [78] and development of cheaper, smaller and more rugged instrumentation continues apace [79]. For example, a miniaturised mid-infrared spectrometer and... 

Ahmed, S. and Sahinidis, N.V. (1998) Robust process planning under uncertainty. Industrial Engineering Chemistry Research, 37, 1883. 

It should be quite clear now that time and money spent designing a robust process (where all of the critical process factors have been defined and their impact well documented) has the potential to save time and money later on, especially during the time leading up to, and immediately after, product launch. Designing an optimal process also has great benefit in the training of process operators so that they become well informed about the critical constraints of that process. 

Robust processes will have owners that have defined roles, responsibilities, and accountabilities. These process owners must be fully dedicated to their process. They must know their process capabilities and expectations, the interrelationship between their process and other processes and manage them like a business unto themselves. Functional management must support process owners, and leadership must understand and lead the QMS effort as an ongoing program, treating it as the integral part of the business that it is. 

An example of a robust process is the design, development, and operation of a nonconformance process. Regulations require an operational process to identify, document, and correct nonconformances occurring in licensed pharmaceutical manufacturing facilities for approved products. Companies spend significant human... 

Leadership expects cost-efficient reliable results from their manufacturing operations. Management requires a capable workforce, equipment, facilities, and materials to manufacture the product. Employees require robust processes that are easy to... 

The palladium catalyzed coupling of haloazines and olefins is a robust process, which is usually run at an elevated temperatures in the presence of a simple catalyst and at least an equimolar amount of base to neutralise the formed hydrogen halide. The presence of a ring heteroatom might in certain cases lead to complex formation, which deactivates the catalyst and kills the process.63 The regioselectivity of the coupling is predominantly governed by... 

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