Robustness, definition

An alternative, perhaps more robust definition of is provided by MP2 as... 

In broad terms, the process for producing a specification for a safe design involves hazard identification (HAZID), which asks what sort of accidents do we need to worry about , followed by detailed analysis to identify the magnitude of potential accidents. From a safety perspective, a most important step is the clear and robust definition of the safety functional requirements, i.e., the requirements for the control and protection systems on the completed plant. The history of accidents involving design failures shows a frequent root cause to be inaccurate or inadequate definition of the safety functional requirements (see Fig. 2.3). 

Note that the simple and robust definition of the delta-funetion proposed by Krishna and Tully ° was used in the above expression, but this ehoiee is by no means restrictive. The anharmonicity and the intermode coupling of the vibrational states enter naturally the expression via the friction-like term, which modulates the strength of the non-... 

The definition of "concepts" must be accompanied by explicit recipes for computing them is actual cases. There is no more space in theoretical chemistty for "driving forces", "effects, etc. not accompanied by specific rules for their quantification. The impact of a new "concept will be greater if the rules of quantifications are not restricted to ad hoc methods, but related to methods of general use in molecular quantum mechanics. A concept based exclusively on some specific features of a given method, e g. the extended Hiickel method, is less robust than a concurrent concept which may be quantified also using other levels of the theory. 

Paraphrasing Corey s historic definition of synthon [203], Desiraju defined a supramolecular synthon as a structural unit within a supermolecule that can be formed or assembled by known or conceivable synthetic operations involving intermolecular interactions [204], The robustness of the XB has allowed several supramolecular synthons based on this interaction to be identified and some examples have been presented in this chapter. 

Whereas this definition of ruggedness directly refers to infer-laboratory studies, the ICH definition of robustness clearly is related to infra-laboratory studies. 

The link between the ecological/ecotoxicological risk assessment and the risk management frameworks is demonstrated. The ecological risk assessment consists of seven interactive elements (Fig. 17). The quantitative and descriptive science used to conduct ERA (Table 5) does not answer, in a direct way, the question of what should be done to manage the risk. Science determines adversity, but the public determines acceptability (Fig. 18). But acceptable risk is a highly subjective and relative term. It is time and space-specific and depends upon definitions of quality of life and robustness of the environment. 

Summing up, a robust and easy to handle SMB-design uses 4 zones, a recycling pump fixed in respect to the columns and two pumps for the control of the outlet flow rates. Extremely high precision of all technical components of the SMB is needed. All pumps and valves have to be exactly synchronized. The flow rates should not vary by more thanl % from the preset value. All connections between the different parts of the system must be carefully optimized in order to minimize the dead volume. All columns should be stable and nearly identical in performance. If the SMB-technology is to be used in Biotechnology, GMP issues (cleaning, process and software validation) also have to be considered. In addition and as with any continuous process in that particular area, the definition of a batch could be a problem. 

However, the procedure for specifying the invertible part Q is not a definite, step-by-step recipe. There are several invertible parts that could be chosen. These problems are discussed in the book by Morari and Zafiriou (Robust Process Control, Prenhce-Hall, 1989). 

Method development and optimization are started with review of the currently available methods within the company or in literature. Available methods are used as a starting point and evaluated against the method requirements set in the method definition. If necessary the method is optimized or redeveloped in order to fulfill the requirements. DOE tools (response surface design) are preferentially applied to obtain the best optimal conditions in terms of robustness. Application of DOE methodology is not new in chromatography and DOE is frequently applied also for enantiomeric separations in Especially in... 

The USP definition of robustness is equal to that of the ICH (International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use), which is given below. 

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