Production operations, performance parameters

Although considerable studies on the use of centrifugal fields in chemical processing have been reported for lab- and pilot-scale operations, little information is public on scale-up criteria for either performance parameters or equipment design. Three examples of commercial use of centrifugal fields are available for review. These include liquid-liquid extraction, water deaeration, and reactive stripping for hypochlorous acid production. 

In volume limited applications, high density propellant combinations are favored and some appropriate trade-off between performance and density is established. In a truly volume limited system as shown in section IV. A. 1., the appropriate performance parameter is the product of the specific impulse and the propellant bulk density, a quantity usually labeled the density impulse. Conceivably, mixture ratio may be determined by yet other vehicle system considerations. If a new propellant combination is to be utilized in an existing vehicle, the optimum mixture ratio may be influenced by such considerations as existing pump flow rate capacities, tank volumes, and structure load carrying capacities. Even other system considerations, such as the desirability of operating at equal fuel and oxidizer volume flow rates to allow interchange of fuel and oxidizer flow hardware, may determine the propellant mixture ratio. 

The preparation of any pharmaceutical product requires controls over the production operations to assure the end result is a product that meets the required quality attributes. The methods utilized for this control are supported by formalized validation studies in which proof of consistency is demonstrated by appropriately designed experiments. The definition of appropriate operating parameters is the primary objective of the development activities and is further confirmed during scale-up to commercial operations. The validation supports that the routine controls applied to the process are appropriate to assure product quality [36], This is typically accomplished in formalized validation activities in which expanded sampling/testing of the product materials is performed to substantiate their uniformity and suitability for use [30],... 

Any given mixing operation is carried out in order to accomplish some particular action. A primary object of a good experimental program is to establish clearly the nature of one or more parameters by which the degree of performance of this action can be expressed. The problem is sometimes simple in the case of chemical reaction without any by-products, product yield is a reliable performance parameter. In more complex cases, both the amount of desired product and the extent and/or nature of other substances produced must be considered in assessing the system performance. Often physical considerations, like particle size of the material produced, must also be considered. 

Electrochemical reaction engineering deals with modeling, computation, and prediction of production rates of electrochemical processes under real technical conditions in a way that technical processes can reach their optimum performance at the industrial scale. As in chemical engineering, it centers on the appropriate choice of the electrochemical reactor, its size and geometry, mode of operation, and the operation conditions. This includes calculation of performance parameters, such as space-time yield,... 

Before execution of the cleaning validation, the cleaning procedures should be in the form of approved standard operating procedures (SOPs). These procedures should be detailed enough to be reproducible. Parameters such as detergent type, detergent concentration, exposure time, rinse temperature/rinse time, and water pressure/flow rate should be included in the procedure. The final rinse is usually performed with water for injection (WFI). The production operators should be trained in these procedures and their training should be documented. 

The launch of a new product, through the manufacturing operation, should be attended by a deliberate but temporary overkill of controls . The intention must be to measure the quality of the product as it progresses from one operation to the next as well as to establish other performance parameters such as ... 

Performance parameters reflect the outcome of a given step and indicate that the process gave the desired result [14] or quality attribute. They are uncontrolled performance variables [15] without a control action [35]. Their natural variation is defined by operating history specifically, their variability is characterized from known historical data or estimated based on similar process performance [35]. Similarly, output variables reflect the step outcome and indicate performance was acceptable in terms of performance attributes for the step (e.g., titer and yield) or properties of the product stream (e.g., product homogeneity, purity, contaminant levels, and chromatography peak shape) [3,14]. Still another term used is critical Ys (analogous to dependent variables), defined as product and process output variables that relate to critical quality attributes (CQAs), which are measurable outputs of each process step that are used to provide evidence that the step performed correctly [37]. 

Process characterization defines process capability and facilitates prospective process validation at the production scale [40]. Full process characterization is valuable in maintaining smooth manufacturing operations and minimizing lost batches, and it provides supporting information for lot release justification for atypical batches [15]. Its goals are to identify key operating and performance parameters, define control limits for key process parameters, demonstrate robustness of the commercial process, and provide technical information about the process [68]. The steps involved in process characterization include risk assess-... 

Operating MSR under novel process windows, the key performance parameters can be increased by a few orders of magnitude. A few examples are presented here. In the case of esterification of phthalic anhydride with methanol 53-fold higher reaction rate between 1 and 110 bar for a fixed temperature of 333 K was observed [14]. A multiphase (gas/liquid) explosive reaction of oxidation of cyclohexane under pure oxygen at elevated pressure and temperature (>200 C and 25 bar) in a transparent silicon/glass MSR increased the productivity fourfold. This reaction under conventional conditions is carried out with air [15]. Another example is for the synthesis of 3-chloro-2-hydroxypropyl pivaloate a capillary tube of 1/8 in. operated at 533 K and 35 bar, superheated pressurized processing much above the boiling point, allowedto decrease reaction time 5760-fold as compared to standard batch operation [16]. The condensation of o-phenylenediamine with acetic acid to 2-methylbenzimidazole in an MSR is an impressive example of the reduced reaction time from 9 weeks at room temperature to 30 s at 543 K and 130 bar [17]. 

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